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Attention Deficit-Hyperactivity Disorder is one of the most common problems of children and adolescents and is a very common reason for visiting a pediatric psychologist or consultant. This disorder which has a profound effect on the lives of thousands of children and their families manifests in early childhood with symptoms of hyper activity, inattention and impulsivity. In studies conducted in western countries it has been pointed out that there is an association between ADHD symptoms and asthma in asthmatic children, and also the response to asthma treatment in children with ADHD is poor. This study is performed with the aim to evaluate the prevalence of ADHD in children referring to the clinic of Kashan Beheshti hospital.


Background: Clinical efficacy of a depigmented polymerized Phleum pollen extract has been shown in one large phase III studies with 1000 DPP/ml. To date dose-response studies are required to show optimal efficacy of an allergen dose. The conjunctival provocation test (CPT) is an outcome parameter accepted from the regulatory authorities (EMA). Method: 308 (ITT) patients with confirmed rhinitis and/or rhinoconjunctivitis were treated in a double-blind study with 4 doses of 100 DPP/ml, 1000 DPP/ml, 5000 DPP/ml and 10.000 DPP/ml allergen extract over 22 weeks in Germany, Poland, Spain and Czech Republic. A 1-day build-up phase applying 0.1 ml and 2 times 0.2 ml extract was followed by a maintenance period applying 0.5 ml in 3-4 weeks intervals. Before treatment a CPT was performed with increasing doses up to 3 HEP/ml of native Phleum extract, after treatment the CPT was repeated with doses up to 30 HEP/ml. The primary endpoint parameter was the percentage of patients with an increase of allergen extract to provoke a positive CPT after Allergen Immunotherapy (AIT). Secondary parameters were specific IgE, IgG1 and IgG4, Vitamin D baseline level as well as safety. The primary endpoint parameter was investigated using a hierarchic test procedure comparing the highest dose against the lowest, if statistically significant testing the next lower dose against the lowest until the difference was no longer significant. Results: The responder rates in the 100 DPP/mL and the 1,000 DPP/ mL groups were 72.9% and 72.3%, respectively (ITT), in the 5,000 DPP/mL (75.3%) and the 10,000 DPP/mL groups (77.4%). The respective differences to the 100 DPP/mL group were -4.5% for the 10,000 DPP/mL group, -2.5% for the 5,000 DPP/mL group, and 0.6% for the 1,000 DPP/mL group (ITT) . No statistically significant difference was found. For the PP set, similar results were observed. Vitamin D baseline results were low in all groups, but had no influence on the results. Specific IgEs remained stable in all groups whereas specific IgG1 and IgG4 showed dose-dependent increases. Systemic reactions occurred in 12.9% (100 DPP/ml), 10.8% (1000 DPP/ ml), 26.4% (5000 DPP/ml) and 33.3% (10.000 DPP/ml) of patients. 79.4% of SR were Grade 1, 8 .7% grade 2 and 1 grade 3 reaction occurred in the 100 DPP/ml group. Conclusion: We determined increased allergen amounts to obtain a positive CPT after AIT from 1000 -10.000 DPP/ml depigmented polymerized Phleum pollen extract. Since the CPT results did not discriminate the different doses the dose-finding study will be repeated with a different assessment method.


Wheat allergy is difficult to diagnose then other food allergens Suman Kumar Ent and Allergy Centre(INDIA), India World Allergy Organization Journal 2016, 9(Suppl 1):A21 Background Wheat allergy is common in children and adults.Skin prick tests and wheat specific IgE tests has low specific value for wheat then other allergens. The challenge tests are to be done to confirm Wheat allergy.It has been noticed that in patients of Wheat allergies the reactions may occur late .In normal food allergen challenges maximum number of reactions are found within one hour of food challenge and others in second hour. In wheat allergen challenge less number of reactions occur in first hour followed by some in second hours and rest occur after 2 hours of test. Objective To see wheather wheat challenge tests have delayed responses in patients of wheat allergy. Methods Database of patients of Wheat allergy attending ENT AND ALLERGY CENTRE(INDIA)PANCHKULA. Retrospective study of wheat allergy patients for last 3 years. Observations 68 patients of suspected wheat allergy were put on Wheat challenge tesrts. 28 were positive, 2 were still not conclusive and 38 were negative. In wheat allergy challenge tests 25% patients showed reactions in 1 st hour. 55% patients reacted in 2 nd hour and 20% reactions occurred after 2 hours.


Tgfβ1 level is associated with VDR gene polymorphism in children with allergy diseases Tatiana Sentsova 1 , Ilya Vorozhko 1 , Olga Chernyak 1 , Vera Revyakina 1 , Anna Timopheeva 1 , Andrey Donnikov 2 Method: Ragweed establishment: 1) Chamber study: Ten plants of ragweed were established in open-top chamber at different concentration of CO2 (380-400, 500-520, 600-620, 1000-1100ppm). 2) Field study: Beginning in March 2012 and 2014, a rural (Pocheon, Kyunggi-do, annual mean CO2: 230ppm) and urban (Kangnam, Seoul, annual mean CO2: 440ppm) locations were established. Seeds of common ragweed (Ambrosia artemisiifolia) and giant ragweed (A. trifida) were obtained from Daejin University from a common seed lot of ragweed. At final harvest, entire plants were collected. To determine qualitative changes in pollen, harvested pollen grains were suspended in 95% ethanol. The crude soluble pollen protein preparations were stored at -20°. Protein content of the extracts was quantified. Concentration of Allergens (common ragweed (Amb a 1) and giant ragweed(Amb t 5) was quantified through use of double sandwich ELISA. Results: 1) chamber study: 1) chamber study: Concentration of Amb a 1 was increased with increased CO2 Conc. (380-400, 500-520, 600-620, 1000-1100ppm: 18.4±5.0, 30.8±13.1, 42.5±11.2, 50 .1±21.2 ng/mL), Concentration of Amb t 5 was increased with increased CO2 Conc. (380-400, 500-520, 600-620, 1000-1100ppm: 22.1±6.8, 36.3±11.6, 48.3±19.5, 64.6±21 .3 ng/mL), 2) Field study: There were not significantly different between Pocheon (CO2 230ppm: 16.0±2.0ng/ mL) and Seoul (CO2 440ppm: 20.3±8.6ng/mL) in Conc. of Amb a 1, also Pocheon (CO2 230ppm: 24.5±6.9ng/mL) and Seoul (CO2 440ppm: 28.3 ±6.2ng/mL) in Conc. of Amb t 5, though Conc. of Amb a 1 and Amb t 5 were increased at Seoul than those at Pocheon. Conclusion: Increased CO2 significantly influence allergenicity and pollen concentration of common ragweed through the chamber and field study. The elementary example given here demonstrates strong probable links between rising CO2 levels and increased allergic diseases. We suggest that urbanization might provide a alternative to current experimental methods evaluating plant responses to climate change. Keywords: Allergens: Plant; Aeroallergens; Allergens: Environmental Control Objective: To observe the dynamic change of specific IgE (sIgE) and specific IgG4 (sIgG4) to house dust mite including Dermatophagoides pteronyssinus (Der p) and its main components Der p1 and Der p2 after specific immunotherapy (SIT), and to evaluate the effect of its application in clinical monitoring of desensitization. Methods: This study observed the immune indexes of 51 children patients including the serum sIgE and sIgG4 to five periods of pre SIT(Pre)and after SIT (half of year (0.5Y),1 year,2 year(2Y) and 3 year(3Y)). 20 patients by conventional drug treatment were collected as control group. Results: After half of year of SIT, the levels of serum sIgE to Der p, Der p1 and Der p2 increased continuously, however, by then began to decline, after three years treatment, the levels of sIgE to Der p1 and Der p2 were reduced step by step, particularly, sIgE to Der p1 were significantly lower than Pre treatment. The levels of sIgG4 to Der p, Der p1 and Der p2 increased significantly along with the process of SIT. The increasing range of Der p sIgG4 reached to the maximum, followed by Der p1 and then Der p2. The sIgE/sIgG4 ratio of three allergens were decreased after SIT, and the biggest dropped degree was the sIgE/sIgG4 ratio to Der p1. The low age group of children (5 to 8 y) response to immune higher and faster than the high age group of children (9-16 y) after SIT, and the levels of components sIgG4 to Der p1 and Der p2 elevated faster than sIgG4 to Der p. Conclusions: In the early stage of treatment, the levels of Der p, Der p1 and Der p2 to sIgE and sIgG4 in serum by the body in a state of immune stimulating were significantly increased. As the SIT, the levels of sIgE gradually decreased, and the levels to sIgG4 increased, namely the sIgE/sIgG4 ratio reduced gradually, and the biggest declined of sIgE/ sIgG4 ratio was Der p1. the fastest degree to SIT reaction was the low age children with allergies.


The present study demonstrates dose-dependent decreases of human β-defensin-2 (HBD-2) mRNA and protein levels in keratinocytes following stimulation to TSLP. In addition, this study demonstrated the effect of TSLP on HBD-2 expression in human skin equivalent models. We further investigated the regulatory mechanisms of TSLPreduced HBD-2 expression in primary human keratinocytes. TSLP induced STAT-3 protein expression in primary human keratinocytes. Data from immunohistochemical stain for skin lesions of atopic patients demonstrated the increased expression of STAT-3 than normal skin. HBD-2 was regulated through STAT-3-dependent pathway in keratinocytes. Our results from chromatin immunoprecipitation (ChIP) assay and electrophoretic mobility shift assay (EMSA) showed the direct regulation of TSLP on HBD-2 promoter. Taken together, this study reveals that TSLP stimulation may reduce HBD-2 expression through a STAT-3 dependent mechanism in human keratinocytes. The present study suggests a novel and key role of STAT-3 in TSLP-mediated immune response in keratinocytes. Moreover, it would be helpful for understanding the pathologic signal transduction in AD.


Oscillometric bronchodilator response in 3 to 5 years old healthy and asthmatic Filipino children Gemmalyn Esguerra, Emily Resurreccion, Kristine Elisa Kionisala, Jenni Rose Dela Cruz Philippine Children's Medical Center, Philippines Correspondence: Gemmalyn Esguerra -Philippine Children's Medical Center, Philippines World Allergy Organization Journal 2016, 9(Suppl 1):A48
Background: Assessment of respiratory function is vital in the diagnosis and monitoring of children with asthma. Measurement of response to bronchodilator (salbutamol) is ideal for children 3-5 years old because it is not effort dependent, less invasive and requires less cooperation from the patient. Objectives: To compare the change in oscillometric parameters after inhalation of a beta 2-agonist among healthy and asthmatic children aged 3 to 5 years old using impulseoscillometry. Methods: The respiratory impedance at baseline and after 15 minutes of one dose of Salbutamol nebulization was measured with the impulse oscillometry(IOS) using the VIASYS (Healthcare ,Leibnizstr. Hoechberg Germany)at resistance at 5Hz and 20 HZ and reactance at 5HZ in 310 children aged 3-5years old. For the calculation of threshold or cutoff values, receiver operating characteristic (ROC) curves were drawn and was determined by the Youden index (J = max{sensitivity + specificity -1}). Partial correlation study was done among multiple parameters to determine best positive correlation for diagnosis of asthma. Results: Fifty-six (18.1%) asthmatic subjects and 254 (81.9%) healthy subjects were able to complete the study. Mean percent (standard error of the mean) baseline pre bronchodilator indices for asthma were 1.21 ± 0.02 kPa/L/s for Z5Hz; 1.15 ± 0.02 kPa/L/s for R5Hz; 0.83 ± 0.01 kPa/L/s for R20Hz and -0.37 ± 0.01 kPa/L/s for X5Hz. In normal healthy subjects, the baseline mean values were 1.09 ± 0.01 kPa/L/s for Z5Hz; 1.04 ± 0.01 kPa/L/s for R5Hz; 0.79 ± 0.01 kPa/L/s for R20 Hz and -0.31 ± 0.01 kPa/L/s for X5Hz. In mean percent change initial values of asthmatics were -29.03% ± 0.73 for Z5Hz; -28.77% ± 0.81 for R5Hz; -22.96 % ± 0.97 for R20 Hz and 36.91 % ± 1.62 for X5Hz. Cut off values for bronchodilator response in diagnosing asthma using the percent change initial were as follows: -19.98% for Z5Hz with sensitivity of 100% and specificity of 96%; -21.25% for R5Hz with sensitivity of 95% and specificity of 98%; -13.96 % for R20 Hz with sensitivity of 93% and specificity of 78% and -24.25 % for X5Hz with sensitivity of 88% and specificity of 88%. Percent initial change of Z5Hz and R5Hz (r = 0.938, p<0.001) are significantly correlated.


Specific sublingual immunotherapy in Korean patients with atopic dermatitis Byung Soo Kim 1 Background: Sublingual immunotherapy (SLIT) with house dust mites (HDM) preparation has recently been proven to be beneficial for treating allergic rhinitis and asthma. However, there has been no report regarding the efficacy and safety of SLIT in Korean patients with atopic dermatitis (AD). Objective: To investigate the efficacy and safety of SLIT in Korean patients with AD. Methods: A total of 34 patients with AD and IgE-proven HDM sensitization (Class ≥ 3) were recruited from Pusan National University Hospital between July 2011 and September 2014. Patients were treated with SLIT for at least 12 months. Eczema area and severity index (EASI) score, total serum IgE level, results of specific IgE assays to Dermatophagoides pteronyssinus and D. farinae, and adverse effects were recorded at each scheduled visit. "Responder" was defined as a patient with ≥ 30% improvement in EASI score after SLIT. Results: Twenty-three patients continued SLIT for 12 months or more, and 11 patients (32.4%) dropped out because of exacerbation of dermatitis or were lost to follow-up. The average duration of SLIT treatment was 22.4 months (range, 12-32 months). EASI scores reduced significantly after 12 months of treatment (p < 0.001) compared with those at baseline. A total of 19 patients (19/23; 82.6%) were determined to be responders to SLIT after 12 months. Total and specific IgE serum levels did not significantly reduce after SLIT. No patients experienced serious adverse events, with the exception of two patients who developed transient lip and tongue swelling. Conclusion: Our study demonstrated that SLIT with HDM extracts is effective and tolerable in Korean patients with AD. Further controlled long-term trials are required to reinforce the current results. Background: Bitter taste receptors (TAS2R) in human airway smooth muscle have been recently shown to have an important role in bronchodilation, together with β2-adrenergic receptors. Object: To evaluate the association between genetic variations in TAS2R and clinical features, including bronchodilator response and asthma control. Method: We analysed the association between single nucleotide polymorphisms (SNPs) of TAS2R10 and TAS2R14 and variables including demographic data, atopy, duration of disease, asthma control status, including variables such as asthma control test (ACT) score, percent predicted value of FEV 1 , forced vital capacity (FVC), and FEV 1 /FVC ratio, and bronchodilator response (BDR), in 721 asthma patients in Korea. Result: Three novel SNPs of M207I, H203Q, and -79G/A in TAS2R10 and three known SNPs of -815C/T, -1267A/G, and -1897C/T in TAS2R14 were analysed. Increased BDR was significantly associated with SNP of -815T>C [OR (95% confidence interval (CI)) = 1.88 (1.01 -3.49), p=0.04], -1267 A>G [OR (95% CI) = 2.07 (1.03 -4.15 ), p=0.04] and -1897C>T [OR (95% CI) = 3.05 (1.01 -9.23), p=0.04, and OR=1.91 (1.08−3.36),


Ogi-kenchu-to is one of the traditional Japanese medical system called "Kampo" medicine formulae. It has been reported that Ogi-kenchu-to shows dominant effects of parasympathetic nerve systems, and clinically used as anti-fatigue effect, immune-activation, and relaxation of peripheral capillaries. Here, I report three infant cases of severe atopic dermatitis with impoverish skin which shows a therapeutically promising efficacy by the treatment of Ogi-kenchu-to. Three infants visited my clinic for the treatment of atopic dermatitis. All three infants showed full body atopic skin with high level of IgE and TARC in serum. Two of three cases had erythroderma, and the other one had persistent airway inflammation. Sufficient volume of steroid ointment treatment was necessary for all three patients to prevent atopic march. However, impoverish skin was found in all cases at initial administration because of long-term insufficient management. Since the impoverish skin is caused by chronic inflammation under the continuous activation of eosinophil which controlled by dominant effect of sympathetic nerve systems, Ogi-kenchu-to was an administrated for tree patients in combination with sufficient steroid ointment treatment. After 3-6 months later, both impoverish skin and atopic dermatitis were improved, and the serum level of IgE and TARC was decreased, which resulted in the decrease of the steroid ointment dose. It has been difficult to continue steroid ointment treatment only for atopic infants with the impoverish skin. My cases indicated that Ogi-Kenchu-to might play an important role for the treatment of impoverish skin in patients with intractable atopic dermatitis. Although the efficacy of kampo medicine has not been clarified enough, several immune-pharmacological studies reported that components related Kampo formulae including Ogi-Kenchu-to might effect on the antiallergic actions. In conclusion, the therapy in combination with Kampo formulae might achieve a better response for atopic dermatitis with impoverish skin, thereby should be extended to common use as complementary medicine.


Histologically, epidermal hyperkeratosis, parakeratosis, and hyperplasia and dermal leukocytes and mast cell infiltration were suppressed by KRG. Immunochemistry of TNF-α, TSLP and IL-31 expression and quantitative RT-PCR showed that KRG effectively suppressed proinflammatory cytokines and Th2 response. Additionally, proactive restriction of scratching behavior by physical barrier reduced scratching counts and this improved clinical symptoms. Also, in non-scratch-able group there was lower inflammatory cell infiltration and lower TNF-α, TSLP, Il-31, and IFN-γ expression in the back tissue as well as lower systemic IL-31 level. Conclusion: Therefore, we expect that the oral administration of KRG may control pruritus and skin inflammation by inhibiting the Th2 response. In addition, restriction of scratching behavior in early stage could be helpful in suppressing the itch-scratch vicious cycle and improving the clinical and systemic inflammations. Chronic Spontaneous urticaria (CSU) is a vexing problem are also subjected to a huge antihistamine pill burden. The symptoms are more in autoreactive urticaria (AU) where autoantibodies in blood flares-up the condition. Search for newer effective modalities which can reduce pill burden is a felt need. URTICRIA is one of the most challenging therapeutic problems faced by a dermatologists. Auto serum therapy is a Therapy in which repeated injections of autologous serum are administered subcutaneously. Complete absorption is possible in subcutaneous autoseru, therapy.This study evaluates the effectiveness of subcutaneous autologous serum therapy (AST) in CSU and also determines its usefulness in Autoreactive Urticaria.


Conclusions: Campylobacter and Roseburia appear to be less frequently detected in stool of 4-week-old Chinese infants who subsequently develop eczema. Microbial diversity is not associated with eczema susceptibility. This study confirms ethnic-specific early-life faecal microbial compositions. Background and objectives: Bakery workers are exposed to wheat allergens, bacterial endotoxins and fungus, which interact to induce allergic responses and work-related respiratory symptoms (WRSs). Our previous studies demonstrated that the WRSs of bakery workers were associated with TLR4 polymorphisms as well as Th2 immune responses, indicating a possible involvement of innate immune responses in the pathogenic mechanisms of baker's asthma. We hypothesized that Chitinase in wheat flour may involve in the development of WRS in bakery workers. We measured serum Chitinase level in bakery workers and analyzed associations with TLR4 polymorphisms in a single cohort of bakery workers. Methods: Three hundred eighty three bakery workers and as controls, 106 unexposed healthy subjects were enrolled. WRSs were evaluated using a questionnaire survey. Serum levels of Chitinase, IL-18, MPO and specific IgE/IgG antibodies to wheat flour extracts were measured by ELISA. The promoter polymorphisms of TLR4 at -2027AG and -1608TC were genotyped. Results: Serum Chitinase levels were significantly higher in bakery workers than in unexposed controls (P=0.026), however, no significant differences were noted according to the presence of WRSs and the prevalence of serum specific IgE or IgG antibodies to wheat flour (P>0.05, respectively). The workers carrying TLR4 -2027GG had significantly higher Chitinase levels than those with TLR4 -2027 AA/GG (P=0.021). Haplotype analysis indicated that the workers with ht1 [AT] had significantly higher Chitinase level that those without it (P=0.22). A significant correlation was found between serum Chitinase and IL-18 level (P=0.021), while no significant correlation was found with serum MPO level. Conclusions: These findings suggest that Chitinase may contribute to develop WRSs in bakery workers through the modulation of TLR4 function. Purpose: Nasal polyps (NP) imply a refractory clinical course in a case of chronic rhinosinusitis (CRS). Although, numerous etiologic factors including allergy, infection and hypoxia associate with nasal polyps (NP), the mechanism underlying NP is not fully understood. Previously, we reported that hypoxia-induced epithelial-to-mesenchymal transition (EMT) is frequently observed in Asian NPs, and HIF-1α could be a therapeutic target for nasal polyposis ( Ref 1) . However, the nasal epithelial cells in NP patients are not only exposed to hypoxia but also to diverse types or combinations of inflammatory milieu. So we hypothesized that specific immunologic endotypes could induce or accelerate EMT in nasal epithelial cells, and lead to nasal polyp formation.


We suggested that management and education of anaphylaxis were not fully carried out in ER. For avoidence of re-experience of anaphylaxis and the education of action plan in emergency state, it is necessary to consult to allergists. Background: Shellfish is the second most common food allergen that causes sensitization in children under 6 years old. Despite its prevalence, clinical management of shellfish allergy is limited to conventional approaches and avoidance. Although tropomyosin has been identified as the major shellfish allergen, no allergen specific immunotherapy (SIT) currently exists to treat or prevent shellfish allergies. To investigate the possibility of DNA vaccines, we constructed two hypoallergens of the shrimp tropomyosin Met e 1: MEM49 and MED171 (Wai et al. 2014 PLoS One 9: e111649) and expressed them in plasmid pCI-Neo. Here we used an established mouse model of shrimp hypersensitivity to examine the immunoprophylactic potential of these two hypoallergen-based DNA vaccines. Methods: 3-4 week old Balb/c mice were randomly divided into five groups (n = 8 per group). Two groups were intradermally injected with 100 μg pCI-Neo clones of MEM49 or MED171 thrice at weekly interval. The remaining groups were injected with naked pCI-Neo or PBS and served as vector, PBS or negative controls. One week after the last injection, all groups (except the negative control mice which were injected with PBS throughout the experiment) were sensitized subcutaneously with Met e 1 adsorbed to Freund's complete and incomplete adjuvant and then orally challenged using a high dose of Met e 1. Blood, spleen and small intestine were collected for antibody, cytokine, gene expression and histological analysis. Results: The PBS and vector control groups displayed typical Th2 responses upon Met e 1 challenge. These mice exhibited high levels of specific IgE and Th2-linked cytokines (IL-4, IL-5 and IL-13), as well as inflammatory responses (mast cell and eosinophil infiltration, goblet cell hyperplasia) in the gut. In contrast, vaccinated groups did not show any systemic allergic symptoms or inflammatory responses in the gut upon challenge. Met e 1-specific IgE and Th2-linked cytokines in these mice remained at basal levels, with the MEM49-encoding DNA vaccine providing more robust protection against Th2 responses. The protection offered by both vaccines included higher levels of specific IgG2a antibodies that possess both in vitro and in vivo blocking abilities, as well as higher splenic levels of Th1-linked cytokines (IL-12 and IFN-γ). MEM49 vaccination increased expression of TGF-β in the small intestine, while MED171 vaccination increased Foxp3 expression. Conclusions: Hypoallergen-based DNA vaccines could effectively protect against tropomyosin sensitization in mice via the establishment of Th1-oriented responses, recruitment of regulatory T cells, and induction of blocking IgG antibodies.


Results: Sputum PTX3 concentration was significantly higher in children with asthma (mean ± SE, 1094.55 ± 224.65 pg/mL) than control subjects (mean ± SE, 177.36 ± 30.00 pg/mL, p < 0.001). Positive significant correlations were found between sputum PTX3 and bronchodilator response (r = 0.25, p = 0.013). Sputum PTX3 levels negatively correlated with FEV1 (r = -0.30, p = 0.001), FEV1/FVC (r = -0.27, p = 0.002), FEF25-75 (r = -0.392, p < 0.001). Sputum PTX3 levels also showed significant negative correlation with post-bronchodilator (BD) FEV1 (r = -0.25, p < 0.001) and post-BD FEV1/FVC (r = -0.25, p < 0.001).


The role of local antibody responses in the nasal inflammation of allergic rhinitis (AR) patients Ji Hye Kim 1 Background and purpose: AR is a common and increasing allergic disease, in which D.farinae is the most common causative allergen. The aim of this study is to compare locally produced antibodies to D.farinae in nasal mucosa between positive and negative responders to nasal provocation test(NPT) to D.farinae and evaluate relationships with the levels of inflammatory mediators. Subjects and methods: Sixty AR patients with went through NPT to D.farinae. The sinus packs were placed into patients' both nasal cavities for 5 minutes to earn nasal secretion after NPT. Total IgE, specific IgE to D. farinae, ECP, IL-8, VEGF and tryptase levels were measured by using ImmunoCAP (ThermoFisher, Uppsala, Sweden). D.farinaespecific IgE, IgA, IgG and secretory IgA antibodies were measured by ELISA. IL-8 and VEGF levels were measured by ELISA kit(Endogen, Woburn, MA and R&D Systems, Inc, Minneapolis, MN, respectively). Results: High levels of total IgE, specific IgE, specific IgG, specific IgA, secretory IgA as well as ECP, IL-8, VEGF and tryptase were detected in nasal secretion, but showed no significant differences between positive and negative responders. Inflammatory mediators including ECP, IL-8 and VEGF were not only detected but well correlated with specific antibodies to D.farinae (P<0.05, respectively). Compared to ELISA method, ImmunoCAP system is more sensitive in detection of specific IgE to D.farinae. Difference between right and left nasal secretion had no statistical significance. Conclusion: These findings confirmed the presence of specific antibodies to D.farinae-sensitive AR patients. Localized antibodies abundant in nasal mucosa may have a role in the nasal inflammation of AR patients sensitized to D.farinae.


A case of ofloxacin-induced anaphylaxis by non-IgE, but specific IgG4-mediated responses Daehong Seo 1 , Ji Hye Kim 2 Anaphylaxis induced by ofloxacin has been rarely reported, and its pathogenetic mechanism has not yet been fully understood. This is a report of non-IgE mediated ofloxacin-induced anaphylaxis in a 20year-old female patient who suffered from allergic rhinitis and had a previous history of acute urticaria induced by nonsteroidal antiinflammatory drugs. She developed generalized urticaria and anaphylaxis following oral ingestion of ofloxacin. When we measured specific serum antibodies to ofloxacin-human serum albumin (HSA) conjugate using ELISA, a high level of specific serum IgG4 was detected, but serum specific IgE was not detectable. Moreover, a basophil activation test showed a significant up-regulation of CD203c with addition of ofloxacin and anti-IgG4 antibody in the patient with no significant changes in 3 non atopic healthy controls. These findings suggest that ofloxacin can induce anaphylaxis via pathogenetic mechanisms involving non IgE-mediated, but specific IgG4-mediated responses.


Background: Beta-glucans are known immunomodulators with anticarcinogenic properties. They may cause skewing of the T helper (Th) 2-mediated immune response to a Th1-mediated response, thus having a potential role in decreasing allergic symptoms among patients with rhinitis and asthma. Methods: To evaluate the effect of CM-glucan on allergic rhinitis symptoms and asthma control among children, 50 poly-sensitized children aged 7 to 18 years with allergic rhinitis and asthma were enrolled. Patients were randomized to receive CM-glucan (10 mg per orem bid) or placebo over a period of 90 days. The Total Nasal Symptoms Score (TNSS) and Asthma Control Test (ACT) questionnaires were used to assess symptom improvement at baseline, 2 weeks, and posttreatment. Lung function parameters and nasal eosinophil counts (%) were measured. Results: Out of 50 patients n=26; placebo, n=24) included in the study, 40 patients (CM=glucan, n=20; placebo, n=20) completed the study. After 90-days treatment, CM-glucan significantly improved runny nose (rhinorrhea) (p=0.002). Nasal congestion, itchy nose, post-nasal drip, and sneezing improved in both treatment groups but did not differ significantly (p> 0.05). The mean nasal eosinophil counts (p=0.025) significantly decreased from baseline to post-treatment; however, no significant difference (p=0.486) between the 2 groups was seen. Similarly, CM-glucan significantly improved nocturnal asthma symptoms (wheezing, coughing, and shortness of breath)(p=0.020). The mean FVC (p<0.001), FEV1 (p<0.001), FEF 25-75 (p<0.001), and PEFR (p<0.001) significantly increased in both groups, although no difference (p>0.05) was found when comparing posttreatment improvements between the 2 groups. Conclusion: CM-glucan significantly reduces rhinorrhea and nocturnal asthma symptoms among children with allergic rhinitis and asthma. Objective: To investigate the role of autophagy in SA pathogenesis. Method: We enrolled 33 SA patients, 14 non-severe asthma (NSA) patients and 33 normal healthy controls (NC). Autophagy was evaluated in sputum granulocytes and peripheral blood cells (PBCs) using Western blot, confocal microscopy, transmission electron microscopy, and flow cytometry. To induce autophagy in vitro, HL-60 cells and primary eosinophil cells were treated with interleukin (IL)-5; A549 cells and primary airway epithelial cells were treated with IL-1β.


With the advent of the Fric test, many of drawbacks of ball point pen can possibly be eliminated. Thus the practicing clinician could assess the severity of the disease and the response to treatment without taking recourse to more expensive investigations. Fric test is useful instrument for assessing severity of symptomatic dermographism.


a case of anaphylaxis due to ginseng and Sanyak which were sensitized via inhalation. A 55-year-old woman presented with symptoms of indigestion, abdominal pain, dyspnea and chest discomfort after ingestion of fresh ginseng and hemp juices. She had been diagnosed as having nonallergic asthma and rhinitis. However she had an OA due to various herbal materials such as ginseng and Sanyak powders which were sensitized working as a pharmacist. Serum total IgE level was increased (247KU/L). Serum specific IgE to ginseng was undetectable, but positive to Sanyak extract by enzyme-linked immunosorbent assay (ELISA). High serum specific IgG4 to ginseng extract was noted however, serum specific IgG4 to Sanyak was not detected IgE ELISA inhibition test showed significant inhibitions by hemp, not by ginseng, while IgG4 ELISA inhibition test showed significant inhibitions by ginseng, not by Sanyak, indicating that both extracts did not have a cross-reactivity which is comparable with taxonomical classification 4-20% sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and IgG4-immunoblot analysis revealed two IgG4 binding components (17kDa, 24kDa). These findings suggest that although IgE or IgG4 sensitization occurs via inhalation routes, repeated exposure via oral route can induce severe food allergy and generalized symptoms such as anaphylaxis. Further additional studies including basophil activation tests with these two extracts will be needed. A retrospective data collection through individual medical record, depending on the presence of EH and hypoalbuminemia, AD children were divided into three groups-EH + (group 1), hypoalbuminemia (group 2) and severe AD (group 3). Results: The male gender was related to the presence of EH (OR, 2.56; 95% CI, 1.19-5.53 , P=0.01), but age were not related. The age was related to the presence of hypoalbuminemia (OR, 3.12; 95% CI, 2.21-6.33, P=0.01), but gender were not related. Serum total IgE and ECP levels were higher in the EH group, but serum total eosinophil count levels were higher in the severe AD. There was a statistical difference between three groups in the skin culture (P<0.05). Even after adjusting for age and gender the correlation between the positive result of skin cultures and the presensce of EH was significant (P<0.01), and MRSA was related to only the EH + group (OR, 0.19; 95% CI, 0.04-0.92, P=0.03). Conclusion: We have identified the male gender, the positive result of skin cultures, and MRSA, as factors influencing factors of EH and age is as influencing factors of hypoalbuminemia in AD children. Innate type 2 response to Aspergillusfumigatus in a murine model of atopic dermatitis-like skin inflammation.
Purpose: Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease mediated by Th2 cells in acute phase. Type 2 innate lymphoid cells (ILC2s) have a role in initiating Th2 response. We investigated whether ILC2s are involved in the skin inflammation in a murine model of AD-like skin induced by Aspergillusfumigatus (Af). Method: We applied Afcrude extract (40μg) to the dorsal skin of BALB/c mice 5 times a week repeatedly with an interval of 2weeks. Clinical score and transepidermal water loss (TEWL) were assessed and histology was examined. The levels of interferon (IFN)-γ, IL-13, IL-17 in skin draining lymph node (LN) and immunoglobulin E (IgE) in serum were measured using ELISA. The mRNA expressions of IL-25, IL-33, thymic stromal lymphopoietin (TSLP) in the skin were measured using Real-Time PCR. The ILC2s of Lin -CD25 + IL-33R + cells in the skin and LN were analyzed using flow cytometry.
Result: The clinical score and TEWL increased in mice applied with Af(Afgroup), compared with control group. Histologic findings showed that epidermal and dermal thickness, and eosinophilic and mast cell infiltration in the skin of Afgroup. The levels of total IgE were increased in the serum of Af group. Moreover, Afgroup showed increased levels of IL-13 in the supernatant from culture of skin draining LN stimulated with Af. The populations of Lin-CD25+ IL-33+cells were increased in the skin of Af group. The mRNA expression of IL-33 was increased in the skin of Afgroup. Background: Sensitive skin is a hyperactive skin condition characterized by sensory symptoms showing exaggerated reactions in response to internal stimulants and external irritants. Recently, using microarraydriven approach, we found that several signaling pathway regulated genes including activin A receptor 1C (ACVR1C) were down-regulated in sensitive skin. ACVR1C, a type I serine/threonine kinase receptor for the transforming growth factor (TGF)-β family, is activated by various ligands such as nodal, activin B. Methods: In this study, we investigate the roles of ACVR1C in the pathogenesis of skin hypersensitivity using an in vitro model as well as human skin. Results: ACVR1C mRNA and protein expressions were significantly decreased in sensitive skin compared with non-sensitive skin. A decreased level of pH in sensitive skin can induce an increase of calcium influx through transient receptor potential cation channel subfamily V member 1 (TRPV1). Indeed, sensitive skin showed excessive calcium accumulation as compared with non-sensitive skin. RD cells transfected with ACVR1C siRNA exhibited markedly enhanced responses in intracellular Ca 2+ concentration following calcium ionophore treatment. Furthermore, knockdown of ACVR1C induced the expression of TRPV1 and calcitonin gene-related peptide (CGRP) indicating the causative role of ACVR1C in the pathogenesis of pain in sensitive skin. Finally, we investigated whether stimulation of ACVR1C pathway has a therapeutic potential to alleviate sensitive skin. Intriguingly, treatment of RD cells with Nodal induced a substantial reduction in the Ca 2+ influx and the expression of TRPV1 and CGRP which was increased by knockdown of ACVR1C, supporting the possible therapeutic role of ACVR1C stimulation in sensitive skin. Conclusions: Taken together, our results demonstrate that ACVR1C play crucial roles in the pathogenesis of sensitive skin and the activation of these signaling pathways in vitro successfully reversed pain sensation in RD cells, thereby raising the possibility of a novel therapeutic approach for skin hypersensitivity.


Clinical values of interferon-gamma enzyme-linked immunospot assays for management of antibiotic hypersensitivity in hospitalized patients Suda Sibunruang 1 , Jettanong Klaewsongkram 2 1 Chulalongkorn University, Thailand; 2 Allergy and Clinical Immunology Research Group, Chulalongkorn University Correspondence: Suda Sibunruang -Chulalongkorn University, Thailand World Allergy Organization Journal 2016, 9(Suppl 1):A88 Background Antibiotic hypersensitivity in hospitalized patients is a challenging dilemma, as sometimes a thorough history might not be sufficient to identify the culprit agents. Vulnerable conditions often hamper investigational in vivo tests. Meanwhile, the decision of which drugs to be further continued or substituted is urgently needed. Enzyme-linked Immunospot (ELISPOT) assay has previously shown effectiveness in detecting drug-specific T cell response. Thus, we conduct this study to assess the role of ELISPOT for management of antibiotic hypersensitivity in clinical setting.


Dominance of Th1-response in children with refractory mycoplasma pneumoniae pneumonia Jun Bao, Yi-Xiao Bao Xinhua Hospital, China Correspondence: Jun Bao -Xinhua Hospital, China World Allergy Organization Journal 2016, 9(Suppl 1):A96 Background: To investigate DNA copy numbers of Mycoplasma pneumoniae and expressions of helper T (Th) cell producing cytokines in bronchoalveolar lavage fluid (BALF) from children with refractory MP pneumonia (MPP). Methods: Of the 90 enrolled children with MPP, 30 cases were assigned as refractory MPP who failed to respond to at least 1-week treatment with macrolide antibiotics, while the other 60 cases were common MPP. A total of 30 children with congenital bronchial atresia or stenosis were included as controls. ELISA was used to assess BALF levels of IFN-γ, IL-4, IL-8 and TNF-α. RT-PCR was used to determine MP-DNA copy numbers in BALF. Results: Compared with the common MPP group, the refractory MPP group had a significantly higher MP-DNA copy number (3715352 ± 3162 vs. 2570 ± 5495; /ml; P<0.01). Children with refractory MPP achieved significantly increased BALF levels of IFN-γ, IL-8 and TNF-α than those with common MPP and the controls (40.55 ± 22.03 vs. 29.71 ± 11.18 vs. 27.54 ± 9.80; 213.58 ± 80.05 vs. 169.83 ± 83.56 vs. 79.50 ± 55.47; 240.90 ± 68.33 vs. 121.85 ± 63.15 vs. 101.33 ± 42.56; pg/ml; P<0.01 Background: There has been a surge in the incidence of bronchial asthma around the world especially in developing countries like India, because of many factors such as change in ambient air quality, increased air pollution, metamorphic change in living habits and lifestyle and climate. The allergens like pollens, fungi, etc. present in the air plays a pivotal role in pathogenesis of several allergic complaints such as allergic rhinitis, bronchial asthma etc. Studies revealed the complex interactions of genetic and environmental factors are involved in asthma. India is the home to around 15-20 million asthmatics and asthma prevalence is increasing in India especially in Kolkata. To provide the patients with best possible diagnosis and treatment, the identification of offending allergens are of major importance. However early detection of individuals who are genetically at risk of developing pollen and mold allergy is also an essential element to adopt effective avoidance strategies and to design appropriate therapies. As accustomed, the information in this respect is mostly available from developed and western countries while preliminary information from developing countries like India, particularly Kolkata Metropolitan areas is still fragmentary and insufficient. Therefore, present study involved identification of offending outdoor aeroallergens and also associated genetic pathway in nasobronchial asthma among Kolkata population. Methods: Skin-prick test was done among 950 asthmatic patients against 17 common aeroallergens and total serum IgE concentration was measured. PCR-RFLP was done in patients and non-asthmatic control (n=220 in each) to characterize a functional polymorphism, C(-159)T, of CD14, a positional candidate gene for allergy. Association of genetic polymorphisms was made with Clinicopathological conditions. Result: Present study identified Cocos as the most predominant outdoor aeroallergen in Kolkata followed by Caesalpinia and Peltophorium, all of which belong to pollen category. Patients with childhood-onset of asthma were significantly more sensitive towards aeroallergens and had significantly higher serum IgE level than that of adult-onset. No significant difference was found in distribution of SNP genotypes of CD14 among case and control. However among patients, frequency of C allele is significantly higher in childhood-onset group than that of adultonset and concordantly in former, CC genotype was associated with significant higher level of total serum IgE than CT and TT. Conclusion: In Kolkata, pollen is common outdoor aeroallergen and Cocos is predominant among pollens. Childhood-onset and adult-onset of asthma showed significant difference in allergen sensitivity and differential association of CD14 polymorphism might be involved in this process.


Background: House dust mite (HDM) allergens are a major cause of asthma worldwide. HDM extracts or purified allergens are the current treatment of choice known as specific immunotherapy. The aim in such strategy is to drive immune reaction away from the allergic Th2 response by inducing Th1 and/or Treg cellular response. In that regard, Toll Like Receptor-activating adjuvants have been used for inducing Th1 response, but adjuvants capable of inducing the somehow safer Treg response are poorly investigated. Methods: We describe the anti-allergic properties, in a therapeutic murine model of asthma, of HDM allergens Der s1 and Der s2 coencapsulated with dexamethasone into dehydration-rehydration vesicles (DRV). Dexamethasone is a cortisol analogue with immunesuppressor activity known to induce specific Treg response, still with some adverse effects associated to systemic or prolonged use. Optimal lipid composition in terms of physical-chemical and antiallergic properties was assessed using DRV liposomes of cholesterol and different phosphatidyl-cholines (PC) encapsulating Der s1+Der s2 allergens. Dipalmitoil-PC:cholesterol liposomes encapsulating different doses of dexamethasone were used to assess anti-allergic effects. Results: All liposomal compositions produced similar vesicle size, protein encapsulation and overall safe profile in treated mice. Preliminary results indicate that encapsulation of HDM allergens Der s1+Der s2 and dexamethasone into liposomes diminishes allergic response traits such as IL-5 interleukin and IgG1 and IgE antibody levels. Conclusion: These results highlight the possibility of using delivery systems such as liposomes to modulate immune response and to prevent adverse reactions to free or soluble pharmacological compounds like dexamethasone. Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is one of the more prevalent chronic inflammatory diseases with significant impact on morbidity and quality of life, yet little is known about its pathogenesis. Objective: We sought to evaluate the immunomodulatory effects of tonsil derived mesenchymal stem cells (T-MSC) in a mouse model of eosinophilic rhinosinusitis with nasal polyp(ERSwNP). Methods: The effect of T-MSCs was evaluated in 32 BALB/c mice that were randomly divided into 4 groups (negative control group; nasal polyp group; T-MSC group and T-MSC(AD) group(T-MSC incubated with adipogenic differentiated medium)). After induction of OVA-induced ERSwNP model, T-MSCs were administered intravenously (T-MSC and T-MSC(AD) groups) on weeks5 to 12 (one time per week)and subsequent OVA+SEB (three times per week in OVA and one time per week in SEB) challenge was conducted until 12 weeks. We studied mRNA and protein expression profiles of cytokine, chemokine and adhesion molecules in nasal mucosa, spleen and lymphnode using molecular, biochemical, histopathologicaland immunohistological methods. Results: Intravenous injection of T-MSCs significantly reduced allergic symptoms, eosinophil, neutrophil, nasal polyp count and serum OVA specific-IgG1 levels. Moreover, the nasal, lymphnode and systemic Th2 cytokine profile and nasal innate cytokines such as IL-25 and IL-33, and chemokines (CCL11, CCL24, Cxcl1, CxCl2, ICAM1 and VCAM1) expression were reduced in T-MSCs injected groups, as compared to the nasal polyp group. Usually T-MSC(AD) group showed better inhibitory effects of inflammation than T-MSC group. In addition, our results showed that the T-MSCs injected groupssignificantly increased IL-10 and Treg positive cells (CD4 + CD25 + FoxP3 + cells) in cervical lymphnode, as compared to the nasal polyp group. Conclusion: We demonstrate the administrationof T-MSCs effectively reduced polyp formation, inflammatory cell influx, cytokine profile, chemokine molecule expression, and T-cell subset distribution, suggestive of the mechanism of reduced CRS inflammation and less polyp formation in mouse model of ERSwNP. Therefore, T-MSC treatment is potentially an alternative therapeutic modality in CRSwNP.


Nitric oxide as a screening tool for evaluation of postoperative state of chronic rhinosinusitis Jae Hoon Lee, Woo Yong Bae Department of Otorhinolaryngology-Head and Neck Surgery, Dong-a University College of Medicine, South Korea Correspondence: Jae Hoon Lee -Department of Otorhinolaryngology-Head and Neck Surgery, Dong-a University College of Medicine, South Korea World Allergy Organization Journal 2016, 9(Suppl 1):A110 Background: Nitric oxide might have a various roles in development or defense of the upper airway inflammation. Fractional exhaled nitric oxide (FeNO) and nasal nitric oxide (nNO) are used as a screening tool to evaluate the airway inflammation such as chronic rhinosinusitis (CRS), allergic rhinitis and so on. But whether the level of FeNO or nNO is increased or decreased at each disease is not evident. This study was performed to assess whether FeNO can be used the screening tool for evaluation of CRS patients and whether it can be used to evaluate postoperative state of CRS. Methods: Thirty patients with CRS and twenty normal control group were recruited. The FeNO measurement was performed using a handheld electrochemical analyzer (NObreath®) through the nasal and oral route and the mean value of the 3 consecutive measurements was recorded. Nasal FeNO and oral FeNO were checked preoperatively and postop-1 month and 3 months. Background: Chronic rhinosinusitis with nasal polyps is hard to treat. The therapeutic effect of doxycycline, oral glucocorticoids, mepolizumab and omalizumab with significant reduction of nasal polyp score was previously investigated by 3 randomized controlled trials. The aim of this study is to compare the effect of these treatments on polyp score, symptom scores and inflammatory parameters. Methods: In total, 100 patients were randomly assigned to receive doxycycline for 20 days (n=14), methylprednisolone in decreasing doses for 20 days (n=14), mepolizumab 2 single intravenous injections (n=20), omalizumab 2 to 4 subcutaneous doses (n=15) or placebo (n=37) in three separate clinical double-blind, placebo-controlled trials. Participants were followed for 8 weeks. Endoscopic evaluation of nasal polyp score, assessment of symptom score and measurement of markers of inflammation in nasal secretions and serum occurred at baseline, week 4 and week 8. All treatments were completed at week 4, except for 2 patients who received a fourth subcutaneous dose of omalizumab at week 6. Results: All treatment options significantly reduced nasal polyp score as compared to baseline, but not placebo. Methylprednisolone has initially the most dramatic effect on symptom scores, but after cessation of treatment symptom scores worsen progressively and return to baseline after 4 weeks. Mepolizumab, doxycycline and methylprednisolone each had a specific effect on local and systemic inflammatory markers. Omalizumab did not alter eosinophilia or markers of inflammation. Conclusions: Omalizumab, mepolizumab and oral doxycycline cause a long-term reduction in nasal polyp size, whereas methylprednisolone initially causes the strongest reduction in polyp size but recurrence occurs earlier. Total symptom scores parallel this trend. Doxycyline works on eosinophilic and neutrophilic inflammation in nasal polyps, whereas the effect of mepolizumab and methylprednisolone is most apparent on eosinophilic markers. Omalizumab did not reduce markers of eosinophilic inflammation, nor neutrophilic inflammation in nasal secretions. The beneficial effect of omalizumab seems to be mediated through a direct effect on IgE or their receptor, rather than through an effect on markers of the eosinophilic cascade. Rationale: To investigate the role of helper T (Th) cells in steroid resistant (SR) asthma, steroid sensitive (SS) and resistant (SR) Th clones were selected in vitro, and then adoptively transferred into unprimed mice. Effect of CTLA4-Ig was analyzed both in vitro and in vivo. Methods: For in vitro evaluation, ovalbumin (OVA) reactive Th clones were cultured with antigen presenting cells and OVA in the presence of various concentrations of dexamethasone (DEX). Proliferative responses of Th clones were measured by 3 H-thymidine incorporation. For in vivo assessments, unprimed BALB/c mice were transferred with Th clones, challenged with OVA, and administered with DEX subcutaneously. Bronchoalveolar lavage fluid (BALF) was obtained 48 hr after challenge, and the number of infiltrating cells was differentially counted. CTLA4-Ig was administered through nasal inhalation or venous injection. Results: SS and SR clones were selected based on the effect of DEX on the proliferative responses of antigen-stimulated Th clones. Airway infiltration of eosinophils and lymphocytes of mice transferred with SS clones were effectively inhibited by the administration of DEX. In contrast, those of mice transferred with SR clones were not significantly inhibited by DEX. Administration of CTLA4-Ig significantly suppressed the proliferation of DEX-treated SR clones in vitro, and the eosinophil infiltration of SR asthma model transferred with SR clones in vivo. Conclusions: Steroid sensitivity of Th clones assessed in vitro was consistent with that of adoptively transferred asthma model assessed in vivo. Costimulatory signal mediated through CD28 is crucial for the induction of steroid resistance both in vitro and in vivo. Periostin is a matricelluar protein, which was synthesized in airway epithelial cells induced by interleukin 4 and 13. Recently, serum periostin level was suggested as a biomarker of TH 2 airway inflammation and a prognostic indicator of asthma treatment. However, serum periostin level in allergic rhinitis was not elucidated well, we aim to investigate the relationship between serum periostin and allergic rhinitis in Korea children.


Background: No standard study protocol or diagnostic criteria based on nasal provocation test (NPT) and acoustic rhinometry (AR) results are available for allergic rhinitis. Objective: We aimed to evaluate the usefulness of NPT plus AR for the differential diagnosis of local allergic rhinitis (LAR), allergic, and nonallergic rhinitis. Methods: The medical records and skin prick test (SPT) and NPT results of 262 patients with symptoms of chronic rhinitis were reviewed. Patients were allocated to one of three groups, that is, Group A (n=110, negative SPT result for Dermatophagoides pteronyssinus [DP]), Group B (n=53, weakly positive result), or Group C (n=99, strongly positive result). Results: Twelve patients had a negative SPT result and provoked response in NPT (≥29% decrease of minimal cross-sectional area [MCA] after DP challenge) were diagnosed to have LAR. After DP challenge, Group C showed significant aggravation of nasal symptoms and a greater decrease in acoustic parameters than Groups A and B (P<0.01). In patients with a ≥ 2 Visual Analogue Scale (VAS) increase in nasal obstruction after DP challenge, the criterion 'a change of total nasal symptom score [TNSS] of ≥ 6.5' , had 90.6% sensitivity and 77.4% specificity for the diagnosis of allergic rhinitis, whereas the diagnostic criterion 'a TNV change at 30 minutes after DP challenge of ≥ 27.6%' had 73.4% sensitivity and 58.1% specificity. Conclusion: NPT with AR could be a useful tool for the differential diagnosis of allergic, non-allergic, and local allergic rhinitis.


Background: Kashmir valley has been witnessing an increase in allergy related disorders with aeroallergens being the most prevalent causative agent. Allergen-specific immunotherapy (allergen-SIT) has been a potentially curative treatment modality in allergic diseases that acts by inducing the peripheral T cell tolerance and promoting the formation of regulatory T-cells. Our study was designed to analyse the treatment response of patients with allergic rhinitis and allergic asthma in Kashmir Valley by using allergen-SIT approach. Method: A total of 754 patients suffering from Allergic Rhinitis and Allergic Asthma were recruited in this study. Skin Prick test (SPT) was performed with panel of aeroallergens. Allergen-SIT was given as a therapeutic modality to 218 SPT positive patients. The symptom score and medication requirement was analysed during the time course of allergen-SIT. Results: Allergen-SIT was effective in reducing severe symptoms in 87% patients of SPT-positive allergic rhinitis and 76% SPT-positive allergic asthma patients. Moreover, allergen-SIT showed reduction in medication of 73% SPT-positive allergic rhinitis and 69% SPT-positive allergic asthma patients during their maintenance therapy, usually after period of one year. Conclusion: Our study proves the efficacy and beneficial effects of allergen-SIT in patients with allergic rhinitis and allergic asthma in Kashmir Valley. Our study shows that allergen-SIT is not only an effective therapy for reducing the allergic symptoms but also acts specifically to restore normal immunity against allergens in the longterm course of the disease.


Uric acid (UA) is an important endogenous danger signal released from injured cells by inflammation and infection. Eosinophils are also involved in innate Th2-type immune responses mediated through endogenous danger signals, including IL-33, uric acid (UA), or ATP, in nonsensitized mice exposed to environmental allergens. However, the mechanism involved in eosinophil responses to these danger signals remains insufficiently understood. Methods: Eosinophils isolated from peripheral blood of normal individuals were incubated in the presence or absence of monosodium urate (MSU) crystals and ATPγS, a non-hydrolysable ATP analogue. To determine the involvement of P2 or P2Y 2 receptors in eosinophil responses to UA and ATP, eosinophils were preincubated with a pan-P2 receptor inhibitor, oxidized ATP (oATP), or anti-P2Y 2 antibody before incubation with MSU crystals or ATPγS. Results: MSU crystals induced adhesion of eosinophils to recombinant human (rh)-ICAM-1 and induced production of superoxide anion. oATP abolished eosinophil responses to MSU crystals, suggesting involvement of endogenous ATP and its receptors. Furthermore, exogenous ATP, as ATPγS, activated eosinophils and induced migration across a model of basement membrane, adhesion to rh-ICAM-1, generation of superoxide anion, and degranulation of eosinophilderived neurotoxin (EDN). oATP and anti-P2Y 2 significantly reduced these eosinophil responses. Conclusions: UA stimulated eosinophils to release ATP. ATP serves as an essential mediator of functional responses in human eosinophils. Thus, human eosinophils may respond to particulate damageassociated endogenous danger signals. These responses by eosinophils to tissue damage may explain the self-perpetuating nature of airway inflammation in patients with asthma.

Anaphylactic Reaction After Inhalation of Budesonide

Results: A patient presented with seasonal allergies and asthma not adequately controlled with inhaled albuterol. Inhaled budesonide/formoterol daily was prescribed for treatment. The first dose was well tolerated, but 15 minutes after the second dose the next day, the patient developed shortness of breath, a feeling of throat tightness, swelling of the lips and tongue and blisters along the oral mucosa. The patient was treated with an oral antihistamine and symptoms abated within one hour. The patient was unaware of any previous allergies to corticosteroids and reported using various topical preparations to treat dermatitis for more that one year without resolution. An open test with an application of budesonide/formoterol was sprayed onto the patient's arm resulting in an erythematous plaque at 72 hours. Patch testing revealed delayed reactions at 48 hours to tixocortol-21-pivalate 1%, budesonide 0.01% and hydrocortisone 1%. Skin tests [ii] were performed to further evaluate and document corticosteroid hypersensitivity using ciclosenide, methylprednisolone, mometasone, budesonide, budesonide/formoterol, formoterol, fluticasone/ salmeterol along with normal saline and histamine as controls. Within 24 hours positive results for two different inhaled budesonide formulations and one for budesonide/formoterol were observed. Conclusions: Inhaled corticosteroids are first line agents in the treatment of persistent asthma. In patients with sensitivity to this drug class, clinicians should be aware of cross-reactivity patterns to identify an appropriate corticosteroid for therapy and test to identify the class of products which would be deemed safe. Furthermore, the practitioner should be aware that prior atopy is a risk factor for sensitization to topically applied therapeutics. Lastly, the anti-inflammatory effects of a corticosteroid may mask the allergy. Although patch and skin tests supported delayed hypersensitivity reactions, this patient presented with an immediate hypersensitivity reaction that is suspected to have occurred from previous sensitization of topical corticosteroid use. Background: House dust harbors ambient immunomodulatory particulates and reflects the living environments. Lipid compounds may have manifold impact on host immunity but have not yet been extensively described. Objective: To investigate and compare the lipids of mattress dust from urban and rural school children in China. Methods: Dusts from beddings of twenty schoolchildren in urban Guangzhou and rural Conghua were collected and extracted following the Bligh and Dyer method. Lipidomic profiling was carried out by ultra-performance liquid chromatography/quadrupole-time-offlight (Q-TOF)-MS-based approach using a Waters Xevo G2 Q-TOF mass spectrometer with an electrospray ion source (ESI). Mass spectra were acquired in the range of m/z 50~1200 in both positive and negative ionization mode. Raw data were then processed using XCMS, SIMCA-P and multivariate statistical analysis, then compared with database to identify lipid components. Results: The established models of lipid profiling were statistically valid and well fit. Urban and rural dusts showed differential composition of lipid molecules. A total of 8986 and 4742 metabolites were detected in positive and negative ionization mode, respectively. Fourteen lipid molecules were finally identified. Oleamide, Cer (d18:0/14:0), MG (0:0/18:3/0:0), two LysoPAs, 16-hydroxy hexadecanoic acid and phytomonic acid were abundant in rural dust, whereas Cer (t18:0/16:0), DG (36:7), two LysoPCs, PA (16:0e/18:0), PC (32:1) and PG (P-16:0/14:1) were abundant in urban dust. Conclusions: This is the first report suggesting that children from urban and rural areas are exposed to discrepant environmental lipids. Potential responses to the identified lipids should be further investigated.


Chronic cough without wheezing in young children as a manifestation of chronic sinusitis Charles Song Harbor-UCLA, USA World Allergy Organization Journal 2016, 9(Suppl 1):A146 Background: Chronic cough without wheezing in young children often presents diagnostic challenge. Objective: To investigate the usefulness of nasal endoscopy in differentiating bacterial sinusitis from viral upper respiratory infection, cough variant asthma, allergic rhinitis, and GERD. Method: We have retrospectively analyzed data from 14 young children under the age of 5 who presented in our clinic with chronic cough without wheezing. Nine children were evaluated with nasal endoscopy. Results: All of 9 (100%) children evaluated with nasal endoscopy had thick purulent discharge in the nasopharynx and five (56%) of them had adenoid enlargement for the age. Ten of 13 (77%) children given antibiotic treatment reported symptom resolution in their two week follow-up appointment. Conclusion: Using nasal endoscopy, we found that the majority of children with chronic cough without wheezing had chronic bacterial sinusitis and had a striking response to an appropriate antibiotic therapy. Adenoid hypertrophy may be the cause or, more likely, the result of chronic upper airway infection.


Significant reduction in allergic features in the offspring of mice supplemented with specific non-digestible oligosaccharides during lactation Astrid Hogenkamp Utrecht University, Netherlands World Allergy Organization Journal 2016, 9(Suppl 1):A149 Background: Earlier it was shown that maternal supplementation with non-digestible carbohydrates during pregnancy led to a significant reduction in the development of several allergic asthma features in adult offspring. In the current study, it was investigated whether maternal supplementation during lactation only would have similar effects. Method: Mice were mated 2 weeks after arrival at 10 weeks of age. Directly after birth of the offspring, mice in the lactation group were transferred to the AIN93 control diet supplemented with short-chain galacto-and long-chain fructo-oligosaccharides (scGOS/lcFOS; ratio 9:1). Mice in the sham and control groups were kept on control AIN93. The male offspring were sensitized to OVA at the age of 6 weeks, with the exception of those in the sham group, and the acute allergic skin response was measured at the age of 8 weeks. Airway hyperreactivity to metacholine was measured after 3 consecutive airway challenges with OVA aerosol. Results: Although the acute allergic skin response and the airway hyperreactivity did not differ between the control group and the lactation group allergic inflammation was significantly down-regulated by the dietary intervention during lactation. Total cells numbers, and percentages of eosinophils and lymphocytes in the bronchoalveolar lavage fluid as markers for allergic inflammation were significantly decreased in the offspring of dams fed scGOS/lcFOS during lactation. Analysis of total and OVA specific immunoglobulin levels showed that the specific diet did lead to lower levels of OVA-specific and total IgG1 levels. OVA-specific IgE levels did not differ between the lactation and the control group, although levels of total IgE were significantly lower in the lactation group. Conclusion: Maternal supplementation with scGOS/lcFOS during lactation did down-regulate allergic inflammation in the lungs. In addition immunoglobulin levels, relevant for allergic disease, were down-regulated as well. In contrast, allergic skin reactions and lung functions were not affected. These data are comparable to studies performed earlier in which dietary intervention with scGOS/lcFOS was performed during pregnancy only although in these animals skin reactions and lung function were affected as well. Altogether, our data suggest that early life dietary intervention with non-digestible carbohydrates may be beneficial for the allergic outcome later in life, which may also be highly relevant for the development of atopic disease in humans. This study is part of a multi-phase project aiming to validate a mouse model to assess the potential allergenicity of hydrolysed infant formulas. The sensitizing properties of 3 partially hydrolysed whey proteins (pWH-A, -B and -C) were investigated in the mouse model as well as the classically used guinea pig model. Mice and guinea pigs were orally sensitized with whey by gavage or ad libitum via the drinking water respectively. In mice, whey-IgE, acute allergic skin responses, mMCP-1 release, body temperature and anaphylactic shock symptoms were determined upon oral challenge in 4 research centers. In the guinea pigs anaphylactic shock symptoms upon intravenous challenge were measured as a single parameter at 1 center. Elevated levels of whey-specific IgE/IgG1 were detected in wheysensitized mice in all centers, although the group-average did not reach significance for IgE in center 2. In contrast to whey-sensitized mice, no acute skin response or mMCP-1 release upon whey challenge was observed in pWH-A-treated mice which corresponded with the absence of anaphylactic shock symptoms in both the mouse and guinea pig model. For pWH-B and pWH-C, that showed positive in the guinea-pig ASA-test, results in mice were inconclusive. None of the centers was able to differentiate between the residual sensitizing capacities of the pWH-B and -C based on a single elicitation parameter and results per center differed. To determine the potential influence of an altered microbiota at the different locations on the sensitizing capacity, an analysis of the microbial composition at the start and end of the study was conducted. Results show that for a well-balanced prediction on the potential allergenicity of hydrolysed infant formulas a multiple parameter model is needed. Therefore, it is concluded that the murine model is suitable to give a safe and nuanced prediction on the allergenicity of pWH's. A future challenge is to develop an overall scoring system for proper risk assessment, taking all assessed parameters into account. Introduction: the eosinophil cationic protein (ECP) is a small polypeptide that originates from activated eosinophil granulocytes. In other studies, the human neutrophils from allergic pateitns were able to produce ECP by IgE-dependent mechanism. Eosinophils have been shown to contribute to T-lymphocyte activation and an increased inflammatory responses during allergic inflammation. Objectives: the purpose of this study was to evaluate the relationship between allergic test; skin test and multiple allergosorbent test system (MAST); and ECP count.


We enrolled the patients with physician-diagnosed ACOS (n = 207) and COPD (n = 258) from the medical records in a university hospital. The patients with ACOS had younger age and lower FEV 1 than COPD patients. With regard to skin prick test (SPT) responses, the overall positive rate was higher in ACOS than in COPD (22.3% vs. 14.3%, P = 0.027). However, the positive SPT responses to each allergen were not different between ACOS and COPD. In addition, there was no significant difference in levels of peripheral blood eosinophil percentage and total IgE. Conclusions: In conclusion, SPT positivity was higher in ACOS, but the other features of atopy were not different between ACOS and COPD. In the diagnosis of ACOS from COPD, SPT positivity needs to be considered as an important clinical feature.


Perceptions and practices of severe asthma and asthma-COPD overlap syndrome among specialists: A questionnaire survey Sang-Heon Kim 1 , Ji-Yong Moon 1 , Jae-Hyun Lee 2 , Ga Young Ban 3 , Sujeong Kim 4 , Mi-Ae Kim 5 , Joo-Hee Kim 6 , Min-Hye Kim 7 , Chan-Sun Park 8 , Hyouk-Soo Kwon 4 , Jae-Woo Kwon 9 , Jae Woo Jung 10 , Hye-Ryun Kang 11 , Jong-Sook Park 12 , Tae Background: Severe asthma and asthma-COPD overlap syndrome (ACOS) are gaining more and more attention since these diseases are hard to control and often associated with poor clinical outcomes. However, the diagnosis and managements varies depending on clinicians because there is no agreement on the definition and therapeutic approaches in these diseases. To evaluate the current understandings and clinical practices on severe asthma and COPD among asthma and COPD specialists in Korea, We designed a questionnaire survey using e-mail and web-based platform. Methods: Subjects were selected based on their clinical specialty from the members of the Korean Academy of Asthma, Allergy and Clinical Immunology and the some study groups of the Korean Academy of Tuberculosis and Respiratory Diseases. Of 432 subjects who received e-mail, 103 subjects (58 allergists and 37 pulmonologists) responded and submitted their answers by online administration. Results: Regarding severe asthma features, the most common type was asthma aggravation by stepping down treatment (21.8%) followed by frequent exacerbation (20.6%), uncontrolled asthma despite higher treatment step (13.4%) and severe exacerbation (12.6%). The subjects responded that the proportion of severe asthma was 13.8% of the asthma patients in their clinic and there was no difference between allergists and pulmonologists. ACOS was estimated to be 20.7% of asthma, 37.9% of severe asthma and 29.5% of COPD, while allergists gave more proportions of ACOS among COPD than pulmonologists (35.4% vs. 22.6%). Regarding the diagnostic criteria for ACOS among asthma patients, smoking history (84.5%), persistently low FEV 1 (80.6%) and low FEV 1 variation (71.8%) were most frequently chosen for major criteria. Contrarily, the highly selected major criteria for ACOS among COPD patients were high FEV 1 variation (85.4%), positive bronchodilator response (77.7%) and personal history of allergy (75.7%). Conclusions: The asthma and COPD specialists had diverse view on the perceptions and clinical practices on severe asthma and ACOS. These heterogeneity needs to be considered in developing guidelines and health policies of severe asthma and ACOS.


Eosinophilic enteritis is rare diseases, which is eosinophilic infiltration of colon mucosa without definite cause of eosinophilia. Patient who has eosinophilic enteritis with intussusceptions is extremely rare in adult, and this case is second report in Korea. Case Twenty-two year-old man visited office due to two months lasting abdominal discomfort and diarrhea. He had no underlying medical diseases, and any other allergic history and family history except being allergic to pupa. On physical examinations, RUQ tenderness had shown. Laboratory findings showed Hemoglobin level 16.6 mg/dL, platelet count 265,000/mm3, WBC counts 6300/mm3 with differential 16.7% of eosinophils on corrected blood chemistry. Blood chemistry excluded the presence of other organ involvement, such as kidney and liver. Serologic marker of parasite and stool study which might cause gastrointestinal symptoms and peripheral eosinophilia such as Ancylostoma, Anisakis, Ascaris, Strongyloides, Toxocara, and Trichinella were done, but any of them had not shown positive results, only positive response to mite and cockroach on MAST. There is no evidence of eosinophilic infiltration on lung and heart in chest x-ray, pulmonary function test and echocardiogram. Performed computed tomography showed proximal small bowel intussusception in ascending colon. Pathologic findings represented eosinophilic infiltration of entire bowel layers. Patient's symptoms were relieved after surgery and followed blood chemistry showed improvement of peripheral eosinophilia 16.7% to 3.5%. Conclusion Eosinophilic gastroenteritis is diagnosed by eosinophilic infiltration of gastrointestinal tract without other causes of eosinophilia. The most common cause of disease is exposure to sensitive food allergen, but the pathogenesis is not well-known. Treatment is based on limited evidence and varies based upon symptoms. In this case, uncertain cause of symptom derive to surgery for diagnostic and therapeutic method. We suggest further clinical experiences and studies would be necessary to make out disease. Background: The value of total IgE varies in wide limits (0 -5000 kU/l) and depends on a lot of factors: genetics, allergy, parasitic infection, age, gender, immune status and geographic region. The aim of this study was to find out the factors influencing the values of total IgE in Estonian children and to establish own reference values. Methods: The study group comprised 385 children from two prospective allergy studies followed from birth up to the age 16 years. Data about allergy symptoms were collected from the interviewquestionnaires, clinical examinations were carried out and skin prick tests were made with the most common food and inhalant allergens during the follow-up investigations. The measurements of total IgE level in sera were made at birth, 3, 6, 12, months and 2, 5, 10/12, 16/ 18 years of life using UniCAP method. Results: The cord blood IgE level did not have any predictive value for allergy development during the first 12 years of life. The value of total IgE increased with the age from 0.4 (95%CI 14.4) kU/l at 3 months of age up to 37.0 (95%CI 45.5) kU/l at the age of five years. The teenage reference value at 10/12 years was lower (34.2 (95%CI 41.2) kU/l) as compared to the preschool children and at the age of 16/18 years (30.0 (95%CI 38.7). Males had higher IgE values in comparison with females at every age, but statistically significant was the difference only at 6 months (3.28 vs. 1.76 kU/L; p=0.01) and at two years (21.8 vs. 11.9 kU/l; p=0.01) of age. The total IgE was higher in children with allergic diseases as compared to non-allergic only at the age of 10/12 years (75.8 vs. 44.3 kU/l; p=0.008), which might indicate quite high prevalence of parasites in non-allergic children. We tested IgE antibodies against Ascaris in children with total IgE level over 20 kU/ at 6 and 12 months and over 200 kU/l at 2, 5, 10/12 and 16/18 years of life. Antibodies against Ascaris were found in 29 of 50 preschool children and in 31 of 56 teenagers. However, there was positive correlation between total IgE and atopy considering positive skin prick test results and presence of allergen specific IgE antibodies in sera in all age groups. Conclusion: The peak value of total IgE was at the age of five and not in teenage as usually referred to in the laboratory manuals. There was positive correlation between total IgE and skin prick test results, allergen-specific IgE antibodies and IgE antibodies against Ascaris in blood but not with allergic diseases except at the age of 10/12 years.


A case of eosinophilic granulomatosis with polyangiitis accompanied by rapidly progressive glomerulonephritis Yu Jin Kim 1 , Sang Min Lee 1 , Shin Myung Kang 1 , Sojeong Kim 1 , Sun Young Kyung 1 , Sung Hwan Jeong 1 , Jeong-Woong Park 1 , Hyunjung Hwang 1 , Yong Han Seon 1 , Sanghui Park 2 , Sang Pyo Lee 1 A 58-year-old man visited local clinic complaining of malaise, weight loss, fever, and dyspnea. Complete blood count was performed, which revealed eosinophilia in peripheral blood. He received antibiotics for 3 weeks, however his symptoms were not alleviated, and multiple purpuric papules on both ankles, left forearm, and buttock with acute renal dysfunction developed. Then, he was referred to university hospital. Pulmonary function test was carried out, which yielded decreased lung function with positive bronchodilator response. Kidney biopsy and skin biopsy were performed, and histological examination showed acute necrotizing crescentic glomerulonephritis and leukoclastic vasculitis in skin, which led to the diagnosis of Churg-Strauss syndrome (eosinophilic granulomatosis with polyangiitis, EGPA) combined with rapidly progressive glomerulonephritis (RPGN). The patient received pulse steroid therapy with parenteral methylprednisolone followed by oral prednisolone. Clinical and laboratory findings improved dramatically and remission was attained rapidly. The patient continued to be in remission for 5 months. EGPA should be considered in asthma patients who present with severe systemic symptoms and eosinophilia. Progressive renal insufficiency can occur during the acute phase of EGPA accompanied by renovascular involvement. Prompt and aggressive treatment with systemic corticosteroid is mandatory to control disease activity and to achieve remission. Background: Urticaria is a frequent skin disease but the majority of cases have an unknown cause (idiopathic urticaria). There is a strong association between infectious triggering factors in the pathogenesis of Acute Urticaria (AU) and infectious triggering factors may also be involved in Chronic Urticaria (CU). Methods: We determined the prevalence of bacterial, viral and parasitic infectious diseases in 217 patients (169 females and 48 males) from North-Eastern Romania with age from 16 to 86 years, admitted in our department in the last 6 months with acute episodes of urticaria (107 females and 27 males) and chronic idiopathic urticaria (62 females and 21 males). In order to identify the infectious triggers, blood samples were used to evaluate the level of antibodies for Toxocara cannis, Toxoplasma gondii, Herpes simplex virus, Epstein-Barr virus, cytomegalovirus and measles virus. Additionaly, microscopic stool examination and fecal antigens essays for Helicobacter pylori and Giardia lambliawere performed. Serum anti-HCV antibodies and HBs antigen were assessed. Results: The most frequent infectious agent detected in cases with AU and CU was Giardia lamblia (17.97% -21 cases with AU and 18 cases with CU), followed by Toxocara cannis (8.29% -11 cases with AU and 7 cases with CU), hepatitis C virus (5.99% -8 cases with AU and 5 cases with CU), Helicobacter pylori (5.99% -8 cases with AU and 5 cases with CU) and hepatitis B virus (1.38% -2 cases with AU and 1 case with CU). Acute infections with Epstein-Barr virus (2 patients) and measles virus (1 patient) were diagnosed only in AU and no cases were found among patients with CU. Only 3 patients (2 with AU and 1 with CU) were diagnosed with acute infection with Herpes simplex virus. All patients had negative results for cytomegalovirus IgM antibodies. Parasitic infections with Blastocystis hominis were found in 6 patients (5 cases with AU and 1 case with CU) and one patient with CU presented Ascaris lumbricoides. Conclusions: Infectious triggering factors, especially parasitic infections are prelevant in developing countries of the world and may play an important role not only in acute episodes of urticaria but also in chronic urticaria. Although we found that parasitic infections are present in both types of urticaria, further studies are needed to elucidate the association between infectious triggering factors and urticaria, and to identify new infectious triggers. Background Many social and cultural factors have influences on sleep patterns, and sleep condition of each child may be different from that of each other depending on the approaches and concerns of their parents. The objective of this study is to assess sleep condition of Korean infants.


Korean infants have a short sleep time and bedtime routine and bed-share of Korean infants showed difference patterns compared with western countries. These results suggest that aggressive education for sleep condition is needed for Korean infants and their parents. Purpose Chronic rhinosinusitis (CRS), with nasal polyposis is a chronic inflammatory disease of the upper airways often associated with asthma and characterized by markedly increased numbers of eosinophils, Th2 type lymphocytes, fibroblasts, goblet cells and mast cells. The inflammation leads to a proliferative response in the extracellular matrix (ECM). Periostin is an ECM protein known to play a role in tissue remodeling in inflammatory diseases of the upper and lower airways. Furthermore epithelial-derived genes such as filaggrin have been highlighted in asthma or atopic dermatitis (AD) or both via its role in barrier function. Here we investigated the expression of periostin and filaggrin in nasal polyps (NP) from atopics and non-atopics in comparison with the nasal mucosa from patients with allergic rhinitis (AR) and its potential role in nasal polyposis. Methods Nasal polyp specimens and biopsies of nasal mucosa were obtained at surgery as part of the treatment for removal of NP or for hypertrophied turbinates. Immunoreactivity for periostin, TSLP, filaggrin and IL-13 in NP from atopic and non-atopic patients and in the nasal mucosa of patients with AR was analyzed by immunohistochemistry using the peroxidase-based Avidin-Biotin Complex (ABC) method. Cell counts were analyzed using an objective micrometer and the density of immunoreactivity was quantified by Image J analysis system. Real Time PCR was done for analyzing the mRNA expression of IL-33.


Based on our previous findings of the high levels of IL-13 and TGFbeta in NP and the present findings of the increased expression of filaggrin and periostin in NP irrespective of the atopic status, filaggrin may potentially play a role in the barrier function and periostin may play a role. Introduction: Although urinary tract infections (UTIs) are considered among the most common infectious disorders in humans, these usually follow an uncomplicated course. Various infections may have a role in inducing HAE attacks. Further, danazol treatment has been associated with hematuria. Our study intended to evaluate the abnormalities of the urinalysis of C1-INH-HAE patients. Methods: Urine specimens contributed by 139 C1-INH-HAE patients at the annual control visits were studied retrospectively (RBC and WBC counts, microorganisms). We analyzed these laboratory parameters in relation of the clinical symptoms and in view of the long-term danazol therapy. Results: Taking into account 3 randomly selected urine specimens, we found that the cumulative number of edematous attacks was higher in patients with than in those without bacteriuria (p=0.019, p=0.022, p=0.014). Considering the same patients (n=76), attack number was significantly higher (14.51 vs. 8.63) in patients with than in those without bacteriuria (p<0.0001). The cumulative incidence of microhematuria found upon a single or repeated examination was 74,8% after the annual check-up per patient. Taking into account an observation period of 3 years, the alterations detected in the urinary sediment were unrelated to treatment with or the dose of danazol. Conclusion: The cumulative incidence of microhematuria was substantially higher compared with the historical data of healthy individuals. As regards the background of this phenomenon, we did not found any relationship with danazol therapy. The main finding of our study was that the increase incidence of edema was associated with bacteriuria. This finding emphasizes the triggering role of bacteriuria in the occurrence of edematous episodes. Supported by OTKA grant 100886 and 112110. Background: Investigation of the role of Helicobacter Pylori (HP) and erosions or ulcers (EU) of upper gastrointestinal tract (esophagus, stomach or duodenum) independently from each other in the development of spontaneous urticaria. Methods: 36 adult patients, 5 with acute and 29 with chronic spontaneous urticaria were examined with upper gastrointestinal endoscopy (UGIE) and HP-testing in gastric biopsies, before and after treatment of the observed abnormalities. Results: HP was found in 26 patients, or 72, 2% (54,8; 85,8) , what was less than across able-bodied population of Moscow -87,9% (85,6; 90,0) 1 , difference insignificant. Wherein EU were found in 50,0% (32,9; 67,1) of patients, and gastric erosions in 41, 7% (25,5; 59,2) , what was 6,1 times more than in 1311 asymptomatic volunteers -6,8% (5,5; 8 ,3) 2 . Two patients with most severe urticaria had duodenal ulcer. Despite these facts, only 23 patients (15,3%) reported mild gastrointestinal complaints after thorough questioning. All 26 HP-positive patients received eradication therapy, and 4 HPnegative patients with EU received only antacid and antisecretory therapy. Second HP-determination by PCR after the therapy was carried out only in 13 patients with chronic spontaneous urticaria (11 HP-positive and 2 HP-negative at first UGIE, 10 patients with EU), as only 13 agreed for a new examination. Where in 7 from 11 HPpositive patients eradication was successful, and in 4 failed. From 7 patients with successful eradication remission was achieved in 2 cases, and in 5 cases there was no remission. In 4 patients with failed eradication remission was achieved also in 2 cases, and in 2 cases there was no remission. Fisher exact test with 1-tailed p=0,47, 2tailed p=0,58 showed highly insignificant result of eradication therapy in the treatment of urticaria in followed patients. At second UGIE, 3 patients from 10 with EU appeared with healed erosions. All of them showed complete remission of symptoms. Whereas 7 patients with unhealed EU, had no improvement at all. Fisher exact test showed significant difference with 1-tailed and 2-tailed p=0,008. Patients with acute spontaneous urticaria were not included in the statistical tests due to high possibility of spontaneous remission. Conclusions: Erosions of upper gastrointestinal mucosa seem to have a very important role in the development of spontaneous urticaria, independently from HP. Introduction: Natural killer (NK) cells are a subset of lymphocytes and that have an important role in innate immunity. NK cells release cytokines such as TNF-α IFN-ɣ during infection. These cytokines stimulate and increased activity of the innate and adaptive immune responses. NKG2D is one of the most stimulating NK receptors that bind to the MIC-A, MIC-B and ULBPs. These ligands are on the tumor and virusinfected cells,which leads to increasing NK secretion lytic proteins such as perforin, granzyme against target cells, and play an important role in the activation of cellular immune function, as well as destruction and elimination of cancer cells. Previous studies have confirmed G2 Vaccine has an important role in the control of asthma via affecting TH2 cells and controls allergic response through preventing increasing eosinophil, basophil, and inhibits TH2-related responses. Thus, in this study, we evaluated the effect of G2 Vaccine on the gene expression and NKG2D receptor presenting on NK cells in peripheral blood. Materials and Methods: To the obtain Nk cell, Blood mononuclear cells after isolation, The 1×10 6 of viable cells were cultured in medium RPMI 1640 and affects by G2 Vaccine in the times of 12, 24 and 48 hours at of 37°. G2 Vaccine is the buffalo spleen extracts that act as TH cells stimulants and first time has been registered by Saleh Mohaghegh Hazrati in IRAN. Then extracting RNA of the cells, cDNA synthesis was performed and gene expression was evaluated by Real-Time PCR. Also receptors presenting on the cell surface was evaluated via monoclonal antibodies by flow cytometry. Results: The results of our study have shown that G2 Vaccine leads to up-regulating gene expression and NKG2D receptor presenting on NK cells. This can lead to increasing NK cells cytotoxicity through this receptor. Conclusion: Due to the increasing NKG2D receptor on NK cells,that can increase NK cell cytotoxicity activity against viral infections and cancers Also, this Vaccine regulate the balance betweenTH1and TH2 and can induce the stimulation of Th1cells. Therefore, In the future this Vaccine can be used in the cancer immunotherapy and treatment of allergic diseases. Keywords: natural killer, NKG2D, flow cytometry, qRT-PCR, Immunotheraphy.


Inflammatory responses of human adipose-tissue derived stem cells to LPS and nanoparticles Hee-Kyoo Kim Background: Human adipose tissue-derived stem cells (hADSCs) have various influences on many types of cells through production and secretion of several cytokines. Some studies presents they have some abilities to suppress or modulate inflammatory responses. By the way, they can show various inflammatory behaviors when meet certain materials or environment. Thus, we investigated the effects of LPS and titanium dioxide (TiO2) nanoparticle (P25) on production of the inflammatory cytokines from hADSCs and A549. Methods: Human adipose tissue-derived stem cells (hADSCs) were cultured in DMEM/F12 medium containing 10% FBS, 10 ng/ml EGF and 2 ng/ml bFGF. A549 cells were cultured in RPMI1640 containing 10% FBS, Cells were treated for 4 hr with LPS (100 ng/ml) and P25 TiO2 nanoparticles (10 ug/ml, 50 ug/ml, 250 ug/ml) and medium as control. Cell viability was determined by MTT assay. The expression levels of IL-1a, IL-8, TNFa, and IL-10 mRNAs were determined by realtime PCR. Results: The viability of hADSCs and A549 cells were not affected by the treatment of LPS and P25 TiO2. LPS increased the expression of IL-8 and TNFa mRNAs, but decreased the expression of IL-10 in hADSCs. P25 TiO2 increased the expression of IL-1a and IL-8 mRNAs, but decreased the expression of IL-10 in hADSCs. In A549 cells, LPS and P25 TiO2 decreased the expression of IL-1a and IL-10 mRNAs, but did not affect the expression of IL-8 and TNFa mRNAs. Conclusion: This study shows the different inflammatory responses of hADSCs and A549 cells to different stimulating materials. The response of hADSCs to inflammatory agents are more dynamics than A549 cells, which suggests that hADSC may facilitate some manipulation in certain inflammatory situation, such as chronic airway disease.

D) Conclusions

A history of immediate reaction to CN and high CN specific IgE were risk factors for a positive OFC. CN OFCs in patients with these risk factors should be performed with caution, considering the possibility of anaphylaxis. Fungal sensitization is not associated with asthma severity: data from a single tertiary hospital in Korea Background: Despite the implementation of guideline-based asthma treatment, 5-10% of asthma population still suffer from severe asthma. In a recent study, fungal allergy was recognized as an important risk factor for severe asthma.We aimed to analyze the prevalence of fungal sensitization in a retrospective cohort of asthma patients, and evaluate differences in clinical characteristics by the presence of fungal sensitization. Materials and Methods: We reviewed medical records of 689 asthma patients who visited a tertiary referral hospital from May 2005 to Jul 2012 and performed skin prick test and pulmonary function test. Cross-sectional data (serum total IgE, blood eosinophil, FEV1, bronchodilator response, PC20, asthma severity), and longitudinal data (number of exacerbations, mean ICS dose, FEV1 variability) were compared by the presence of fungal sensitization, defined as positive (A/H > 1 or mean wheal diameter greater than 3mm) skin prick test to fungal allergen (Aspergillus, Alternaria, Cladosporium, Epicoccum, Fusarium, Penicilliium, Trichopyton). Furthermore, we compared these variables according to the degree of sensitization (negative, A/H ratio > 0.5, A/H ratio > 1). FEV1 and ACT variability was calculated as the average of absolute value of subtraction (FEV1, ACT values which were measured every 3 months), and severe asthma was defined as pre-bronchodilator FEV1 lower than 60%.
Results: The proportion of severe asthma among asthma patients with fungal sensization was approximately 7% (11/74) and 11% (133/634) among those without fungal sensization and the difference was not statistically significant. Serum total IgE was increased with higher degree of fungal sensitization (p=0.001), however, FEV1, PC20, bronchodilator response, blood eosinophil, number of exacerbation, FEV1 variability, mean ICS dose were similar across the three groups. Conclusions: Fungal sensitization did not correlate with asthma severity and the degree of fungal sensitization was not associated with any other clinical variable than total IgE. Additional studies with larger number of patients are required for better understanding of the role of fungal sensitization in asthma. Introduction: Atopic dermatitis (AD) is the most common chronic inflammatory skin disease with a prevalence of up to 20% in children. Children with AD and their parents face difficulties related to daily care and management during a relapsing course that may be aggravated by multiple triggers. Recently therapeutic patient education (TPE) and individual consultation have been in use in the treatment of many chronic diseases for optimal management. Therefore, we preliminarily evaluated the necessities of TPE and individual consultation program of therapeutic management in AD. Subjects and Methods: We organized an individually tailored TPE and consultation program provided by multispecialty of allergist, nurse, nutritionist and environmental coordinator. The program is a patient-centered process consisting of informative consultation which addresses the patient's specific problems including psychosocial support. Enough time was allowed for parents to ask questions during the program. We conducted a questionnaire survey on the disease knowledge before and after the program at the center initially visited. After 3.5 months (min-max: 1-6), participants were contacted by nurses for a telephone interview (TI) with a structured questionnaire (efficiency of the TPE program, symptoms, and quality of life (QOL)). The severity of AD was assessed by allergist using SCORing Atopic Dermatitis (SCORAD). Results: Parents of 135 children with AD took a TPE program and completed the questionnaire survey between May and November 2014. Children with AD were most commonly in the age group of 1~3 years (48, 36%), followed by < 1 age group (36, 27%). The mean SCORAD index of patients was 30.8 (0.0-78.0). The percentages of children with mild, moderate and severe AD were 24, 46, and 30 %, respectively. There was significant improvement in disease awareness by 17.2 from 78.9 to 96.1. Among 135 parents, 100 responded to the questionnaire on the TI. At follow-up TI, 92% answered the TPE program was useful in managing problems related with AD and 86% experienced improvement of the AD symptoms. Furthermore, there was positive change of the QOL in 85% parents. Conclusion: The results of this study demonstrate the usefulness and need of TPE and individual consultation to enable children and their families to care themselves in daily conditions and prevent avoidable complications while improving QOL, ultimately for optimal therapy of AD. Background: IMMULITE 2000 3gAllergy (3gAllergy) is a new method to measure serum antigen-specific IgE levels. Alpha-lactalbumin is one of milk components but its utility in milk allergy has been rarely reported. Objectives: The purpose of this study was to evaluate the utility of alpha-lactalbumin (ALA) specific IgE levels using 3gallergy in predicting clinical tolerance in patients with milk allergy. Method: Forty-three (43) patients with milk allergy (30 boys and 13 girls, age 12 months to 13 years, median 4 years old) were examined for ALA specific IgE levels using 3gAllergy and ImmunoCAPspecific IgE assay (ImmunoCAP). In addition, specific IgE for cow's milk, casein, and beta-lactoglobulin (BLG) were measured by 3gAllergy and ImmunoCAP. Subjects were categorized into 3 groups according to how much heated milk the patient could tolerate, group A, less than 10ml (n=14), group B, 10ml to 100ml (n=15), and group C, 100ml or more (n=14). Two patients had avoided cow's milk product strictly because of severe anaphylactic history with milk intake and others had been undertaking oral immunotherapy with heated milk. Since all data were not assumed Gaussian distributions, they were shown as (median, range(minimum -maximum), and were analyzed by Spearman's method or one-way ANOVA with Dunn's multiple comparisons.
Results: The levels of cow's milk specific IgE using 3gAllergy were significantly correlated to the levels using ImmunoCAP (r=0.958, p< 0.0001). Likewise, the casein, BLG, and ALA specific IgE levels showed similar correlations: (r=0.9766, p< 0.0001, r=0.9793, p< 0.0001, and r=0.821, p<0.0001, respectively). Month of age and serum total IgE levels were not significantly different among the groups. The ALA specific IgE levels with 3gAllergy in group A (44.6 UA/ml, (2.92-478) ) and in group B (8.43 UA/ml, (1.09-152) were significantly higher than those in group C (0.994 UA/ml, (<0.1-53.1), p< 0.0001 and p<0.05). but there was no significant difference between levels in group A and in group B. Levels of milk, casein, and BLG showed similar results. However, the ALA specific IgE -total IgE ratios in group A (0.05, (0.0132-0.1146) were significantly higher than those in group B (0.0155 (0.0024-0.0691)) and those in group C (0.0034 (0.0007-0.0234), p< 0.0001 and p<0.05), as well as the ratios in group B were significantly higher than those in group C, (p< 0.05). On the other hand, there were no significant differences of ALA data using ImmunoCAP among the groups. Conclusions: The ALA specific IgE levels using 3gAllergy is useful to evaluate the clinical tolerance of milk allergy, especially when considered influence of total IgE levels. Background: Anti-tuberculosis drugs (ATDs) which are a combination of isoniazid, rifampicin, pyrazinamide and ethambutol are commonly used for the treatment of tuberculosis, but occasionally associated with drug-hypersensitive immune reactions such as drug rash with eosinophilia and systemic symptoms (DRESS) syndrome and hepatitis. The culprit drug and mechanistic basis of the hypersensitive reaction has not been defined. Objectives: The aim of this study was to find whether drug-responsive T cell response was detectable in patients with ATD-related DRESS and characterize the mechanistic features of the T-cell response. Methods: A lymphocyte transformation test (LTT) and IFNγ-ELISpot assay using ATDs were performed using peripheral blood mononuclear cells from the patient. Subsequently, drug-specific T-cell clones were generated by serial dilutions. Results: High proliferative responses to isoniazid or rifampicin were detectable in the patient with DRESS by LTT. Isoniazid/rifampicinspecific T-cell clones were generated from blood of the patients, but not pyrazinamide or ethambutol. The T cell clones proliferated and secreted IFNγ when stimulated with isoniazid or rifampicin. They did not cross-react with each other. Conclusion: These studies identify isoniazid/rifampicin-specific T-cells in peripheral blood of certain patients with ATD-induced DRESS. Further studies are needed to define the mechanisms of drug-responsive T cell activation.


Objective: To assess the role of oral drug provocation test in the diagnosis of NSAIDs hypersensitivity and find out the safe alternative drugs. Method: Provocation tests with four types of NSAIDs (aspirine -A, ibuprofene -I, meloxicam -M, etoricoxib -E) were administered in patients suspected to be intolerant to NSAIDs by specialists in the Centre of Allergy and Clinical Immunology in Bach Mai hospital. Results: A total of 156 patients having history suspected of being allergic to NSAIDs (F/M: 81/75: 51,9%/48,1%, mean age: 34,9 ± 14,2 years) were enrolled between May 2012 and April 2015. 624 oral provocation tests with NSAIDs were performed and 299 of them were positive. 142/ 156 patients (91%) had positive tests, 24 (16,9%) of them were positive for one drug (A: 11 patients, I: 7 patients, M: 5 patients, E: 1 patients) and 83,1% with two or more drugs. Prevalence of A, I, M and E hypersensitivity were 90,8%, 88%, 9,2% and 0,7%; respectively. The average dose (mg) for positive result of A, I, M, E was 60,9±37, 6, 118,4±43,4, 6,9±1,1, 30; respectively. The average response time (minutes) from the last dose of A, I, M, E was 63,4±24, 1, 69,3±23,4, 78,1±18,7, 120; respectively. Prevalence of cross-reactivity with A of I, M, E was 91,5%, 6,2%, 0%. The main clinical manifestation as positive test was combined allergic rhinitis and urticaria angioedema (42,5%), only one patient had bronchospasm and no patient had anaphylaxis. Conclusion: This research showed oral provocation test is a safe test and also a "gold standard" for NSAIDs hypersensitivoty diagnosis. Choosing altenative NSAIDs should base on single-blind provocation tests.


Antagonism of microRNA-21 suppressed the airway inflammation in a mouse model of bronchial asthma Background: In previous reports, microRNA-21 (miR-21) was upregulated in allergic airway inflammation mediating Th2 immune response [1, 2] . This study was designed to investigate the effect of miR-21 antagonism on mouse model of acute bronchial asthma. Methods: BALB/c mice were sensitized and challenged with ovalbumin (OVA). Anti-miR-21 antagomir and control scrambled RNA was daily injected by intranasal inhalation from the day of sensitization 5 times a week. Changes of cell counts, Th2 cytokines in bronchoalveolar (BAL) fluid and airway hyperresponsiveness (AHR) were evaluated. Histopathologic changes and expression of miR-21 were compared in lung tissues between antagomir treatment group and control groups. Results: Treatment of anti-miR-21 antagomir suppressed AHR compared with OVA challenged group and scrambled RNA treatment group. Antagomir treatment reduced total cell counts and eosinophil counts in BAL fluid. Th2 cytokines such as IL-4, IL-5 and IL-13 were significantly decreased in BAL fluid of anti-miR-21 antagomir treatment group. Conclusions: Antagonism of miR-21 by antagomir inhalation had suppressive effects on development of allergic airway inflammation in acute bronchial asthma model. These results suggest that miR-21 antagomir could be a potential target agent for the treatment of bronchial asthma. Chlorhexidine is a widely used antiseptic and disinfectant. An increasing number of immediate, IgE-mediated, reactions to this drug have been reported. We present two cases of very severe reactions after its topical use.


Conclusions: Proportion of patients with NA sensitized to environmental allergen was equal to NNA. Th2 immune response to aeroallergens might be contributed to development of neutrophilic inflammation in asthma. Urticaria is a common disease and is one of the most common cause of emergency unit visit in children. However, there is no standardized management about acute urticaria and few articles report about urticaria in infants and children. The aim of this study was to define the clinical features, causes, and current status of treatment in infants and children in emergency department.


Association between genetic polymorphisms of costimulatory molecules and antituberculosis drugs induced hepatitis Sang-Hoon Kim 1 , Jang Won Sohn 2 , Ho Joo Yoon 2 , Dong Ho Shin 2 , Jae Hyung Lee 1 , Byoung Hoon Lee 1 , Youn-Seup Kim 3 , Jae-Seuk Park 3 , Young-Koo Jee 3 , Sang- Backgrounds: While the pathomechanisms of antituberculosis drugs (ATD)-induced hepatitis is poorly understood yet, a growing body of evidence supports roles of adaptive immune response in ATDinduced hepatitis. Costimulatory molecules have modulatory effects on activation of T cell, B cell and antigen presenting cell. We examined if the polymorphisms in costimulatory molecules (CD28, CTLA-4, CD40 and CD40L) are associated with ATD-induced hepatitis. Methods: We enrolled 80 patients with ATD-induced hepatitis and 238 ATD-tolerant subjects. DNA was isolated from whole blood and genotyped for the single nucleotide polymorphisms (SNPs) in CD28, CTLA4, CD40 and CD40LG. Genotype frequencies of SNPs and haploptyes were compared between patients with ATD-induced hepatitis and ATD-tolerant patients.


The Fatty Acid Binding Protein Der p 13 Is a Minor House Dust Mite Allergen Able to Activate Innate Immunity Pattraporn Satitsuksanoa 1 , Narissara Suratannon 2 , Jongkonnee Wongpiyabovorn 2 , Pantipa Chatchatee 2 , Kiat Ruxrungtham 2 , Alain Jacquet 2 1 Faculty of Medicine, Thailand; 2 Chulalongkorn University Correspondence: Pattraporn Satitsuksanoa -Faculty of Medicine, Thailand World Allergy Organization Journal 2016, 9(Suppl 1):A207 Background: Compared with other group 13 house dust mite (HDM) allergens, Der p 13 remains very poorly characterized. We recently produced a recombinant form of Der p 13 in P.pastoris and demonstrated that this allergen binds lipids/fatty acids. This study investigated IgE sensitization to rDer p 13 in a large thai HDM allergic cohort as well as the allergen-induced airway epithelial cell activation. Methods: The IgE reactivity to rDer p 13 was analysed by ELISA using 644 sera with a positive skin prick test (SPT) to D.pteronyssinus and collected from four different hospitals in Bangkok. The allergenic activity of rDer p 13 was tested using IgE-loaded rat basophil leukaemia cells (RBL) expressing human FcεRI. The direct airway epithelial cell activation by rDer p 13 was also evaluated. Results: Only 6% of 644 HDM-allergic patients showed IgE-reactivity to rDer p 13 whereas the IgE binding frequency to rDer p 2 reached more than 60%. In RBL assays, rDer p 13 triggered basophil degranulation but the effector activity was lower than that measured for rDer p 2. Treatment of BEAS-2B respiratory epithelial cells with rDer p 13 triggered the production of IL-8 in a concentration-dependent manner. Conclusions: Although rDer p 13 displays allergenic activity, its weak IgE reactivity clearly confirmed that Der p 13 is a minor allergen. We hypothesized that the poor IgE binding frequency of Der p 13 is in line with the apparent very limited amount of this allergen in mite fecal pellets aqueous extracts. Nevertheless, Der p 13, through its fatty acid binding capacity, could play a role in the activation of innate signaling pathways to initiate the allergic response. Background: Nationwide incidence of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) is hard to estimate. We report nationwide incidence of SJS and TEN using an administrative database. Method: We used the database of the Health Insurance Review and Assessment Service (HIRA) in Korea. We employed the HIRA database from 2009 to 2013 to estimate the annual incidence, in-hospital mortality, related complications due to SJS and TEN. In this study, using the International Classification of Diseases-10th Revision (ICD-10), target study population was defined as patients with SJS or TEN, who had the primary diagnostic codes of L511 (SJS) or L512 (TEN), respectively. Result: During four-years study period, estimates of annual incidence of SJS and TEN were 4.9-5.5 and 0.9-1.4 per million people. Mortality rate were 5.7% for SJS and 15.1% for TEN. Mean age was about 50 years old and female predominance was not so apparent in our data. Ocular and urethral sequelae were the most significant sequelae clinically that more than 40% of patients with both diseases suffered from ocular sequelae and about 6% of SJS and 9% of TEN patients were affected by the urethral sequelae. Mortality rate increased as the patients' age got older. Conclusion: The incidence of SJS and TEN was not so much changed since 1990's. However, the mortality rate was decreased and this would be due to the evolution of supportive management.

Regional Differences of Vitamin D and Food-Induced Anaphylaxis in Korea

Methods: The HealthNuts population-based cohort consists of 5300 children recruited at age 1 year. All infants underwent skin prick test to egg, peanut and sesame, and those sensitized had food challenges. At age 4 years, food challenges were repeated in those children previously identified as food allergic to determine persistence or resolution. Weight and height at 1 and 4 years were reported by parents from the child health record. Weight and height z-scores were determined from the World Health Organisation growth charts, standardised for age and sex. Multivariate linear regression models were fitted to examine the effect of food allergy and eczema at age 1 on weight and height z-scores at ages 1 and 4, adjusted for birthweight, prematurity, socioeconomic index, ethnicity and duration of breast feeding. Results: Compared to children with no food allergy or eczema, children with both eczema and food allergy at age 1 had lower weight (β=-0.217, p<0.001) and height (β=-0.206, p=0.008) at age 1 and lower weight at age 4 (β=-0.159, p=0.026) after controlling for potential confounders. There was no difference in children with only food allergy or only eczema. At age 1 the height differences were greater in those with egg allergy and eczema (weight β=-0.240, p<0.001; height β=-0.215, p=0.009) than with peanut allergy and eczema (weight β=-0.292, p=0.011; height β=-0.145, p=0.281) compared to those with no eczema or food allergy. The differences continued at age 4 for children with egg allergy and eczema at age 1 (weight: β=-0.162, p=0.032 height: β=-0.120, p=0.234), particularly those who had persistent egg allergy and eczema at age 4 (weight β=-0.277, p=0.061; height β=-0.490, p=0.013). Peanut allergy, with or without eczema, at age 1 was not associated with differences in weight or height at age 4. Conclusions: Children with IgE-mediated food allergy with eczema at age 1 have reduced growth parameters at age 1 and age 4, while eczema or food allergy alone was not associated with reduced growth. These results emphasise the need for adequate nutritional follow up in food allergic children in infancy, particularly those with eczema. Background: To preliminary determine the impact factors on the clinical efficacy by periodically follow-up visiting dust mite allergic asthma and rhinitis children with one year treatment of dust mite specific immunotherapy. Methods: All of 70 dust mite allergic asthma and rhinitis children with mild to moderate severity were enrolled (male 52, female 18, 4 to 14 years old) February to November in 2011. 57 patients took add-on therapy of sublingual dust mite specific immunotherapy (SLIT) while the other 13 patients with subcutaneous immunotherapy (SCIT). The patients were visited at the baseline period and followed up every three months to assess asthma control test (ACT), visual analog scale (VAS) of asthma and rhinitis symptom and spirometry for pulmonary function test. All the subjects were required to continuously record daily symptom and medication score (SMS) by diary card and to monitor morning and night peak expiratory flow value (PEFR) each day. The controller medication were adjusted to step up or down according to the control level. At the baseline period and after treatment for 6 months and 12 months, serum sIgE and sIgG4 to dermatophagoides pteronyssinus and dermatophagoides farinae, total IgE were determinated by enzyme-linked immunoassay with immunCAP system. Results: (1)The analysis of clinical efficacy of dust mite specific immunotherapy in allergic asthma and rhinitis children. 54 patients completed treatment for 12 months. The average daily SMS was used as the evaluation index, the clinical response to SIT (effective cases) at 3, 6, 9 and 12 months after SIT were 72.2%, 75.9%, 81.5% and 87.0%, respectively. The ACT/C-ACT assessment, average daily SMS, VAS score, FEV1%pred, MMEF%pred, FEV1%pred, MMEF%pred were all improved than before treatment. (2)The analysis of the impact factors in the clinical efficacy of dust mite specific immunotherapy. The SMS at the baseline period, the asthma history and PEF%pred at the baseline period could affect the clinical efficacy of dust mite specific immunotherapy. Conclusions: 87.0% of the patients showed effective response to SIT for one year. The patients with higher baseline SMS, shorter asthma history and lower PEF%pred responsed more effectively to SIT. Background: While otitis media with effusion (OME) is a well-known disease entity of a chronic inflammatory disease of the middle ear space characterized by the accumulation of fluid, but allergic otitis media is still not well-recognized. Previous investigations have suggested that the composition of the inflammatory substrate in the effusions of allergic otitis media is similar to the late-phase allergic response seen elsewhere in the respiratory tract, such as in asthma and in allergic rhinitis. In this study, we aimed to determine whether the prior treatment of Der f can effect on the inflammatory response induced by the subsequent LPS infection and which signaling pathway is involved. Method: Primary human middle ear epithelial cells (HMEEC) were exposed to Der f crude body extract, LPS or both in different sequences, and the magnitude of each immunologic response produced by the HMEEC was compared. The mRNA expression level of mucin gene (MUC) 8, GM-CSF, TNF-a, TLR 4 and MD 2 were evaluated by using real-time polymerase chain reaction (qRT-PCR). The MUC proteins level before and after knocking out the TLR 4 and MD2 via siRNA transfection were assessed by Western blot analysis. Accordingly, the involved cell signaling pathway was evaluated by Western blot analysis and confocal microscopic image. Results: The inflammatory response of cytokines (GM-CSF, TNF-a) and the expression of MUC 8 were augmented by the pretreatment of Der f followed by LPS, however, sequential treatment of HMEEC with LPS and Der f or adding together at the same time did not induce the same amount of response. The MUC expression was decreased by prior knockdown of TLR4 with siRNA but not by the MD2-siRNA. The MUC proteins level were increased by the pretreatment of Der f followed by LPS and decreased by the treatment of SB203580 (p38 inhibitor) and Bay (NF-kB inhibitor). The nuclear factor kB (NF-kB) translocation was demonstrated in the pretreatment of Der f followed by LPS condition. Conclusion: Theses results suggest that Der f may act as a substitute for MD2 and make a strong augmentative response to the subsequent LPS infection. There was an increase in p38 and NF-kB activation within human middle epithelial cells, suggesting an important role for the development of OME in patients with concealed allergy airway sensitization. Objective. To determine the relationship between familial and personal antecedent of allergy, active smoking, and alcohol consumption with drug allergy in pregnant adolescents. Methods. We conducted research on 785 pregnant adolescents by means of a cross-sectional study. Data collection was performed by using a self-administered questionnaire. We evaluated the difference of drug-allergy risk in 785 pregnant adolescents through familial and personal antecedent of allergy, active smoking, and alcohol consumption, calculating Odds ratios (OR) and 95% Confidence intervals (95% CI) by both uni-and multivariate regression analyses. Results. Prevalence of drug allergy was 9.2% and of familial and personal antecedent of allergy, 8.7 and 21.0%, respectively. Percentage of active smoking was 17.6% and of alcohol consumption, 38.1%. Results of multivariate logistic regression analysis show that the familial history of atopic (Adjusted OR = 3.51; 95% CI = 1.85-6.29; p = 0.000), personal antecedent of allergy (Adjusted OR = 4.11; 95% CI = 2.48-6.81; p = 0.000), active smoking (Adjusted OR = 1.92; 95% CI = 1.10-3.35; p = 0.021), and alcohol consumption (Adjusted OR = 2.44; 95% CI = 1.48-4.06; p = 0.000), are significantly associated with drug allergy. Conclusion. Familial and personal antecedent of allergy, active smoking, and alcohol consumption appear to be important factors for development of drug allergy in pregnant adolescents aged 13-19 years. Background: REALISE Asia is a two-part study (Part 1 -patient survey and Part 2 -physician survey) conducted to understand patients' and physicians' perceptions and perspectives towards asthma and its management. We report here the extent of discrepancy in the understanding of well-controlled asthma between patients and physicians in Asia. Methods: REALISE Asia was conducted in two parts across the following 8 countries in Asia: China, Hong Kong SAR, Indonesia, Malaysia, Philippines, Singapore, South Korea, and Taiwan. Part 1 was an online, questionnaire based survey involving 2,467 patients with asthma aged 18-50 years. Part 2 was carried out through face-to-face and online interviews amongst 375 physicians managing asthma patients, 54% of which are specialists (i.e. respiratory medicine, allergy, and clinical immunology) and the rest in primary care practice. Results: A significantly higher proportion of specialists (95%) compared to primary care physicians or PCPs (65%) reported that they use Global Initiative for Asthma (GINA) in assessing asthma control. Only 2% of specialists stated that they do not use any guidelines compared to 22% of PCPs. While 89% of patients considered their asthma to be controlled, physicians perceived 53% of their own patients as well-controlled. Both are overestimation of the actual proportion of patients achieving control (18%) based on GINA-defined criteria. Seven out of 10 physicians mentioned that their patients' definition of well-controlled asthma is aligned with their definition. Physicians perceived that patients relate well-controlled asthma to minimal impact on daily life (50%), absence of symptoms (48%), and no/reduced attacks (21%). This is in stark contrast with patients understanding of the concept as they related control more to having medications to cope with their symptoms (26%) or quickly control asthma attacks (15%) reflective of the crisis-oriented mind-set they have towards their disease. Conclusions: Physicians and patients overestimate their level of asthma control. These highlight the importance of accurate assessment in clinical practice, and the role of physicians in improving the understanding of concept of well-controlled asthma amongst their patients. Standardized tools may aid in better assessment of control while using shared language in discussing treatment goals may help ensure physicians' and patients' concept of well-controlled asthma are more aligned.


The Different Influence on the Regulatory T Cell Response Between Subcutanous Immnuotherapy(SCIT) and Sublingual Immunotherapy(SLIT) in Children with Asthma Qing Miao, Li Xiang Beijing Children's Hospital, China Correspondence: Qing Miao -Beijing Children's Hospital, China World Allergy Organization Journal 2016, 9(Suppl 1):A219

Prediction of the Success of Our Desensitization Protocol with Symptoms and Results of a Skin Prick Test in Patients with

Background: The prevalence of immediate hypersensitivity reaction (IHSR) to platinum-based chemotherapy has been rising, with the increase of chemotherapy usage. Although there is a proven ultimate solution, desensitization protocol, it has not yet applied in many institutes because of impracticalities such as cost, procedure duration and lack of trained manpower. Prediction of the success of a desensitization protocol will help reduce unnecessary workload. Objective: We aimed to determine the clinical characteristics and currently adopted measures against oxaliplatin IHSR and to predict the success of our newly developed practical desensitization protocol. Methods: We retrospectively reviewed 2,640 cases of oxaliplatin IHSR in 271 oxaliplatin users who admitted to Severance hospital. We prospectively used our new desensitization protocol 31 times in 12 patients with hypersensitivity to platinum-based chemotherapy. The new desensitization protocol was conducted with escalating of infusion rate regularly regardless of the concentration of bags, in order from 60 mL/h to 120 mL/h and 240 mL/h about every 15 minutes. Results: In 271 patients who administered oxaliplatin, 45 patients (16.6%) experienced oxaliplatin IHSR. In 39 patients, who experienced IHSR but need to keep oxaliplatin, 6 patients (15.4%) stopped due to the IHSR and 33 patients (84.6%) kept the regimen regardless of the anticipated risk. Any significant risk factor for the IHSR was not found. The new desensitization protocol was successfully completed in 12 patients (100%). However, among these 12 patients, the protocol was ineffective in 3 patients having fever without urticaria and a negative response in a skin prick test. Conclusions: Many patients who experience oxaliplatin IHSR are required to stop the effective regimen or maintain the regimen without desensitization with the anticipated risk of IHSR. Our new practical desensitization protocol might be applied easily and conveniently in real clinical practice. Fever without urticaria and a negative response in a skin prick test indicate that this desensitization protocol might be ineffective. Background: Bacterial flagellin, which is a Toll-like receptor5 agonist, is used as an adjuvant for immunomodulation. Recently, intranasal administration of OVA flagellin mixture was reported to be effective in allergic inflammation. In this study, we aimed to evaluate the effect and its mechanism of intralymphatic administration of OVAflagellin mixture in the treatment of allergic rhinitis. Materials and Methods: BALB/c mice was sensitized with OVA and treated with OVA-flagellin (FlaB) mixture via intranasal, sublingual and intralymphatic routre to evaluate the effect of intralymphatic administration. Then several parameters of allergic inflammation was assessed including symptom score, eosinophil and neutrophil infiltration in the nasal mucosa, systemic cytokine levels, and Total and OVA-specific imuunoglobulin E. To evaluate the mechanism of intralymphatic injection, local cytokine, chemokine, and innate cytokine analysis was undertaken using real time PCR, western blot and immunohistochemistry. Results: Intralymphatic injection by OVA-FlaB mixture reduced symptom score, eosinophil infiltration in the nasal mucosa and total and OVA-specific IgE levels more significantly than intranasal and sublingual administration. The systemic cytokines(IL-4, IL-5, IL-6, IL-17 and IFN-r) and local cytokines(IL-4, IL-5) production were also decreased significantly in intralymphatic injection by OVA-FlaB. Double administration of mixture was more effective than single administration. Moerover, the expression of innate cytokine such as IL-25, IL-33 in nasal epithelial cells were decreased and the chemokine expression such as CCL24(eotaxin-2) and CXCL1,2 were decreased in the nasal mucosa, suggesting the underlying mechanism of intralymphitc administration of OVA+FlaB mixture. Conclusion: Intralymphatic administration of OVA+FlaB mixture was more effective in alleviating allergic inflammation than intranasal and sublingual administration in mouse model of allergic rhinitis and this effect could be attributed to reduced expression of innate cytokine and chemokines. This modality could be considered as a new therapeutic method and agent. Background Nonsteroidal antiinflammatory drugs (NSAIDs) hypersensitivity is a commonly found drug allergy, in which two major phenotypes, respiratory (aspirin-exacerbated respiratory disease ) and cutaneous (aspirin-exacerbated cutaneous disease or aspirin-intolerant acute urticaria ) types were noted in this country. Periostin is an extracellular matrix protein and structurally homologous with fasciclin I, an insect adhesion molecule. Previous study demonstrated that serum periostin level was significantly higher in AERD than in aspirin tolerant asthma. To evaluate serum periostin level as a biomarker for differentiating the phenotypes of NSAIDs hypersensitivity, we compared serum periostin levels between respiratory and cutaneous types of NSAID hypersensitivity. Methods Serum periostin levels were measured by human periostin ELISA in sera from 326 adult patients with NSAID hypersensitivity and 87 healthy normal controls (NC). The phenotype of NSAID hypersensitivity was defined according to previous histories of adverse drug reaction and/or aspirin provocation test. Results There were 45.7% of respiratory type of NSAID hypersensitivity (n=149) and 54.3% of cutaneous type (n=177). Mean serum periostin level was significantly higher in respiratory type (82.6 ± 38.8 ng/mL) than in cutaneous type (39.7 ± 31.1 ng/ML) and NC group (46.2 ± 29.0 ng/mL). However, there were no significant differences of serum periostin levels between AECD and AIAU groups (P = 0.708), between AECD and NC groups (P = 0.195) , and between AIAU and NC groups (P = 0.110). The ROC analysis revealed that serum periostin level could differentiate AERD from cutaneous type of NSAIDs hypersensitivity (AUC = 0.826, P < 0.001) and cut-off level was 42.5 ng/mL with 93.3% of sensitivity and 61.0% of specificity. Conclusion These findings suggest that serum periostin level can be a useful biomarker for predicting the phenotype of AERD among NSAID hypersensitivity patients. Background: An early identification of sensitization pattern in suspected allergic children may supply evidence-based clues for prevention and management of allergic disease. Objective: To analyze the sensitization status to common inhalant allergens for children with suspected allergies in Beijing Children's Hospital in year of 2013. Methods: The enrolled children were screened for allergies through a semi-quantitative testing method (Mediswiss Allergy Screen allergen testing system, Germany), and a further comparison for sensitization patterns among different subgroups was performed. Results and conclusion: A total of 21,134 children had screened for allergies. In out-patient subjects, the positive rate of sIgE was 45.99% (8266/17974 cases), the top three positive allergens were mold, dog hair and dust mites. For the inpatient group, the positive rate of sIgE was 29.34% (927/3160 cases) and the top three allergens were dust mites, dog hair, and mold. It was also found that the highest positive rate was from children suffering from the nose or eye disease (outpatient:2092/3126,66.92%; in-patient:14/26,53.85%). Especially for the inpatients HSP children, when co-infected with lower respiratory tract infections(LRI), the positive rate was increased (HSP: 370/1024, 36.1%; HSP+LRI: 370/1024, 42.7%, P<0.05), and it was more likely to lead to the appearance the multiple sensitization. Therefore, it is necessary to keep a watch on the variation in the sensitization state, and to pay greater attention on interpreting testing results, which enables to supply the pediatrician a rational treatment and prophylactic strategy on the allergen avoidance. Oxidative stress has been postulated to play an important role in the pathogenesis of allergic airway inflammation. Nrf2 is involved in the transcriptional regulation of many antioxidant genes. In the present study, we investigated the role of Nrf2 on an experimental model of Ovalbumin (OVA) -sensitized and challenged allergic airway inflammation in both of BALB/c and C57BL/6 mice. Nrf2−/− and Nrf2+/+ mice were used in both of BALB/c and C57BL/6 mice. Allergic airway inflammation was generated in the mice by intraperitoneal sensitization with OVA/alum on days 0, 6 and 7. The mice were challenged with OVA intranasally on day 21. After OVA challenge twenty-four hours, we examined the cell populations in bronchoalveolar lavage (BAL) fluid, and the IgE levels in the serum.
Airway hyperresponsiveness (AHR) was assessed by whole-body plethysmography with a free-moving application. The number of total cells, macrophages and eosinophils in BAL fluid was decreased in Nrf2-/-compared with Nrf2+/+ mice, this was also the case for the AHR changes in both of BALB/c and C57BL/6 mice. The number of neutrophils in BAL fluid and the IgE levels in the serum were significantly increased in Nrf2-/-compared with Nrf2+/+ in BALB/c mice; in contrast, there was no significantly different between Nrf2-/-and Nrf2+/+ in C57BL/6 mice. In conclusion, the role of Nrf2 in the generation of allergic airway inflammation differs markedly between mouse strains. Our results suggest that Nrf2 may play a key role in the development of allergic airway inflammation related to neutrophils in BALB/c mice. Background: Neutrophils play an important role in the development of persistent airflow limitation in asthma, particularly in patients who show poor response to corticosteroids. Human mesenchymal stem cells (hMSCs) has emerged as a new treatment option due to its immunomodulatory effect, however, the role of hMSCs in neutrophilic asthma is not yet understood. Method: BALB/c mice were exposed to ovalbumin and poly IC to induce neutrophilic airway inflammation. hMSC was administered intravenously, and then, bronchoalveolarlavage (BAL) was done to evaluate differential cell count and measure inflammatory cytokine including IL-8, IL-5, IL-10, IFN-gamma. We also measure cytokines include IL-17, IL-4, IL-10, IFN-gamma released from lymphocyte in pulmonary lymph node. In addition, lung histopathology was done to show peribronchial and perivascular inflammation. Result: hMSC treatment decreased BAL total cell count (P < 0.001), neutrophils (P < 0.001) and lymphocyte (P < 0.01) IL-5 in BAL fluid was decreased in hMSC treatment group (P < 0.01), however, IL-8, IL-10 and IFN-gamma showed no differences compared with wild type. IL-17 released from lymphocyte in pulmonary lymph node was significantly decreased (P < 0.05). Histopathologic examination revealed that peribronchial inflammation was dramatically decreased in hMSC treatment group. Conclusion: hMSCs inhibited airway inflammation in poly IC induced neutrophilic asthma model. The mechanism underlying its immunomodulatory effect might be associated with down regulation of IL-17 which has key role in Th17 mediated inflammation. Background: Although several studies have claimed that mesenchymal stem cells (MSCs) derived from human tissues can ameliorate allergic airway inflammation, the immunomodulatory mechanism of MSCs remains unclear. Objective: We aimed to determine the effects and underlying mechanism of tonsil derived MSCs (T-MSC) on allergic inflammation as compared to adipose tissue derived stem cells (ASCs) in mouse model of allergic rhinitis (AR).


Food and drug allergies are common causes of anaphylaxis. Shellfish is the most common food allergen. Anaphylaxis caused by drugs, stinging insects and shellfish was more common in adults, whilst anaphylaxis caused by peanuts and tree nuts is more common with children. Background: Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease characterized by dry skin with severe itching. Children with AD and their caregivers report disease associated sleep disruption, irritability, anxiety, behavior problems. Moreover, AD places a significant economic burden on the patient, family and society. So, an integrated health care service can be useful to comprehensively evaluate triggers and response to treatment, address confounding factors including psychological problems, and educate patients and family. Method: This study was designed to evaluate the effectiveness of integrated health care service in children with AD according to quality of life and clinical symptom scores. 134 children were referred from local health care office to Seoul Medical Center for management of AD from July to December, 2011. The questionnaire developed by the 'Atopy Free Seoul' research project in 2008 was used for quality of life (QOL) survey, and SCORing of Atopic Dermatitis (SCORAD) was done at each visit. Results: The study targets were 134 children with the average age of 6.11 years with AD and visited the hospital 2.01 times on average. It was found that the QOL scores of patients participated in our integrated health care service was reduced by 10.43 after treatment compared before intervention (p<0.0001). In 46 children among them, SCORAD also averagely decreased by 5.78 after treatment (p<0.0001). Moreover there is positive correlation between changes in scores of QOL and SCORAD of 46 patients (r=0.46, P<0.001). 74.6% was satisfied with improvement degree of symptoms after integrated health care service and 70.1% was satisfied with improvement degree of daily life. Conclusion: Integrated health care service for children with AD improved disease severity and quality of life. The results from our multidisciplinary approach supported the need for and feasibility of integrated care for children with AD and their families. Backgrounds: A substantial proportion of patients with chronic urticaria (CU) is refractory to antihistamines. It remains unknown how we identify a subpopulation whose urticaria is not completely controlled by antihistamines. Autologous serum skin test (ASST) response has been suggested as a potential predictor of urticaria control. We sought to identify proteins that were differentially expressed in the sera between patients with positive and negative ASST. Method: The proteomic analysis was performed using sera from 3 patients with positive results on ASST compared with those with negative ASST. Seven upregulated and 5 down-regulated proteins were identified by matrix-assisted laser desorption/ionization time-offlight mass spectrometry in the positive ASST group compared with the negative ASST group. Results: Proteins differentially expressed according to the ASST results in CU patients were classified into 5 groups: apolipoproteins, glycoproteins, modified albumin, haptoglobulin, and plectin. Among them, apolipoprotein J or clusterin was validated by using ELISA. Clusterin levels in 69 ASST positive patients were significantly higher than those in 69 ASST negative patients and in 86 healthy controls (median 227.6, min-max 108. 5-359.9 vs 209.4, 117.3-288 .0 vs 133.2, 0.06-277.6 μg/ml, P <0.001). Furthermore, it differs significantly between patients with well responsive and refractory to antihistamine treatment within 3 months (227. 6, 117.3-359.9 vs 197.5, 108.5-309 .8 μg/ml, P = 0.002). Receiver-operating characteristic (ROC) curve analysis yielded 202 ug/ml of serum clusterin as the optimal cut-off for discriminating the responsiveness to antihistamines in CSU patients (AUC 0.759, 95% CI 0.679-0.839, P < 0.001). Criteria combining ASST results and serum clusterin levels can predict 92.7% of CU patients whose urticaria would be refractory to antihistamines. Conclusion: Considering on that clusterin is able to modulate complement function, we suggest that serum clusterin can be a prognostic marker to determine the responsiveness to antihistamine treatment in patients with CU. This work was supported by grants from National Research Foundation of Korea funded by the Korean Government (MSIP: NRF-2012R1A5A2048183). Several biomarkers have been developed to address airway inflammation in bronchial asthma (BA), including exhaled nitric oxide, sputum eosinophils. However it is challenging and sometimes considered to be rather invasive to appropriately obtain those biomarkers in young children. Since urine is a non-invasive and easy-toobtain samples in children, urinary leukotriene E4 (uLTE4) is one of the most potent biomarkers to address airway inflammation in infants. To ask whether uLTE4 can be used for the diagnosis of BA in young children, we determined concentrations of uLTE4 of wheezing children. A total of 184 patients at an outpatient clinic in Saitama prefecture in Japan for wheezing from February 2012 to August 2013 participated in the study. Urine samples were collected and immediately frozen until use. LTE4 was collected with an anti-LTE4 antibody and the concentrations were determined by ELISA. Urine creatinine (uCr) levels were also determined. Since uCr levels differ among different ages, we first corrected all the uCr values with those at corresponding ages. uLTE4 was then normalized to age-corrected uCr levels. Patients consisted of the first wheezers with or without a family history of BA, the first wheezers with RSV infection, intermittent BA, mild persistent BA and controls with fever but not wheezing. uLTE4 levels of the first wheezers with a family history who responded to inhalation of bronchodilator (n=33) and intermittent BA (n=25) were higher (p<0.01) than those of controls. There were no significant differences between uLTE4 in other groups and controls. These results suggest that uLTE4 can be a marker of allergic airway inflammation in young children. We are currently following clinical courses of those patients to ask whether uLTE4 can be a predictive marker for the development of BA. Background: Orally ingested food proteins normally result in the induction of oral tolerance, whereas allergic sensitization to food proteins in mice is induced in the presence of a mucosal adjuvant like cholera toxin (CT). CT is therefore often used as a tool to unravel the mechanisms behind allergic sensitization, although CT is not involved in the onset of allergic sensitization in humans. The mycotoxin deoxynivalenol (DON) is among the most frequently detected contaminants of wheat and wheat-based products, and is able to impair intestinal barrier function. As such, we hypothesize that DON may represent a more human-relevant mucosal adjuvant and therefore the present study investigated the capacity of DON to act as a mucosal adjuvant in a mouse model of whey-induced food allergy. Methods: Female C3H/HeOuJ mice (n=8 per group) were orally exposed to DON plus whey once a week for 5 weeks, while control mice received DON in PBS. Acute allergic skin responses, change in body temperature and other anaphylactic shock reactions were measured upon whey-challenge. Allergen-specific antibodies and ST2 were measured in serum. mRNA expression of claudin-2 and -3, Ecadherin and IL-33 were determined in intestinal tissue and ST2 was measured in serum 6h after a single oral DON-exposure. Results: Mice exposed to DON plus whey showed whey-specific IgG1, IgG2a and IgE antibodies in serum and an acute allergic skin response upon intradermal whey challenge compared to control mice. Furthermore, a significant time-dependent increase in soluble ST2 in serum was observed in DON plus whey sensitized mice compared to control mice. In addition, analysis of intestinal tissues, isolated 6h after a single oral exposure to DON, revealed increased mRNA expression of the tight junction proteins claudin-2 and -3 and the adherens junction E-cadherin, as well as an increase in IL-33 mRNA accompanied by an increase in the soluble IL-33 receptor ST2 in serum.


Using Allergen specific IgE as standard (Cut off of 0.1 kua/l), the sensitivity & specificity of Phadiatop in Group I was 62.1% and 98.4% respectively. Phadiatop sensitivity increased if only Allergen specific IgE values >0.5 kua/l were considered, i.e those more likely to be involved in symptomatic allergic disease. Phadiatop missed cockroach and shrimp positive sera. Though Phadiatop is not intended to screen for food allergies, cross reactivity between certain pollens and foods yielded few positive screening results. The sensitivity & specificity of Total IgE in Group II was 40.8 % and 100% respectively. Total IgE not only missed low level sensitization, but also missed some sera with high positive allergen specific IgE results. Conclusion Phadiatop TM was found to be a satisfactory screening test for atopy and outperformed Serum Total IgE. Looking at the trends in inhalant and food allergen seroprevalence, current study was able to establish a preliminary list of allergens relevant in the Indian context. These could be tested in addition to a Phadiatop or as a follow-on to a negative Phadiatop TM in the event of strong clinical history of allergic disease. Background: We previously reported that skin prick test was sensitive and serum specific IgE test was specific for predicting positive airway responses to house dust mites (HDM) in asthma. Because nose and bronchus are one airway, nasal provocation test would be more specific than skin test for predicting bronchial responses to HDM. Methods: Allergy skin prick test, and nasal and bronchial provocation tests using HDM Dermatophagoides farinae were done in 35 young men (19~28 years-old) who wanted a military certification for asthma. The nasal responses to HDM were scored according to the severity of 3 nose symptoms (rhinorrhea, sneezing, and nose itching). Results: The prevalence of positive skin test (≥3+) to HDM was not significantly different between the patients with (n=23) and without (n=12) a positive response (early or late) to bronchial challenge (87.0% vs. 66.7%, P=0.200). However, the nasal response score was significantly higher in the responders than the others (1.00±0.24 vs. 0.25±0.13, P=0.011). The concordance of positive response not to the skin test (k=0.225, P=0.154) but to the nasal test (cutoff score: ≥2) (k=0.306, P=0.012) was significant with the positive bronchial response. The diagnostic sensitivity of the nasal test (47.8% at cutoff≥1, 39.1% at cutoff≥2) was lower, but the specificity (75.0% and 100%, respectively) was higher than that of the skin test (sensitivity: 87.0%, specificity: 33.3%).


The skin test is more sensitive, whereas the nasal test is more specific for predicting a positive bronchial response to HDM in asthma. Background: Recurrent wheeze in preschool age consists of several phenotypes, each of which may represent different underlying pathology and differential response to treatment. However, phenotypebased recommendations for treatment have not been established since most of clinical trials have targeted to broad ranges of phenotypes, not to a specific phenotype. In order to identify a novel clue to the drug choice for preschool wheeze, we investigated possible utility of biomarkers by comparing efficacy of 2 treatment options in a specific biomarker-defined subgroup. Serum eosinophil-derived neurotoxin (EDN) and sensitization to house dust mite (HDM) were employed as biomarkers in this study. Methods: Children of 1 to 5 years old who had more than 3 episodes of recurrent wheeze with documented reversibility were enrolled in the study. They were tested for specific IgE to HDM and serum EDN at the entry. Then, they were randomized to receive budesonide or montelukast for 12 weeks if they were HD-sensitized, high serum EDN >53 ng/ml and symptomatic during run-in period. Primary outcome was asthma controlled days (ACDs). Non-eligible patients were also followed up for the same period with administration of montelukast. Results: Ninety-eight subjects were enrolled in the study and 42 were eligible for randomization. Both group responded well to treatment and there was no difference in ACDs between the groups. However, serum EDN levels significantly decreased in montelulast group, not in budesonide group. Serum EDN levels in non-eligible group treated with montelukast also significantly decreased. Conclusions: Budesonide and montelukast had the same efficacy to HDM-sensitized and high EDN subgroup of preschool wheeze and the biomarkers did not represent differential responses to the 2 treatment options. EDN reducing effect of montelukast, however, warrants further investigation. Background: Anti-tuberculosis drugs (ATD) are major causes of drug induced liver injury (DILI) around the world. Compared with general population, the patients with connective tissue diseases (CTD) are suspected to be at higher risk of DILI, since they are frequently exposed to various medications including immunosuppressive agents. We aimed to assess the incidence and severity of DILI in CTD patients in comparison with non-CTD patients. Methods: In this retrospective case control studies, we enrolled the patients with newly diagnosed tuberculosis and treated with the first line ATD for two years in a university hospital. DILI was defined as increase of serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) greater than threefold of the upper limit of normal (ULN). Results: Of a total of 279 enrolled patients, 40 patients (14.3%) had CTD, such as rheumatoid arthritis (n = 19), systemic lupus erythematosus (n = 10) and ankylosing spondylitis (n = 6). The frequency of DILI caused by ATD in CTD patients was not significantly different from non-CTD patients (7.5% vs. 11.3%, P = 0.346). While severe DILI (AST/ALT > 5 x ULN) was observed more frequently in CTD than controls, there was no statistical significance (7.5% vs. 5.9%, P = 0.451). Conclusion: The frequency of DILI in patients with CTD was not significantly different from non-CTD patients. These findings suggest that CTD is not a significant risk factor for DILI induced by ATD. Background: Japanese cedar pollinosis is a disease with a variety of symptoms; in particular, ocular and nasal symptoms occur frequently. The incidence of these cedar pollinosis symptoms reportedly differs year by year, and due the large amount of Japanese cedar pollen dispersed in Japan, they are often more severe than the symptoms of seasonal allergic rhinitis in Europe and the United States. Although pollen allergy prevalence symptoms in Europe (Canonica et al. 2007) and the United States (Schatz 2007) has been reported, the prevalence of ocular symptoms due to cedar pollinosis in Japan has yet to be determined. Methods: We used the Japanese Rhinoconjunctivitis Quality of Life Questionnaire to examine symptoms and quality of life in 633 patients who consulted our hospital or ear, nose, and throat clinic between 2009 and 2014 during the peak cedar pollen season and who had not received any previous treatment. Results: Ocular symptoms were seen in 87% of patients. Itchy eyes were more prevalent than watery eyes, with 84%of patients experiencing itchy eyes and 63% watery eyes, even in a year with low pollen dispersal. Responses for the occurrence of nasal and ocular symptoms indicated that a more severe score for nasal symptoms was correlated with better eye symptoms. Comparison of annual pollen counts revealed a correlation between worsening of itchy eyes and increased pollen counts. However, the severity of watery eye symptoms did not differ significantly between years with small and moderate pollen levels, indicating that watery eyes develop when the amount of pollens is high.


Conclusions: Approximately a half of milk allergy children can tolerate baked milk product. Component-specific IgE and IgG4 titers could be useful as a predictor for tolerability of baked milk. Background: SP-D is a hydrophilic lectin and involves in a host defense mechanism against respiratory pathogens and modulates immune responses against bacteria or allergens.
Results: The SP-D levels in sera of AERD patients were significantly lower than those of ATA and control groups. The ROC curve indicated that SP-D at 1755.82pg/ml can be an optimal cutoff value for predicting the phenotype of AERD with 64.3% sensitivity and 62.4% specificity. No associations were found with clinical parameters such as atopy, chronic rhino-sinusitis, eosinophilic/neutrophilic asthma or severe/non-severe asthma. A significant negative correlation was found between serum SP-D level and the fall of FEV1 (%) after inhaled lysine-ASA in asthmatic patients. Conclusion: These findings suggest that SP-D may involve in the pro-inflammatory response of airway mucosa which contribute to bronchoconstrictive response to inhaled ASA in AERD patients.


The reliability of self-reported BL allergy is low and questionable. Skin tests and specific IgE determination are safe to diagnose patients with an immediate reaction to beta-lactams. Drug allergy de-labeling is needed to distinguish true allergic patients from non-allergic cases, particularly in certain circumstances when alternative antibiotics are not available nor appropriate. Background: To investigate the protective role of the sonic hedgehog (SHH) signaling associated with a lipopolysaccharide (LPS)-induced acute lung injury (ALI) in a mouse model. Methods: Male BALB/c mice were randomly divided into three groups, control, LPS, and LPS-C group. ALI was induced by LPS ip injection (5 mg/kg). The sonic hedgehog inhibitor cyclopamine was given to the LPS-C group (50 mg/kg) at 30 min after LPS injection. Lung injury was observed histologically in hematoxylin and eosin (HE) stained tissue sections, semi-quantified by lung tissue injury score, and the lung tissue mass alteration was measured by wet to dry weight ratio (W/D). mRNA levels of TNF-α, SHH, Patched (PTC) and GLI1 in lung tissue were studied with real time quantitative PCR (RT-PCR), while the protein expression of SHH and GLI1 was determined by western blot analysis. Results: Lung tissue injury score, W/D, and mRNA expression levels of TNF-α were significantly higher in the ALI mice than the normal mice (P<0.05). The mRNA levels of SHH, PTC, and GLI1 in the ALI mice were significantly higher at 12h and 24h after LPS injection, but not at the 6h time point. Protein production of SHH and GLI1 at 6h, 12h, and 24h in the lungs of ALI mice significantly increased, in a time-dependent manner, compared with that in normal mice. Cyclopamine intervention in ALI mice led to a reduction in mRNA levels of SHH, PTC, and GLI1 as well as SHH and GLI1 protein levels; meanwhile, the pathological injury scores of lung tissues, W/D, and mRNA expression levels of TNF-α increased compared to mice receiving LPS only. Conclusions: The SHH signaling pathway was activated in response to LPS-induced ALI, and up-regulation of SHH expression could alleviate lung injury and be involved in the repair of injured lung tissue. Knowledge and skills required for the use of adrenaline autoinjectors (AAI) are lacking in school settings, causing considerable uneasiness among teaching staff about administering AAI to students. Objective This study aimed to elucidate the factors behind the negative attitudes toward the administration of AAI in school settings.


Method: This research was conducted using the data from the 4th and 5th Korea National Health and Nutrition Examination Surveys (KNHANES), which were conducted from 2008 to 2011. Of the subjects on whom dual-energy x-ray absorptiometry (DXA) was performed to confirm their body composition, 1,219 COPD patients aged over 40 years showed an FEV1/FVC < 70%. COPD is classified into three groups-mild, moderate, and severe-according to the airflow limitation. In this study, 534 subjects had mild COPD; 613, moderate; and 72, severe. For the criteria for sarcopenia, the recommended criteria of the European Working Group on Sarcopenia in Older People (EWGSOP) and of the Asia Working Group for Sarcopenia (AWGS) were used. Results: The ASMI of each group was categorized according to the COPD severity into 7.04±1.034, 6.83±1.030, and 6.45±1.071, respectively. Thus, there were differences between all the groups, and the higher the severity, the lower the results were (p < 0.001).When the sarcopenia classification of EWGSOP according to the ASMI was applied, each group's FEV1(L) was 2.26 ±0.673, 2.20±0.633, and 1.94±0.730, respectively. In the case of Class II sarcopenia, it was lower than that in the normal case and in the case of the Class I sarcopenia.(P=0.003)When the sarcopenia criteria of AWGS was applied, the FEV1(L) was 2.30±0.667 and 2.09±0.651, and the pulmonary function of the sarcopenia group was low (p < 0.001). The correlation of the FEV1(L) with the ASMI was analyzed as 0.521, higher than with the BMI or the FFMI (p < 0.001); and the regression analysis also confirmed that the ASMI had a higher R2 and standardized regression coefficient than the BMI, FFMI, and skeletal muscle mass index (SMI) (p < 0.001).It was found that when the ASMI was used, the sarcopenia risk increased in all the cases in which the criteria recommended in EWGSOP and AWGS were used; and when the criteria of the AWGS were used, the moderate and severe stages showed the odds ratios of 1.587 (95% Cl, 1.109-2.271, p = 0.012) and 3.127 (95% Cl, 1.438-6.802, p = 0.004), respectively, compared with those of the mild stage. Conclusion: ASMI is a fast and accurate predictor of skeletal muscle abnormality caused by an increase in the severity of the airflow limitation of COPD patients. Background: Oral allergy syndrome (OAS) is defined as the symptoms of IgE-mediated immediate allergy localized in the oral mucosa, and the characteristics depend on the lability of the antigen. OAS is regarded as uncommon manifestations of pediatric population. This study focused on the allergenic relationship between pollen and food allergen of oral allergy syndrome in Korean children. Methods: The study was based on a data analysis of patients, who were diagnosed with oral allergy syndrome at Ajou University hospital, Severance children's hospital, Kangnam severance hospital from January 2008 to December 2014. Clinical details were collected by medical history and telephone survey. Results: The subjects were 59 male and 38 female with median aged 9 years. In 97 children with oral allergy syndrome, most common causative food of allergy syndrome was apple. Pollen with the highest rate of positive responses is birch. In children with oral allergy syndrome, children sensitized birch have high risk of reaction to apple. The youngest patient with oral allergy syndrome is 3 years old girl. 65 children had reaction to more than 2 foods. Conclusion: oral allergy syndrome may commonly affect children who are allergic to pollen. For children with oral allergy syndrome, knowledge of specific sensitization patterns has consequences for dietary management. Background: Numerous epidemiological studies have shown adverse associations between increases in outdoor air pollution and health outcome. The majority of studies focused on daily concentrations of air pollutions and small-scale variation in daily averages and peak concentrations has not been able to characterize. We investigated the seasonal association between diurnal variation of traffic-related air pollution and the exacerbations of asthma symptoms among the middle-aged and the elderly in urban settings. Methods: To address the health effect of diurnal variation of traffic-related air pollutants on asthma-related emergency department (ED) visits, we applied generalized linear model with over dispersed poison distribution to daily asthma-related ED visits between 2008 and 2011 in Seoul, Korea. The indicator variable of diurnal variation of traffic-related air pollutant, the diurnal range of NO 2 (drNO 2 ) was adopted and defined as the difference level of NO 2 between 10:00 and 05:00 in the morning. The statistical analysis was conducted to estimate the effect of drNO 2 adjusted for temperature, relative humidity, air pressure, PM 10 , O 3 , influenza epidemic indicator, day of week, and time trend. Agespecific effects and seasonality were tested and the age-specific groups were defined as the middle-aged aged between 50 and 74 and the elderly aged above 75. Results: Among the total 19,702 asthma-related ED visits during study period, 6,933 were recruited with the middle-aged 4,503, and the elderly 2,430 and the increased overall risk were suggested with relative risk percent change with 95% confidence interval (95% CI); middle-aged [2.1 (95% CI; 17.6) ], and the elderly [23.6 (95% CI; 3. 1, 48. 3)] at lag0-8 by 1 interquartile range (IQR) increase of drNO 2 . Season specific effect for the middle-aged were (95% CI; 11.6) This study suggests an adverse relationship between ambient drNO 2 with the risk of asthma-related ED visits and the level of drNO 2 was related to asthma exacerbations especially during spring and winter period and the delayed effect were varied by age-groups.


Maternal allergy, age and height of infant were found to be significant factors in the severity of acute bronchiolitis in infant. Further study is needed to determine if maternal allergy allow for prediction of long term respiratory outcomes, such as asthma, following bronchiolitis because infants with severe bronchiolitis were more likely to have a familial atopic predisposition, which may partly explain subsequent increased asthma risk. Keywords: Allergy: Pediatric Background: Refractory asthma is characterized by poor response to corticosteroid treatment followed by increased burden of the disease. Therefore, development of endotypes related with refractory asthma is important for diagnosis and treatment. The aim of the study was to determine the level of inflammatory mediators in sputum and to evaluate usefulness of the protein profiles as an endotype of refractory asthma. Methods: Total 238 asthmatics (216 never smokers and 22 exsmoker less than 10 pack years) were enrolled and sputum was induced using isotonic saline containing a short-acting bronchodilator. Differential cell count was performed. The concentration of S100A9, IL-1b, -5, -8, -13, -17A, -32 and -33 was determined using ELISA, then normalized with total protein in supernatant of sputum. Statistical analyses, clustering and decision tree analysis were performed using SPSS 12.0. Results: There were positive correlations between levels of S100A9 with those of IL-1b and IL-13, between IL-8 with IL13 and IL17A, between IL-17A with IL13, IL32 and IL33 and between IL-32 and IL-33 (p<0.05). The level of IL-13 was inversely correlated with IL-33. The subjects were clustered into four major groups according to the sputum level of cytokines; subjects with high level of IL-17A and IL-1b (group 1), with relatively low levels of cytokines with modest increase of IL-33 (group 2), with high IL-8 and IL-13 (group 3) and with highest S100A9 with moderate increase of IL-8 (group 4). The clinical features of the group 1 were younger, high airway hyperreactivity and increased numbers of WBC in blood. While group 2 showed highest % of eosinophils and low neutrophils in sputum, Group 3 showed highest % of neutrophils. Group 4 showed 2ndly highest % of neutrophils in sputum, old age, and relatively normal airway hyperreactivity. However, lung functions and exacerbation status were comparable between groups. In decision tree analysis for exacerbation, the patient were classified into three groups according to the level of cytokines; group 1 with lower IL-17A level (<=1.093 pg/ug), group 2 with higher IL-17A (>1.093 pg/ug) and low IL-32 (<=1.336 pg/ug) and IL-33 levels, and group 3 with higher IL-17A, IL-32 and IL-33 levels. The patient in group 1 was old-age and greatest pack years of smoking. They showed significantly higher serum level of total IgE, and neutrophil% in sputum than those of other groups. The lung function of the group was lowest in spite of treatment with highest dose of inhaled corticosteroid. Patients in group 3 showed significantly frequent exacerbation per year (P = 0.0001). Conclusion: The level of IL-17A, IL-32 and IL-33 in sputum may be a surrogate set of markers for predicting treatment outcomes in asthmatics and an endotype for refractory asthma. Background: Autophagy has been investigated to be involved in many inflammatory diseases, but its expression and clinical significance in asthma has rarely been studied. The aim of this study was to evaluate the role of autophagy and the therapeutic potentials in an OVA-specific mouse model of severe allergic asthma. Method: BALB/c mice were sensitized by intraperitoneal injection of ovalbumin (OVA) on days 0 and 14, followed by aerosolized primary OVA challenges on day 28 -30. Two weeks after the primary allergen challenges, mice received a secondary allergen challenges with two different concentrations (1% or 2%) of OVA solution on days 44 -46. Forty eight hours after the last OVA challenge, mice were assessed for airway responsiveness (AHR) to inhaled methacholine, cell composition and cytokine levels in bronchoalveolar lavage (BAL) fluid. LC3 expression in lung homogenate was measured by Western blot to evaluate the development of autophagy. Finally, 3-methyladenine (3-MA), and Atg5 knockdown were applied to investigate the potential role of autophagy in severe allergic asthma of mice. Results: The AHR, total airway inflammatory cell number and eosinophilia in BAL fluid were significantly higher in 2% OVA challenged mice compared to those of 1% OVA challenged mice (P < 0.01 and P < 0.05, respectively) indicating that 2% OVA challenges could induce a mouse model presenting more severe eosinophilic asthma. The severe allergic asthma mice showed significant higher LC3 expression compared to that of mild asthma mice. Additionally, more prominent autophagosomes were noted in the cytoplasm of eosinophilis. Inhibition of autophagy by 3-MA treatment and Atg5 knockdown could induce significant improvement of AHR, eosinophilia and IL-5 levels in BAL fluid and airway inflammation in histology. Anti-IL-5 antibody treatment significantly reduced eosinophil counts and IL-5 levels in BAL fluid, as well as LC3 expression in the lung tissue homogenate. Conclusions: Our findings suggest that the expression of autophagy is correlated with the severity of asthma through eosinophilic inflammation, and autophagy inhibitions may provide novel therapeutic targets for the treatment of severe allergic asthma. Background: As of possible role of interleukin-9 (IL-9), a proinflammatory and Th2 cytokine, and interleukin-33 (IL-33), a member of IL-1 cytokine family, in pediatric asthma, this study was performed to measure IL-9 and IL-33 serum levels in pediatric patients with asthma. Methods: In this study, 61 patients with asthma and 63 healthy age-and sex-matched subjects were enrolled. Serum levels of IL-9 and IL-33 were measured in asthmatic patients and healthy subjects by sandwich ELISA.


Oral immunotherapy (OIT), a novel therapeutic approach to food allergy, appears to be effective in increasing the threshold for clinical reactivity to food. The aim of the study is to assess the risk factors associated with rush OIT (ROIT) for treating anaphylaxis induced by allergy to hen's egg (HE), cow's milk (CM), wheat (W), or peanut (P). Methods HE, CM, and W anaphylaxis in our department confirmed by the positive double-blind, placebo-controlled food challenge test received following treatment with ROIT. Patients were treated with a combination of rush phase followed by a slow build-up of maintenance doses. patients who had ingested trial foods (HE, heated-whole egg [60 g]; CM, 200 ml; W, Udon noodle [200 g]; P, peanut powder [3 g]) without any symptoms for several months, then they underwent the final oral food challenge (OFC) after allergen avoidance for 2 weeks to confirm the development of clinical tolerance. Any changes in antigen specific IgE levels during OIT treatment were documented. Results A total of 224 subjects (HE, n = 70; CM, n = 87; W, n = 38; P, n = 29) with an average age of 9.1 years, who had been receiving ROIT for 1 & 1/2 year or more, were enrolled in the study. One and half year later, 75 subjects (33%) passed the final OFC (tentative tolerance group, HE, 33; CM, 17; W, 11; P, 14), whereas 149 subjects (67%) had reacted to the trial foods (Allergic group). Background: ABCC4 (ATP-binding cassette, sub-family C, member 4) is a protein-coding gene which codes for transmembrane protein. ABCC4 protein transports various molecules across extra-and intra-cellullar membranes, including PGE 2 and cAMP. Studies have reported that PGE 2 and cAMP play an important role in the regulation of immune responses and airway inflammation. In this study, we investigated the associations of ABCC4 gene polymorphisms and clinical characteristics of asthmatic patients to understand the role of ABCC4gene in asthma pathogenesis. Methods: 269 asthma patients and 118 normal healthy controls were enrolled in the study. Two single nucleotide polymorphisms (SNP) (-642G>C and -1508A>G) in the ABCC4promoter region were genotyped by TaqMan allelic discrimination assay. Functional variabilities in the promoter polymorphisms were analyzed by gene reporter assay. Inflammatory cytokine levels in serum were measured by ELISA. Results: There were no significant differences in genotype frequencies between two study groups. Asthmatic patients carrying G allele at -1508A>G had significantly higher periostin levels in sera (P=0.018) and lower PC 20 methacholine levels (P=0.008) compared to non-carriers. No significant difference was noted in sputum eosinophil count according to each genotype. Gene reporter assay showed that the promoter SNP tagged by G-1508 allele conferred significantly higher promoter activity (P<0.01) compared with A-1508 allele in A549 cell line. Conclusion: These findings suggest that ABCC4 gene polymorphism at -1508A>G may enhance periostin production and could involve in eosinophilic asthma.


Relative risks were 1.032[95% CI, 0.82, 1.29] at Mid-high condition, 1.132[0.88, 1.46] , at High and 1.543[0.69, 3 .46] at Extreme high. Conclusion: We found that DTR had adverse effect to ED visits in Korea. And effect of DTR showed non-linear relationship and was significant up to 10 days. Therefore as DTR increases, the more vulnerable people and public health authorities should pay special attention to an acute exacerbation of asthma. Backround. Mannan-binding lectin (MBL) is a serum protein involved in opsonization and complement activation, which contains lectin and collagen domains, synthesized in the liver. MBL binds to Nacetylglucosamineand mannan structures on thesurface of bacteria, fungi, viruses and protozoa, leading to opsonization, phagocytosis and activation ofcomplement system through lectin pathway, independent of an antibody. Most of the allergic diseases are dominated by the preferential development of specific Th2 type of adaptive immune responses against innocuous antigens in atopic individuals. Low level of serum MBL is associated with increased susceptibility to infectionsand high risk of some allergic and autoimmune diseases. The recently assigned roles of MBL in inflammatory diseases due to increased complement activation have stimulated research into the contribution of MBL and its associated complement activity in asthma and respiratory allergy. Purpose. Main aim of our study was to determine theprofile of MBL serum level in Mongolian atopic subjects.


To investigate the prevalence of atopic eczema (L20), we did analyze the nationwide database (National Health Insurance Corporation) which included the health-care records of 48.1 million individuals between January 1, 2003, and December 31, 2014 Objective: Recurrent wheeze is one of the predictive markers of asthma in preschool children. The aims of this study were to investigate airway inflammation, lung function, airway hyperresponsiveness (AHR), and the prevalence of allergic rhinitis (AR) and atopic dermatitis (AD) in preschool children according to recurrent wheeze. Methods: We performed a population-based, crosssectional study with 933 children aged 4-6 years. A total of 900 children completed a modified International Study of Asthma and Allergies in Childhood questionnaire and eligible for the study. We measured exhaled nitric oxide (eNO), spirometry, methacholine bronchial provocation, and impulse oscillometry. Recurrent wheeze was defined as having a lifetime wheeze more than 3 times. Results: The prevalence of recurrent wheeze was 13.4%. Children with recurrent wheeze showed higher prevalence of lifetime and current AR and lifetime AD, not current AD. Recurrent wheeze was associated with lifetime emergency room visit more than 1 time and history of more than one admission within 12 months due to wheezing episode. High eNO, post-bronchodilator change of R 5 Hz, and blood eosinophils as well as low FEF 25-75% were associated with recurrent wheeze. However, dose response slope by methacholine test, prevalence of atopy or AHR, and serum IgE levels showed no significant differences between two groups. Conclusions: Recurrent wheeze in preschool children may be associated with lower lung function and airway inflammation, not with AHR or atopy. Backround. Mannose-binding lectin (MBL) is a protein, which contains lectin and collagen domains, synthesized in the liver. MBL binds to N acetylglucosamine and mannan structures on the surface of bacteria, fungi, viruses and protozoa, leading to opsonization, phagocytosis and activation of complement system through lectin pathway, independent of an antibody. MBL is a vital protein of innate immune system and has two critical functions: complement activation through the lectin pathway and opsonization. Low level of serum MBL is associated with increased susceptibility to infections and high risk of some allergic and autoimmune diseases.


Objective: The aim of study was to identify the expression of CLDN 5 and response to steroid treatment in a mouse model of asthma (i.e. ovalbumin (OVA)-induced allergic lung inflammation) and in human lung microvascular endothelial cells (HLMVEC) and normal human bronchial epithelial (NHBE) cells. Methods: Mice were treated with saline (sham), OVA sensitized and challenged (OVA), or OVA with dexamethasone. Lung CLDN5 levels were assessed with qRT-PCR, ELISA, immunoblotting, immunohistochemical stain, and confocal imaging. HLMVEC were treated with host dust mite peptidase (Der p1) or interleukin 4 (IL-4) and CLDN5 mRNA and transmembrane endothelial electrical resistance (TEER) measured. Results: Airway inflammation, hyperresponsiveness, cytokines, and CLDN5 transcript and protein increased in OVA sensitized/challenged mice and these responses were reduced by dexamethasone treatment. The AKT1/FOXO1/CTNNB1 pathway was involved in CLDN5 protein expression. Der p1 increased CLDN5 protein expression in HLMVEC (but not NHBE) cells and decreased trans-endothelial electrical resistance. IL-4 also increased CLDN5 in HLMVEC, decreased TEER, and these effect were inhibited by dexamethasone. Conclusion: CLDN5 is implicated in the pathogenesis of bronchial asthma and represent a potential target for therapeutic intervention. Keywords: Tight junction, claudin 5, bronchial asthma Objective: The aim of this study was to identify the expression of claudin 4 (Cldn4) and the impact of acrolein on Cldn4 in a mouse model of allergic asthma. Methods: Using mice sensitized with ovalbumin (OVA) and OVA challenged (OVA sensitized/challenged mice) as well as mice treated with saline and challenged with air, and mice exposed to acrolein 5ppm on days 21-23, The effect of acrolein on Cldn4 was estimated using qRT-PCR, ELISA, immunoblotting, immunohistochemical stain, and confocal imaging. Results: Lung Cldn4 transcript and protein were significantly increased in OVA mice than in sham mice. Acrolein exposure reduced the increase in inflammatory cytokine levels, airway inflammation, and bronchial hyperresponsiveness in OVA mice. Increased lung Cldn4 transcript and protein in OVA mice were decreased in acrolein exposed mice. Background: This study investigated the efficacy and safety of sublingual immunotherapy (SLIT) with house dust mite in house dust mite sensitized children with allergic rhinitis. Method: 14 children who were sensitized to house dust mites treated with SLIT enrolled between August 2013 and July 2014. Nasal symptoms (rhinorrhea, sneezing, nasal obstruction, nasal itching, sleep disturbance), antiallergic medications use and presence of adverse events were assessed at 1 month, 2 month visit and thereafter every 3 months visits. Results: The symtoms of allergic rhinitis started to improve after 1 month of SLIT and significantly improved after 12 months of SLIT (P<0.05). The antiallergic medications use decreased significantly with time (P<0.05). The incidence of adverse events was 21.4 % and most occured within the first month of SLIT and disappeared with time. There were no severe adverse events. Conclusion: SLIT for house dust mite is effective and safe in house dust mite sensitized children with allergic rhinitis. The aim of this study was to evaluate whether low vitamine D levels were associated with skeletal muscle dysfunction in COPD.


Our finding suggest that low vitamine D level is associated to decrease of skeletal muscle mass, particularly in limb muscle dysfunction, which may be a risk factor of sarcopenia in COPD. Purpose: Recent experimental evidence shows that extracellular vesicles (EVs) in indoor dust induce neurtrophilic pulmonary inflammation. In addition, IgG sensitization to indoor dust EVs appears to be a correlation for the development of asthma, COPD, and lung cancer, irrespective of cigarette smoking. In this study, we analyzed indoor dust and dust extracellular vesicles (EVs) microbiome in the apartment and hospitals. Also, we evaluated whether IgG sensitization to bacteria devrived EVs is a risk for the development of asthma, COPD, or lung cancer. Methods: In the apartment and hospital, we collected summer and winter dust. After genomic DNA was extracted from the dust and dust EVs, 16s ribosomal DNA was amplified using the universal primer, sequenced through the next generation sequencer, and then the sequenced data was analyzed using bioinformatics. Then, Serum IgG antibody against major bacteria derived EVs in dust were measured in 90 healthy control subjects, and 294 asthma, 242 COPD, and 325 lung cancer patients. Result: Bacteria and bacteria derived EVs did not differ in diversity and community composition. Our data suggests the composition of a major dust microbiome that includes Pseudomonas, Acinetobacter, Enterococcus, and Staphylococcus. As a result of comparing the bacterial composition, Pseudomonas was dominant from apartment and summer, while Acinetobacter was dominant from hospital and winter. Especially in the winter of hospital, Acinetobacter was increased remarlably and diversity was reduced. As a result of Serum IgG antibody against major bacteria derived EVs in dust, adjusted multiple logistic regression revealed that sensitization to each bacteria derived EVs in dust were an independent risk factor for asthma, COPD and lung cancer. Conclusion: Dust microbiome from bacteria and bacteria derived EVs were mostly composed of Pseudomonas, Acinetobacter, Enterococcus, and Staphylococcus. IgG sensitization to bacteria derived EVs of indoor dust appears to be a major risk for the development of asthma, COPD, and lung cancer. Background: Asthma is the most common chronic disease in childhood and is a common cause of hospitalization for children. In 2011, at Samitivej International Children's hospital (SMICH), there were 210 asthmatic children aged less than 15 years old. 29 of them were hospitalized due to acute asthma exacerbation. One of them was needed to be in PICU and none was dead. A clinical care program to deliver integrated multidisciplinary and organized care plan with continuous quality improvement of hospital system is considered to be the standard care for asthmatic children. Methods: Core team and childhood asthma framework were set up including Pediatric Allergists, Pediatric Pulmonologists, General Pediatricians, Pediatric Nurses at OPD, ER & ward including PICU, Pharmacists at SMICH, which aim to provide comprehensive clinical care program for childhood asthma (CCP-Childhood Asthma) in 2012. We enrolled children with diagnosis of asthma and acute wheezing at OPD/ER, evaluated and considered diagnosis of asthma, then started treatment and re-evaluated for clinical asthma controlled every 1-3 months as to GINA Guideline for Children. All general pediatricians and Pediatric nurses at OPD, ER and ward were trained and implemented about clinical pathway. We initiated Childhood Asthma Camp to provide education about disease to parents and caregivers, together with workshop for inhaler medicines used, self assessment with asthma action plan, and environmental allergen avoidance. Performance measurements included: 1. Administration of systemic corticosteroids during hospitalization within 12 hours, 2. Evaluation of inhaler medicines technique used correctly in each visit, 3. Pulmonary function testing in children older than 7 years old, and 4. Influenza vaccination annually, data were collected and analyzed yearly. Results: Patients in CCP-Childhood Asthma at SMICH were enrolled from 81 children in year 2012 to 119 children in year 2014, the number of hospitalization from asthma exacerbation was decreased from 24 patients in year 2012 to 20 and 13 patients in year 2013 and 2014, respectively. All patients in CCP-Childhood Asthma were received systemic corticosteroids within 12 hours of hospitalization. No any patient was admitted in PICU. More than 80% of patients could demonstrate inhaler drugs used correctly and >60% of them received pulmonary function testing yearly. Influenza vaccination rate in asthmatic children increased from 30.8% in year 2012 to 57.6% and 63% in year 2013 and 2014, respectively. Our CCP-Childhood Asthma was accredited by Joint Commission International (JCI) from USA. in August 2012 which is the first clinical care program outside USA. certified by JCI. Conclusion: Care of children with asthma, which is a chronic disease burdens to their families and needs a comprehensive multidisciplinary team care. This will help improving quality of care for childhood asthma. Background: IL-9 is known to participate in induction of allergic responses. The purpose of this study is to investigate the effects of IL-9 on allergen specific immunotherapy in a mouse model of allergic rhinitis. Methods: Six-week-old female BALB/c mice divided into 4 groups: control group, allergic rhinitis (AR) group, immunotherapy (IT) group, and IT with anti-IL-9 antibody (anti-IL-9 Ab) group. All mice except control group were sensitized with ovalbumin (OVA) and aluminum hydroxide 3times for two weeks consecutively. After two weeks, mice except control group and AR group underwent immunotherapy by feeding of OVA. During the immunotherapy, mice in anti-IL-9 Ab group were injected with purified anti-mouse IL-9 Antibody. All sensitized mice were challenged intranasally with OVA. Allergic symptoms and eosinophils in nasal mucosa, interferone-γ, interleukin (IL)-4, IL-9, IL-17, TGF-ß, IL-10, Tbet, GATA-3, ROR-γ t and Foxp3 mRNA expression in nasal mucosa and serum OVA-specific IgE were measured. Results: Serum OVA-specific IgE and Eosinophil counts were significantly decreased in anti-IL-9 Ab group compared with IT group (p<0.05). The levels of mRNA expression of IL-4 were significantly decreased in anti-IL-9 Ab group compared with IT group (p<0.05). The levels of mRNA expression of IL-10 and Foxp3 were significantly increased in in anti-IL-9 Ab group compared with IT group (p<0.05). The levels of mRNA expression of IL-10 and Foxp3 were significantly increased in in anti-IL-9 Ab group compared with IT group (p<0.05). Conclusion: Administration of anti-IL-9 antibody increased the induction of tolerance in a mouse model of allergic rhinitis. These results suggest that anti-IL-9 antibody have immunomodulatory effect on immune tolerance. We claim that the application of this property can enhance the efficiency of allergen-specific immunotherapy. Objective: Fractional concentration of exhaled nitric oxide (FeNO) is a known marker of airway inflammation. The aims of this study were to evaluate FeNO, impulse oscillometry (IOS), and spirometry in preschool children and to investigate their relationship with wheeze and airway hyperresponsiveness (AHR). Methods: We performed a population-based, cross-sectional study with 561 children aged 5-6 years. A total of 544 children completed a modified International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire and eligible for the study. We measured FeNO, spirometry, methacholine bronchial provocation, and IOS. AHR was defined as the induction of a 20% decrease in FEV 1 (PC 20 ) by a methacholine concentration ≤ 8.0 mg/dL. Results: Children who had wheeze or AHR had higher FeNO levels than children without these symptoms. However, neither IOS nor spirometry parameters showed significant differences between children with wheeze or AHR and those without. FeNO was associated with AHR, whereas IOS or spirometry parameters showed no association. Mean FeNO levels were positively correlated with a doseresponse slope for methacholine, but neither IOS nor spirometry parameters showed significant correlations. Conclusions: FeNO is a more sensitive measurement of AHR and wheeze than spirometry or IOS in preschool children. Back ground: Hand eczema is a commonest disorder afflicting the hands with various morphological forms and with variable severities. Emollients, barrier creams and topical steroid are known to be effective in the majority and form the mainstay of treatment. But in some severe cases or in acute phases of hand eczema, systemic treatment can be very helpful. Among systemic therapy cyclosporine is known to be effect but response rate, remission period and recurrence rate is not well known. Objective: Evaluate the efficacy of systemic cyclosporine in hand eczema patients who are refractory to conventional therapy. Methods: 17 patients with hand eczema were chosen among the patients who had negative patch test results and the patients who had never diagnosed with psoriasis through biopsy. Patients with contraindications of using cyclosporine were excluded. Response rate were evaluated through ‡@Patient's satisfaction (DLQI), ‡AClinical examination by a physician (PGA) and ‡BPhotographical observation by scoring using total hand eczema severity index (HECSI). Result: Total 17 patients were enrolled and among them 10 were male and 7 were female. Average age was 49 and average disease duration was 2.4 years. 13 patients had hyperkeratotic subtype, 2 with fissured subtype and 2 with pompholyx subtype. 1 patient couldn't finish the study because of the medication side effect (dizziness). Average initial treatment period was 6.7 weeks 16 patients and all had clinical and subjective improvement after 2-4 weeks of initial treatment. (53% improvement in DLQI, 34.4% improvement in PGA, 63.3% improvement in HECSI) But recur occurred in 4 patients within 4 months after discontinuing the medication (average 2.3 months, recur rate 25%). Conclusion: Systemic cyclosporine can be an effective and relatively safe treatment option in hand eczema patients who are refractory to other treatments, although recur is quite common. Backgrounds: Atopic dermatitis (AD) is a chronic pruritic recurrent inflammatory skin disorder, which can significant cause of morbidity. Obesity has been shown to have pro-inflammatory immune response. Leptin are adipokine are the obese gene product and secreted by adiposites. The prevalence of both childhood obesity and AD has increased in past few decades. The association between obesity and AD has not been well established. Methods: A total of 227 subjects out of 2207 were defined as having AD based on questionnaire survey. Ninety AD children, aged between 6 and 12 years, completed scoring of severity of AD (SCORAD), blood tests for serum total IgE, blood eosinophil counts, serum eosinophil cationic protein (ECP) and lipid profiles. Serum levels of adipokines such as adiponectin and leptin were measured. Results: There were no significant differences in terms of age, BMI, percentage of breast milk feeding, mode of delivery and prevalence of atopy between boys and girls, and between atopic subjects and non-atopic subjects. Lipid profiles were not different between boys and girls, and between atopic subjects and non-atopic subjects. Regarding to the adipokines, serum leptin levels were significantly higher in girls (2.44 ng/mL [1.40 -4.22 ]) compared to boys and, atopic subjects (2.25 ng/mL [1.27 -3.97 ]) compared to non-atopic subjects. There were no significant correlations between SCORAD index and serum adiponectin or leptin concentrations. Conclusions: Although serum leptin levels were significantly higher in girls or non-atopic subjects, the SCORAD index was not correlated with those serum lipid profiles or adipokine levels. The lipid profiles and serum adipokine level are not influenced by the severity of AD in these pre-adolescent elementary school children in South Korea. Background and Objectives: Antihistamines and Leukotriene receptor antagonists (LTRA) are both approved treatments of Allergic rhinitis based on the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines. Recent studies have shown that the combination of second generation antihistamines and montelukast had significant improvement in the nasal symptoms and quality of life of patients with persistent allergic rhinitis. Recently, montelukast and levocetirine combination has been made available in a single tablet form but it has not been evaluated and compared with individual preparations as to its efficacy and control of symptoms in patients with Allergic rhinitis. This study aims to evaluate the efficacy of levocetirizine and montelukast combination tablet versus individual tablets in alleviating symptoms of patients with Moderate to Severe Persistent Allergic Rhinitis.

Pre-Coseasonal Treatment with a 5-Grass Pollen Sublingual Tablet in Adults Demonstrated a Reduction on Asthma Symptoms in Réunion Island

Bashir Omarjee D'allergologie Et Exploration Du Sommeil, Reunion World Allergy Organization Journal 2016, 9(Suppl 1):A336 Background: Asthma is a heterogeneous disease, not only in its clinical expression and course but also in its response to treatment. Most patients are clinically stable with current therapies, while a substantial part of the asthma population develops exacerbation during grass pollen season. The purpose of this study is to document the impact of a grass allergy immunotherapy tablet (AIT) on the symptom severity in patients with severe allergic rhinitis (SAR) and persistent allergic asthma (PAA). Method: This study included 22 adults, aged 20-45 yrs, with PAA and SAR who met the following inclusion: ≥ two severe asthma exacerbations requiring oral corticosteroids while receiving high dose ICS (≥1600 ug BECLOMETHAZONE daily or equivalent), additional controller medications (long acting B2 agonist) during one year prior to screening. Patients were examined at baseline and received a tablet 300IR (GRAZAX® ALK or ORALAIR® Stallergènes SA) approximately 2 months before the expected start of the grass pollen season in Réunion Island and then throughout the season between November 2013/April 2014 and November 2014/April 2015. Results: AIT significantly reduced scores from baseline in ocular and nasal symptoms. Reductions were also seen in the asthmatic scores: improvement of FEV 1 (p<0.05 of predicted values) and breathlessness scores (p=0.0002). The asthma quality-of-life (AQLQ) questionnaire scores improved from baseline after AIT: p=0.003. At the final visit only 24% had daily activity impairment and 34% had some sleep impairment. Conclusion: The Pre-Coseasonal treatment with 5-grass AIT showed effective symptom control in severe persistent allergic asthma. Symptoms of comorbidities such as rhinitis and conjunctivitis were decreased. Object: To obtain the peak expiratory flow meter rate (PEFR) normal value in healthy children 5 to 14 years old from Beijing urban area and to establish the predicted equations of PEFR in children. We also compare the values of PEFR measured by the Mini Wright peak flow meter with peak expiratory flow (PEF) measured by the spirometry. Methods: F425 healthy school children (213 boys and 212 girls) aged 5 to 14 years old were chosen from kindergarten, primary and middle schools in Beijing urban area. We used peak flow meter (Mini -Wright, AFS) from PARI company of German to measure peak expiratory flow rate and recorded gender, age, height, weight and other physical parameters. Flow-volume curve was carried out using Jaeger spirometry instrument and peak expiratory flow (PEF) values were adopted. The difference peak expiratory flow values between two measures were compared using SPSS13.0 statistical software. Stepwise multiple linear regression was used to derive the regression equations. Results: The values of PEFR increased along with age among children. There were statistically significant difference between different age groups (P <0.05). The PEFR values of boys were higher than those of girls and the difference between males and females reached significant level at the age of 11, 13 and 14 (P <0.05). Either in boys or girls, PEFR significantly correlated with age, height, weight, the high degree of correlation existed with height and then age and weight. The predicted equations of PEFR reference values was established in children 5-14 years old living in Beijing urban area as follows: PEFR(L/min)=5.29×H |427.1(boys)and PEFR(L/min)=4.94×H |399.8(girls) respectively. The PEFR value measured by peak flow meter (309.1 ± 74.1 L/min) was higher than those measured by spirometry (298.9±91.3 L/min), and the difference between was statistically significant (P < 0.001). Conclusions: New reference values of the peak expiratory flow rate were determined, and the predicted equations were built for children 5 to 14 years old in Beijing urban area, and providing evidence for the clinical management of respiratory diseases. Background: Food-dependent exercise-induced anaphylaxis (FDEIA) is a disorder where exercise following allergen ingestion triggers anaphylaxis although exercise and allergen exposure are independently tolerated. There are an increasing number of reported cases of anaphylaxis due to soybean, but FDEIA due to soybean is a rare disorder. Methods: We characterized the clinical features of a 10 year old boy with a history of walnut allergy who developed FDEIA due to tofu (a soybean product). The patient developed anaphylaxis while running during his physical exercise class after eating tofu. He presented with symptoms of cough, nasal obstruction, generalized urticaria, loss of activity and cyanosis. His symptoms improved an hour after treatment with loratadine but he was not administered epinephrine. In order to detect the causative allergenic food and other cofactors that induced the symptoms of FDEIA, we performed specific IgE test, skin prick test and ISAC. Immunoblot analysis for soybeans and soybean products using the patient's serum was also performed. Provocation tests with ingestion of tofu followed by exercise is also scheduled to be done to further confirm the diagnosis. Results: Skin prick test with raw soybean product (tofu, fried tofu and soy milk) was strongly positive. The level of serum specific IgE to soybean was 11.90 UA/ml. The ISAC(Phadia, Uppsala, Sweden) results revealed Gly m 4, Gly m 5, and Gly m 6 as 3.3, 0.3, and 7.1 ISU, respectively. About a year and a half later, the specific IgE to soybean, Gly m 4, Gly m 5, Gly m 6 were 40.2, 3.61, 21.4, 51.7 UA/ml, respectively. The patient is well tolerant to soybean products in the absence of any exercise following the intake of the soybean products. Immunoblot analysis of soy powder with patient's serum showed positive band between 50 and 70 kilo daltons, indicating the presence of specific IgE against storage proteins Gly m 5 and Gly m 6. Conclusions: These results suggest the strong possibility of storage proteins such as Gly m 5 and Gly m 6 as the causative allergen of FDEIA induced by soybean (tofu). The prevalence of allergic disease has risen in the last few years in Mongolia. Artemisia species is an anemophilous genus included in the Compositae family and is widely spread the Mongolian temperate climate zone. Pollen from the various Artemisia vulgaris (mugwort) is one of the main causes of allergic rhinitis in late summer and autumn in Mongolia, where the frequency of sensitization approximately 67% of 256 adult patients with sensitized plant pollen in 2010. We aim to determine the sensitivity for pollen allergy of mugwort and lamb's quarters. Method: The Research is been done under the department of Cellular biology Biochemistry of Pharmacy -Bio Medicine School, MNUMS with the help of " Effect" Allergy -Asthma Hospital. During the study of research, one period descriptive research is done by studying the selected 191 patients who are diagnosed positive for the pollen allergens by skin pricking test and these group is chosen from the airborne allergic patients "Effect" Allergy -Asthma Hospital in 2010-2012 census. Results: We were chosen 191 subjects who are sensitized to pollen allergens. All of cases with age range between 3-74 years old and sex ratio is women and men are 42.3% and 57.7%. 169 (88,48%, 95% CI:) out of total subjects were sensitized to allergens of different plants pollen. the average diameters of wheals that had sensitized to mugwort (Artemisia vulgaris) was 9.29±5.01 mm 2 , to lamb's quarter was 4.85±2.15 mm 2 , to positive control histamine hydrochloride 0.1% was 4.89±1.33 mm 2 . Conclusion: The sensitization of levels to Mugwort increased in last few years and the wheals size is increasing year by year. Allergic rhinitis (AR) is an airway hyper-responsiveness (AHR) and mucosal inflammation disease mediated by IgE-associated processes that is characterised by sneezing, nasal congestion, and rhinorrhea. The imbalance of Th1/Th2 immune response is considered to contribute to allergic diseases, however the interval between inflammation and AHR remains unclear. Growing information illustrated that nerve growth factor (NGF), a neurotrophin, plays an important role in neuroimmune interactions by augmenting an existing Th2 immune response. Since probiotics and biocompatible water-soluble chitosan (WSC) have been demonstrated to have anti-inflammatory properties that could inhibit the development of allergic Th2 response, we aim to assess the effect of WSC and probiotic extracts on NGF in Dermatophagoides pteronyssinus (Der p)-induced AR murine model. Intranasal administration of both WSC and probiotic extracts attenuated AHR in Der p-challenged mice due to a lower respiratory resistance and improved the nasal congestion by manifestation higher respirator rate than non-treated mice. Under management of both WSC and probiotic extracts, the thickness of nasal respiratory epithelium was reduced in microscopy. Both of WSC and probiotic extracts treatment moderated allergic inflammation including a decreased level of total and Der p-specific IgE in the serum, lowered expressions of IL-4, IL-5, and IL-13 in nasal lavage fluid, as well as less eosinphil infiltration in the nasal cavity. In particular, therapeutics with both treatments reduced NGF performance in nasal lavage fluid along with its receptors, p75NTR and TrkA, in the respiratory epithelium of nasal mucosa in Der p-stimulated mice. We suggested that the reduced NGF and its receptor levels may correspond to a decrease in AHR and mucosa inflammation by both WSC and probiotic extracts treatment. Background: Mimotopes are short peptides mimicking epitopes. The potential of mimotopes as treatments for allergy diseases were investigated. Methods: Mimotopes specific to the epitopes of the major shellfish allergen tropomyosin were identified by screening the one-bead-one-compound (OBOC) peptide library. The OBOC library is a chemical synthetic library allowing high throughput screening of mimotopes with quantitative estimation on binding affinity. This method is advantageous over the conventional phage-displayed libraries by allowing the use of polyclonal antibodies or even untreated serum samples. The mimicry potential of the mimotopes was validated by both in silico and in vivo analysis. To investigate the therapeutic potential of mimotopes for allergy diseases, we used a mouse model of shrimp allergy through intragastric gavage of tropomyosin with cholera toxin as adjuvant followed by oral challenge. Splenocyte proliferation and local cytokine expression in the jejunum were analyzed to elucidate possible mechanisms of therapeutic effects of the mimotopes. Results: Twenty-five mimotopes specific to shrimp tropomyosin were identified by screening OBOC peptide library. In silico analysis revealed six clusters of mimotopes, with the mimotopes in each cluster sharing at least three or more identical amino acid residues at the same position. With the automated epitope mapping tool EpiSearch, the six clusters of mimotopes could be mapped to six epitope regions of shrimp tropomyosin, of which five were identical to the previous reported epitopes. One mimotope from each cluster were synthesized and conjugated to the carrier protein keyhole limpet hemocyanin (KLH) for in vivo analysis. BALB/c mice immunized with mimotope-KLH conjugate were found to have an elevated level of tropomyosin-specific IgG but not in mice immunized with KLH alone or an irrelevant mimotope. The therapeutic potential of these mimotopes were further investigated with the use of the BALB/c mouse model of shrimp allergy. Sensitized mice were injected with a mixture of six mimotope-KLH conjugates, one from each cluster, before receiving a subsequent oral challenge. Compared to the control mice receiving KLH alone, the mimotopes-treated mice demonstrated a suppressed splenocyte proliferation response to tropomyosin and a reduced expression of cytokines in the jejunum. Conclusion: The OBOC peptide library is a useful tool in identifying mimotopes for allergens with multiple epitopes. Mimotopes specific to the tropomyosin were identified by screening OBOC library and validated by in silico and in vivo experiments. The mimotopes could be potential therapeutic candidates for allergy diseases. Background: Therapeutic education is important for successful management of Atopic dermatitis (AD). To provide effective therapeutic education, common misunderstandings and demands about AD among patients and caregivers need to be reviewed. Methods: A questionnaire survey about the course, etiology and management of AD was conducted for patients and caregivers who visited Department of Dermatology at Seoul National University Hospital, Seoul, Korea. Results: A total of 177 subjects participated in the study. A few subjects understood natural course of AD. Only 34.5% of subjects was aware of natural course of AD that usually improves with age. Many subjects (52.6%) misunderstood relapse of AD symptoms for development of tolerance to topical steroids. 158 (89.3%) subjects believed that enhancement of patients' immune system can improve the symptoms of AD. Dietary restriction is considered as an essential management strategy (72.9%), and many of them (55.4%) agreed to postpone the beginning of weaning food in patients with AD. Food, thought to be associated with an aggravation of AD were as follows in the order of; instant food, snack, egg and wheat (38 (25.6%), 32 (21.5%), 19 (12.8%) and 18 (12.1%) of 149, respectively). Most subjects did not have accurate information about cleansing. In particular, 34.3% of subjects reported that they used only water without any cleanser, and 27.3% agreed that soap made of natural ingredients should be used to avoid harmful effects of chemical substances. Most subjects (57 of 115, 49.6%) obtained information about AD from medical doctors, and consider them as the most reliable sources (137 of 164, 83.5%). Subjects prefer printed materials (69 of 162, 42.6%) to seminars or video-clips for obtaining educational contents. Conclusion: In this study, we found that patients and caregivers have lots of misunderstandings about AD. Therapeutic education about the course, etiology and management of AD with printed materials made by physicians will be valuable for the effective management of AD. Background: It is recommended to use 200 (2 puffs) or 400 (4 puffs) ug of salbutamol in the bronchodilator response (BDR) test. We aimed to compare the difference between these two dosages with regard to the small airway dysfunction. Methods: Subjects, who had never been diagnosed as asthma, were consecutively enrolled from June 1st to November 31st, 2013. Based on the subject's past and family history, we evaluated the possibility of asthma by scoring each subject on a scale of 0 to 10 (pre asthma score). The subjects were randomly assigned the bronchodilator tests of the two dosages without physician's knowledge and performed the BDR tests using the spirometric and impulse oscillometric lung function. Asthma diagnosis (post asthma score) was later reevaluated after BDR test. Results: A total of 119 subjects participated in this study, and the mean age was 7.8 (±3.6) years. The number of participants who were assigned 2 puffs and 4 puffs were 59 and 57, respectively. The mean age of 4 puffs group was older than the 2 puffs group (p=0.012). Before the BDR test, there was no statistical difference in pre asthma score between the two groups (2 puffs = 5.46 vs. 4 puffs = 4.9) (p=0.428). After the BDR test, the post asthma scores of the two groups were 5.8 (±3.4) and 4.7 (±3.4), respectively, which also showed no statistically significant difference between the two groups (p=0.098). The pre asthma score was significantly correlated with forced expiratory volume in 1 sec/forced vital capacity (FEV1/FVC) (r=−0.212, p=0.021), forced expiratory flow at 25% to 75% (FEF25-75) of FVC (r=−0.184, p=0.046) and reactance at 5 Hz (Xrs5) (r=0.201, p=0.029) Z score. However, there was no significant difference in FEV1 and FEV1/FVC of spirometric parameters, and resistance at 5 Hz (Rrs5) and Xrs5 of impulse oscillometry system (IOS) value between the 2 puffs group and 4 puffs group. Conclusion: There was no significant relationship between the amount of bronchodilators administered and the small airway dysfunction in children. However, Xrs5 showed a significant correlation with the physician's asthma predictive score. Objective: To study the effect of natural killer-T (NKT) lymphocytes and CD4+ NKT lymphocytes levels in peripheral blood onset of children with asthma. Methods: 85 asthmatic children who were diagnosed and treated by pediatric department of Renmin Hospital Affiliated to Wuhan University from Jan. 2012 to Dec. 2014 were selected as asthmatic group. 76 healthy children were selected as control group. The peripheral blood mononuclear cells were collected by using the density gradient centrifugation method. The ratio of peripheral blood NKT cells and CD4+ NKT cells were measured by immunofluorescence and flow cytometry assays. The relationships between the NKT cells number, CD4+ NKT cells and the total IgE level were observed. The levels of IL-4,IL-13, IFN-γ in peripheral blood were detected by enzymelinked immunosorbent assay after proliferate in response to α-Galcer. Results: Compared with the control group, the ratio of NKT cells and CD4+ NKT cells in peripheral blood in asthmatic group were significantly decreased (t=3.795, P<0.05; t=4.106, P<0.05). There was no significant correlation between the NKT cells, CD4+ NKT cells and the total IgE (t=1.032, P>0.05; t=0.856, P>0.05). The levels of IL-4 and IL-13 in asthmatic group were higher than that of the control group (t=4.683, P<0.05; t=3.992, P<0.05). There was no significant difference in the level of IFN-γbetween the two groups (t=0.877, P>0.05). Conclusion: The dysfunction of NKT cells and CD4+ NKT cells and the functional change of cytokines may play an important role in the pathogenesis of asthma.


Without validated skin test, OPT helps evaluate NSAIDS hypersensitivity patients. Our 4-year patients cohort with a positive OPT rate of 24.5% confirmed diagnosis of NSAIDs hypersensitivity. With low positive OPT rate of 6.9%, selective COX-2 inhibitor can be used as alternative in these patients. Purpose: Bronchial hyperresponsiveness (BHR) is a key feature of asthma, but the natural course of BHR is heterogenous. We divided the BHR changing pattern into 4 different phenotypes and investigated the characteristics and the risk factors from the longitudinal study. Methods: Total 658 (male 342, female 316) elementary school children were included from the CHEER (children's health and environment research)study. The ISSAC questionnaire, serum total IgE level, blood eosinophil percentage, skin prick test, pulmonary function test and methacholine challenge test were done at age 7 for baseline and age 11 years after follow up. BHR was defined as provocative concentration of 20% decrease of FEV1 (PC 20 ) below 16 mg/m. We divided 4 different phenotypes of BHR change pattern (BHR never, BHR remission, BHR new, BHR persistent). Multinomial logistic regression analysis was done to evaluate the risk factors for each type. Results: Four phenotypes of BHR were composed of 376 (BHR never), 152 (BHR remission), 48 (BHR new), 82 (BHR persistent) respectively. Parental allergic disease (aOR=3.334, 95% CI 1.188-9.358) and asthma (aOR=4.623, 95% CI 1.790-11.944) history at age 7 years were risk factors for BHR remission group. Atopic sensitization (aOR=3.233, 95% CI 1.436-7.279) at age 7 years was a risk factor for BHR new group. Eosinophil percent (aOR=1.280, 95% CI 1.123-1.458), logIgE (aOR=2.757, 95% CI 1.443-5.269), and atopic sensitization (aOR=2.461, 95% CI 1.163-5.208) at age 7 years were risk factors for BHR persistent group. Dp sensitization was a risk factor for for BHR new group at age 7 years (aOR=3.036, 95% CI 1.295-7.118). Dp, Df sensitization were risk factors for BHR persistent group at age 7 years (aOR=2.383, 95% CI 1.120-5.071; aOR=3.084, 95% CI 1.524-6.239). Dfwas a additionally sensitized allergen as a risk factor for BHR new group at 11 years (aOR=3.267, 95% CI 1.388-7.692) and grass pollen for BHR persistent group at 11 years (aOR=6.441, 95% CI 1.239-33.472). Conclusion: Children with BHR remission were associated with family history of asthma and low sensitization at age 7 years. Children with BHR new showed high sensitization and normal lung function, but low eosinophil at age 7 yrs. Children with BHR persistent were associated with high atopic condition including high eosinophil, high IgE, high sensitization, and low lung function at age 7 yrs. These findings suggest that the natural course of childhood BHR has different phenotypes and we can predict the future prognosis of BHR by these phenotypes. Background: Allergic rhinitis is usually thought to be a minor irritating disease, but it can cause significant morbidity. Rhinitis is characterized by chronic or recurrent sneezing or by runny or blocked nose. Pollen, fungi, animal dander, house dust mites, domestic pets, and insects are of particular importance as triggering factors. Objectives: This study was designed to determine whether the sensitivity of a spectrum of allergens using skin-prick test correlates with symptom severity in allergic rhinitis and asthma patients. Material and method: A detailed history taking and clinical examination was carried out for each patient (i.e., for those satisfying the inclusion criteria), which includes a diagnostic nasal smear and skin prick testing (SPT). The allergens selected for SPT was based on the reference pollen calendar of Bangalore city created by us and clues from the patient's exposure to the probable allergens in his surroundings. Result: We studied a total of 120 patients. The overall rate of sensitisation to any allergen was 96 %. The most common allergen was House Dust Mite (HDM 35%), while the most prevalent House Dust Mite was found to be Mite D-Pteronyssinus. Sensitivity towards pollens and fungal spores was 16% respectively. 57.5% of the Allergic Rhinitis patients had Persistent Allergic Rhinitis, out of which 78% were Moderate-Severe grade and 38.3% had Intermittent Allergic Rhinitis, of which 73% were Moderate-Severe. Conclusion: In light of the findings of the present study, it can be concluded that appropriate preventive strategies can decrease the cost and morbidity of therapeutic measures. The representation of the SPT reactivity to the House Dust Mite allergen may be a useful reference to counsel patients with allergic rhinitis. Backgroud and objective: Asthma is most common chronic disease in childhood and is well known association between risk factors and asthma progression in children with wheeze. The aim of the present study was to investigate the prevalence of wheeze and risk factors predicting asthma in young children. Method: The Green Breath for Children (GBC), a Korean children in Chungbuk province, have recruited 3194 preschool children ≥ 2 yrs of age, annually since 2011. Physical examinations, questionnaire for allergic and respiratory disease and skin prick test were performed. Results: Among these children, 2745 (85.9%) has completed response to questionnaire. Complete data were available for 2453 (76.7%) children about wheeze, medical history and skin prick test. The prevalence of wheeze was 22.7%. It was found that incidence of current wheezing illness within one year was declined and incidence of aeroallergen sensitization was increased with age (from 21.5% in 2 year old to 39.0% in 6 years old). Two hundred and sixty nine children had wheeze episode ≥ 3 among children > 3 year old (n=2253). Among these children, 175 (65.1%) has current wheeze illness within 1 year. Sensitization with A/H ratio grade ≥6+, allergic rhinitis, parental asthma was significantly higher in children with current wheeze illness. Diagnosis of allergic rhinitis and parent with asthma were also significantly associated in logistic regression. Conclusion: There were high prevalence of wheeze and presence of risk factor of asthma progression, especially higher sensitization rate and atopic dermatitis in preschool children. So it is needed that quantitative measurement of atopic status or biologic marker monitoring for discriminating children who will have asthma progression among preschool children with wheeze. Primary Immunodeficiency Diseases (PIDs) are a heterogeneous group of inherited disorders, characterized by defects in one or more components of the immune system, leading to a variety of clinical manifestations, particularly recurrent severe infections, autoimmunity, lymphoproliferation, and malignancies. PIDs usually present with one of the following eight characteristic clinical presentations: Recurrent upper or lower respiratory tract infections, Failure to thrive (FTT) from early infancy, Recurrent pyogenic infections, Unusual severe infections, Recurrent infections with the same type of pathogen, Autoimmune or chronic inflammatory disease and/or lymphoproliferation, Characteristic combinations of clinical features in eponymous syndromes, and a number of characteristic presentation such as angioedema. The first step in the diagnostic process starts from clinical screening, while suspicious to a number of certain PIDs could be made, according to their clinical phenotypes. Using a limited set of tests which is available in most hospital, including complete blood count (and differential), a first screen for PIDs can be reliably performed; meanwhile screening laboratory tests for each category of defects in the immune system is needed, considering the characteristic clinical presentations; e.g., immunoglobulin assays for antibody deficiency or CH50 and AP(AH)50 assays for complement deficiency in those with recurrent sinopulmonary infections with encapsulated organisms; or B-and T-lymphocyte subsets enumeration for combined immunodeficiency in those with FTT or early onset severe infections; or chemotaxis, nitroblue tetrazolium (NBT) dye reduction test, dihydrorhodamine (DHR) oxidation test for phagocyte defects in those with recurrent pyogenic infections. It should be noted that more elaborate tests, including specific antibody responses to protein or polysaccharide antigens, lymphocyte proliferation tests, advanced immunophenotyping, random migration, phagocytosis, and intracellular microbial killing by phagocytes, and a chemiluminescence assay can be performed in immunological laboratories. Meanwhile the definite diagnosis of PIDs relies on genetic tests. The Effect of Helicobacter Pylori Infection in Atopic Individuals Background: The role Helicobacter pylori (H. pylori) infection in the aetiology of atopy remains unclear, although a possible protective role has been hypothesized. Objective: The aim of this study was to evaluate the prevalance of H. pylori in the atopic individuals. Methods: We conducted a retrospective, observational and crosssectional study which included 104 patients, aged between 18 and 70 years. Total serum IgE (Immage 800, Beckman Coulter, Ireland) and H.pylori IgG (DIA.PRO, Italy) were measured in all participants by using nephelometric method and ELISA respectively. Results: One hundred four patients included in the study. The avarage age was 38, and 74 of the patients were female (71.2%). The average IgE was measured to be 165 IU/mL. Fifty-two (50%) patients were diagnosed with an allergic disease according to anamnesis, laboratory results, and skin prick test. H. pylori infection was found in 61.5% of patients with allergic diseases. H.pylori was more frequent in the patients with allergy, unless that difference is not statistically significant (p:0.685, chi -square:0.165) Conclusion: The prevalence of allergic disorders, including asthma, atopic dermatitis,urticare, and allergic rhinitis has been increasing, and the prevalence of H. pylori infection has been decreasing. In the previous studies, an inverse association has been observed between H. pylori infection and many allergic diseases such as recent wheezing, allergic rhinitis, dermatitis, eczema or rash. In our study, H.pylori was found more frequently unless that difference is not statistically significant (p:0.685, chi -square:0.165). Background: Chronic urticaria (CU) lasting for 6 weeks or longer can be classified into chronic spontaneous urticaria (CSU), urticarial vasculitis, and inducible (physical) urticaria. A cause for CSU is not identified in approximately 60% of patients. Thirty to 50 percent of adults with CU achieved remission 1-3 years after onset. This study investigated the clinical spectrum and natural course of CU in Chinese children and identified possible predictors of disease remission. Methods: This single-centre retrospective study identified 96 patients with CSU below 18 years of age who were followed in our allergy clinic for ≥ 6 months. Disease-related factors such as occurrence of urticaria, angioedema and anaphylaxis as well as familial history, environmental exposures, co-morbid allergies, immunological investigations and drug treatments were retrieved from medical records. Patients were considered to be in remission when they were symptom-free for ≥ 3 months. Natural history of CU was delineated by Kaplan-Meier analysis, and factors associated with disease remission were analysed by log-rank statistics. Results: The mean (SD) age of patients at baseline was 9.0 (5.2) years, and 53 (55%) of them were male. They were followed for a median of 4.0 years. Coexisting asthma, rhinitis and eczema affected 47%, 51% and 24% of these patients. Sixty-seven percent (53/79) of patients were atopic. Forty-seven (49%) patients had urticarial episodes at least once weekly, and 33 patients had both urticaria and angioedema. Both patients who developed anaphylaxis (one respiratory and one cardiorespiratory) had persistent disease. Seventy-nine patients had concomitant inducible urticaria. Laboratory investigations revealed positive anti-nuclear antibody in 26% (12/47; none with anti-thyroid antibodies), circulating eosinophilia in 24% (14/59), increased serum total IgE in 68% (40/59) and low plasma C3 and/or C4 levels in 30% (16/53). Fifty-six patients were treated with nonsedating antihistamines alone and 15 had combined non-sedating antihistamines and H2 antagonists. Sixty (63%) patients were in remission at a median of 2.4 years from disease onset. None of the clinical and laboratory parameters was associated with disease remission. Conclusions: Childhood CU has in general favourable prognosis, and two-thirds of them achieve disease remission. This study cannot identify any clinical or laboratory factor for the resolution of CU. Background: Allergic rhinitis (AR) is the most prevalent of all allergic diseases. Aeroallergens play a major role in the pathogenesis of respiratory allergic diseases, like AR and asthma. Pollen, fungi, animal dander, house dust mites, domestic pets, and insects are of particular importance as common triggers. Objectives: The main objective of this study was to assess the sensitivity to common pollen allergens in patients with Allergic Rhinitis (AR) patients visiting the ENT Allergy clinic in a tertiary care hospital in urban Bangalore. Material and method: A detailed history of the symptoms of AR and clinical examination was carried out for each patient. The ARIA classification was used for elucidating the severity of AR. We also performed a nasal smear test for eosinophilia and skin prick testing. Result: Out of the 100 patients with AR, 59% of the patients had persistent AR, out of which 46% were of moderate-severe persistent AR. The overall rate of sensitisation to any allergen was 95.2 %. The most prevalent aeroallergen sensitization was found to be Parthenium hysterophorus (33%), Amaranthus spinosus (23%), Eucalyptus (21%), Cynodan dactylon (20%), followed by Casuarina equisetifolia (19%). Conclusion: Bangalore has a high prevalence of AR. The successful treatment of this condition needs appropriate diagnosis and therefore a better understanding of the aeroallergen spectrum and sensitivity patterns. Background: Seasonal variation of asthma-related hospitalizations has long been recognized, however, little is known about asthmarelated ICU admissions. To identify seasonal trend of asthma-related hospitalizations and ICU admissions may allow preventive strategies to be developed. Methods: We analyzed the National Emergency Department Information System (NEDIS) records of 117 emergency room in Korea of all patients aged between 3 and 18 years with asthma during six years (from 2007 to 2012). Data was tabulated and graphed to show seasonal trends in the monthly number of ED visits, general ward(GW), and ICU admissions for asthma. Results: A total of 41,128 subject were found and the male to female ratio was 1:0.5. GW admissions as a percent of ED visits were 42.6% (n=17,524), and ICU admissions, 0.8% (n=335). Monthly number of ED visits and GW admissions for asthma showed the seasonal variability with high peaks in fall (September to November) and low rates in summer (June to August). ICU admissions, however, showed different peaks at each year. Despite this finding, ICU admissions were at a minimum in fall as a percent of general ward admissions. Conclusions: There were important differences in the seasonal pattern of ED visits, general ward(GW), and ICU admissions for asthma. The combined analysis of these three data sets provides a new perspective on the epidemiology of asthma. Background: Aims of this study were to investigate prevalence and severity of atopic dermatitis (AD) and to analyze its associated risk factors in a total of 2,109 children (1,040 boys, 1,069 girls) from 5 elementary schools within Gyeonggi-do, South Korea. Methods: We conducted questionnaire survey using a Korean version of International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire and anthropometric evaluation from October to November in 2012. AD was defined by existence of chronic eczema over 6 months based on the ISAAC questionnaire. SCORAD (SCORing Atopic Dermatitis) index were evaluated for 227 children with AD. Children were divided into 2 groups according to the SCORAD index : 1) mild-to-moderate AD (SCORAD index < 40); 2) severe AD (SCORAD index ≥ 40). Skin prick test to 18 allergens and blood test were completed for 188 children with AD. Results: Among 2,109 children, 543 children (25.0%) were designated as having AD. One hundred and ninety children had mildto-moderate AD (83.7%) and 37 children had severe AD (16.3%). Prevalence of obesity (BMI ≥ 95p) in AD group (n=38, 8.0%) was significantly higher than that of non-AD group (n=62, 4.5%). Proportion of children experienced breast milk feeding over 6 months in AD group (n=250, 46.7%) was significantly higher than that of non-AD group (n=635, 41.3%). There were no significant differences between AD group and non-AD group in terms of sex, age, BMI, history of breast milk feeding ever and mode of delivery. Geometric means (range of 1 SD) of blood eosinophil percentage (5.78% [3.35-10.00]) and serum eosinophil cationic protein concentration (48.98 μg/L [43.84-2,189.52]) in severe AD group were significantly higher than those of mild-to-moderate AD group (3.64% [1.67-7.96], 33.28 μg/L [12.02-92.20]). There were no significant differences between mild-to-moderate AD group and severe AD group in terms of age, BMI, birth weight, obesity, mode of delivery, history of breast milk feeding ever, serum hemoglobin and total IgE concentration. Risk factors for having AD were male sex (aOR 1.25 [1.01-1.55]), obesity (aOR 1.08 [1.17-2.76] ) and history of breast milk feeding over 6 months (aOR 1.25 [1.01-1.55]). Atopy in skin prick test to 18 allergens was observed in 70% of AD group children. Majority (57.8%) of children were reactive to house dust mites, followed by pollen (29.9%), animal dander (26.2%), mold (18.7%) and food allergen (9.1%). Conclusions: Prevalence of AD is 25.9% in the Gyeonggi-do, South Korea and it is similar to the prevalence of recent Korean nationwide study in 2010 (27.0%). Male sex, obesity and history of breast milk feeding over 6 months independently increase risk of having AD. Background: Recently, several clinical trials reported that intralymphatic immunotherapy (ILIT) for some allergens including cat dander and birch or grass pollen induces tolerance faster than conventional subcutaneous immunotherapy with comparable duration of effect after only 3 injections, but without serious local or systemic reaction. However, the efficacy and safety of ILIT for various allergens in allergic rhinitis still remains to be investigated. We evaluated the efficacy and adverse effect of ILIT for house dust mite, cat, and dog allergy in patients with allergic rhinitis. Methods: A total of 9 subjects with allergic rhinitis sensitized to Dermatophagoides farinae, Dermatophagoides pteronyssinus, cat, and/or dog allergen were treated with 3 intralymphatic inguinal injections of causal allergen extract (HollisterStier, New Orleans, USA). Rhinoconjunctivitis quality of life questionnaire (RQLQ), sino-nasal outcome test 20 (SNOT-20), and rhinitis symptoms during exposure to causal allergen were evaluated before, 4 and 12 months after 1 st injection of ILIT. Results: RQLQ and SNOT-20 were significantly improved 4 months after ILIT from 71.2 (range 50-105) and 34.3 (range 3-70) to 52.3 (range 37-89) and 22.7 (range 8-52), respectively (P < 0.05). Allergy symptom during exposure to causal allergen including rhinorrhea, sneezing, nasal obstruction, and itching sensation on eye, nose, and contacted skin were also significantly reduced (P < 0.05, respectively). In five subjects who visited hospital 12 months after 1 st injection of ILIT, rhinorrhea, sneezing, and nasal obstruction during exposure to causal allergen remained to be alleviated also (P < 0.05). We observed two cases of anaphylaxis and one case of severe cutaneous erythema and edema at injection site after ILIT. Conclusions: ILIT can rapidly improve allergy symptoms in daily life, especially those provoked by allergen exposure, and this effect lasts for a year. However ILIT can also cause severe systemic or local hypersensitivity reaction. Acknowledgement: This work was supported by the Gachon University Gil Medical Center (Grant number: 2013-11). We thank to ThermoFisher Scientific Korea for support in measuring serum total and allergenspecific IgE/IgG 4 (ImmunoCAP®). For providing allergen extracts which were used for NPT, we also appreciate Research Center for However, there are no available data characterizing IL-33 expression after infection with other respiratory viruses and on cell types producing this cytokine. The aim of this study was to evaluate the effect of respiratory syncytial virus (RSV) infection on the IL-33 expression in vivo. Methods: Female BALB/c mice, aged 8 weeks, were divided into 3 groups. The first group was intranasally (i.n.) infected with 50 μl/ mouse RSV strain A2 (5×10 5 TCID 50 /mouse). The second group received UV-inactivated RSV. The third group was treated with PBS only. On day 6 after infection, airway hyperresponsiveness (AHR) to methacholine was measured by whole-body plethysmography. The left lung was removed for histological analysis. One lobe of the right lung was taken for viral RNA (vRNA), mRNA-IL-33 evaluation by qPCR and the other lobes was used for preparing of cell suspension by collagenase digestion. Cell suspension was stained with fluorophore labeled antibodies to determine IL-33 intracellular expression in CD45 + 3 + T cells, CD45 + 19 + B cells, CD45 + CD3 -CD19 -Ly-6Gcells, CD45 -324 + epithelial cells by flow cytometry.

Prevalence of Atopic Dermatitis and Its Associated Risk Factors in Elementary School Children: A Cross-Sectional Study in Gyeonggi-Do, South Korea

Results: vRNA copy number in lung tissue of RSV-infected animals was 4.3-fold higher than in mice treated with inactivated virus. AHR to inhaled methacholine in RSV-infected animals was increased compared to mice treated with inactivated virus or PBS. Histological analysis revealed the presence of inflammation characterized by infiltration of lymphocytes into the lung tissue of RSV-infected animals. These data indicate RSV infection in the mouse lungs. mRNA-IL-33 expression in lungs was 2.5-fold up-regulated upon RSV infection. Flow cytometry analysis revealed 1.7-and 1.5-fold increase in the percent of IL-33 + Tcells and CD45 + CD3 -CD19 -Ly-6G -IL-33 + cells, respectively. We found that RSV increased (1.5 fold) the mean fluorescence intensity of IL-33 on B-cell population. In addition, IL-33 intracellular protein expression was slightly increased in epithelial cells (1.2-fold) . Conclusion: Our results provide evidence for up-regulation of IL-33 in T-, B-and CD45 + CD3 -CD19 -Ly-6Gcells in RSV-infected murine lungs that may indicate an important role of IL-33 in virus-induced lung infections. The study was supported by RSF Grant 14-15-00894. Background: The prevalence of food allergy has increased worldwide. In Malaysia, food allergy prevalence has never been studied. Prevalence data is important to assess the burden of food allergy in order to establish the requirement of allergy services. Objectives: We aimed to determine the prevalence of parent-perceived food hypersensitivities in Malaysian paediatric population and evaluate the spectrum of clinical manifestations and allergens involved. Methods: We conducted a cross-sectional parent-questionnaire survey among preschool children attended the outpatient general paediatric clinic. We evaluated the associated factors for hypersensitivity reactions to food. Results: A total of 333 children were included in the study. Eighty (24.0%) parents reported that their children have ever had hypersensitivity reactions to food. The major food allergens were shellfish (45%), egg (36.2%), cow's milk and dairy products (28.8%) and peanut (27.5%). Reactions to multiple foods were reported in 57.7% children. The most commonly reported symptoms were hives and itchiness (46.3%), eczematous skin rash (45%) and chest tightness and wheeze (31.3%). Significant factors associated with parentreported food hypersensitivity were history of eczema (OR, 7.3: 95% CI 3.15-17.08), and allergic conjunctivitis (OR, 6.2: 95% CI 1.82-20.57) in the children and siblings with food allergy (OR, 3.72: 95% CI 1.22-11.37). Conclusion: Parent perception of food hypersensitivity reactions is common in pre-school children. Further studies with a larger sample size and longer duration are required to determine the prevalence of food allergy in Malaysia. Background: Chitin is polymer of N-acetyl-b-D-glucosamin and founded in various organism such as house dust mite. Generally, chitin is applied in medical material, because it is known to not induce the immune response. However, according to recent reports, chitin induced innate & adaptive immune response. In this point, we can postulate that HDM chitin induce the immune response, but exact effect & mechanism is unknown. Objective: To evaluate the immunological side in the development of airway inflammation induced by sensitization with allergens plus house dust mite derived chitin. Method: To induce the airway inflammation by HDM derived chitin, 6 weeks-old mice were administrated intranasally four times with 75 μg of ovalbomin (OVA) and 100 μg of HDM chitin, and then challenged intranasally 4 times with 50 μg of OVA on days 14, 15, 21, and 22. Lung inflammation and immunologic parameters were evaluated 48 h after the final allergen challenge and 6 h after allergen challenge on day 21, respectively. Result: Intranasal administration of HDM (house dust mite) induced Th2 dominant, but mixed, airway inflammation and chitinase treatment induced down-regulation of Th2 immune response. Refined HDM chitin with allergen sensitization up-regulated the production of Th2 cytokine, dominantly, and chitinase treatment showed similar manner of HDM treatment results. This immune responses are mediated through TLR2, which is known to receptor of chitin recognition, and macrophage derived TNF-a and NKT cell. Conclusion: These findings indicate that airway inflammation sensitized by HDM derived chitin induces Th2 dominant immune response, which is mainly dependent on TNF-a produced by macrophage cell and NKT cell. Background: Inhalant allergen sensitization is a major risk factor for allergic disease, which is largely influenced by living environments. Despite substantial geographic variations in allergen sensitization in the literature, comprehensive studies are still lacking in Korean adults. Objective: We aimed to investigate recent patterns of inhalant allergen sensitization among Korean adult patients with suspected history of respiratory allergy, and also examine the geographic variations of the sensitization profiles in Korea. Methods: From 2009 to 2014, a total of 34,289 patient records were retrieved for a retrospective analysis, from 12 referral allergist clinics in 9 different regions. Inclusion criteria were Korean adults (≥18 years old) who underwent inhalant allergen skin prick test for suspected history of respiratory allergy. Primary outcome was the detailed profile of inhalant allergen sensitization. Sensitization to allergens was defined by allergen-to-histamine wheal ratio ≥ 1. Demographic and clinical information, and residential area of participants were also collected. Regional sensitization profiles of individual allergens were calculated after adjusting age and sex. We meta-analyzed the regional sensitization profiles, and then estimated both overall atopy and individual allergen sensitization profiles in general. Geographic variations of sensitization between allergen groups were statistically compared by using Cochrane Q and I 2 -statistics.
Results: Overall prevalence of atopy was 44.8% (95% CI [38. 5-47.8] ). In overall, Der F and Der P were the most commonly sensitized allergens (29.5% and 28.7%, respectively), and followed by cat (8.0) and birch (8.0%), hazel (7.4%), alder (7.2%), mugwort (7.0%), beech (6.7%), oak (6.6%) and Tyrophagus putrescentiae (5.8%). The ten common inhalant allergens were similar between regions. However, in Jeju, 6 among 10 common allergen were different from other regions. Sensitization to Japanese cedar (12.4%), rye (8.7%), velvet (8.3%), Kentucky (8.1%), timothy (7.5%) and vernal grass (7.4%) were more prevalent in Jeju. According to allergen groups, geographic heterogeneity were highest in outdoor molds and cockroaches. Sensitization to animals, weeds and mites showed less dependent to locations. Sensitization to pollen from early-and mid-blooming trees were significantly high in Gangwon, Gyeongbuk and Busan. Conclusion: As overall, common inhalant allergens were Der P, Der F, cat, birch, hazel, alder, mugwort, beech, oak and Tyrophagus putrescentiae. Sensitization to inhalant allergens showed geographic variations, particularly in Jeju. This study was the largest scale conducted, so far, on the aeroallergen sensitizations in Korean adults. We hope our findings could contribute to the establishment of skin prick test panels for use in clinical practice and epidemiological surveys. Background: The purpose of this study was to develop a mouse model of asthma (MMA) using house dust mite Dermatophagoides pteronyssinus (Der p) extract. Methods: BALB/c mice were i.p. immunized with different doses of Der p lyophilized extract three times in three week interval in the mixture with Al(OH) 3 . 8 weeks after the final immunization mice were challenged with Der p during five consecutive days by intranasal applications (INA) or aerosol administration (AA). All mice were divided into 5 experimental groups: group 1 was immunized with 50 μg/mouse of Der p (in protein equivalent) in the mixture with 2 mg/mouse Al(OH) 3 and challenged by INA; group 2 was immunized in the same way and challenged by AA; group 3 was immunized with 100 μg/mouse Der p in the mixture with 2 mg/ mouse of Al(OH) 3 and challenged by INA; group 4 was immunized in the same way and challenged by AA; group 5 (negative control) was immunized and challenged with saline. 24 hours after the last challenge airway hyperresponsiveness (AHR) to different concentrations of methacholine was evaluated in all groups by whole-body plethysmography. 48 hours after the last challenge in all groups blood was collected for differential cell count, brochoalveolar lavage fluid (BALF) was sampled for the determination of inflammatory cells and lungs were removed for histological analysis. Histopathological changes were graded according to semi-quantitative scoring system. Serum anti-Der p IgE, IgG1 and IgG2a antibodies were detected by ELISA seven days after the last immunization and 48 hours after the challenge. Results: The highest level of serum Der p-specific IgE antibodies was observed in group 2. The levels of Der p-specific serum IgG1 and IgG2a antibodies in group 2 were significantly higher than that of other experimental groups. The maximum of AHR was observed in groups 1 and 3 challenged by INA. Analysis of cell composition in BALF demonstrated elevated number of basophils in group 3 in comparison with other experimental groups. No significant differences in peripheral blood cell counts were observed among experimental groups. Histological picture of allergic inflammation in lungs (peribronchial and perivascular infiltration with inflammatory cells) was the most expressive (according to score system) in group 3 in comparison with other experimental groups. Conclusion: Data obtained indicate that sensitization with Der p in a dose 100 μg/mouse together with Al(OH) 3 and challenge with Der p by INA is a suitable approach for modeling of mouse allergic asthma. Methods: Two patients had severe respiratory symptoms and signs with high fever. The blood test, inflammatory reactant test and serologic test were performed. The mycoplasma pneumonia was confirmed by positive IgM and also rising titers of IgG antibody of M. pneumoniae or cold agglutinin more than four times later. The chest radiograph and computed tomography (CT) scan were checked serially. Results: In one case of necrotizing pneumonia, 3-year-boy had protracted clinical course of high fever and moderate respiratory distress despite of the appropriate antibiotic therapy. A chest CT scan revealed profound lung tissue destruction in the right middle lobe. After 2 month of intensive antibiotic therapy, he was finally recovered completely without sequela. In case of bronchiolitis obliterance, 2-year-boy showed a patch infiltration in the right middle lobe. The mycoplasma pneumonia was effectively treated with appropriate antibiotics. After 3 month of discharge, the chest CT scan showed the segmental consolidation of the right middle lobe with bronchial wall thickening and hyper-lucency. He had recurrent pneumonia clinically and the right lung lesions were progress to be collapsed totally, called as destroyed lung till 3 years of infection. After 10 year of follow up, the chest CT scan was stationary without clinical problems. Conclusions: We reported two cases of necrotizing pneumonia and bronchiolitis obliterance followed by destroyed lung after mycoplasma pneumoniae pneumonia. Background: Effective educational tools and implementation strategies are important for the dissemination of guideline. We developed the computer-based interactive education program of asthma guideline named as Virtual Learning Center for Asthma Management and evaluated its usefulness in terms of the improvement of awareness and user satisfaction. Methods: 170 physicians were enrolled from six tertiary hospitals. They utilized the interactive education program for 2weeks for the learning of asthma management guideline. We compared awareness of asthma guideline before and after utilization of the program and investigated the user satisfaction with questionnaire survey. Results: Mean age of study subjects was 28.2±3.1 and 78(49.4%) of subjects were male. The total score of awareness of asthma guideline was significantly improved from 80.3±6.3 to 85.1±6.9 (p<0.001). All categories of awareness including knowledge, attitude and practice were improved significantly after learning with the program (p<0.001). Satisfactions of users were high in the aspects of usefulness, convenience, interest, improvement of understanding of guideline and elevation of confidence. The most useful section of the program was virtual cyber management of asthma patient. Conclusion: Interactive education program is a useful and effective tool for dissemination of asthma guideline. Background: House dust mite (HDM) is well known organism as source of major allergen. Besides, HDM also possesses bacteria in their digestive system, so it is also founded feces of HDM. According to recent study, bacteria is able to secrete small circular 'vesicles' , which is contain diverse molecules in its original bacteria. In addition, administration of these vesicles from specific bacteria induced airway inflammation and tissue destruction. In this point, we hypothesized that HDM derived vesicles play an important role on the development of airway inflammation. Objective: To evaluate the role of HDM derived vesicles on the development of airway inflammation, and define the origin of them. Method: To induce the airway inflammation by HDM, 6 weeks-old mice were administrated intranasally four times with 100 μg of HDM, and then challenged intranasally 4 times on days 14, 15, 21, and 22. Lung inflammation and immunologic parameters were evaluated 48 h after the final allergen challenge and 6 h after allergen challenge on day 21, respectively. In the case of HDM derived EV administration, 6 weeks-old mice were administrated intranasally four times with 75 μg of ovalbomin (OVA) and 10 μg of HDM EV, and then challenged intranasally 4 times with 50 μg of OVA on days 14, 15, 21, and 22. Especially, polymyxyn B treatment was done simultaneously during intranasal sensitization. Result: HDM induced Th2 dominant mixed inflammation in the airway, and it contains bacteria. In addition, vesicles was also identified from HDM, and it is possible to induce immune responses in macrophage and epithelial cell. In the side of ability of inducing inflammation, HDM derived vesicles induced airway inflammation potentially compared than free LPS and soluble portion. This immune responses are mediated LPS recognition, and the source of it is gram negative bacteria in HDM. Conclusion: These findings show that HDM derived vesicles induced airway inflammation potentially via recognition of LPS derived from gram negative bacteria in dust mite. Background: Studies evaluating whether allergy patients change their recognition of causal allergen, its avoidance, and allergen specific immunotherapy (SIT) during diagnosis and treatment of their diseases are relatively rare. The objective of this study is to evaluate those changes after skin prick test / intradermal test (SPT/IDT), nasal provocation test (NPT), and allergen-specific intralymphatic immunotherapy (ILIT) for causal allergen among patients with allergic rhinitis. Method: After informed consent, nine subjects with allergic rhinitis in whom allergens including D. farinae, D. pteronyssinus, cat hair, and dog hair/dander were proven to provoke their rhinitis symptoms by history taking, skin prick test, and measurement of serum specific IgE were asked to respond to the following questions: "Do you agree that allergen provokes allergic symptoms in daily life?", "Do you agree that allergen avoidance can reduce allergic symptoms?", and "Do you agree that allergen specific immunotherapy can reduce allergic symptoms?" Thereafter, they underwent SPT/IDT, NPT, and ILIT for their causal allergens. They were repeatedly asked to respond to those questions immediately after SPT/IDT, NPT, as well as 4 and 12 months after ILIT. Results: The agreement (%) to "Allergen provokes allergic symptoms in daily life" changed from 67.7 ± 34.2 to 79.3 ± 25.7 (after SPT/IDT), 85.7 ± 13.4 (after NPT), 93.1 ± 11.7 (4 months after ILIT), and 90.6 ± 12.9 (12 months after ILIT). The agreement (%) to "Allergen avoidance can reduce allergic symptoms" changed from 67.7 ± 34.2 to 82.2 ± 20.6 (after SPT/IDT), 82.1 ± 27.8 (after NPT), 90.9 ± 12.6 (4 months ILIT), and 90.6 ± 12.9 (12 months after ILIT). The agreement (%) to "Allergen specific immunotherapy can reduce allergic symptoms" changed from 65.6 ± 29.3 to 81.5 ± 15.5 (after SPT/IDT), 85.7 ± 19.7 (after NPT), 86.3 ± 23.3 (4 months after ILIT), and 81.3 ± 11.6 12 months after ILIT). Conclusion: Allergy skin test, nasal provocation, and SIT themselves can intensify patients' recognition of causal allergen, its avoidance, and allergen-specific immunotherapy. Background: Although IL-17-producing peripheral blood CD177+ neutrophils have recently been shown to increase in allergic asthmatic subjects, the mediators and mechanism regulating this increase in neutrophil derived IL-17 during asthma has not been properly investigated. IL-21, along with IL-6 and IL-23 cytokines, is important for the promotion of naïve CD4+ cells to differentiate toward the Th-17 cell lineage and the release of IL-17 cytokines. In this study, we explored the possibility that IL-21, IL-22 and IL-23 cytokines may activate peripheral blood neutrophils of asthmatic patients to release IL-17 cytokines and postulate that the response to stimulation could be different to that of neutrophils from non-asthmatic subjects. Methods: Peripheral blood neutrophils isolated from asthmatic as well as healthy controls were stimulated, or not, with IL-21, IL-23, and IL-6 cytokines and levels of gene as well as protein expression of IL-17 cytokines were determined using RT-PCR and flow cytometry, respectively. In addition, to investigate the mechanism of IL-21, IL-23, and IL-6 induced IL-17 release, level of Stat3 phosphorylation in neutrophils was determined following stimulation with these cytokines. Results: IL-21, IL-23, and IL-6 induced the production of IL-17 cytokines within peripheral blood neutrophils. Interestingly, the level of induced IL-17 cytokine were significantly higher in asthmatic compared to healthy control neutrophils. Stat3 phosphorylation was required for induction of IL-17 within neutrophils suggesting that a Stat3-RORgt pathway is involved and critical for regulating IL-21, 23, and 6 induced IL-17 production from neutrophils. Conclusion: Th-17 regulatory cytokines, IL-21, IL-23, and IL-6 induce the production of pro-inflammatory cytokine IL-17 from neutrophils in a much higher levels during asthma. This environment of high IL-17 levels could stimulate neutrophils to produce highly reactive oxygen radicals that would exacerbate the airway inflammatory response during asthma via their cytotoxic and tissue-destructive activity. Objective: As the avoidance of trigger allergen is a major treatment in allergic rhinitis, evaluation of trigger allergen is important for the treatment and prevention of allergy. However, the correlations between clinical symptom, MAST and total IgE are not clearly identified. In this study, we compared serum total IgE, MAST and allergic symptoms in allergic patients to analyze the diagnostic value of serum total IgE. Also, we analyzed the cut off value of serum total IgE to predict positivity of allergen specific IgE by using the sum of square estimator recently proposed by Froud et al. Methods: A total of 1945 patients with allergic symptoms underwent MAST and serum total IgE tests. 39 panels were evaluated in MAST and allergens with results greater than class 2(≥0.7 IU/ mL) in considered as positive. To analyze the results of serum total IgE with clinical symptoms, Total nasal score(TNS) was evaluated as sum of 4 nasal symptoms(rhinorrhea, nasal obstruction, sneezing and itching sense). The patients were divided into high(≥100 IU/mL) and low(<100 IU/mL) groups of total serum IgE level and the positive rates and number of positive allergen specific IgEs were evaluated in each group. Furthermore, we calculated cut off value of serum total IgE to predict positive allergen specific IgE. Results: Nasal obstruction turned out to be the most common symptom (65.6%). Total score of TNS showed significant correlation with serum total IgE quantity. High total serum IgE group showed significantly higher positive rates and number of positive allergen specific IgEs on MAST. (p<0.05). Number of allergen specific IgEs showed good correlation with serum total IgE(r=0.521, p<0.05). With use of ROC curve, cut off value of serum total IgE was computed as 108 IU/mL(sensitivity 72.42%, specificity 72.87%). Due to low sensitivity, we analyzed positive predictive value of serum total IgE divided into each group. We suggested 50 IU/mL is more predictable. Conclusions: Serum total IgE appears to be useful in predicting positive results of allergen specific IgEs in MAST. Also, serum total IgE with level of 50 IU/mL turned out to be most reliable to recommend MAST. Background: The response to bronchodilators for asthma diagnosis is generally defined as an increase in FEV1 >12% and >200 mL from baseline after bronchodilators. However, an increase in FVC >12% and >200 mL from baseline not due to increased expiratory time after bronchodilators could also mean bronchodilation. So we evaluated diagnostic values of the FEV1 and/or FVC bronchodilator response. Methods: The patients who were performed both methacholine challenge tests and pulmonary function tests with bronchodilator for suspected asthma from 2002 to 2013 were selected and the results of the tests from order communication system were reviewed. Diagnostic criteria of asthma were defined by one or more of following: the provocative concentration of methacholine causing a 20% fall in FEV1 from baseline (PC 20 ) or extrapolated PC 20 less than or equal to 25 mg/mL (1st criterion), an increase in FEV1 of >12% and >200 mL from baseline after 200 μg of salbutamol (2nd criterion), an increase in FEV1 of >12% and >200 mL from baseline after anti-inflammatory treatment or a variation in FEV1 of >12% and >200 mL between visits within 1 year and FEV1/FVC ≤0.75 at least once (3rd criterion). FEV1 and/or FVC bronchodilator response was defined as increases in FEV1 and/or FVC >12% and >200 mL from baseline after 200 μg of salbutamol. The sensitivity and the specificity of the FEV1 and/or FVC bronchodilator response for asthma diagnosis were calculated. Results: A total 2616 pulmonary function tests with salbutamol and 1496 methacholine challenge tests in 1434 patients from 12 to 89 years old were analyzed. The diagnostic criteria of asthma were satisfied in 874 (60.9%) patients. Among them, numbers of patients who met each criterion were 831 (95.1%) for 1st criterion, 120 (13.7%) for 2nd criterion, 181 (20.7%) for 3rd criterion. Among 1834 pulmonary function tests in the asthma patients, 191 (sensitivity 10.4%) tests showed positive FEV1 and/or FVC bronchodilator response, while only 152 (sensitivity 8.3%) tests showed positive FEV1 bronchodilator response. False positive results in FEV1 and/or FVC bronchodilator response were shown in only 3 of 782 pulmonary function tests of patients without asthma (specificity 99.6%). The false positive results were shown in 3 different patients. Among them 2 patients were real asthma patients according to the results of other pulmonary function tests which were not evaluated in this study and the other patient had history of asthma. Conclusions: An increases in FEV1 and/or FVC >12% and >200 mL from baseline after bronchodilators could have also diagnostic value for asthma. Background: The aim of the present study was to see whether measurements of bronchodilator response (BDR) and fractional exhaled nitric oxide (FeNO) in combination are informative for upcoming loss of asthma control among children with atopic asthma. Methods: Two hundred one patients aged 8 to 16 years with atopic asthma were recruited. Pulmonary function tests including BDR and FeNO were serially measured 10 times or more over 2 years when subjects were not receiving controller medications. After completion of monitoring, 1-year observation for loss of asthma control was performed. Results: At least 1 positive BDR (≥12% improvement in FEV 1 in response to inhaled short-acting b 2 -agonist) and high maximum FeNO (mFeNO) (≥35 parts per billion (ppb)) were confirmed over the 2-year observation period in 59% and 77% of study participants. There was no difference in FeNO levels between individuals with positive and negative BDRs. Risk of asthma control loss increased by 40% for patients with mFeNO ≥ 35 ppb [Hazard ratio (HR) = 1.94; P < 0.01], and by 26% for those with positive BDRs (HR = 1.40; P < 0.01). Risk of asthma control loss was greatest for patients with either (HR = 5.31; P < 0.01) or both positive BDRs and mFeNO ≥ 35 ppb (HR = 5.65; P< 0.01). Conclusions: High FeNO was better able to predict upcoming loss of asthma control than BDRs, but use of both markers together provided a better indicator of asthma control loss. Purpose: IgA antibody is massively produced in the intestinal Peyer's patches, and the secretory IgA (sIgA) plays an important role on immune responses. It is considered that sIgA regulates the cause of allergic reactions, but the relationship between IgA levels and allergic reactions is not fully understood. We studied sIgA levels and antigen-specific IgA levels in allergic children and studied their relationship with allergy symptoms. Methods: It is a retrospective study using medical records of infants (from 6 months to 6 years old) who presented to our hospital for evaluation of allergy. We classified the groups according to the results of physical examinations with or without allergic symptom (eczema, wheezing, food allergy). In addition, we investigated the white blood cell counts (eosinophils and basophils) and the serum levels of total IgE, antigen-specific IgE, total IgA, sIgA, antigen-specific IgA. Results: Children who were low levels in sIgA have past histories of atopic dermatitis, and their serum levels of antigen-specific IgE was significantly higher (p=0.008) but their serum IgA level was significantly lower (p=0.021) compared with children who does not have allergic symptoms. And serum levels of antigen-specific IgA were significantly lower (p=0.038) in allergic children. Especially, ovomucoid specific IgA levels were low in children who has ovalbumin allergy. Conclusions: Secretory IgA levels are important to the onset of allergic reactions, and antigen-specific IgA might be played an important role in allergic reactions. IgE antibody contributes to immediate type allergic reactions, and the presence of the specific antibody can be an evidence of the diagnosis of allergic reactions. Moreover, we suggested that measurement of sIgA and antigen-specific IgA can be also useful in prediction of allergic reactions. Background Anaphylactic shock is a life threatening circumstance which requires urgent and proper medical management. Epinephrine is the first-line and life-saving medication in the acute management. The delay in making an accurate diagnosis, initiating appropriate treatment and inappropriate use of epinephrine can lead to death. Objectives This study is designed to evaluate and emphasize the paramount importance of the trainee knowledge about anaphylaxis, the treatment methods, life-saving medications, the route of administration and the dosage. Our aim is to bridge the gap between knowledge and real life practice and enable the trainee to act undoubtfully when facing a patient with anaphylaxis. Method This is a cross-sectional two phase questionnaire based survey at Hamad General Hospital's Pediatrics department, the only tertiary hospital in Qatar.


In phase 1, the questionnaires were distributed to 96 trainees. The response was 98% (94 responses), 55 females and 39 males. 84 trainees (89% ) reported knowing how to treat and a total of 44 (50%) claimed not being trained at all. Epinephrine was selected as a life saving drug by 89 (94%). IM as a route of administration was selected by 76 (80%). Correct Epinephrine concentration was known by 77 (83%). For phase 2, questionnaires were distributed to 94 trainees who responded to the stage 1 and the response rate was 89% (84). 84% claimed they heard about Epinephrine Autoinjector, 5 fellows claimed they never heard about it. 72% claimed knowing when to use it .23 (27%) did not know, 9 of them were Fellows. Anaphylaxis was the case of using it in 71%. Only 43 (51%) know the right location and the method of injection. Sub Cutaneous injection was selected in 20 (23.8%).
In the AR group, 43/132 (32.6%) patients presented a positive response to NPT. In the NAR group, 11/69 (15.9%) patients had a positive response to NPT. NPT was negative in 17/18 healthy controls (94.4%). The majority of rhinitis patients had moderate-severe nasal symptoms. LAR and AR subjects had a similar pattern of nasal symptoms in frequency and severity. However, significant differences were detected between LAR and NAR. Conclusion Local allergic rhinitis is a prevalent entity in patients evaluated with rhinitis. LAR and AR subjects had a similar pattern of nasal symptoms in frequency and severity. Conventional skin tests were significantly well correlated with nasal provocation tests. Background. The role of allergen immunotherapy (AIT) in the treatment of patients with atopic dermatitis (AD) is quite controversial, since its efficacy has been poorly investigated in the past years and eczema exacerbations have been reported following AIT. We investigated the tolerability of hypoallergenic AIT, its benefit on eczema and its influence on the progression of the allergic disease.

Evaluation of Serum Levels of Osteopontin As a Potential Biomarker of Immune Activation in Patients with Allergic Diseases

Anand Andiappan 1 , Rosalba Minisini 2 , Olaf Rötzschke 1 , Elena Boggio 3 , Luca Gigliotti 3 , Nausicaa Clemente 3 , Annalisa Chiocchetti 3 , Umberto Dianzani 3 , Mario Pirisi 3 , Elisa Villa 2 1 Agency for Science, Technology and Research (A*STAR), Singapore; 2 University of Eastern Piedmont, Italy; 3 University of Eastern Piedmont "Amedeo Avogadro" Correspondence: Elisa Villa -University of Eastern Piedmont, Italy World Allergy Organization Journal 2016, 9(Suppl 1):A375 A) Background: Osteopontin (OPN) is a pleomorphic cytokine known to influence a range of immune cells, including macrophages, neutrophils, dendritic cells, T and B cells. High OPN levels are associated with a significantly increased risk of autoimmune lymphoproliferative syndrome, multiple sclerosis and systemic lupus erythematosus, suggesting that OPN is a candidate biomarker of these conditions. In the present cross-sectional study, we aimed to verify if serum levels of OPN may qualify as a biomarker of an activated immune response in allergic patients. B) Method: Serum OPN levels were measured by an enzyme-linked immunosorbent assay (ELISA) (Human Osteopontin Duoset, R&D Systems). A series of 77 adult patients (median age females: 49 years; males: 47 years) with different allergic diseases, was studied: 34 patients (44%) had allergic rhinoconjunctivitis, 15 (19%) asthma, 17 (22%) hymenoptera venom allergy, 5 (6%) allergic contact dermatitis, 3 (4%) food allergy and 3 (4%) IgE-mediated hypersensitivity to betalactams. 116 healthy subjects with similar demographic characteristics served as controls. Data were analyzed comparing cases to controls, as well as looking for subgroup differences within the group of allergic patients. C) Results: OPN serum levels were significantly higher in cases in comparison to controls (median 12181 pg/ml, interquartile range 6953 -19359 pg/ml vs 6099 pg/ml, interquartile range 3122 -14520 pg/ml; p = 0.0010 by the Mann-Whitney test). The highest serum OPN levels were observed among patients with asthma (median: 15668 pg/ml; p = 0.0156) followed by those observed in the hymenoptera venom allergy group (median: 14239 pg/ml; p = 0.0080). Lower values of OPN were detected in the group of patients with rhinoconjunctivitis (median: 10291 pg/ml; p = 0.0436), allergic contact dermatitis (median: 9088 pg/ml) and food allergy (median: 4386 pg/ml). Patients with IgE-mediated sensitization to beta-lactams had heterogeneous values, not statistically different in comparison to controls. D) Conclusions: Serum OPN levels may represent a novel, potentially useful biomarker of allergic respiratory diseases and hymenoptera venom allergy. Consideration should be given to explore clinical correlates of high OPN levels in these conditions.

Prevalence of Food Sensitization, IgE-Mediated and Non-IgE-Mediated Food Allergy Among Pediatric Patients Diagnosed with Autism Spectrum Disorders

Aimee Lou Manalo Nano University of the Philippines Philippine General Hospital, Philippines World Allergy Organization Journal 2016, 9(Suppl 1):A384 A) Background: Autism spectrum disorders and food allergies are conditions with increasing prevalences. Studies have investigated the link between intake of certain food among ASD patients and onset of adverse reactions. Results of these studies are varied and conflicting. This is the first local study on the prevalence of food allergies among these patients. This study aims to determine the prevalence of food sensitization, IgE-mediated and non-IgE-mediated food allergies among pediatric ASD patients. It also aims to determine the prevalence of perceived food allergies, and its triggers and the types of reactions of perceived food allergies and on open food challenge. B) Methods: This is a cross-sectional, prospective study. Pediatric patients diagnosed with Autism Spectrum Disorders were enrolled in the study. Excluded were: children with uncontrolled asthma, with a recent anaphylactic reaction, and those on chronic high dose steroid therapy. Required sample size is 92. Complete history and PE were obtained and previous reactions to food and suspected allergens were duly noted. All patients underwent skin prick testing (SPT) to cow milk, wheat, soy and other perceived food allergens. Those with perceived food allergies underwent open food challenge to specific food allergens. Frequencies and proportions were determined to analyze the different variables. C) Results: Data were gathered from 84 patients diagnosed with ASD. 32/84 (38%) have perceived food allergies, mostly to milk (31.3%), chocolate (25%), and egg (18.8%). Most commonly perceived allergic reactions to food allergens were: hyperactivity (53.1%), loose stools (25%), pruritus (15.6%), and wheals (12.5%). A total of 17 (20.2%) patients had (+) skin prick test result, hence food sensitization, to at least 1 food allergen, mostly to soy (41.2%) and milk (35.3%). Of these patients, 8 had perceived food allergies. 6 of these patients underwent open food challenge and all of them had (-) results. D) Conclusion: Prevalences of perceived food allergies and food sensitization are higher among ASD patients in this study compared to the general population. The most common perceived food allergens are similar with that of other children. Notably, the common perceived allergic reactions to food were behavioral or gastrointestinal symptoms, which may be non-IgE mediated or not food allergies at all. Hence, ASD patients with adverse food reactions are recommended to undergo complete, systematic evaluation and possible restrictive diets should be based on welldocumented food allergies Background: Little is known about the data on component-resolved diagnosis (CRD) for allergy to Dermatophagoides pteronyssinus (Der p) in the Chinese population. We aimed to measure the prevalence of sensitization to Der p allergen components among patients in southern China. Methods: 200 Der p-positive and 20 Der p-negative subjects were tested for serum immunoglobulin E (sIgE) against Der p 1, Der p 2, and Der p 10 using ImmunoCAP 100. 75 poly-sensitized patients were further examined with ImmunoCAP Immuno Solid-Phase Allergen Chip (ISAC). Der p 10-positive subjects were tested further for sIgE to crude extracts of cockroach, moth, and shrimp. Results: 91.5% (183/200) patients were sensitized to Der p 1 and/ or Der p 2. 6% (12/200) Der p-positive patients were sensitized to Der p 10. The positive proportion and median level of sIgE against Der p 1 were higher in children than in adults. Der p 1 and Der 2 correlated with Der p in sIgE levels (r=0.862, 0.799, P<0.001). ImmunoCAP ISAC demonstrated 100% specificity and 84% sensitivity in detecting Der p 1, p 2, and p 10 compared to ImmunoCAP 100. According to ImmunoCAP ISAC, 8 of these 12 Der p 10-positive patients were triple positive and 3 patients were triple negative to Pen m 1, Bla g 7, and Ani s 3; one was solely positive to Pen m1. Sensitization to Der p 10 correlated well with sIgE to shrimp, moths, cockroaches, Pen m 1, Bla g 7, and Ani s 3. Conclusions: The detection of Der p 1 and Der p 2 well reflected atopy to Der p in a Chinese cohort. Sensitization to Der p 10 may result from cross-reactivity to seafood and cockroaches in coastal southern China. ImmunoCAP ISAC may offer a useful tool for CRD with performance comparable to ImmunoCAP 100. The type of allergic disease, the allergens producing sensitivity, the vaccine content, the adjuvant content, and the effects of treatment phase on frequency of adverse effects were investigated. Results: Out of 329 patients included, there was local reaction in 11.9%, large local reaction in 6% and systemic reaction in 4.7%; local reactions were observed in 0.38% of all injections, whereas a systemic reaction was observed in 0.1% of all injections. Local reactions were frequent at the initial phase and systemic reactions were frequent at the maintenance phase (p=0.01). Adverse reactions were more common in patients vaccinated (SCIT) with multiple allergens and house-dust-mites (p=0.002) (p=0.001). No statistically significant difference was found between the content of the adjuvant and the frequency of adverse effects (p=0.319). Conclusion: The frequency of local and wide local reactions during subcutaneous immunotherapy were lower than expected. Although systemic reactions are frequently seen, no fatal reaction was observed in the current study. Mite immunotherapy and multiple allergen use increase the risk of reaction. Background: Cyclical anaphylaxis is a rare reaction occurring in the luteal phase of menstruation. Presentation may include dyspnea, respiratory distress, cutaneous and gastrointestinal symptoms. Previous successful treatment options of this condition have been limited to medical or surgical ovulatory suppression. At present, the use of IgE-inhibition with the drug omalizumab has shown success in multiple individuals, making it the favorable treatment over oophorectomy for women looking to conceive. We report the first successful case series of four patients treated with omalizumab for cyclical anaphylaxis. Methods: A literature review was conducted of published data pertaining to cyclical anaphylaxis in the luteal phase of menstruation. This information was summarized and the four patients from our center were included in this summary. Results: Omalizumab has resulted in symptom resolution or significant reduction in symptoms in all four patients. There is no consistent literature definition of cyclical anaphylaxis and the nomenclature of similar and/or overlapping conditions makes any uniform treatment decisions challenging to make consensus recommendations for. For cyclical urticaria and anaphylaxis, omalizumab and represents a safer and preferable treatment option for this rare condition(s). Conclusion: Through evaluating data regarding the use of omalizumab it can be noted that this is the preferred treatment of cyclical anaphylaxis for women who would like to maintain the option of conception later in life. Continued research is necessary in order to fully understand the generalizability and reliability of study data to the population. We also propose a more systematic classification of this and related conditions to better direct future research. Acute lung injury (ALT), which is associated with a high mortality and morbidity in both infants and adults, is caused by severe lung inflammation resulted from a variety of local and systemic infection such as sepsis and pneumonia. According to the disease procession, there are three stages: exudate formation, proliferation, and fibrosis. Idiopathic pulmonary fibrosis (IPF) is another chronic, progressive and lethal fibrotic lung disease. The etiology of IPF is still unknown. However, both diseases have some similar hallmarks such as hypoxemia and respiratory failure. Surfactant protein D (SP-D), a C-type lectin, which is produced by alveolar type II cells, is important on respiratory innate immunity and anti-inflammation. The action of SP-D in these diseases is still unrevealed. In this study, we used bleomycin to induce the animal model of ALI and IPF. Bleomycin is a chemotherapeutic antibiotic drug clinically used in lymphoma and squamous cell carcinomas, but the following overproduction of reactive oxygen can lead to irreversible lung injury. In this animal model, we have found that 14-day-course was the group presenting the most severe resistance and the poorest elastance of lung tissue. In addition, the proinflammatory cytokines (interleukin-6, interleukin-17, tumor necrosis factor-α, interferon-γ and nitric oxide) were followed by increased expression of pro-fibrotic cytokines (transforming growth factor-β1). The histological alterations caused by bleomycin such as mural incorporation of collagen and obliteration of the alveolar space are similar to human IPF. In ex vivo study, pretreatment with recombinant human SP-D or native SP-D can significantly decrease the production of pro-inflammatory cytokines. In in vivo study, treatment with native SP-D in bleomycin-induced lung fibrosis in mice also showed significant body weight increase, recovery of lung function, decline of the production of transforming growth factor-β1 (TGF-β1) and nitric oxide. Therefore, we conclude that SP-D may have prominent anti-inflammatory and anti-fibrotic effects on ALI and IPF, and also have the potential to become a novel treatment of ALI and IPF in the near future. We have previously demonstrated that Hsp90 release by activated endothelial cells leads to conversion of prekallikrein to kallikrein if prekallikrein is bound to HK. Kallikrein formation is therefore stoichiometric and occurs in the absence of factor XII. Since kallikrein activates factor XII, we theorized that endothelial cell activation might first generate kallikrein which then recruits factor XII. We now demonstrate that estrogen, interleukin 1, and to a lesser degree TNFa can activate endothelial cells to release Hsp90. The dose range tested for each in ng/ml was 0, 0.5, 1.0, 5.0, and 10.0. A dose-response for estrogen or IL-1 was maximal at the 10 ng/ml dose while TNFa was best between 0.1 and 5 ng/ml. A time course for each up to 4 hrs incubation revealed maximal Hsp90 secretion between 30 and 60 min with a significant increase noted by 15 min for each. Our observations are particularly relevant for types I and II HAE (C1 inhibitor deficiency) where estrogen and inflammation are known triggers of angioedema events and for HAE with normal C1 inhibitor (HAE-N) where estrogen exposure is a key precipitant. For the latter, studies of endothelial cell release of urokinase and tissue plasminogen activator are in progress given recent observations regarding inhibitors of fibrinolysis. sunny days and in 56 days limits for dust and polyaromatic hydrocarbons were overthrown. In the medical professional institute Metylovice located 410 meters above sea level found in Štramberk highlands during a 4-week stay for treatment with vitamin D, we investigated the effect of climate on the parameters of bronchial asthma and changes of physical parameters by modified Cooperoe test in asthmatic children. The main goal of the study is to assess the effectiveness and benefits of the stay with described treatment.

Comparison of Some Vitamin Groups in Asthmatic Patients

Method: Respiratory fuction tests were conducted on 302 patients (193 female-109 male, totally with age group of 18-79) who applied to Chest Diseases Polyclinics between January-May 2015. Patients were classified as mild, moderate and severe due to GINA 2014 criteria. Vitamin A, vitamin D, vitamin E, folic acid and vitamin B12 levels were investigated. Statistically, Mann Whitney U, Kruskall Wallis-H and Post-Hoc tests were applied. Results: In all age groups, vitamin A and vitamin D values of females were significantly lower than those of males (p<0.05). In patients of age 29 and lower, folic acid values were significantly low. Due to vitamin A, vitamin D, vitamin E, vitamin B12 and folic acid, no statistically significant difference was detected among astmatic levels of patients enrolled in the study (p>0.05). Conclusions: Beside physiopathologic changes during astma, evidence of free oxygen radical release out of inflammatory cells and decrease in antioxidant levels give an impression of oxidant-antioxidant disequilibrium role in astmatic pathogenesis. As a defence mechanism of body against oxydative stress, outsourcing of vitamins is therefore essential. Low values of vitamin A and vitamin D values in astmatic patients encourage astmatic symptom severity, in addition to exhaustion, fatigue, bone ache and eye diseases. Reinforcement of vitamins through nutrition and medication is believed to be useful in treatment of asthma. Purpose: There are few recent epidemiologic data regarding allergic sensitization of atopic dermatitis (AD) in Korea. The aim of this study was to investigate patterns of sensitization in children with AD. Methods: This retrospective study included pediatric patients (0-18 years old) with AD who visited Samsung Medical Center from 1998 to 2014. The serum specific IgE (sIgE) levels of egg white (EW), cow's milk (CM), peanut, wheat, soy, buckwheat, tree nuts, crustaceans, meats and house dust mites (HDMs) were reviewed. The sIgE level ≥ 0.35 kU/L was regarded as positive. AD was categorized into the extrinsic type (ADe) and the intrinsic type (ADi) according to the presence or absence of positive sIgE. We compared the proportion of sensitized children according to their ages using Chi-Square Test. The prevalence of immediate-type egg and CM allergies was also evaluated based on the previously reported diagnostic decision point (DDP). 1) Results: Data were collected from total of 4775 children (2928 boys and 1847 girls). We identified 3321 (69.5%) children with ADe type, and 1455 (30.5%) with ADi type. There was no difference in the proportion of sensitized patients according to their age (P value = 0.538). Ratio of positive sIgE among the individual food item was the highest in EW (2348/3994, 58.8%), followed by CM (1776/3836, 46.3%), peanut (1244/3848, 32.3%), wheat (1119/3546, 31.6%), soy (984/3503, 28.1%), and buckwheat (267/1118, 23.9%). Among the food groups, tree nuts (405/715, 56.6%) were the most common allergens. Sensitization to Dermatophagoides farinae and D. pteronyssinus was found in 43.5% (799/1837) and 39.3% (722/1837), respectively. In addition, 10.9% (435/3994) and 7.4% (284/3836) showed the higher levels of sIgE to EW and CM than previously reported DDP. Conclusions: The frequency of ADe among all the children with AD was 69.5%. The most frequently sensitized food allergen was EW, followed by CM and peanut. Background: The pathogenesis of asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS) is supposed to be multifactorial but unclear. Recent evidence suggests staphylococcal enterotoxin IgE sensitization (SE-IgE) to be a risk factor for asthma and its severity in adults, including the elderly. We hypothesized SE sensitization contributes to the development of fixed airway obstruction in asthma, leading to an ACOS phenotype. The present study aimed to examine the associations of SE-IgE sensitization with fixed airway obstruction in elderly asthma patient. Methods: We compared baseline characteristics between elderly controls, asthma and ACOS patients (≥65 years). Baseline assessment included demographics, lung functions, comorbidities, and serum total IgE and SE-IgE levels. SE-IgE sensitization was classified as negative (<0.10 kU/L), moderate (0.10-0.35 kU/L), and high (≥0.35 kU/L). SE-IgE sensitization was defined positive as ≥0.35 kU/L. Lung functions were serially checked every 3 month for two years in elderly asthma patients, and their best FEV1/FVC ratio was used to define fixed airway obstruction (persistently FEV1/FVC<0.7 during 2-year of asthma management). Exacerbation frequency was assessed during 1-year prospective follow-up. Results: A total of 338 elderly subjects were analyzed (89 controls, 172 asthma, and 87 ACOS). Serum SE-IgE levels were higher among elderly ACOS and asthma patients, compared to controls (mean±SD; 0.74±1.34, 0.56±2.32, and 0.20±0.36, respectively). SE-IgE sensitization rates significantly differed between groups (high SE-IgE sensitization; 44.2% in ACOS, 27.9% in asthma, and 14.6% in control; P<0.001). The presence of fixed airway obstruction (FEV1/FVC<0.70) showed relationships with male sex, smoking history, chronic rhinosinusitis (CRS), and SE-IgE sensitization. In multivariate analyses, smoking history and high SE-IgE sensitization had independent relationships with fixed airway obstruction. In both of asthma and ACOS groups, SE-IgE levels showed significant correlations with exacerbation frequency. Conclusions: Staphyloccocal enterotoxin could have a pathogenic role in the development of COPD overlap in late-onset elderly asthma. These findings warrant further investigation for mechanisms of SE in mediating airway remodeling. Probiotics are normal inhabitants in the gastrointestinal tracts of man and are widely considered to exert a number of beneficial roles including immunomodulation, interference with enteric pathogens, and maintenance of a healthy intestinal microflora. In recent years, studies of probiotics have also confirmed their extra-intestinal effects, particularly for the prevention of allergic diseases. However, the antiallergy mechanism of probiotics is still unclear. In the first part of this study, we found that continuous feeding of Lactobacillus gasseri (L. gasseri) 10 7 CFU/200 ml or 10 9 CFU/200 ml for 4 weeks in Der p-sensitized and challenged mice could prevent allergen-induced airway inflammation. There were also significant changes of airway hypersensitivity, T H 1 and T H 2 cytokine patterns, lymphocyte proliferations and immunoglobulin production between L. gasseri -treated and non-treated mice. In the second part of study, we applied microarray analysis of the lung draining lymph nodes and mesenteric lymph node of mice to detect genes expression signal pathways and genetic profiling of immunological tolerance induced by L. gasseri that plays an essential role of in the prevention and therapeutic on allergic asthma. We found that there was significantly decrease of inflammatory and chemokines genes expression and increased of carbohydrate and lipid metabolism genes expression in the L. gasseri-treated mice as compared to non-treated sensitized and challenged mice. Thirdly, we have picked up one candidate targeted gene, PPARγ (peroxisome proliferator-activated receptor γ), to study the beneficial effect of probiotics on the allergic induced airway inflammation. Previously, it has been reported that PPARγ is a member of the nuclear hormone receptor family that not only is prominently involved in adipogenesis and metabolic regulation but also exerts pleiotropic anti-inflammatory effects in the lung, we hypothesized that PPARγ may play an important role in allergen-induced airway inflammation. The allergen-sensitized effect on murine model of asthma was applied in PPARγ P456L mutant mice by evaluating AHR, total numbers of inflammatory cells and cytokines secretion in bronchoalveolar fluid (BALF), and lung inflammation after mite allergen sensitization and challenge. Moreover, probiotics treatments PPARγ P456L mutant mice and wide type mice were administrated in allergen-sensitized mice. In summary, our results showed that PPARγ play important role in the inhibitory effect of allergen-induced airway inflammation in mice. And the anti-allergic effect on L. gasseri may through activation of PPARγ to alleviate airway inflammation in allergen-sensitized murine model of asthma. Objective: To explore the views of adult patients on AAI design. Methods: Thematic analysis of semi-structured interviews with 30 adult patients prescribed AAIs. Discussion was facilitated by a variety of AAI models (both commercially available and prototypes). Results: All participants spoke spontaneously about the size of the device, they wanted it to be portable without needing a bag. Many favoured a smaller device, but others were tolerant of bulky designs and the inconvenience associated, because of the 'lifesaving' characteristics of their AAI. The increased size of some recent products on the market were not welcomed. However significantly smaller designs were not necessarly perceived as preferable because of the potential difficulties of locating them in an emergency. Some argued for greater visibility achieved by bright colouration, others found bright colours 'frightening' or attracting unwanted attention to the fact that they carried and AAI. Grey was considered an undesirable colour ('Grey is quite depressing'). Patients wanted instructions that were brief, simple and made full use of illustrations. Middle aged respondents commented on the need for adequate font size, while younger people recognised that if without their reading glasses bystanders assistance could be impaired through existing presentation styles. Integrated instructions on devices, that were intuitive to use, and 'not fiddly' needed to be prioritised. Consistency was requested; it was recognised that the different ways of highlighting the safety cap on some devices and the needle end on others was potentially confusing. A strong and resilient protective casing was thought to be mandatory, several respondents described casings deteriorating before the AAI expiry date. Several novel design features were suggested by the patients based on many years of experience. Conclusions: Size and aesthetics of were two of the most important AAI design issues for patients. Greater involvement of patients in the development of new AAIs (patient centered design) could potentially increase the carriage of devices. This is important because however good the ballistic characteristics are of any device, the patient cannot benefit from this technology unless the AAI is carried, and utilised when needed. Background: Allergic asthma is a chronic pulmonary disease characterized by a Th2 inflammatory response. Th-2-biased immune responses are known to play a key role in the pathogenesis of allergic asthma. In particular, the macrophage derived chemokine CCL22 is directly implicated in Th-2-associated inflammatory reactions. In this study, we investigated the immune modulation using CCL22 miRNA would be induced therapeutic effects on ovalbumin-sensitized and -challenged asthmatic mice. Methods: The recombinant strain of Salmonella typhimurium expressing CCL22 miRNA (ST-miRCCL22) was prepared for in vivo knockdown of CCL22. Using an ovalbumin-induced asthma model, mice were sensitized and challenged, and then treated with ST-miRCCL22. Results: We constructed a recombinant strain of Salmonella typhimurium expressing CCL22 miRNA (ST-miRCCL22) for the in vivo knockdown of CCL22. The treatment of mice with established allergy led to attenuation of eosinophilia, Th2 cytokines and airway hyperresponsiveness. ST-miRCCL22 treatment also induced an increase in OVA-specific IFN-γ levels and in the frequency of lung inflammatory monocytes. Conclusions: In our research, the CCL22 microRNA was treated to modulate imbalances in the disease. The CCL22 miRNA reduced Th1 immune responses and induced therapeutic effects on OVA-Induced mouse model of asthma. These results suggest that CCL22 miRNA could potentially be used as an effective therapeutic agent for treating asthma. Background Head and neck dermatitis (HND) is a unique subtype of atopic dermatitis (AD) which commonly manifests in late adolescence or adulthood. HND is often refractory to therapy and affects patient's quality of life greatly. However, presence of HND is often underappreciated in clinics and detailed studies on its characteristics are limited.


These findings reaffirm that HND is a clinical subtype of AD that needs distinction from classical AD. In the future, further investigation of skin microbiome and inflammatory factors involved in vasculatures of facial lesions in AD will lead to development of potential therapeutic targets. Background: MicroRNAs (miRNAs) modulate gene transcription in response to environmental stressors and other stimuli. A role for miRNAs in inflammation and immunity has been demonstrated and further evidence suggests that miRNAs also play a role in atopic dermatitis. In this study, we hypothesized the immune suppression using miR-432 would be induced therapeutic effects on atopic diseases. Methods: The Ig-E, Interleukin-4 (IL-4), CCL22 and interferon-g (IFNg) were examined after treatments with miRNAs in murine atopic model. In addition, atopic patient's blood samples were collected and examined for miRNA expression. Results: miR-432 reduced CCL22 chemokine gene in activated lymphocytes. In mice with a cutaneous disease similar to atopic dermatitis, Interleukin-4 was inhibited and interferon-γ was induced after treatments with miR-432. Furthermore, miR-432 levels were suppressed in the atopic patients. Conclusions: miR-432 suppressed Th1 immune responses and induced therapeutic effects in atopic mouse model. A) Background: Cross-reaction between food and inhalant allergens usually show mild symptoms. However, severe asthma symptoms, exercise-induced anaphylaxis, urticaria and "recall urticaria" at the site of immunotherapy injection may occur after ingestion of snails by patients allergic to house dust mites (1) . B) Methods: We report the case of a 23-years old woman who suffered from an acute severe asthma attack complicated by asphyxic evolution leading to cardiopulmonary arrest. Cardiopulmonary resuscitation was successful, subcutaneous emphysema occurred, left pneumothorax was treated by chest tube. The clinical course was benign, and the patient returned from hospital to home after a few days with no complication. Medical history revealed that she had had asthma for 10 years, with allergy to inhaled allergens (grass pollen, house dust mites, pets dander). She had been treated 9 years earlier by subcutaneous specific immunotherapy against house dust mites for 2 years. Medications taken included albuterol, beclomethasone, salmeterol and montelukast. She ate Norway lobsters and snails 5 hours before the beginning of acute severe asthma attack and had sexual intercourse with no condom 3 hours before. C) Results: Skin prick tests (SPT, diameters of the wheals and flares in mm) and serum specific Ig E (SSIg E, Pharmacia Unicap 1000) confirmed sensitization against snails (SPT = 7/30; SSIg E 7,37 kUI/l) but not against Norway lobsters (SPT = 0/0; SSIg E < 0,35 kUI/l) nor human seminal fluid (SPT = 0/0; SSIg E < 0,35 kUI/l). No Ig E sensitization was later found against prawn nor house dust mites tropomyosin (rPen a 1 < 0,35 kUI/l, Pharmacia Unicap 1000 ; rDer p 10 < 0,10 kUI/l, Phadia Immunocap 1000). No severe asthma attack did occur thirteen years after beginning of eviction diet and continuation of asthma treatment. More than 100 cases of allergic symptoms after consumption of snails among patients allergic to house dust mites were published. These allergic symptoms may occur after the first ever ingestion of snails and may be life-threatening. They begin usually 5 to 60 minutes and rarely 1 to 5 hours after the ingestion of snails (1, 2) . Cross-sensitivity between snails and house dust mites is probably due to common epitopes as haemocyanin. D) Conclusions: Allergic patients to house dust mites should be informed about the possibility of severe cross-allergy symptoms after eating snails. Background: Distinctive pattern and diversity in early intestinal colonisation are shown to influence immune maturation and potentially development of allergic disease. We recently demonstrated that prenatal supplementation with Lactobacillus rhamnosus GG (LGG) during late pregnancy can influence infant gut colonisation by particular Bifidobacterium species directing towards healthy infant-type microbiota. We investigated whether this early-life gut colonisation with Bifidobacterium species is associates with systemic immune responses at 12 months of age. Methods: Faecal samples were collected from infants during the first 3 months of life. Bacterial DNA was extracted from the faecal samples and Bifidobacterium longum, B. lactis, B. breve, B. angulatum, B adolescentis, and B. catenulatum were detected by real time PCR. Infants' peripheral blood mononuclear cells at 12 months were stimulated with ovalbumin (OVA), heat-killed LGG (HKL) (the probiotic used in the original study), tetanus toxoid (TT), anti-CD3 or without stimulus. Cells were analysed by flow cytometry for markers of dendritic cells phenotype and regulatory T cell (Treg) numbers. Culture supernatants were analysed for IL-4, IL-6, IL-10, IL-13, IFNγ and TNF-α by multiplex ELISA, while TGF-β1 and IL-12p40 were measured using ELISA. Results: Colonisation with B. longum at day 7 of life was associated with significantly higher (p < 0.01) levels of Th1 cytokine (IFN-γ) and pro-inflammatory cytokines (IL-6 and TNF-α) and increased (p < 0.05) secretions of Th2 (IL-13) and regulatory cytokine (IL-10) in infants at 12 months. However, colonisation with B. adolescentis at day 3 was associated with higher secretion of IL-4 cytokine. A significantly increased numbers of Treg were observed in infants colonised with B. adolescentis at 7 days of age.
Conclusions: Colonisation with specific Bifidobacterium species in early life can influence cellular immune function, namely cytokine profiles and Treg later at 12 months. This suggests that probiotic treatment during pregnancy may modulate infant immune function as late as 12 months of age, feasibly mediated by modulation of infant microbiota. However, the immune mechanism that might protect against allergic disease is still unclear. Background: Curry spice allergy in children is extremely rare in Japan. In addition, food-dependent exercise-induced anaphylaxis (FEIAn) as a manifestation of spice allergy against curry powder is quite uncommon. Methods: We report a case of FEIAn due to curry spice allergy in a 14-year-old boy. The boy had a history of several episodes of exercise-induced anaphylaxis since the age of 12 years, which were suspected to be FEIAn. He developed pollinosis in spring and autumn, and had increased levels of specific IgE antibodies against many different kinds of allergens such as food and pollens, including, celery, white birch, and mugwort. Among several different foods consumed before the last three episodes of anaphylaxis, we found that curry powder was the common ingredient in all of them. Since the curry powder did not induce symptoms without exercise, we suspected FEIAn caused by curry spices. Results: The results of the exercise challenge test conducted after ingestion of curry were positive and accompanied by skin flare, itching, urticaria, and bulbar conjunctival hyperemia. We recorded a 10.0% decrease in forced vital capacity, and a 13.5% decrease in forced expiratory volume in 1 s on respiratory function testing. The patient was diagnosed as having FEIAn in response to curry powder. The patient was found to be sensitized to coriander, a curry powder ingredient, on ImmnoCAP. Sensitization to several other spices was also detected with skin-prick testing. The patient was instructed to refrain from exercise for 2 h after ingestion of curry powder and has not shown any symptoms since then. Conclusion: Based on history and investigation results, we suspected that the celery-birch-mugwort-spice syndrome was caused by IgE cross-reactivity between pollens and spices. Background: Atopic dermatitis (AD) is a chronic, relapsing, inflammatory skin disorder characterized by multifactorial pathophysiologic aspects. Pruritus and sleep disturbance are cardinal symptom of atopic dermatitis. Several scoring systems are available, Eczema Area and Severity Index (EASI) is a tool commonly used to measure the severity of atopic dermatitis. Correlation between Visual analogue scale (VAS) of pruritus and loss of sleep (LOS) and the EASI score is not fully investigated yet. Objective: This study was designed to evaluate the association of pruritus and sleep disturbance in atopic dermatitis with objective disease severity and laboratory parameters.


We assessed EASI score as an objective disease severity, VAS of pruritus and LOS (0-10 point) as a severity of pruritus and sleep disturbance in 1877 AD patients at our dermatology clinic from 2007 to 2013. We also measured Eosinophilic count, total IgE and specific IgE in peripheral blood. Correlation of pruriruts and sleep disturbance with disease severity and laboratory parameters were determined by Pearson's correleation analysis using SPSS version 21.0. Results: The mean VAS of pruritus and LOS were 5.93±2.53 (Mean ± SD) and 4.67±3.00. The mean EASI score was 14.0±12.1. Our study revealed that the EASI score showed weak statistical significance with VAS of pruritus and LOS. (EASI vs VAS of pruritus; r = 0.31, EASI vs VAS of LOS; r = 0.36) The eosinophil count revealed weak statistical significance with VAS of pruritus and LOS. (VAS of pruritus; r = 0.10, VAS of LOS; r = 0.23) The total IgE level showed no statistical significance with VAS of pruritus and LOS. Specific IgE titer to Dermatophagoides farinae (D2) showed weak statistical significance with VAS of pruritus and LOS. (VAS of pruritus; r = 0.10, VAS of LOS; r = 0.14). Conclusions: Our results demonstrated that EASI score weakly reflect the subjective severity (pruritus and LOS). Since severe pruritus and LOS can affect the quality of life of atopic dermtaittis patients and they are not strongly correlated with disease severity measured by dermatologists, dermatologists should aware the subjective symptoms from patients and consider to manage the subjective symptoms together with objective symptoms. Background: Hereditary factors of atopic dermatitis(AD) have been emphasized recently. AD-related gene mutations vary significantly across ethnicities. We tried to find mutations in FLG, SPINK5 and KLK7 genes from Korean AD patients and we aimed to develop a reverse blot hybridization assay(REBA) to apply to AD-related genes for the first time. Methods: We divided the AD subjects into moderate to severe AD and mild AD groups and also divided them into extrinsic and intrinsic AD groups. We checked on gene mutations using the REBA in AD and non-atopy control subjects. Results: The mutant type(MT) of KLK7 was significantly more frequent in AD subjects than in control and higher in the moderate to severe group compared to the mild group. The MT frequency was not different between the intrinsic and extrinsic AD groups. In the SPINK5mutation, AD subjects more frequently had the mixed type of 603-49A>T(Glu335Val), the MT of 1188T>C(His396His) and 2475G>T(Glu825Asp) compared to control, but there was no difference between intrinsic and extrinsic AD. Among AD subjects, the moderate to severe AD group had more gene mutations compared to the mild group. Conclusion: We found a correlation between the KLK7 mutation, the mutations in 1188T>C and 2475G>T, and 603-49A>T of SPINK5and AD which have not been reported in Asians including Koreans. Above all things, we verified that the REBA can be applied to detect multiple barrier-related gene mutations in AD easily, simply, and accurately. Background: Diagnostic work-up in patients suffering life-threatening drug anaphylaxis is difficult in clinical practice owing to the low sensitivity of the laboratory tests and the risk of anaphylaxis using in vivo tests. Flow cytometry-assisted basophil activation test (BAT) is suggested a safe diagnostic method, although it is more expensive and technically challenging compared to conventional in vitro or in vivo tests. We sought to evaluate the diagnostic utility of this testing in clinical practice. Method: Nineteen patients with a drug-induced anaphylaxis were recruited. Basophil activation test, skin tests, and measurement of commercially available specific IgE to drugs were performed for diagnostic evaluation. A stimulation index≥2 and an absolute activated basophil percentage≥5 were considered positive response to BAT. Results: All patients met the FAAN/NIAID criteria for anaphylaxis. Causality assessment using the WHO-UMC classified them into the categories 'certain' or 'probable'. Male to female ratio was 1:1.1 and the mean age was 46.0 ± 12.0 yrs. Five patients presented severe anaphyalxis such as hypotension, hypoxia or loss of consciousness, and the others were moderate severity. The involved drugs were cephalosporin antibiotics in 9 patients, eperisone 2, ranitidine 3, and aminoglycoside, glimepiride, humalog insulin, paclitaxel, tradamol, propofol in one patient each. BAT using CD 63 marker was positive in 12 (63.2%), and negative in 7 patients, whereas BAT using CD203c was positive in 9 (47.4%) and negative in 10 patients. When both markers applied, 14 patients (70.0%) showed positive to BAT. Skin test was positive in 8 (47.0%), negative in 9, and nonapplicable in two patients. Conclusion: The BAT proves to be a useful diagnostic tool for druginduced anaphyalxis. In addition, this test can identify the causative drug in patients with negative skin test or unavailable to sIgE measurement. Background: Bacterial colonization of the infant gut begins at birth and the gut microbiota in infant was unstable. The initial gut microbiota plays an important role in the development of immnue system. Disruption of the gut microbiota has been linked to the development of allergic diseases. Especially, feeding method has a significant impact on allergic diseases. Objective: We investigated the composition of gut microbiota according to feeding method and the association with serum IgE in infants. Materials and methods: Fecal samples were collected at 6 month from 47 infants in the COCOA birth cohort. Microbiota characterization was performed by using 16S rRNA shotgun sequencing. Results: The species richness (alpha-diversity) was not different according to feeding method. The significant higher level of Firmicutes and lower level of Actinobacteria detected in mixed milk (breast and formula milk) feeding infants than breast milk feeding infants at phylum level. The proportion of Bifidobacterium was significantly reduced, while Clostridium_g4, Clostridium, and Clostridium_g6 were highly enriched in mixed milk feeding infant than breast milk feeding infant at genus level. And the level of Escherichiapositively correlated with the total serum IgE at age 1 year in mixed milk feeding infant, but not in breast milk feeding infant.


We report a 5 years old boy that developed anaphylaxis after eating gummy bears. He was referred for evaluation after 2 episodes of anaphylaxis after ingestion of gummy products. The first episode occurred within 10 minutes of consuming more than 1 package of Haribo Gold Bear Candy with development of diffuse urticaria and generalized rash, angioedema, and pruritus with wheezing. Approximately 2 months later, a second episode occurred after ingesting Mygummy fruit snack 1 package. Ten minutes after ingestion, he had generalized urticaria and erythema, which resolved after receiving antihistamine. Prick to prick skin testing of gelatin-containing gums (Haribo and Mygummy) soaked in water and porcine gelatin were positive reactions. And additional intradermal testing with a 1:100 gelatin was strongly reactive. ImmunoCAP testing showed an increasd IgE level to bovine gelatin, at 4.50 kUA/L(Porcine gelatin in not available in Korea. Mammalian gelatins are well known that there is crossreactivity). Double-blind, placebo-controlled food challenge is the gold standard for the diagnosis of food allergy. However, this was not conducted in this patient, because he had already had several reactions to foods that contained gelatin, including anaphylactic reactions, and he had evidence of specific IgE to gelatin, skin testing and intradermal test. The patent was advised to avoid all gelatin-containing food, medications, and vaccines. Asthma is a chronic inflammatory disease, in which the airway progressively undergoes structural changes collectively termed as airway remodeling. Severe refractory bronchospasm elicits mechanical stress of bronchial wall and it is responsible for airway inflammation and remodeling. In this study, we planned to examine the relationship between asthmatic lung functions and the serum folliculin level. Folliculin is released from bronchial epithelial cells in response to compressive stress, mimicking bronchospasm.


Results: We showed that alteration of filaggrin and corneodesmosin (CDSN) proteolytic processing was co-related with AD development. New-borne rat showed well-developed epidermis, which became thinner till 2 week-age when hair began to grow. After that, epidermal thickness gradually increased, which was co-related with expression of epidermal differentiation markers, suggesting of U-shape epidermal development. To investigate relationship between AD and epidermal development, neonate, 2 and 4 week-age rats were injected with capsaicin and AD symptoms were monitored. A more late injection produced earlier development of AD but AD symptoms were less severe and shorter duration, suggesting of stimulation in neonatal period potentiated AD symptoms. Subsequent immunohistochemical staining showed increase of Lgr6 expression, which is known as epidermal stem cell marker. Conclusions: These results suggested that postnatal epidermal development may influence on AD development. Background: Little is known regarding possible association between lung clearance index (LCI) monitoring the lung heterogeneity and asthma control and exacerbation. The aim of the study was to determine the relationship between LCI, level of asthma control, and the C-ACT (Childhood Asthma Control Test) score in asthma patients. Method: This study included 97 patients who visited the outpatient department and admitted to the Department of Pediatrics, the CHA Bundang Medical Center, CHA University from October 2013 to December 2014 due to asthma control and exacerbation. The level of asthma control was classified according to the GINA guideline and asthma exacerbation was applied to asthma patients who were hospitalized. We measured the baseline IOS (Impulse oscillometry system), FeNO (Fractional exhaled nitric oxide), spirometry, and LCI, and evaluated the C-ACT score for each subject. Results: Of the 97 subjects, the numbers of patients in the asthma control group, the partly controlled group, the uncontrolled group, and the asthma exacerbation group were 33, 23, 18 and 23, respectively. The mean age of each group was 7.64 ± 2.66 years; there was no statistical difference across the groups (P=0.733). The Spearman correlation coefficients revealed a significant correlation between C-ACT and LCI 2.5% (P=0.001) and Scond VT (P=0.003), but no significant correlation between C-ACT and FEV1 (r=0.136, P=0.08), FEV1/ FVC (r=0.086, P=0.47), Rrs5 (r=0.000, P=0.998), Xrs5 (r=0.017, p=0.872) Z score, and FeNO (r=0.015, P=1.00). There were significant differences in LCI 2.5% (P<0.001), ScondVT (P<0.001), FEV1 (P<0.001), and FEV1/FVC (P=0.010), but no difference in Rrs5 (P=0.949) and Xrs5 (P=0.077) between the controlled group and the uncontrolled group. Conclusion: LCI and Scond VT were closely correlated with the C-ACT score and were good parameters in differentiating the level of asthma control. Background: Chronic inflammation of the airways and airway hyperresponsiveness (AHR) are key pathological features of asthma. The fraction of exhaled nitric oxide (FeNO) is closely related to eosinophilic airway inflammation and corticosteroid responsiveness. AHR is being used as an indirect marker of the degree of airway inflammation, and AHR to mannitol is more closely related to airway inflammation compared with AHR to methacholine. We sought to evaluate the association between FeNO and AHR in adults with and without asthma. Methods: In 304 patients with symptoms suggestive of asthma, FeNO and AHR to mannitol or methacholine were measured. A total of 180 who underwent both tests were analyzed and were divided into four groups : low (<25ppb)/high FeNO and with/ without AHR. Results: FeNO and response to mannitol was measured in 90 patients (group±), and FeNO and response to methacholine in 90 (groupII). Current asthma was diagnosed in 31 (group±, 34.4%) and 37 (groupII, 41.1%). In non-asthmatics, those with low FeNO/-AHR, low FeNO/+AHR, high FeNO/-AHR, high FeNO/+AHR was 78%, 1.7%, 18.6%, 1.7% in group ±; 66%, 0%, 34%, 0% in groupII. Of the asthmatics, 45.2%, 3.2%, 12.9%, 38.7% in group±; 27%, 24.3%, 8.15, 40.6% in groupII, and neither showed significant difference in atopy, duration of asthma, use of inhaled corticosteroid, blood and sputum eosinohils with regard to distribution of FeNO or AHR, except only in FEV1. A significant correlation was observed between log FeNO and log response-dose rate (RDR) mannitol (r=0.411, P=0.024) and also between log FeNO and log RDR methacholine (r=0.336, P=0.042) in only asthma patients. Conclusions: In asthma patients, the association between FeNO and AHR was stronger in mannitol than in methacholine. However, a significant proportion of patients had high FeNO and no AHR to mannitol and low FeNO and AHR to methacholine.

Comparison of Methacholine and Mannitol to Predict Exercise-Induced Bronchoconstriction in Children with Asthma

Background: Bronchial hyper-responsiveness (BHR) can be assessed by performing bronchial provocation tests (BPTs) with direct stimuli such as methacholine, or indirect stimuli such as mannitol. The aim of this study was to examine the diagnostic properties of methacholine and mannitol challenge to predict exercise-induced bronchoconstriction (EIB) in athmatic children. Methods: Eighty-nine asthmatic children between 6 and 15 years old were enrolled. Exercise challenges were conducted in all subjects. 72 subjects underwent methacholine BPTs and 36 subjects underwent mannitol BPTs. 18 subjects underwent both mannitol and methacholine BPTs. BHR to exercise was defined as a ≥ 15% fall in FEV1 after exercise, to methacholine a PC20 ≤ 25 mg/ml and to mannitol a 15% fall in FEV1 at ≤ 635 mg. Results: Thirty-seven (41.6%, 37/89) subjects with asthma had a positive exercise challange test. The maximum decreases in %FEV1 after exercise were positively correlated with mannitol PD15 (r=-0.540, p=0.038) but not correlated with methacholine PC20 in asthmatics with EIB. The sensitivity of methacholine to identify EIB was 93.3% (28/30) and the specificity was 52.4% (22/42). The sensitivity of mannitol was 66.7% (14/21) and the specificity was 40.0% (6/15). Conclusion: The maximum decreases in %FEV1 after exercise was significantly correlated with mannito PD15 but not with methacholine PC20. However, methacholine is more sensitive than mannitol to identify EIB in asthmatic children. Background: Human metapneumovirus (HMPV) and respiratory syncytial virus (RSV) share some epidemiological and clinical characteristics; however, few studies have examined whether these viruses induce similar cytokine responses. This study compared cytokine profiles in HMPV and RSV patients to investigate their inflammatory pathways. Methods: 128 nasopharyngeal aspirate specimens were collected from 128 pediatric patients hospitalized with acute respiratory infection including wheezing and tested for 7 common respiratory viruses. They were divided into HMPV (n=27) and RSV groups (n=101). Th1(IFN-γ), Th2(IL-4, IL-13) and Th17(IL-1β) cytokine profiles were analyzed.

Analysis of Follow-up Results of Mannitol Challenge Test in Asthma Patients

Background: Asthma is characterized by chronic inflammation associated with airway hyperresponsiveness (AHR) which is measured using bronchial challenge testing. Mannitol as an indirect challenge has showed better reflect the complex effects of inflammation compared with direct challenges, and which is simple, safe, and more practical to use. Following airway hyperreactivity may be a useful strategy in asthma management because hyperreactivity may be abnormal even in patients with mild asthma and normal lung function. Airway hyperreactivity may better reflect airway inflammation and risk for deterioration than dose lung function or asthma symptoms. We investigated to analyze the follow-up results of mannitol challenge tests in asthma patients. Methods: A total of 59 asthmatics repeated mannitol tests at Dong-A university hospital from May 2010 to February 2015. We compared the clinical characteristics between negative conversion and persistent AHR group. Results: Fifty-three (89.9%) showed AHR to mannitol at initial test, 28 (47.5%) of whom had no AHR (negative conversion, groupI) and 25 (42.4%) had persistent AHR (group II) at follow-up test. Six had no AHR at initial test, 2 had response to mannitol at follow-up test. There were no significant differences in sex, age, smoking habits, levels of eosinophil of serum and sputum, and baseline lung function. A longer duration of asthma and high frequency of asthma exacerbation was observed in group IIthan in group I, while the proportion of atopy and steroid-naïve patients were higher in group I. Total IgE and sputum eosinophil was much more decreased in group I compared with group II. Conclusions: In this study, 42.4% of asthma patients showed persistent AHR to mannitol. The negative conversion group of AHR may be associated with atopy, history of no ICS use, and improving of eosinophilic inflammation.


The Relationship Between Airway Hyperresponsiveness to Mannitol and Atopy in Asthmatic Children Woo-Hyeok Choi, Heysung Baek Kangdong Sacred Heart Hospital, South Korea Correspondence: Woo-Hyeok Choi -Kangdong Sacred Heart Hospital, South Korea World Allergy Organization Journal 2016, 9(Suppl 1):A428 Aim: The relationship between airway hyperresponsiveness (AHR) and atopy has been previously investigated, but there are still some issues to be clarified. The aim of this study was to assess the link between AHR to mannitol and atopy in asthmatic children. Methods: We evaluated 70 children with asthma, aged six to 16years-of-age, using skin prick tests (SPTs), serum total and specific immunoglobulin E (IgE) levels. Pulmonary function tets were performed: baseline, postbronchodilator inhalation and mannitol inhalation. The response to mannitol was expressed as the dose causing a 15% decrease in forced expiratory volume in one second (FEV1) (PD15). Atopy as the presence of at least one positive allergenspecific IgE test result (IgE ≥0.35 kU/l) or a finding on SPT. Results: 49 subjects (70%) with asthma showed a positive result in mannitol bronchial provocation test (BPT). In the mannitol BPT-positive group, 43 (43/49, 87.8%) subjects were diagnosed to atopy, In the mannitol BPT-negative group, 20 (20/21, 95.2%) subjects were diagnosed to atopy. There was no significant difference in atopy prevalence between mannitol BPT-positive and BPT-negative group. We found a correlation between mannitol PD15 and serum total IgE (r= -0.326; p=0.031). Conclusion: In children with pediatric asthma, we could not find a significant correlation between AHR to mannitol and atopy prevalence. Acetaminopen is one of the drugs most commonly used in intentional self-poisoning. N-acetylcysteins (NAC) is an effective antidote for acetaminophen overdose, which is usually given intravenously for 20-36 hour. When used intravenously, NAC can cause anaphylactoid reactions. Most of the adverse reactions are cutaneous manifestation involving flushing, pruritus, rash and urticaria. However, a few are systemic reactions, such as bronchospasm and hypotension. The etiology of the anaphylactoid reaction is not entirely understood, and the data are conflicting. No study has been conducted to evaluated the IgE response to rule out a true anaphylactic reaction to intravenous NAC. They typically occur within 15-60 minute after NAC infusion and appear to be dose related rather than true anaphylaxis. We report a case of anaphylactoid reactions to NAC has not yet been reported in Korea. A 17-year-old female was admitted via emergency department. She had 2-year history of depression. She ingested 20 tablets of Gewori-n®(isoporylantipyrine 150mg, acetaminophen 300mg) in a suicide attempt precipitated by a family quarrel. She suffered from dizziness and vomiting. Gastric lavage was done and then she was immediately treated with NAC. The standard regimen consists of intravenous infusion of NAC 150 mg/kg as a bolus, 50 mg/kg over 4h and repeated infusions of 100 mg/kg over 16h until three consecutive recovering values of the INR have been demonstrated. Immediately after infusion of NAC, she developed generalized urticaria, nausea, vomiting, chest tightness, dyspnea, and hypotension. Administration of NAC was stopped, epinephrine and antihistamine was administered. Additionally activated charcoal was used to prevent drug absorption. Laboratory abnormalities was not seen including serum tryptase. She recovered completely without any sequelae within 24hours. Background: Recently, we found prenatal maternal depression and anxiety were related to their offspring's respiratory infection and atopic dermatitis in infancy. Psychological stress should be considered an important programming factor for wheezing and lung development in early life. Moreover, genetic susceptibility influences the effects between offspring's health and maternal prenatal distress. Objective: To investigate whether prenatal maternal distress is associated with offspring's recurrent wheezing (RW) and GSDMB polymorphism influence this relationship in early childhood. Methods: The study population consisted of 1074 mother baby dyads recruited from COCOA birth cohort study. Prenatal maternal distress was evaluated by self-reported questionnaires at 36 th weeks of pregnancy. Center for Epidemiological Studies-Depression-10 (CESD-10) and State-Trait Anxiety Inventory-Trait subscale (STAI-T) were used to measure maternal depression and anxiety, respectively. Genotyping for GSDMB (rs4794820) performed by TaqMan assay. Diagnosis of RW was assessed by parental report of a physician's diagnosis at 6 months, 1, 2, and 3 year of age and RW was defined as ≥3 reports of wheezing in the first 2 years of life. We also used Cox regression to estimate the association between prenatal maternal distress and offspring's RW. Results: The cumulative incidence (CI) of RW was 18.9% by age 2. Prenatal maternal depression (aOR 2.75, 95% CI 1.28-5.93) and anxiety (aOR 2.83, 95% CI 1.09-7.35) increased their offspring's RW by age 2. The hazard ratio (HR) of having a RW up to 3 years of followup was 1.43 (95% CI 1.08-1.90) for depression and 1.63 (95% CI 1.21-2.20) for anxiety. Furthermore, the GA and AA genotypes of GSDMB was associated with a higher risk of RW. With GSDMB GA and AA genotypes, prenatal maternal depression (aOR 8.21, 95% CI 2.51-26.86, p for interaction 0.75) and anxiety (aOR 20.94, 95% CI 2.36-186.40, p for interaction 0.34) increased the risk of offspring's RW. Conclusion: Prenatal maternal depression and anxiety increased the risk of RW in early childhood. In addition, prenatal maternal depression and comorbid anxiety was associated with a higher risk of offspring's RW. The effect of maternal prenatal distress on the development of RW may be modified by GSDMB polymorphism although no significant interaction was found between prenatal distress and GSDMB. Our findings suggest that preventive strategies for reduction of prenatal distress may improve the risk of RW in the offspring. Introduction: Vitamin D has emerged to play a key role in the allergic disease by influencing to the immune system. Some studies had suggested a relationship between vitamin D status and allergic rhinitis, and others did not. We aimed to systematically review observational studies investigating the level of vitamin D on the prevalence of the current allergic rhinitis (AR) and the development of AR. Methods: We used standard Cochrane systematic review methodology. We searched MEDLINE, EMBASE, the Cochrane Library and KoreaMed to February 28, 2015. We put no restrictions on language or year of publication in our search. Two reviewers completed in duplicate and independently study selection, data abstraction, and assessment of risk of bias. We selected the studies about the current 25-hydrohyvitamin D (25OHD) levels and the prevalence of the current AR, and the other was about the 25OHD levels of cold blood or previously sampled serum and the development of AR. Results: We selected 10 cross-sectional studies about the current 25OHD levels and the prevalence of the current AR and 6 prospective studies about the development of AR relating with the previous 25OHD levels. Meta-analysis was performed to pool odd ratios from 10 cross-sectional studies ( Discussion: Available evidence from this meta-analysis suggests that the 25OHD level may not relate with neither the prevalence of the current AR nor the development of AR. Since these studies were very heterogeneous and the retrospective or the observational cohort studies, large randomized controlled trials are needed to determine whether vitamin D supplementation may be beneficial in the prevention of AR. Background: Impulse Oscillometry (IOS) was developed as a noninvasive method to evaluate lung function by measuring respiratory resistance and reactance. Respiratory resistance and reactance were measured over tidal breaths (whole-breath analysis) and measured separately during inspiration and expiration (inspiratory-expiratory analysis). It was known that reactance from inspiratory-expiratory analysis can detect expiratory flow limitation. We investigated characteristics of inspiratory-expiratory measurement obtained by IOS in children with asthma. Methods: We enrolled 96 children with asthma (66 male) and 30 healthy controls (16 male) aged 4 to 18 yrs. All children with asthma were diagnosed in accordance with ATS/ERS guideline. Spirometry and whole-breath and inspiratory-expiratory impulse oscillometry were performed in all enrolled children. The measurements were assessed in asthmatic children compared to control subjects. Results: In whole-breath IOS analyses, asthmatic children had increased resistance at 5Hz (0.82 ± 0.3 vs. 0.69 ± 0.2 kPa/L/s, P = 0.009), increased R5-R20 (0.64 ± 0.17 vs. 0.54 ± 0.15 kPa/L/s), decreased reactance at 5 Hz (-0.42 ± 0.2 vs.-0.3 ± 0.14 kPa/L/s, P = 0.001), and increased reactance area (AX) (3.3 ± 1.8 vs. 2.3 ± 1.2 kPa/ L, P = 0.001) than control subjects. In inspiratory-expiratory IOS analysis, expiratory AX was higher than inspiratory AX in both asthmatic children (3.5 [2.4 -4.8] vs. 2.8 [1.8 -3.7 ] kPa/L, P < 0.001) and control subjects (2.2 [1.5 -3.4 Conclusions: Children with asthma significantly differed from healthy controls in whole-breath impulse oscillometry. Larger inspiratoryexpiratory variation in AX analysis asthmatic children than control subjects could reflect airway narrowing on expiration in childhood asthma. Keywords: Impulse oscillation system, Asthma, whole-breath analysis, inspiratory-expiratory analysis


Objective: Diagnosis of asthma is challenging in preschool children who wheeze. The Asthma Predictive Index (API) is used as a tool to predict asthma and decide whether to initiate controller therapy in preschool children. The aims of this study were to investigate whether the API was associated with doctor's diagnosis of asthma in preschool children with recurrent wheeze and find the most relevant criteria to asthma. Methods: We performed a population-based, cross-sectional study with 933 children aged 4-6 years. A total of 900 children completed a modified International Study of Asthma and Allergies in Childhood questionnaire and 121 children with recurrent wheeze were enrolled. Recurrent wheeze was defined as having a lifetime wheeze more than 3 times. Results: The prevalence of doctor's diagnosis of asthma was 39%. The percentage of children who met the API was 79.5% (major; 64.4%, minor; 57.5%). Positive API showed tendency of association with doctor's diagnosis of asthma in preschool children with recurrent wheeze (OR; 4.69, 95%CI; 0.97-22.61). Among the API criteria, only doctor's diagnosis of allergic rhinitis (AR) was significantly associated with asthma (OR; 4.16, 95%CI; 1.86-9.30). Conclusions: Doctor's diagnosis of AR is likely to have the highest association with asthma among the criteria of API in preschool children with recurrent wheeze. Background: Respiratory syncytial virus (RSV) is the most common cause of lower respiratory illness (LRI) during infancy and early childhood. RSV has been reported to induce Th2 immune response with increased IgE production during acute infection. We aimed to investigate the relationship between serum total IgE levels and clinical characteristics in the children with RSV-associated LRI (RSV-LRI). Methods: One hundred and seven children under 3 years of age who were admitted with RSV-LRI (bronchiolitis and/or pneumonia) were enrolled. The patients were divided into 2 groups according to their total serum IgE levels on admission: High IgE group (N=39) and normal IgE group (N=68). High IgE levels were defined as values higher than 2 standard deviations (SDs) from the age-matched mean value. The medical records of the patients were investigated to determine if there was any difference in demographic characteristics, clinical and laboratory findings during admission, and recurrence of wheezing within 1 year after discharge between these 2 groups. Among 107 patients, 76 had LRIs for the first time in their lives, from whom we re-analyzed the data in relation to IgE levels. Additionally, difference between children with isolated RSV infection (N=107) and mixed infection with other viruses (N=88) was examined. Results: Median age was 15 months in high IgE group and 5.6 months in normal IgE group (P<0.001). Male preponderance was observed only in the high IgE group (P<0.01). The frequency and duration of fever, severity of symptoms, and concurrence of respiratory difficulty were significantly higher in high than normal IgE group (P<0.05). There was no difference in admission days and parental allergic diseases. Nearly same findings were observed in re-analysis of data from the patients with the 1st RSV-LRIs, but recurrence of wheezing after discharge was significantly higher in high IgE group (P<0.05). The children with isolated RSV infection showed more frequent and prolonged wheezing than those with mixed infection. Conclusions: In our study, the children who presented with high serum IgE levels during RSV-LRI had more severe symptoms comparing with those with normal IgE levels. Our results suggest that increased Th2 immune response induced by acute RSV infection might be associated with severe clinical presentation of LRI. Pollen is closely related to health issues such as allergenic rhinitis and asthma as well as intensifying atopic syndrome. Information on current and future spatio-temporal distribution of allergenic pollen is needed to address such issues. In this study, the Asian Dust Aerosol Model 2 (ADAM2) was utilized as a base modeling system to forecast pollen dispersal from oak trees. Pollen emission is one of the most important parts in the dispersal modeling system. Areal emission factor was determined from gridded areal fraction of oak trees, which was produced by the analysis of the tree type maps (1:5000) obtained from the Korea Forest Service. Daily total pollen production was estimated by a robust multiple regression model of weather conditions and pollen concentration. Hourly emission factor was determined from wind speed and friction velocity. Hourly pollen emission was then calculated by multiplying areal emission factor, daily total pollen production, and hourly emission factor. Forecast data from the UM LDAPS (Unified Model Local Data Assimilation and Prediction System) was utilized as input. For the verification of the model, daily observed pollen concentration from 12 sites in Korea during the pollen season of 2014. Although the model showed a tendency of over-estimation in terms of the seasonal and daily mean concentrations, overall concentration was similar to the observation. Comparison at the hourly output showed distinctive delay of the peak hours by the model at the 'Pocheon' site. It was speculated that the constant release of hourly number of pollen in the modeling framework caused the delay. Background: The objective of this study is to investigate the shortterm effects of meteorological factors and air pollutants on the severity and persistence of atopic dermatitis (AD) symptoms in infants and young children. Methods: In the present study, 176 infants and young children with AD aged under 6 years living in Seoul Metropolitan Area in Korea were enrolled and were followed for 17 months between August 2013 and December 2014. AD symptoms describing the degree (a scale of 0 to 4) of itching, sleep disturbance, erythema, dryness, oozing, and edema were recorded on a daily basis. Generalized linear mixed models (GLMM) with binomially distributed errors were used to estimate of the effects of meteorological factors (daily mean temperature, relative humidity, and diurnal temperature range (DTR)) and air pollutants (PM 10 , nitrogen dioxide (NO 2 ), and ozone) on the AD symptoms. Potential confounding factors including age, sex, symptom severity (SCORAD) at initial visit, the presence of fever, and day of week were controlled. Moving averages up to previous 5 consecutive days were used to represent the lag effect of meteorological variables and air quality on AD symptoms. Results: Of the 34,978 person-days, the rate of positive AD symptoms was 44.12% during the study period. Increase in daily mean temperature by 5°C and relative humidity by 5% were significantly associated with 13.36% (95% CI: 11.03 to 15.63) and 2.70% (95% CI: 1.25 to 4.14) of decrease in AD symptoms, respectively. Particularly in spring, an increase in 5°C of DTR was related with 53.26% (95% CI: 12.39 to 108.99) of increase in AD symptoms when the effect of moving average from the same day through previous three consecutive days was estimated. An increase in 10 μg/m 3 of PM 10 concentration increased 2.95% of AD symptoms (95% CI: 1.35 to 4.5). An increased concentrations in 10 ppb of NO 2 and ozone were associated with increase in AD symptoms by 4.31% (95% CI: 0.75 to 7.99) and by 5.55% (95% CI: 2.78 to 8.39), respectively. The hazardous effect of PM 10 on AD symptoms was noted significantly in spring and those of NO 2 and ozone were found in winter. Conclusions: Short-term exposure to temperature, humidity, and air pollutants are strongly associated with the AD symptoms. Clean air quality is essential for the appropriate management of AD symptoms in children. Background: Pulmonary fibrosis is a lung disease which is hardly to cure and has a high mortality rate. Recently, the studies suggested that TGF-β plays a central role in the pathogenesis of pulmonary fibrosis. Compound V, isolated from natural source, is used as the antioxidant, however, we find this compound can suppress the expression of collagen on TGF-β treated lung fibroblast cell line. Therefore, we would like to realize the influence of this compound on lung fibrosis animal model. Methods: To establish pulmonary fibrosis of animal model, we treat mice with bleomycin on day 0 by intratracheal injection, so as to treat compound V by oral daily from day -7 to day 7.Afterwards, we collected mice bronchoalveolar lavage fluids, spleen and lung section and observed the effect of compound V on pulmonary fibrosis of animal model through ELISA, histology and SCIREQ(the machine which detect mice lung function). Results: Compound V can improve lung fibrosis in physiology significantly by SCIREQ. The collagen expression in lung sections also decreased apparently. Conclusions: These findings indicate that compound V can reduce collagen expression on bleomycin-induced pulmonary fibrosis animal model. We will further figure out the mechanism of compound V on pulmonary fibrosis. Objective: To explore the vitamin D(Vit D) level and analyse the correlation with immunoglobulin E (IgE) in children with allergic respiratory diseases in Guangzhou China. Methods: 40 children(4.6±2.6yr) from 209 patients with allergic respiratory diseases(Jun to August) in 2013 and 2014 as the experimental group, detecting 11 kinds of serum specific IgE and total IgE antibody. 40 health children as control group,both using Elecsys to detect the Vit D concentration. Results: The Vit D average concentration of the experimental group is 35.4±9.7ng/ml(Male 35.4 ±10.3ng/ml,Female35.3±9.1 ng/ml), the control group is 33.3±9.8 ng/ml(Male 30.4±8.4 ng/ ml, Female36.3±10.4 ng/ml), there were no significant difference between two groups and sex. Age and Vit D concentration were negatively correlated(experimental group:r s =-0.605, p=0.000; control group: r s =-0.328, p=0.039). In experimental group, levels of total and Dp specific IgE were negatively correlated with serum concentration of vitamin D (r s =-0.579, p=0.001; r s =-0.334, p=0.035, respectively), level of cow's milk specific IgE was positively correlated with serum concentration of vitamin D (r s =0.544, p=0.000). Using multivariate linear regression analysis after adjusted with sex and age,there is significant association between the total IgE and serum vitamin D (B -4.386, 95%CI -8.488--0.285, p=0.037) in 40 children with allergic respiratory diseases, and also significant association between both total and Dp specific IgE and serum vitamin D (B -9.56, 95%CI -15.405--3.715, p=0.003; B -0.857, 95%CI -1.561--0.153, p=0.02, respectively) in 21 children with Dp sensitization. Conclusions: Serum Vit D level could be associated with an increased risk of allergic disease development. Introduction: Eosinophilic gastroenteritis(EG) is a rare disease with various gastrointestinal symptoms, and characterized by prominent eosinophilic infiltration. EG has heterogeneous clinical manifestations and its etiology remains unknown. We here describe two cases of EG associated with allergic disease. Cases: First case is a 35-year-old man who visited our emergency room complaining abdominal pain, diarrhea, and nausea for the last 5 days after upper respiratory infection. He had an experience of being treated for EG and pancreatitis with ascitis 10 years ago. In his laboratory finding, peripheral WBC count was 21,600 mm 3 with 60% eosinophilia. After endoscopic study and abdominal computed tomography, he was diagnosed with EG and referred to allergic clinic. He didn't complain any food related allergy symptoms except intermittent mild rhinitis symptoms and cough. He exhibited elevated serum total IgE level and positive responses to house dust mite and Japanese hop pollen on skin prick test. Lung function test showed obstructive pattern with positive response to bronchodilator. Finally, he was diagnosed as EG with allergic rhinitis and bronchial asthma. He was treated with prednisolone therapy for EG, recommended to take anti-allergic medication as well. The second case is a 42-year-old female with nausea and indigestion of several months. She has been treated for eosinophilic gastritis on the endoscope for one month at another hospital. But, the symptoms were persisted and more aggravated after milk ingestion. Moreover, urticarial was newly developed form 3 weeks ago. WBC count was 6750 mm 3 with 5.5 % eosinophilia. Skin prick test showed positive response to house dust mite and grass pollen. High serum specific IgE levels to milk were noted. She was diagnosed as EG with food allergy and urticaria. She was recommended avoiding milk with oral antihistamine therapy. Three months after food restriction and medication, her symptom was improved and endoscopic study was normal. Conclusion: We report two cases of EG associated with respiratory and food allergy, respectively. Although EG has various clinical manifestation, our report suggests that the possibility of co-existence of EG and allergic disease should be considered. There are many studies that investigate genetic factors that cause predisposition to drug hypersensitivity. However, most studies have focused on specific phenotypes or drugs. Thus, we planned to perform a genome-wide association (GWAS) study to discover the common genetic markers associated with both in immediate and delayed drug hypersensitivity reactions.

A First Case of Lymphocytic Interstitial Pneumonitis in Healthy Child

Ji-in Jung, Ha-Su Kim, Hyun-a Kim, Jin-a Jung Dong-a University Hospital, South Korea Correspondence: Ji-in Jung -Dong-a University Hospital, South Korea World Allergy Organization Journal 2016, 9(Suppl 1):A445 Introduction: Lymphocytic interstitial pneumonitis(LIP) is an uncommon histopathologic entity characterized by infiltration of the interstitium and alveolar spaces of the lung by lymphocytes, plasma cells and other lymphoreticular elements. LIP in children has been most commonly associated with human immunodeficiency virus(HIV) infection. We report a first case of LIP in a HIV-negative healthy adolescent. Case Report: An 13-year-old boy represented with pneumonia on chest X-ray in routine health examination. He had no respiratory symptoms and there was no abnormal findings on physical examination, A chest CT showed multiple ill defined centrilobular nodules and peribronchial air space nodules with mild volume loss in RLL. There was no increase of IgG Mycoplasma pneumoniae antibody titer in 3 serial tests between 7 days interval. Tuberculin skin test and Tbc specific antigen induced interferon-gamma(IGRA) test were negative. Chest x-ray in regular intervals during 6 months showed improvement of pneumonic consolidation, but new pneumonic consolidation on other site. Therefore, open lung biopsy was performed, and it showed diffuse interstitial lymphocyte infiltrate. The lung tissue was negative for EBV by DNAPCR and EBV serology showed all-negative. Serum immunoglobulins were normal and autoimmune studies were negative. The total lymphocyte count and lymphocyte subset were normal. He was started on oral prednisone (1 mg/kg/day) for 2 months and the chest x-ray returned to normal. Then he was tapered oral prednisone for 2 months and follow-up chest CT showed no abnormal finding. He has been followed for 8 months after diagnosis without complications. Conclusion: We report a first case of HIV-negative, EBV-negative LIP in a healthy child. Background: Epidemiological data from cohort studies indicate associations between Caesarean section and development of allergy in infants. Besides the delayed colonization of commensal bacteria (which in turn affect the immune system development), the cytokine profile in C-section delivered infants could be different, which may be implicated in infant's immunity. Methods: A clinical study was conducted at KK Women's and Children's Hospital, where 55 cord blood samples from Caesarean section-delivered infants were collected to evaluate the response to allergens in the cord blood cells. Freshly isolated cord-blood mononuclear cells (CBMCs) were cultured in a 96-well plate at 100,000 cells per well (in triplicate per condition) and stimulated with the extracts from either one of major house dust mite species: Blomia tropicalis (BloT) and Dermatophagoides pteronyssinus (DerP). Phytohemagglutinin (PHA) and Lipopolysaccharide (LPS) were used as positive controls. The supernatants of these cutures were harvested after 5-day stimulation and were analyzed using the Bio-Plex Pro TM Human Cytokine assay. The production of IL-5, IL-13, IFN-gamma and TNF-alpha by the allergen-stimulated CBMCs were analyzed.
Results: DerP stimulation induced a higher response as compared to BloT stimulation. Following DerP stimulation, the median value of IL-5 was 2.5 pg/mL (0-172 pg/mL), IL-13 -9.1 pg/mL (0-158 pg/mL), IFNgamma -321 pg/mL (69-1978 pg/mL) and TNF-alpha -1393 pg/mL (74-5658 pg/mL). Among the 55 analysed subjects, while 3 subjects (5%) showed higher expression of IFN-gamma (above 1000 pg/mL) and lower expressions of IL-5 and IL-13 (both below 20 pg/mL), 6 subjects (11%) displayed higher expressions of IL-5 and IL-13 (both above 20 pg/mL). TNF-alpha levels were detected high in most subjects. Of note, no correlation between strong production of T H 2-like cytokines (IL-5 and IL-13) and parental allergy history was observed. Conclusion: We observed a strong production of T H 2-like cytokines in 11% of C-section-delivered infants upon DerP stimulation. Interestingly, these infants did not have any history of parental allergy. This finding might indicate in utero sensitization of these infants. The TH2-like cytokine profile in cord blood might be useful as an early sign of atopic manifestations in future. We plan to follow-up these subjects in order to monitor the development of allergic response later in life.


This research was supported by a grant from Ministry of Food and Drug Safety to operation of the regional pharmacovigilance center in 2015. Background: IL-23 has been postulated to be a critical mediator contributing to airway inflammation. House dust mite (HDM) is one of the most common allergens. However, the role of IL-23 in HDMinduced mouse model is not well understood. Objective: To evaluate roles of IL-23 in HDM-induced allergic asthma model, particularly during the allergen sensitization period. Methods: BALB/c mice were repeatedly administered with HDM intra-nasally, to develop acute allergic asthma model. Anti-IL-23p19 antibody was given during HDM sensitization period. And we analyzed the activation of DC in LDLN after last sensitization. In addition, to evaluate the roles of IL-23 at bronchial epithelium contacted with HDM, in vitro BEAS-2B cell experiments were done with HDM stimulation and/or anti-IL23 antibody treatment. Results: Anti-IL-23 antibody treatment during allergen sensitization significantly diminished several phenotypes of allergic asthma; particularly, eosinophilic inflammation and airway hyperresponsiveness were markedly reduced. In bronchoalveolar lavage fluid, IL-4, IL-5, and IL-17A cytokine levels were significantly reduced in anti-IL-23 antibody treated mice. And the activation of DC in LDLN was significantly reduced by anti-IL-23 after last sensitization. In in vitro study, anti-IL-23 treatment prevented pro-inflammatory and pro-allergic cytokine responses in HDM-stimulated BEAS-2B cells.
Conclusion: IL-23 may play a significant role in allergic asthma during allergen sensitization period. Particularly, it may be significantly involved in allergen-contacted epithelial cell responses finally leading to allergic sensitization. Background: High prevalence rates of asthma and allergic rhinitis have recently been shown in South Korea. For better prevention of development or exacerbation of both allergic diseases, the secondary prevention from symptoms of atopic dermatitis (AD) could be effective, in the aspect of "allergic march". For this reason, we aimed to explore how the variation of indoor risk factors may be linked with the change of symptoms of AD or development of asthma and/or allergic rhinitis. Methods: We recruited homes of AD patients aged with around 24 months old, along with SCORing Atopic Dermatitis (SCORAD) Index of greater than 25 through the both Environmental Health Centers for Asthma and Atopic allergy. Total volatile organic compounds (TVOC), formaldehyde (HCHO), airborne mold and bacteria, and particulate matter with diameter less than 10 mm (PM 10 ) were measured in their dwellings in both indoor and outdoor. Particularly, the levels of TVOC and PM 10 were monitored for 24 hrs using direct reading instruments as well. Results: Both environmental surveys were performed in a total of 51 houses. The mean age (± standard deviation, SD) and SCORAD Index of subjects was 2.2 ± 0.2 years old and 39.5±18.3, respectively. The geometric mean (GM) concentrations of airborne mold were 526.6-565.5 CFU/m 3 , which refer to above the recommended level of WHO. However, the corresponding value of airborne bacteria were below the Korean standard guideline (800 CFU/m 3 ). For exposure level of gaseous pollutants in indoor, TVOC and HCHO ranged from 566.6-748.3 μg/m 3 and 31.0-35.9 μg/m 3 , respectively, but the outdoor levels were 382.4-453.1 μg/m 3 ; for TVOC and 4.0-4.6 μg/m 3 for HCHO. The highest levels of TVOC and PM 10 monitored using each direct reading instrument were observed after midnight and in the evening, respectively. Conclusions: Our findings indicate that a comparable amount of bioaerosols and gaseous pollutants in indoor were observed in patient's dwellings. Particularly, different exposure patterns for particulate matter and TOVC were shown time -dependently, and so a proper prevention strategy should be prepared. Background: Peripheral blood eosinophilia is a common clinical manifestation which draws medical attention. However there are little reports on blood eosinophilia in the elderly. We aimed to investigate the normal ranges of blood eosinophils and associated factors including allergic parameters, using the dataset of a communitybased random elderly population in Korea. Methods: A cross-sectional analysis was performed using the database of Korean Longitudinal Study on Health and Aging, a community-based elderly cohort. The primary outcome was peripheral blood eosinophil counts and the upper limit of the 95% confidence interval for absolute count of blood eosinophil counts was calculated for normal ranges. Demographic, socioeconomic, metabolic, comorbidities, allergic parameters, and lung function were analyzed. Atopy was defined with skin test by positive to any of 12 common inhalant allergens. Allergic history and symptoms were assessed by questionnaires. Results: Cutoff value for blood eosinophilia was less than 406.6x10 3 / mL (n=1,000). The prevalence of eosinophilia (>500x10 3 /mL) and hypereosinophilia (>1,500x10 3 /mL) were 4.12% and 0.20%, respectively. In univariate analyses, blood eosinophil counts was significantly related to male sex, and smoking status. However, in multivariate analyses, the association of blood eosinophil count with male sex appeared to be at least partly dependent on smoking status. Other potential determinants (P<0.10 in univariate analyses) were body mass index, atopy, current wheeze, and physician-diagnosed asthma. In multivariate linear regression analyses, the relationships between blood eosinophil counts and potential determinant factors were examined. Conclusion: The normal range of peripheral blood eosinophils in the Korean elderly was ≤ 406.6 x10 3 /mL (upper 95th percentile), which was almost identical to the reference range in the literature. Smoking was a major determinant factor for eosinophilia, and explained the association of eosinophilia with male sex. Other determinant factors were body mass index, atopy, and asthma. These findings could suggest a potential role of blood eosinophils as an epidemiologic marker for atopy and asthma in the elderly population. Stevens-Johnson syndrome (SJS) is severe acute mucocutanous bullous disorders that are most commonly drug-induced. Antibiotics are the most common cause of SJS, followed by analgesics, nonsteroidal anti-inflammatory drugs, anticonvulsants, and antigout drugs. Methotrexate, a folic acid antagonist, has been used in the treatment of psoriasis, rheumatoid arthritis and neoplastic disease including leukemia and lymphoma. Its principal toxic effects are bone marrow suppression, gastrointestinal mucositis, hepatitis, renal impairment, and erythematous rashes. SJS has been reported in a few patients receiving intermediate or high dose methotrexate. Whether the epidermal necrolysis is an allergic or dose-related toxicity reaction is still controversial. We report a case of SJS in a patient receiving low dose methotrexate for psoriasis. A 67-year-old male presented with a generalized erythematous rash and erosion, and severe oral ulcers. He had started allopurinol and well tolerated for 1 year. The patient had a history of low-dose methotrexate treatment (5 mg/day) 6 days before the development of his complaints. On the second day after methotrexate treatment, erythematous itchy and edematous rash developed on his legs, which spread widely on his trunk and extremities with subsequent bullous formation. He suffered from aggravation of oropharyngeal ulcer. He was admitted to a local hospital and treated with systemic corticosteroids for 5 days. Skin lesions improved, but he was transferred to our hospital for persistent painful ulcer and odynophagia. He was treated with topical steroid for skin lesion and total parenteral nutrition had been started because he had difficulty in eating. He recovered gradually and was discharged with supportive therapy but without additional systemic corticosteroid.

Genetic Determinants for Lung Function Growth in Asthmatic Children

Methods: We conducted a retrospective analysis of medical records of 157 patients received AIT, and compared the clinical characteristics between conventional (CIT) and rush immunotherapy (RIT). A total of 56 were performed a questionnaire survey. Results: Of 157 patients, 108 (68.8%) were treated with CIT, and 49 (31.2%) with RIT. There were no significant differences in allergic diseases, allergens in immunotherapy, and the frequency of systemic adverse reactions during build-up phase. The rate of missing patients was higher in CIT than RIT (18.5% vs 10.2%). Patients initiation with AIT was mainly according to physician recommendation (76.3% for CIT vs 55.6% for RIT). Patients with RIT had personal insurance more and showed better treatment satisfaction than those with CIT. Concern about adverse events was the main reason for start CIT, while frequent hospital visits for start RIT. Conclusions: A majority patients initiated AIT according to physician recommendation and showed good treatment satisfaction. RIT may give better clinical outcomes than CIT. Background: Immune responses to staphylococcal enterotoxins may contribute to the pathogenesis of asthma. Objective: To investigate roles of staphylococcal enterotoxin B (SEB) in mouse asthma models Methods: BALB/c mice were intranasally sensitized with Dermatophagoides pteronyssinus (Der p) and/or SEB to develop acute asthma models. Mice were grouped to see effects of SEB and Der p interactions during the sensitization and challenge periods. Outcomes were evaluated for methacholine airway hyperresponsiveness (AHR), lung inflammatory cells, lung cytokines, serum IgE, and in vitro Der p-stimulated splenocyte responses. Results: Intranasal SEB exposure increased lung macrophage, lymphocyte, and neutrophilic infiltration; but SEB alone did not develop any typical asthmatic phenotypes. Effects of SEB on asthma phenotypes were the most evident when co-administered with Der p during the sensitization period, developing more AHR and lung eosinophilic inflammation on Der p challenge. Serum Der p specific IgE levels were also amplified by SEB co-sensitization. In in vitro Der p re-stimulation experiments, IL-5 and IL-13 responses were also increased in splenocytes from the mice co-sensitized by SEB and Der p. Conclusion: The present findings indicate the roles of SEB in Der p-induced allergic asthma, particularly during the sensitization period. Background: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare disease which can cause severe morbidity and mortality. We have reported DRESS syndrome was not more uncommon than generally recognized in the previous study. Objective: We investigated the clinical manifestation of DRESS syndrome and compared with previous data. Methods: A total of 100 patients were prospectively collected from October 2011 to March 2015 (period I, 43 months). We compared these data to those of 42 DRESS patients from September 2009 to August 2011 (period II, 24 months). Results: The most common causative drugs were antibiotics, followed by anticonvulsants and antituberculosis drugs in both periods (37%, 17%, 17% in period I vs 31%, 24%, 13% in period II, respectively). Eosinophilia in peripheral blood and hepatic involvement was more frequently noted in period II, while enlarged lymph nodes in period I significantly. The mean latency period was 32.6 ±107.5 days (range, 1-1095) in period I, and 20.2±24.3days (range, 2-120) in period II (P=0.255). The longest latency period was noted for the antituberculosis drugs, followed by anticonvulsants and antibiotics in both periods. Systemic corticosteroids were administered to 22 patients (20%) and 10 (22%) in each period. All the patients showed complete recovery in period ±, while 2 patients (4.4%) had poor outcomes. Conclusions: The clinical manifestation of DRESS syndrome was variable. Antibiotics were the most frequently implicated drugs and antituberculosis drugs had a long latency period. A majority of patients showed good clinical outcomes without administration of systemic corticosteroid.


Food allergy is one of the common allergic diseases in the world. Probiotics are shown to promote the endogenous host defense and modulate the host's immune responses to potentially harmful antigens. In this study, we first established a mouse model of food allergey by i.p. sensitization with OVA or β-lactoglobulin, and were orally challenged with protein allergen, OVA, or β-lactoglobulin in BALB/c mice. We found that the body weights and body temperatures immediately after food allergen challenged were significantly decreased as compared with the control mice. And the symptoms of food allergy, the levels of total IgE, allergen-specific IgE, IgG1, IgG2a, IgA of sera and the levels of IgE, IgA, IL-4 and IL-17 of intestine lavage fluids (ILF) of food allergen mice were significantly increased as compared with the control mice. After oral administration with 10 7 CFU Lactobacillus gasseri PM-A0005 (L. gasseri ) at the same time during food allergen sensitization and challenge, the body temperature, body weight, the levels of antigen-specific IgA of sera, and IL-10 concentration of the ILF, and the levels of IL-10, IL12, INF-γ, TGF-β of the culture medium and the cellular numbers of CD11c + CD103 + , CD11b -CD8a + dendritic cells (DCs), CD4 + FoxP3 + (Treg cells), CD4 + T bet + (TH1 cells) in the Peyer's patches and draining lymph nodes of L. gasseritreated mice were significantly increased as compared with the nontreated food allergy mice. In contrast, the food allergy symptoms, the levels of antigen-specific IgE, IgG1 of sera and the levels of total IgE, antigen-specific IgE, IgG1, α1-antitrypsin, IL-17, IL-6 of the ILF and the concentrations of TNF-α, IL-23, IL-6 of the culture medium and the cellular numbers of CD4 + RORγt + (TH17 cells), CD4 + GATA3 + (TH2 cells), lymphocytes proliferation and the intestinal inflammation of L.gasseri-treated mice with food hypersensitivity were significantly decreased as compared with the non-treated control mice. To further explore the anti-allergy effect of L. gasseri of dendritic cells (DCs) on food allergy development, bone marrow-derived dendritic cells (BMDCs) isolated from naïve mice were stimulated for 24 hrs with recombinant of L. gasseri. The PMA5P40-primed BMDCs were collected and adoptive transfer to mice sensitized and challenged with food allergens. These finding suggested that L. gasseri and recombinant of protein PMA5P40 have anti-allergy effect on the mice sensitized and challenged with food allergens, such as OVA and cow's milk. And this anti-allergic effect may be mediated through the tolergenic effect of dendritic cells that enhance immune-regulatory effect on T and B lymphocytes, which may have clinical application in patients suffered with food allergy. Background: Folate, a dietary methyl donor, is known to alter gene expression influencing immune system through epigenetic modification. However, the relationships between folate level and the risk of allergic and respiratory diseases in children are still unknown. Objectives: To investigate whether or not serum folate levels are associated with atopic biomarkers and also with the risk of allergic and respiratory diseases in children. Methods: Data of 462 children with complete information from a birth cohort in South Korea were available. Serum folate levels were analyzed at 24 months of age in children. Atopic biomarkers such as total Ig E, IL-10 and eosinophil counts were also measured at 24 months. Information on maternal demographic and obstetrical characteristics and that on children's allergic and respiratory outcomes was obtained from questionnaire. Results: Serum folate levels were inversely associated with eosinophil counts (r = -0.192, P < 0.001). Total IgE levels and eosinophil counts decreased significantly in the group whose serum folate was above the median value (17.6 ng/mL) compared to the other counterpart group (P = 0.013, P < 0.001 respectively). A multivariate logistic regression analysis revealed that folate level above the median value (17.6 ng/mL) was associated with a decreased risk for atopic dermatitis (AD) (adjusted odds ratio [aOR], 0.57; 95% confidence interval [CI], 0.34-0.95) at 24 months of age. However, no significant association was observed between serum folate levels and respiratory outcomes in children. Conclusions: Serum folate level is associated with a lower risk of developing AD in early childhood. Background: The dysregulated mucosal inflammation in chronic rhinosinusitis (CRS) is often difficult to control with pharmacotherapy alone. We sought to determine whether the immunomodulatory properties of vitamin D might have beneficial effects on CRS.
Methods: We performed a randomized, placebo controlled trial in adult subjects meeting the research criteria for CRS, with low serum vitamin D levels (<40 ng/mL), and having no contraindications to vitamin D therapy. Subjects were randomized to receive vitamin D (n=12) or placebo (n=12) for 12 weeks in addition to their standard regimen. Peripheral blood mononuclear cells (PBMCs) and nasal epithelial cells (NECs) were collected at the beginning and end of the trial and we analyzed the upregulation of molecules involved in mucosal immunity by RT-PCR. Clinical response was analyzed using SNOT-22 and the SF-36. Results: The Levels of vitamin D in the serum were elevated in the vitamin D group and unchanged in the placebo group. Cathelicidin, human b-defensin and autophagy related protein light chain 3 alpha (LC3A, a molecule involved in autophagy) were upregulated after vitamin D administration in PBMCs with similar results observed in NECs. There was no significant change in the upregulation of these mediators in the placebo group. No symptomatic changes were observed in SNOT-22 or SF-36 scores in either group. There were no side effects or adverse events during the study. Background: Systemic contact dermatitis (SCD) is an inflammatory skin disease that may occur in persons with contact allergy when they are exposed to the allergens systematically including orally, transcutaneously, per rectum, intravesically, intravenously, or by inhalation. The most common causes of SCD are drugs used both topically and systemically. Other causes are ubiquitously occuring haptens, such as the metals nickel, cobalt, gold, and chromate, and aromatic substances such as spices. SCD from plants has been seen following ingestion of various rhus preparations. In Korea, Rhus has been used as a folk medicine to cure gastrointestinal diseases and as a health food, it is common to observe patients with accidental or occupational Rhus dermatitis, and also SCD caused by ingestion of Rhus. Objective: We investigated the clinical features of SCD caused by Rhus. Methods: We conducted a retrospective analysis of 11 patients with SCD caused Rhus in Dong-A University hospital and Haeundae Paik Hospital. Results: Nine (81.8%) were women, and average age was 58.91 ±10.29 years (range 45-75). The way of Rhus ingestion was boiled chicken with Rhus (n=9, 81.8%), Rhus vegetables (n=1), and Rhus sap (n=1). All patients experienced generalized pruritus and erythematous maculopapular rash. The patients developed erythema multiforme (n=2), vesiculobullous lesion (n=3), urticaria (n=3), and angioedema (n=1). Extracutaneous symptoms were duodenal ischemia (n=1), hypotension (n=2), fever (n=4), and oral mucositis (n=1). The mean latency period was 1.45±0.69 days (range 1-3), and mean recovery times were 12.27±3.77 days (range [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] . Systemic corticosteroid was administered in 10 (90.9%) for 18.09±15.44 days (range 4-47). Conclusions: SCD from ingestion of Rhus showed various cutaneous manifestation mainly erythematous maculopapuar eruption, and also extracutaneous symptoms. Most of the patients recovered well with the treatment of systemic corticosteroids. Background: Atopic dermatitis (AD) is currently regarded as an allergic inflammatory disease. Many studies have shown AD to have multiple causes that activate complex immunological and inflammatory pathways. However, aeroallergens, and especially the house dust mite (HDM), play a relevant role in the elicitation or exacerbation of eczematous lesions in many AD patients. Accordingly, allergenspecific immunotherapy has been used in AD patients with the aim of redirecting inappropriate immune responses. Sublingual immunotherapy (SLIT) is especially preferred because of its easy application and safety. The aim of this study was to describe the effect of SLIT in patient with AD. Methods: Patients with AD who allergic to HDM were evaluated. Patients who allergic to HDM have been treated with SLIT for over 1yr. The effect of patients on clinical course of SLIT with Dermatophagoides pteronyssinus and Dermatophagoides farinae in a standardized extract was assessed and the side effect of SLIT were recorded. Results: The records of 20 patients (13 males and 7 females) were studied. The mean age for starting SLIT was 16.3 years (aged 6-36 years, median age 13years). Treatment was deemed effective or very effective in 70% of the patients. The majority of the patients were satisfied with their treatment, which was well tolerated. There were no serious side effects except transient nausea, abdominal pain and oral itching sensation in the first few days. SLIT had to be discontinued in 2 patients (10%) because of exacerbation of asthma and dermatitis. Especially, the compliance of patients with AD and allergic rhinitis were better than patients with AD only. Conclusions: SLIT reduces symptoms of AD, the amount of drug consumption and the progression of the disease. Especially, SLIT is recommendable to patients with AD and allergic rhinitis. We believe SLIT can be an alternative, safe treatment option for allergic AD refractory to long-term conventional treatment. Background: Adverse drug reactions (ADRs) frequently occur in hospital setting, and serious ADRs (SAEs) may threaten the patient's life and lead poor clinical outcome. Early detection and urgent medical intervention is required to prevent development of SAEs. This study was conducted to investigate the clinical characteristics of SAEs in a single university hospital. Methods: ADRs reported to hospital Pharmacovigilance Center were collected from Jan 2012 to Dec 2014, and cases of SAEs were selected. Clinical information was collected from electronic medical records. Results: A total of 283 (3.7%) SAEs among 7,629 ADRs were identified through spontaneous reporting system. A gradually decreased tendency in the frequency and incidence of SAE was noted from 2012 to 2014. SAEs were reported by doctors (40.6%), nurses (11.0%), and pharmacists (48.4%). ADR related-hospitalization or prolongation of existing hospitalization (53.2%) was the most common cause of SAEs, and other medically important event was the second cause. SAEs were developed from the injections (54.4%), PO medications (44.9%), and the patch type agents (0.7%). Antineoplastic agents (40.9%), anti-infectives (16.8%), and anti-tuberculosis drugs (6.9%) were the drug class commonly involved. White cell and RES disorders (21.6%) were frequently involved system organ classes, and skin and appendages disorders (16.4%) were the next. Leukopenia and neutropenia were the most frequently noted SAEs. Conclusion: Antineoplastic agents, anti-infectives, and anti-tuberculosis drugs can elicit SAEs most frequently. A decreased tendency for the development of SAEs was noted, and this might be result at least partly from the pharmacovigilance activity and ADR monitoring. Comprehensive prophylactic approaches will be required to prevent development of predicted SAEs, and to reduce the chance of unpredicted SAEs. Background. Allergic contact dermatitis is a common diagnosis in eyelid dermatitis. Sensitization to metals are prevalent in eyelid dermatitis and color cosmetic products are frequently suspected as the source of metal exposure. This study was performed to investigate the recent contact allergens for eyelid dermatitis and to assess metal contents in eye shadow products. Methods. Data were collected in the department of dermatology of Ewha Womans University hospital from December 1998 to February 2014. A total of 983 patients were patch tested during the period and 67 patients had eyelid dermatitis among them. To examine metal elements in color cosmetic products for eyes, randomly selected 10 eye shadows were analyzed. Results. Frequent allergens were metals, thimerosal, and phenylenediamine in patients with eyelid dermatitis. The sensitization rates of individual allergens were not significantly different between patients with eyelid dermatitis and without eyelid dermatitis. All 10 eye shadow products contained more than 5 ppm of at least one element, nickel, cobalt or chromium. Conclusion. Metals were top-rank allergens in eyelid dermatitis and eye shadow products contained significant amount of nickel, cobalt or chromium to elicit allergic reactions. Patients with eyelid dermatitis and metal allergy should be informed that color eye make-up products can elicit or aggravate their symptoms. Background: Recent studies suggest that dietary change may influence programming of the immune system in favor of development of allergic disease. However, the results for the effect of fat status on development of allergic or respiratory disease in children are still conflicting. Methods: A total 426 children were included in this study from a birth cohort in South Korea. Data regarding the children's allergic and respiratory outcomes were obtained from standardized questionnaires completed by the mothers. Serum total cholesterol, triglyceride (TG) and high-density cholesterol (HDL) levels were measured in children at 24 months of age. Atopic biomarkers including total Ig E, IL-10 and eosinophil counts were also measured at 24 months. Results: Serum HDL cholesterol levels were inversely associated with the eosinophil counts counts (r = -0.221, P < 0.001). Total IgE, eosinophil counts, and IL-10 levels increased significantly in the group whose serum HDL cholesterol levels was above the median value (51mg/dL) compared to the other counterpart group (P = 0.014, P = 0.003, P = 0.040 respectively). However, there was no association between lipid levels and risks of respiratory outcomes and AD at 24 months in logistic regression analysis. Conclusions: We found that the HDL cholesterol levels were associated with lower atopic biomarkers in children at 24 months, but not with risk of allergic or respiratory diseases. Interleukin-32 (IL-32), first reported as an inducer of tumor necrosis factor-α, is a pro-inflammatory cytokine involved in various chronic inflammatory diseases. This study evaluated the relationship between sputum IL-32 expression and severity of asthma. Methods IL-32 was determined in induced sputum samples of patients with asthma (n = 137) using sandwich ELISA. Relationships among sputum IL-32, airway obstruction (FEV 1 ), inflammation (neutrophil and eosinophil % of the airway) and exacerbation frequency were evaluated.


Results: The sensitization rate of potassium dichromate was 5.9% (n=58) and women comprised 72.4% (n=42) of chromium (+) group. Hands and feet were more frequently affected in chromium (+) group (P=0.002, 0.019). Occupational dermatitis was not significantly more common in chromium (+) group. Chromium allergy was most prevalent in patients in their 50s (8.4%). The prevalence of chromium allergy was 13.5% during 1998-2002 but decreased to 5.4% during 2010-2014. Conclusion: The characteristics of patients with chromium allergy suggested that chromium exposure in daily activities, including leather exopsure, is more relevant than occupational exposure in most patients. The prevalence of chromium allergy has been decreased in Korea, which may be an effect of voluntary regulation of chromium extent in cement by manufacturers A) Background: Chronic hand eczema (CHE) may severely reduce patient's quality of life. CHE refractory to topical corticosteroids currently have limited treatment options suited for chronic use. In demand of safe new therapy, oral alitretinoin, 9-cisretinoic acid, was proposed, but the economic burden limits its broad use. Acitretin is a well-known second generation vitamin A derivative, widely used in palmoplantar psoriasis with less cost. The investigation was performed to assess the efficacy and safety of acitretin in chronic hand eczema patients. B) Methods: Total of 25 patients diagnosed with CHE were enrolled in the prospective open-label study. All patients were administered with oral acitretin, start dose of 10mg twice daily and tapered to 10mg once daily, during 8 week period. CHE severity was evaluated using a hand eczema severity index and 5-grade physicial global assessment (PGA). C) Results: Severity of hand eczema decreased by 58% in average. The improvement was more remarkable in hyperkeratotic type than other types of hand eczema (p<0.004). Clinical responses, defined as clear or almost clear, were achieved in up to 36% of patients. No serious side effects were reported except of mild cheilitis in 2 patients and abdominal discomfort in 1 patients. D) Conclusion: Oral acitretin is well-tolerated with effectively improving chronic hand eczema, especially in hyperkeratotic type.

Case 2

A 26 year-old man presented to an Emergency Department with a sensation of throat and tongue swelling and voice hoarseness. He had earlier self-medicated with intra-muscular metoclopramide, intra-muscular prochlorperazine and oral ondansetron for intractable vomiting due to cyclical vomiting syndrome. No evidence of haemodynamic compromise, urticaria or airway oedema was found. Promethazine & intravenous hydrocortisone were given for suspected anaphylaxis, followed by low dose midazolam aimed at laryngeal relaxation. His symptoms improved rapidly thereafter. Mast cell tryptase level was normal during the event and allergen-specific IgE to temporally relevant allergens was undetectable. A similar episode a few years previously followed self-administered large doses of metoclopramide. This case represents recurrent laryngeal dystonia in response to large doses of metoclopramide, possibly aggravated by co-administration of prochlorperazine. Fortuitously, the anticholinergic effect of the promethazine would have helped relieve the dystonia.


We found that the both age and dermatitis were the factors influencing to the causative factors in OAS. Our finding suggest that the number of the positive components was higher in the subject accompanied with AD compared to the subjects without AD. Thus, it assumed that the subjects with AD might be highly susceptible to OAS. Objectives Allergic skin test is a commonly used test to evaluate an immediate immune response either by skin prick test (SPT) or intradermal test. SPT is widely used Several methods have been proposed to interpret SPT. However, there has been no comparison study about inter-test relationship. The aim of this study compare three different interpreting methods and define the relationship among them.


The patient was issued an adrenalin auto-injection certificate. He was instructed about auto injection technique. He was adviced not to ever consume prawn from now on. He was also adviced to be cautious about restaurants serving prawn since certain kitchen equipments might be contaminated with prawn particles. Background: The increasing prevalence of allergic disease has been attributed in part to reduced microbial exposures associated with a modern lifestyle. An altered compositional signature and reduced diversity of the intestinal microbiota are linked to development of allergic disease. We investigated the relationship between dominant Bifidobacteriumspecies in stool during the early postnatal period and subsequent development of eczema, IgE-associated eczema and sensitisation in the first year of life. Methods: Faecal samples were collected at age 1 week, 1 month and 3 months from infants at high risk of allergic disease, who were followed prospectively to age 12 months. Bifidobacteriumspecies were analysed by quantitative PCR and terminal restriction fragment length polymorphism. Infants were examined at 3, 6 and 12 months, and skin prick test performed at 12 months. Eczema was diagnosed according to the UK-Working Party criteria. Results: The presence of B. catenulatum at 3 months was associated with a higher risk of developing eczema (OR adj = 4.5; 95% CI 1.56 to 13.05, P adj = 0.005). Infants colonised with B. breve at 1 week (OR adj = 0.29; 95% CI 0.09 to 0.95, P adj = 0.041) and 3 months (OR adj = 0.15; 95% CI 0.05 to 0.44, P adj = 0.00001) had a reduced risk of developing eczema. Furthermore, the presence of B. breve at 3 months was associated with a lower risk of atopic sensitisation at 12 months (OR adj = 0.38; 95% CI 0.15 to 0.98, P adj = 0.046). B. brevecolonisation patterns were influenced by maternal allergic status, household pets and number of siblings. Conclusions: There are temporal variations of Bifidobacterium colonisation patterns early in life and these variations differentially modulate later development of eczema and/or atopic sensitisation in infants at high risk of allergic disease. Modulation of the early microbiota may provide a means for prevention of eczema in high risk infants. Background: Recent epidemiological studies demonstrate significant associations of Staphylococcal enterotoxins (SE) with asthma. In addition, clinical studies suggest that the enterotoxin exposure could contribute to the development of fixed airway obstruction in asthma, leading to a COPD-overlap phenotype. In previous experiments of mice, a short-term exposure to staphylococcal enterotoxin B (SEB) induced extensive inflammatory responses in lungs, including lymphocytes, neutrophils and eosinophils. Therefore, we hypothesized chronic repeated exposure to SEB could induce tissue remodeling in lower airways. Objective: To investigate effects of repeated SEB exposure on airway remodeling in OVA-induced chronic allergic asthma model. Methods: BALB/c mice were intra-peritoneally sensitized with ovalbumin (OVA)-aluminum hydroxide at days 0 and 14, and were intranasally challenged with OVA and/or SEB for the next 6 weeks(50 ug OVA, 10 or 100 ng of SEB, 3 times per week over a period, total 18 exposure). At 8 weeks, mice were sacrificed and assessed for histopathology, bronchoalveolar lavage fluid (BALF) cell counts, lung cytokines, methacholine airway hyper-responsiveness (AHR), and serum immunoglobulins. Results: OVA sensitization followed by repeated OVA exposure resulted in the development of Th2 asthma and inflammation, including BALF cell counts, lung cytokines, histopathology, AHR and serum immunoglobulins. However, repeated SEB exposure did not aggravate OVA-induced pathologic changes, or induce any remarkable pathologic changes when administered alone. Serum total IgE levels were also not influenced by repeated SEB exposure. Rather, chronic repeated SEB-exposed mice showed lower levels of lung inflammation and remodeling, but higher levels of IL-10 and TGF-β, compared to non-SEB-exposed mice. Conclusion: The present study demonstrates unpredicted suppressive effects of chronic repeated exposure of SEB in allergic asthma models, leading to the speculation that SEB exerts bi-directional effects depending on the timing of exposure. The mechanisms of anti-inflammatory effects warrant further investigation.


Skin Prick Test Result and Allergen Immunotherapy in Children with Allergic Rhinitis Grace Shieh UST Hospital, Philippines World Allergy Organization Journal 2016, 9(Suppl 1):A482 Background: Allergic rhinitis represents a global health problem that causes major illness and disability worldwide. Immunotherapy is effective in the management of allergic rhinitis. Skin prick test is a reliable method to diagnose IgE-mediated allergic disease. Up-to-date, no biomarker has yet been validated to be a good predictor of clinical response to allergen immunotherapy. Method: This is a cohort study to determine the association of skin prick test result to allergen immunotherapy efficacy in children with allergic rhinitis. Patients seen at a tertiary hospital diagnosed with allergic rhinitis and on allergen immunotherapy were included in the study. Skin prick test results were recorded and total nasal symptom score (TNSS) were obtained at the start of immunotherapy and monthly for six months. The correlation of the baseline skin prick test to the change in TNSS for each monthly endpoint was done to check for the association between the baseline skin prick test and the efficacy of immunotherapy measured as the improvement in TNSS scores. Results: A total of 18 patients who have completed at least six months of immunotherapy were included in this study. Average age is 13.22 + 3.62 years old, and were predominantly male (11 out of 18, 61.1%). The average skin prick test to D.farinae was 7.72 ± 3.80 mm, while that of D.pteronyssinus was 8.56 ± 4.34 mm. At baseline, the TNSS of the subjects had a median score of 7.5 which gradually decreased to a median score of 3 by the sixth month of immunotherapy. There was generally low and inverse correlation between D.pteronyssinus immunotherapy and skin prick test results for the first four months of immunotherapy, after which, there was a direct and moderate correlation from the fourth to sixth month of immunotherapy (p=0.3128), however it was not statistically significant. There was a low and inverse correlation between D.farinae immunotherapy and skin prick test results for the first four months of immunotherapy, after which, there was a direct but low correlation from the fifth to sixth month of immunotherapy (p=0.2550). Conclusion: The larger the size of the skin prick test to D.pteronyssinus, the greater the improvement of the total nasal symptom score from the baseline at six months of immunotherapy. Background: The chitinase 3-like 1 (CHI3L1), has been demonstrated its requirement for optimal allergen sensitization and Th2 inflammation in various chronic inflammatory disease including asthma. But, the role of Chi3L1 in airway hyperresponsiveness (AHR) induced by respiratory viruses has not been proved yet. The purpose of this study is to figure out the relationship between BRP-39, mouse chitinase 3-like 1 protein (CHI3L1), and Respiratory syncytial virus (RSV)induced AHR. Methods: We used C57BL/6 mice and BRP-39 null mice. Mice were inoculated with live A2-strain RSV and control PBS. Methacholine challenge test to measure airway resistance worked on day 5 after inoculation. And bronchoalveolar lavage fluid (BALF) samples were obtained and lung specimens were also harvested on days 5 after inoculation to assess lung inflammation, cytokine expression and BRP-39 production. BRP-39 expression was evaluated by ELISA. RSV loads were assessed by culture and real-time polymerase chain reaction (PCR). Histological evaluations of H&E and PAS staining were used to evaluate inflammation and tissue remodeling. Results: Level of BRP-39 in BALF was significantly increased in wildtype (WT) mice after RSV infection, but not observed in BRP-39 null mice. Inflammatory changes induced by RSV infection were less in BRP-39 -/mice rather than WT mice. In WT mice, RSV infection caused loss of body weight and significant increase of total cells, macrophages and neutrophils in BALF. And exaggerated AHR was also noted in WT mice after RSV infection. But, BRP-39 -/mice showed decreased responses in each of these parameters. Between RSV infection groups, histological tissue inflammation was also decreased in BRP-39 -/mice. Conclusions: The role of early-onset wheezing with respiratory viral infections in childhood asthma inception has received attention. RSV has known as a significant risk factor for asthma that extends into adolescence and adults and its mechanism is still under investigation. In this study, expression of BRP-39 increased by RSV infection in mice. And inflammatory changes and AHR induced by RSV were decreased in BRP-39 null mice. These findings suggest Chi3L1 could contribute to airway inflammation induced by RSV infection in mice. Furthermore, Chi3L1 might be considered as a therapeutic target against viral wheezing or virus-induced asthma.


One in four or one quarter of the apparent healthy adults of the cohort suffered from undiagnosed airway obstruction. Association had been documented between cigarette smoking and the development of airway obstruction and symptoms. Background: Sputum eosinophilia is a useful biomarker for corticosteroid response in patients with asthma or chronic cough. However, sputum induction requires specialized personnel and facilities and is not always feasible. Recent evidence suggests a moderate degree of diagnostic utility of less invasive biomarkers, such as blood eosinophils, in predicting sputum eosinophilia in asthma. However, none in the literature has examined the diagnostic utility of blood eosinophils for sputum eosinophilia in patients with non-asthmatic chronic cough. Methods: We examined the datasets of elderly asthma and nonasthmatic chronic cough recruited from previously established cohorts. The inclusion criteria were as follows: 1) elderly subjects (≥65 years old), 2) no current oral or inhaled corticosteroids and 3) no significant comorbidities. Sputum eosinophilia was defined as induced sputum eosinophils≥3%. The diagnostic utility was assessed using receiver operating curve (ROC) analyses for blood eosinophils in predicting sputum eosinophilia. Results: A total of 74 elderly asthma and 75 non-asthmatic chronic cough patients were analyzed. There were no significant difference in their demographic profiles (age, gender and smoking) between two groups. Of them, 59 elderly asthma and 45 non-asthmatic chronic cough patients had sputum eosinophilia. In Spearman tests, the correlations between blood eosinophils% and sputum eosino-phil% were significant in eosinophilic asthma (r=0.577, p<0.001) but not in non-asthmatic eosinophilic bronchitis (r=0.019, p=0.870). In ROC analyses for sputum eosinophilia, blood eosinophils showed a moderate utility (the area under the ROC curve [AUC] 0.838) in asthma, but no utility (AUC 0.489) in non-asthmatic chronic cough. Conclusions: Unlike asthma, blood eosinophils did not have any diagnostic utility for sputum eosinophilia in non-asthmatic chronic cough. These findings could suggest a different pathophysiology in airway eosinophilic inflammation between two entities.


Approximately 36.2% of the adult patients thought that the treatments were effective. The main reasons for CAM use were safety, convenience and low price. However, the group who spent more than $1,000 on CAM felt more dissatisfaction and anxiety related to treatment at the hospital. The situation of CAM practice was not consistent and was instead influenced by the backgrounds of the subjects. Conclusion: Many patients who receive CAM report feeling that the effects of treatment provided by hospitals are insufficient and have concerns about the side effects of such treatments. Information regarding standard treatments, as described in the guidelines, should become widely known and diffused, and strong communication with patients should be considered. Background: The assessment of disease severity and courses is important to achieve well-controlled status of asthma. In elderly population, cognitive and physical impairments are noted with aging process, which may impact on asthma control. We aimed to evaluate the impact of cognitive function on the assessment of asthma control in elderly asthmatics. Method: Fifty mild to moderate asthmatics were enrolled over 60 years old. Questionnaires including ACT, asthma specific quality of life (AQOL), and geriatric depression scale (GDS) were performed. Seoul neuropsychological screening battery-dementia version (SNSB-D), Korean version of mini mental status examination (K-MMSE), and Seoul instrumental activities of daily living scale (SI-ADL) were done for neuropsychological assessment. Results: Mean age was 67.0 ± 4.9 years. Thirty patients were female (60.0%). According to GINA, 12(24%) were in well-controlled, and 38(76%) were in not-controlled. However, according to ACT, 37(74%) were in ≥20 group, and only 16(32%) were in <20 group. The sensitivity and specificity of ACT to determine wellcontrolled asthma were 91.7% and 39.5%, respectively. Overestimation of asthma control status was 56%, using ACT compared to GINA. Regarding neuropsychological assessment, 22(44%) had mild cognitive impairment, 4(8.7%) had dementia, and 17(34%) had depression. Depression was more common in patients with uncontrolled asthma(42.1% vs. 8.3%, P=0.039). Total SNSB-D score was significantly higher in patients with ACT≥20 (187.9 vs. 217.3, P=0.015). The ACT score was significantly correlated with degree of cognitive function (adjusted using age, sex, education, and GDS; P=0.004). Conclusion: There is discrepancy between self-reported ACT and physician's decision by GINA in the assessment of asthma control in elderly asthma, in which ACT score is affected by cognitive function. Elderly asthmatics with higher cognitive function can achieve better asthma control. Background: Many aspects of the relationship between allergic inflammation and reactive oxygen stress are unclear. Aims: To elucidate the associations between respiratory syncytial virus (RSV) infection and reactive oxygen stress and between wheezing illness and reactive oxygen stress. Method: Subjects were 61 children aged ≤4 years who were hospitalized with RSV infection(42 patient; RS group), bronchial asthma without RSV (8 patients; BA group), and acute bronchitis and pharyngitis(11 patient; Br group). Levels of blood nitric oxide (NOx), high mobility group box-1 (HMGB-1), thioredoxin, and eosinophil-derived neurotoxin and urine 8-hydroxydeoxyguanosine (8-OHdG), NOx, biopyrrin, and 8-isoprostanes were measured on admission day(acute phase), on hospital days 3-5(recovery phase), and 1-2 weeks after discharge(late phase). This study was approved by the Ethics Committees of National Hospital Organization Fukuyama Medical Center, and the parents of all subjects provided written informed consentin accordance with the Declaration of Helsinki. Results: HMGB-1 was higher in the RS and BA groups during the recovery and late phases than during the acute phase, and higher during the late phase in the RS and BA groups than in the Br group(RS group: recovery/acute 1.19, late/acute 1.37; BA group: 1.20,1.47; Br group:1.12,1.14,respectively). Urine 8-OHdG was higher in the RS group than in the BA and Br groups during the recovery and late phases (RS group: recovery/acute 4.03, late/acute 1.92; BA group: 1.51, 0.61; Br group:1.77, 0.93, respectively) . No significant differences were found in other biomarkers. Conclusion: In young children with acute respiratory tract illness with wheeze, reactive oxygen stress was high during the recovery and late phases. Lower respiratory tract inflammation might persist after the acute phase leading to bronchial hyperresponsiveness. Purpose: The effect of allergic rhinitis [AR] on pulmonary function and risk factors of AR are controversial. The purpose of this study was to analyse the risk factors and pulmonary function in dust mite sensitized, current AR children who were never diagnosed as having asthma. Methods: A cross-sectional study of 1,792 children aged 9-12 years from Korea was conducted. Demographic and disease related information was obtained via a detailed questionnaire, skin prick test, pulmonary function test, and methacholine challenge test. Results: A total of 672 children were included in the analysis. 583 children who were not sensitized to common 16 allergens and not having any allergic diseases were classified as the control group. 89 children were classified as the current AR with dust mite sensitization group. The binary logistic regression analysis evidenced that nonfarming parents(adjusted odds ratio[aOR] 1.95, 95% CI 1.00-3.08 ), no older siblings(aOR 1.99, 95% CI 1.22-3.25), use of antibiotics during infancy(aOR 2.18, 95% CI 1.13-3.70), helminth infection(aOR 2.61, 95% CI 1.13-6.03), low income (aOR 0.33, 95% CI 0.12-0.92), and pet ownership(aOR 0.24, 95% CI 0.11-0.51) were risk or protective factors. There was no difference in spirometry between control and current AR groups. None of children showed bronchodilator response. However, methacholine PC20(provocative concentration of methacholine causing a 20% fall in forced expiratory volume in 1 second[FEV1]) less than 25, less than 16, less than 8mg/mL were 8.5%, 7.1%, 2.1% in control group and 28.7%, 23.0%, 8.0% respectively in allergic rhinitis group (p=0.00). Conclusions: We might reduce the prevalence of dust mite sensitized current AR by controling some environmental factors. Even the spirometry seems to be normal, bronchial hyperresponsiveness occurs more frequently in children with dust mite sensitized AR than normal children. Background Blomia tropicalis is a common house dust mite in tropical regions. Although the predominant sensitizations to Blomia allergens were clearly demonstrated in some South-East Asian countries as Singapore or Malaysia, the prevalence of B.tropicalis hypersensitivities as well as the identification of the major allergens remains to be elucidated in Thailand. The goal of the study is the cloning and expression of recombinant Blo t 7 (rBlo t 7) allergen in Pichia pastoris.

Contribution of Stem Cell Factor Autocrine/Paracrine Mechanism to Aberrant Proliferation of Mast Cells

Yosuke Amagai, Akane Tanaka, Hiroshi Matsuda Tokyo University of Agriculture and Technology, Japan Correspondence: Yosuke Amagai -Tokyo University of Agriculture and Technology, Japan World Allergy Organization Journal 2016, 9(Suppl 1):A497 A) Background: Mast cells originated from canine mast cell tumors are useful tools to investigate KIT-dependent or -independent proliferation of mast cells. It is well known that gain of function mutations in the c-kit gene are seriously associated with neoplastic proliferation of mast cells in humans, rodents, and dogs. However, KITindependent malignant proliferation of mast cells has been rarely explored. Since most patients of mast cell leukemia/sarcoma and more than 70% of patients with cutaneous mastocytosis preserves wild type KIT but not mutant KIT, we attempted to find out KITindependent mechanisms that induce tumorigenic proliferation of mast cells. B) Methods: We investigated a mechanism of tumorigenesis using a wild-type KIT-expressing canine mast cell line. Western blot analysis was conducted to detect KIT phosphorylation. Both RT-PCR and flow cytometry analysis were carried out to examine the stem cell factor (SCF) expression. Inhibitory effects of a SCF neutralizing antibody and RNA interference for SCF on the cell proliferation were also evaluated. SCF production in xenografts consisted of wild-type KITexpressing tumor was identified. C) Results: High expression of SCF was detected in the canine mast cell line with wild-type KIT used in this study. In the cells, KIT was spontaneously phosphorylated. Neutralization of SCF as well as SCF gene silencing inhibited the growth of the cells, suggesting SCF autocrine/paracrine action. Production of SCF was also observed in several mast cell lines originated from humans and rodents, which was enhanced after PMA/ionomycin stimulation. Ki-67-positive cells in the xenografts were markedly positive for SCF. Moreover, SCF was strongly detected in 3 of 5 samples isolated from canine mast cell tumors that express wild-type KIT. D) Conclusion and discussion: These results indicate the broad contribution of SCF autocrine/paracrine to the neoplastic proliferation of wild-type KIT-expressing mast cells not only in dogs but also both humans and rodents. It suggests that targeting SCF production may become a novel strategy for treatment of mast cell malignancies. Background: Mites tablets of monomeric allergoids have been developed for sublingual immunotherapy in patients suffering from allergic rhinoconjunctivitis (ARC). The purpose of this trial was to determine the efficacy and safety of four different doses of mites tablets compared to placebo. Method: Out of 160 patients recruited, 131 adult patients with ARC induced by HDMs were randomized for this dbpc phase II study (EudraCT No 2013-000617-20) conducted in Germany. Treatment consisted of either 300 UA/d; 1,000 UA/d; 2,000 UA/d; 3,000 UA/d or placebo over a course of 12 weeks. Efficacy was assessed by the improvement of reactions to a titrated conjunctival allergen challenge. Safety was assessed by frequency, type and severity of treatmentrelated adverse events (TRAE). Results: After a 12-week course of immunotherapy, 88.5% and 76.0% of the patients treated with 2,000 UA/d and 1,000 UA/d, respectively, showed a tenfold improvement in the threshold of allergen concentration compared to 64.2% under placebo (p<0,05 and p=0.358). Neither treatment related SAEs nor cases of anaphylaxis were reported, so there was no need for the use of epinephrine. In total, of all patients under active treatment 4.95% experienced local TRAEs while 6.93% had systemic TRAEs. Conclusions: The treatment with mite monomeric allergoids is a well-tolerated and safe treatment for patients suffering from HDM induced ARC. The highest proportion of patients with improvement in the CPT threshold of allergen concentration was found in patients treated with 2.000 UA/d corresponding to approximately 168.000 UA cumulative dose during the course of the trial. Background: Depression and allergic diseases have been reported to be frequently comorbid. However, their associations have been under evaluated in a comprehensive way, particularly in the elderly. Objective: We aimed to examine the associations between allergic parameters and depression in a community-based elderly population. Methods: The present analyses were performed using the baseline data set of the Korean Longitudinal Study of Health and Aging, consisting of 1,000 elderly subjects (aged over 65) randomly recruited from an urban community. Depression was assessed by geriatric depression scale (GDS), the Center for Epidemiologic Studies Depression Scale (CES-D scale), the Hamilton Rating Scale for Depression (HRSD). Allergic parameters included questionnaires and allergen skin tests.Asthma symptoms and history were defined by structured questionnaires, and atopy was defined by inhaled allergen skin prick test. General quality of life scale (SF-36) and comorbidity were assessed. Results: The prevalence of asthma and major depression disorder were 6.6 % and 5.3%, respectively. The prevalence of depressive symptoms was not statistically significant between non-asthmatic and asthma group (19.0% vs. 10.6%; p = 0.088). In additional analyses, however, individuals reporting symptom such as usual cough, chronic cough and nocturnal cough were at higher risk of major depression and lowered SF-36 (Adjusted using age, gender, education and income, p<0.05). Furthermore, rhinitis, atopy and eosinophilia were not related to depression. Risk factors for geriatric depression were identified as female sex, advanced age, low income (≤1 million won a month), dementia, solitary life and comorbid medical condition. Conclusion: It was concluded that asthma is not associated with depression in the elderly. In comparison, asthma symptoms profoundly affect objective depression scales. The present study indicates that an appropriate treatment of asthma control has the potential decreased depressive disorder. Background: Allergic diseases are mainly mediated by immune responses with IgE antibodies specific for allergens and orchestrated by various immunological factors including immune cells and cytokines. It was known that the level of total IgE, helper T cells and some cytokines were associated with allergic inflammation and disease development. Evaluation of the correlation between them is needed to examine their possibilities as a reference factor for the diagnosis and monitoring of allergic diseases. Methods: We previously investigated the serum level of total IgE, 22 allergy-related cytokines, and the ratio of Th1/Th2 cells respectively in both normal individuals and allergic patients. Each factor was compared in normal and allergic participants to examine their significant difference. The correlation of total IgE with other immunological factors was investigated by various statistical analysis using integrated results of each factors. Results: The serum level of total IgE in allergic patients was significantly higher than normal subjects (265.6 vs. 47.16 kU/L, p<0.0001). Th1 cell percentage was also different (6.54 vs. 8.60, p=0.001), but Th2 cell percentage and Th1/Th2 ratio showed no significant difference between normal and allergic participants. Nine of 22 cytokines were analyzed in allergic patients and their levels increased in patients compared to normal individuals, particularly Platelet-Derived Growth Factor BB (PDGFBB) was much higher in allergic patients (1491.3 vs. 536.0 pg/ml, p<0.0001). By integrated analysis in all participants, total IgE had a significant correlation with Th1/Th2 ratio and Th2 cell percentage (p=0.02 and p=0.04, respectively). Conclusion: In this study, we found that Th1 cell percentage decreased in allergic patients, supporting Th1 cells might be important roles in allergic responses. Our results also showed that PDGFBB could be responsible for allergic responses, suggesting its possibility as a reference factor for allergic diseases. We demonstrate that the correlation of total IgE with Th1/Th2 ratio and Th2 cell percentage might be relevant to corroborate the immunological function of Th2 cells for IgE-related responses. Background: To study the pattern of allergic diseases among military servicemen and women referred from the Singapore Armed Forces (SAF). Methods: Referrals to the Tan Tock Seng Hospital Clinical Immunology/Allergy Clinic from 1 Jan 1998 to 15 May 2015 were retrospectively reviewed. The demographic profile of servicemen, types of allergic/immunologic diseases and definitive therapies prescribed were studied. Results: There were 247 referrals comprising 90.7% males, predominantly active full-time national servicemen (NSF) and regulars. The mean age at diagnosis was 24±6 years. They comprised 88.3% Chinese, 5.3% Malays and 3.3% Indians. The most common referring diagnoses were for insect venom allergy (37.5%), urticarial/angioedema (18.3%), anaphylaxis (17.8%); drug allergy (15.4%), food allergy (9.1%), nonsteroidal anti-inflammatory drug [NSAID] hypersensitivity (6.3%) and allergic rhinitis (5.8%). Following evaluation by the allergist, insect venom allergy (36.5%), anaphylaxis (24.0%), allergic rhinitis (23.8%) and NSAID hypersensitivity (20.7%) were the most common conditions. Of the 32 servicemen diagnosed with insect venom anaphylaxis, 9 (28.1%) underwent allergen immunotherapy (AIT), of whom 6 were regulars and 3 NSF. All received yellow jacket and paper wasp venom AIT, and 1 in addition received honey bee venom AIT. No serviceman developed systemic reactions during AIT. Only 1 serviceman has completed 5 years of AIT, the mean duration of all servicemen on AIT to date being 2.2±1.3 years. Conclusions: Insect venom allergy, anaphylaxis, allergic rhinitis and NSAID hypersensitivity were the most common referrals from the SAF. Medical officers in the military should be trained and equipped to manage military servicemen with these conditions at primary care level: in particular knowledge of the anaphylaxis action plan, and when and how to use epinephrine autoinjectors. Knowledge of NSAID hypersensitivity reactions is also important especially since non-selective NSAIDs are commonly used in the treatment of musculoskeletal injuries during training. Anti-tuberculosis (Tb) drugs can cause various adverse drug reactions (ADRs) including hypersensitivity syndrome. Because multiple drugs are concomitantly administered, the detection of culprit drug is essential for successful treatment. Lymphocyte activation test (LAT) is one of the promising methodologies to evaluate delayed drug hypersensitivity, but its role in anti-Tb hypersensitivity remains controversial. A 41-year-old man was referred to allergy clinic with high fever, headache, and skin rash on both arms and legs. He was diagnosed as pulmonary Tb and has started combination anti-Tb drug therapy consisting of isoniazid, rifampicin, ethambutol, and pyrazinamide for 10 days. Body temperature was 38.0°C. Erythematous maculopapular rash was on both upper and lower extremities and several tender lymph nodes were palpable on cervical area. There were increased levels of aminotransferase (AST) 110 IU/L and alanine transaminase (ALT) 180 IU/L. All anti-Tb drugs were ceased. Patch test showed weak reaction to both rifampin and pyrazinamide. However, only rifampin was strong positive in LAT test. We successfully reintroduced rifampicin by oral desensitization without complication. Our experience suggests that LAT could be helpful to determine culprit drug in poly-pharmacy, especially in anti-Tb drugs. Background: Anaphylaxis is a catastrophic systemic reaction and drugs are responsible for 20% to 40% of anaphylaxis. However, little is known about the characteristics of drug-induced anaphylaxis in Korea. The aim of this study is to investigate causal drugs and clinical features of the drug-induced anaphylaxis in Korean by using data from the adverse drug reaction (ADR) reporting system to the Korea Institute of Drug Safety & Risk Management (KIDS). Methods: Among Individual Case Safety Reports (ICSRs) to KIDS from January, 1989 to June 2014, cases of drug-induced anaphylaxis were selected and age, gender, causative agents, and fatal cases resulting in death were analyzed. Results: A total of 2,190 cases were identified. Male was 912 (41.6%) and mean age was 49.81 ± 18.40 years. Most common causal drug was antibiotics (576, 26.3%), followed by aspirin/nonsteroidal anti-inflammatory drugs (NSAIDs) (390, 17.8%), contrast media (339, 15.5%), and anticancer drug (273, 10.7%). There were 25 fatal cases and antibiotics (8 cases) and contrast media (4 cases) were the two most common causative drug category. Of 186 drugs reported at least two times as suspected causative agents, 19 drugs (10.2%) did not reflect anaphylaxis in their drug labeling information. Conclusions: Antibiotics, aspirin/NSAIDs, contrast media, and anticancer drugs were 71.3% of causative drugs among anaphylaxis ICSRs in Korea. Antibiotics and contrast media were also main causative agents responsible for fatal drug induced anaphylaxis.


In addition to the initial test on textiles, as for medical devices of higher class, monitoring manufacturing processes certification is necessary to ensure the quality of the finished product, especially when using nonwoven fabric. Therefore, ISO 13485 certification is a relevant criteria for anti-mite covers quality and thus effectiveness. Subcutaneous immunotherapy is an effective treatment for allergy. It works by helping to re-balance an individual's immune response to allergens and the ability to drive an antibody titre response is greatly improved by the use of adjuvants, the most common being aluminium hydroxide. No data or preclinical model on the localisation kinetics of aluminium after subcutaneous injection, based on allergy formulations, currently exists. Methods Albino rats of the Crl:WI(Han) strain each received a single subcutaneous administration on 4 occasions with a 3 or 4 day intervals of a Birch concentrate formulated with either Alhydrogel or L-Tyrosine as the representative depot adjuvant. Dose sites were extracted and digested up to 6 months after final administration and aluminium (Al 3+ ) analysed via ICP-MS.
The localisation kinetics of aluminium after subcutaneous injection, based on allergy formulation, has been investigated with the rate of clearance of aluminium from the injection site calculated from a rat model. Granuloma formations are one of the most common unwanted adverse reactions when a patient receives allergy subcutaneous immunotherapy. The results presented herein support current understanding that aluminium has the propensity to form focal accumulations in the body, beginning at the site of administration. Background: Periostin is considered a biomarker of Th2-driven allergic inflammation and predictor of airway eosinophilia. Periostin levels in exhaled breath condensate (EBC) in athletes have not been evaluated. Aims of the present study included: comparison of periostin levels in EBC from athletes, asthmatics and healthy controls (HC); assessment of the effect of exercise and the influence of ambient conditions on EBC periostin. Methods: Study group consisted of 15 competitive athletes (5 speed skaters and 10 swimmers) aged 15-25. Control groups comprised 10 mild-to-moderate asthmatics aged 19-39 (asthma controls, AC) and 7 healthy, non-smoking subjects aged 21-27 (healthy controls, HC). Control subjects were not performing sports on a reglar basis. Athletes were assessed in two timepoints: in-training (period 1) and out-of-training (period 2) depending on individual training schedule. Treadmill exercise challenge was conducted according to the ATS guidelines. EBC was collected immediately before and 30 minutes after exercise. Periostin levels in EBC were assessed by ELISA. Results: Periostin EBC levels before and after exercise challenge were significantly decreased in athletes during in-training period as compared with out-of-training period (1.87±0.69 vs 2.36±0.77 ng/ml, mean±SD, p<0.02) and with AC subjects (1.87±0.69 vs 2.72±0.62 ng/ ml, p<0.01). Exercise challenge did not induce significant changes in EBC periostin in any of the groups. In athletes during training period, significant positive correlation was observed between baseline EBC periostin levels and mean daily air temperature on the assessment day (day 0) (R=0.57; p=0.02), mean temperature during 7 days preceding the assessment (R=0.56, p=0.02), dew point temperature on day 0 (R=0.60, p<0.02) and mean dew point temperature during 7 days preceding the assessment (R=0.57, p=0.02). In asthmatics a significant negative correlation was observed between baseline EBC periostin and mean daily air temperature on day 0 (R=-0.58; p=0.04). No correlations were observed in athletes during off-training period and in HC subjects. Conclusions: Regular exercise may contribute to decreased expression airway periostin level. Ambient conditions seem to influence periostin release into the airways. Asthma exacerbations are an exaggerated lower airway response to an environmental exposure. Triggers of asthma exacerbation include virus infection, allergen, environmental pollutants, occupational sensitisers and irritants, and some medicine such as aspirin. It is well known that respiratory viral infection is the most common cuase for severe asthma exacerbation. The double-stranded RNA (dsRNA)-activated serine/threonine kinase R (PKR) is well characterized as an essential component of the innate antiviral response. Moreover, PKR activation is associated with IgE class switching and subsequent induction of IgE-mediated disorders such as allergy and asthma. Meanwhile, PKR phosphorylates e-IF2α, one of branches for unfoled protein response (UPR).

Diversity of Clinical Manifestations and Treatment Responses for Idiopathic Hypereosinophilic Syndrome

Joo-Hee Kim, Sunghoon Park, Young Il Hwang, Seung Hun Jang, Ki-Suck Jung Hallym University Sacred Heart Hospital, South Korea Correspondence: Joo-Hee Kim -Hallym University Sacred Heart Hospital, South Korea World Allergy Organization Journal 2016, 9(Suppl 1):A508 Background: Idiopathic hypereosinophilic syndrome (IHES) is a rare disorder defined by persistent blood eosinophilia, absence of secondary causes, and evidence of eosinophil-associated organ dysfunction. In some patients with hypereosinophilia (HE) may cause lifethreatening complications, whereas other patients, referred to "hypereosinophila of unknown significance (HE, US)" do not exhibit any measurable organ damage. Although clinical diversities of HES have been recognized, only isolated case reports are available in Asia. This retrospective analysis sought to summarize the baseline demographic, clinical, and laboratory characteristics in a cohort of patients with HES and HE, US and to review responses to treatment. Method: Clinical and laboratory data from 25 patients with IHES or HE, US, seen between January 2004 and December 2014 at Hallym Sacred Heart Hospital, were collected retrospectively after chart review.
Result: A total of 25 patients were enrolled; 7 patients (28.0%) were diagnosed with HE, US and 18 patients (72.0%) with IHES. The mean number of white blood cell and peak total eosinophil count (TEC) were significantly increased in patients with IHES, compared to those with HE, US (p=0.008, respectively). Fip1-like1-platelet-derived growth factor receptor a (FIP1L1-PDGFRA) mutation analysis was done in 9 of 25 patients using in situ hybridization, and all showed negative results. In patients with IHES, the most common clinical presenting symptom was gastrointestinal (44.4%), followed by constitutional symptoms (33.3%) such as fever, myalgia, weakness, and weight loss, and pulmonary (11.1%). All patients received corticosteroids (0.25~1.0 mg/kg) as initial therapy. Seven patients (38.8%) showed complete response and 11 patients (61.1%) with partial response within a month. However, 9 patients (50.0%) recurred during tapering or discontinuation of corticosteroid. There was no significant association between treatment response and laboratory parameters including peak TEC, total IgE, eosinophil cationic protein or marrow eosinophilia. Conclusion: The majority of patients with IHES respond to corticosteroid therapy, however, discontinuation of corticosteroid is associated with recurrence. There are no clinical or laboratory markers to predict the prognosis of IHES.


Vaccines and allergen-specific immunotherapy typically contain adjuvants that facilitate immune responses in humans and animals. For almost a century, salts of aluminium (hydroxide and phosphate) were the only approved adjuvants in humans. One major problem of aluminium adjuvants is that they are not biodegradable and that they typically stimulate so-called T-helper type 2 (Th2) as opposed to Th1 immune responses, which again affects the type of antibody responses produced. The goals of new adjuvants are therefore (i) to facilitate recognition of antigen/allergen, (ii) to be biodegradable and biocompatible, (iii) to be without toxic or inflammatory side effects, and (iv) to trigger protective Th1-like immune responses as well as allergen-neutralising antibodies. Co-precipitates of micro crystalline tyrosine (MCT) and proteins have been suggested as candidate adjuvants for allergen-specific immunotherapy. Methods Immunogenicity testing of MCT-ovalbumin vaccines in naïve BALB/c and C57BL/6 mice was undertaken. Three injections were performed at 2 week intervals, and the mice were tail bled prior to each injection as well as at different time points after the last injection. The obtained sera were analysed for OVA-specific antibodies, while spleen cells were tested for T-cell responses including cytokine secretion after re-stimulation of the cells in vitro with ovalbumin.


MCT has good adjuvant properties, comprising a high adsorptive power for proteins, and enhancement of Th1-like and associated immune responses, highlighting its potential of action as a biodegradable depot adjuvant in allergen-specific immunotherapy. MCT is naturally metabolised and the pharmacokinetics of MCT present a half-life at the injection site of 48 hours; this is a particular benefit for allergy SCIT, a traditionally long course treatment, minimising the need for accumulation of non-biodegradable adjuvant.


The ability of MCT to readily adsorb MPL compared to aluminium and calcium adjuvants supports a characteristic association based on both tyrosine's structure and MCT's physical properties. MCT is an effective depot candidate for allergy immunotherapy formulations and vaccines. Background: Inflammatory bowel disease (IBD) is an inflammatory disorder of unknown pathogenesis. Recent studies showed that interleukine-22 plays an important role in inflammatory processes during the disease. The purpose of this case-control study was to explore the association between IL-22 gene polymorphism (rs2227501) and susceptibility to IBD. Methods: 89 patients and 201 healthy individuals referred to the Namazi Hospital of Shiraz, Iran were entered in this study. Blood samples were collected and genomic DNA was extracted. Restriction fragment length polymorphisms polymerase chain reaction (PCR-RFLP) was performed, and data were analyzed using Chi-square and Bonferroni tests. Results: The frequency of the A allele was significantly greater, and the T allele was significantly lower in patients compared to controls (P value = 0.02). In addition, there was a statistically significant relationship between AA genotype and IBD (P value = 0.01). Conclusion: This is the first study of evaluating rs2227501 in Iranian patients with IBD. More studies are required in order to clarify the exact role of IL-22 polymorphisms in pathogenesis and susceptibility of inflammatory bowel disease. Background and Objectives: Several studies have demonstrated that adipose-derived stem cells (ASCs) can ameliorate allergic airway inflammation by shifting to a Th1 from a Th2-biased immune response. The ASCs secrete a variety of autocrine/paracrine factors, called secretome, that protect cells from apoptotic cell death and modulate immune system. In this study, we evaluated the effects of ASCs-derived secretome on allergic airway inflammation in ovalbumin (OVA) induced asthmatic mouse model. Materials and Methods: C57BL/6 mice were sensitized to OVA by intraperitoneal injection and challenged intranasally with OVA. To evaluate the effect of ASCs-derived secretome on allergic airway disease, 1 μl/ml of ASCs supernatant were administrated intranasally before OVA challenge. We evaluated airway hyperresponsiveness (AHR), the proportion of eosinophils in bronchoalveolar lavage fluid (BALF), lung histology, serum total and OVA-specific antibody, cytokine profile of BALF and lung draining lymph nodes (LLN), and T cell population of LLN. Results: ASCs-derived secretome significantly inhibited eosinophilic inflammation in the lung. AHR, total immune cell and eosinophils in the BALF, and mucus production were significantly reduced after ASCs-derived secretome administration. ASCsderived secretome significantly decreased the serum total and allergen-specific IgE and IgG1 level. ASCs-derived secretome significantly inhibited Th2 cytokines and enhanced Th1 cytokine (IFN-γ) and regulatory cytokines (IL-10 and TGF-β) in the BALF and LLN. In addition, CD25 + Foxp3 + and IL-10 + T cells in LLN were significantly increased after ASCs-derived secretome administration. Conclusions: ASCs-derived secretome ameliorated allergic airway inflammation and improved lung function through the induction of Tregs expansion. Secretome may be a promising candidate for a novel cell-free therapy for allergic airway diseases that has many advantages in overcoming the limitations and risks associated with the cell-based therapeutics. Alveolar hemorrhage with anti-neutrophil cytoplasmic antibody (ANCA) is a rare disease in children. ANCA is associated with certain diseases such as granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EPGA). This group of disease, characterized by necrotizing small-vessel vasculitis show autoantibodies in patients serum, directed against neutrophil cytoplasmic constituents, especially proteinase 3 (PR3) and myeloperoxidase (MPO). In these diseases, affected vessels have changed with focal necrosis in pathologic findings and patients suffer from pulmonary, cerebral, gastrointestinal, other hemorrhagic complication and also renal dysfunction represented by crescentic glomerulonephritis. A 8-year-old previous healthy girl presented with acute onset dyspnea, cough, hemoptysis, chest discomfort, fever and hypoxemia. Her chest CT scan showed diffuse consolidation and ground glass opacity in both lungs, hemoglobin was 3.9g/dL, hematocrit 12%, so she was diagnosed as diffuse alveolar hemorrhage. Bleeding diatheses were excluded by laboratory testing, and Anti nuclear antibody(ANA) and P-ANCA were positive. Myeloperoxidase-ANCA (MPO-ANCA) was positive but proteinase 3-ANCA was negative. Antiglomerular basement membrane antibodies(Anti-GBM) was negative. urinalysis showed RBC 21-30/HPF, creatinine 0.48mg/mL but there were no RBC casts or protein. This patient had been diagnosed for microscopic hematuria, but her kidney function was normal and other symptoms of ANCA associated vasculitis had never been appeared. The patient's alveolar hemorrhage recovered on immunosuppresive therapy with cyclophopamide and corticosteroids. We report 8-year old girl case, treated for severe alveolar hemorrhage and microscopic hematuria with positive ANCA. Background: The correct severity assessment is important for treatment of Atopic dermatitis (AD) Although the levels of serum Thymus and activation-regulated chemokine (TARC)/CCL17 is well known as a proper means for assessing severity of AD, the levels of TARC are different according to the month of age. We examined a correlation of serum TARC level and Severity Scoring of Atopic Dermatitis (SCORAD) index in patients with AD in early infancy.
Results: 9 patients (2-14years) which were recruited to the study, 8 (88.8%) were finished the protocol. One couldn't accomplished the protocol because of recurrent sever anaphylactic reaction and remained on 10 gr of bread B. SPT wheal was significantly reduced at the end of maintenance phase. Conclusion: We have demonstrated that wheat tolerance could be achieved in a stepwise OIT regimen in anaphylactic patients. Apparently, further investigation will need to confirm safety and effective wheat OIT protocol. Background: Filaggrin is a key protein involved in skin barrier function. Mutations in the gene encoding filaggrin (FLG) have been identified as the cause of ichthyosis vulgaris and have been shown to be major predisposing factors for atopic dermatitis (AD). Objective: The purpose of this study was to investigative the clinical characteristics of AD patients with FLG mutations and determine the differences between AD patients with and without FLGmutation. Methods: We identified the FLGmutations of AD patients by complete sequencing and snapshot methods and then analyzed the data on clinical characteristics from questionnaire responses. Results: We found that earlier age of AD onset (p=0.047), tendency to respiratory atopy (p=0.029), more severe AD clinical characteristics (higher EASI score, p=0.018), and decrease in skin hydration (p=0.04) were associated with FLG-related AD. Conclusion: Our data demonstrate that FLG mutations are indicators of a poor prognosis in AD and are predisposing factors that exist in early infancy and persist into adulthood. The aim of the project 'Early diagnosis of asthma and allergies among children attending primary schools in Wroclaw' was to preselect the group of high risk of asthma/allergy development using a questionnaire and then to confirm the diagnosis at the physician's office.


Objective: Many reports exist on the effectiveness of oral tolerance induction for food allergies. However, few comprehensive reports exist on its effectiveness for wheat allergy. Subjects: Among subjects who had a positive result in an oral food challenge test for udon (wheat noodles), informed consent was obtained from 49 subjects who were judged to be capable of starting intake at 0.5-5 g dried noodle weight based on the final dose and induced symptoms. Method: Oral tolerance induction was performed after randomly dividing the subjects, with consideration of age, into the following two groups according to intake frequency: the frequent group, intake at six times/week or more; and the intermittent group, intake at two times/week. After six months of tolerance induction, the ability of these patients to ingest the noodles at the target dose was evaluated. Results: Of the 49 subjects, 32 were finally considered in this study, and each group had 16 subjects in whom intake could be totalled based on intake diaries, and who were able to maintain intake at five times/week or more (frequent group) or two times/week (intermittent group). After six months, the proportion of subjects who had a negative result on testing with the target dose (20 g dried noodle weight for subjects ≤3 years of age, and 50 g dried noodle weight for those ≥4 years of age) or who were capable of the target intake within six months was 73% on the whole, and no differerence in both groups. Conclusion: The findings suggest that even when intake frequency in oral tolerance induction for wheat is reduced to twice/week, no clear difference is seen with the target dose after six months of tolerance induction. Background: Aspirin exacerbated respiratory diseases (AERD) are characterized as an acute bronchospasm by ingestion of aspirin and heavy infiltration of eosinophils, which is contributed by altered synthesis of cycteinyl leukotrienes. Although the acquired Th2 response is apparently revealed in IgE -dependent asthma, but not obvious in AERD. Recently, IL-25, TSLP and IL-33 appears as key molecules of the innate Th2 response in allergic inflammation. Thus, we tried to reveal the relation of the innate Th2 molecules with development of AERD. Methods and Materials: The level of IL-25, IL-33 and TSLP were measured in plasma before and after aspirin challenge to the subjects with AERD (n=18) and ATA (n=16) using an enzyme-linked immunosorbent assay (ELISA), and then normalized with plasma protein.
Results: The plasma level of IL-25, IL-33 and TSLP were comparable before aspirin challenge between AERD and ATA. After aspirin challenge, however, concentrations of IL-25 were robustly increased in AERD compared to those before aspirin challenge while did not change in ATA. The post challenge level of IL-25 was significantly higher in AERD more than that of ATA (0.34 pg/mg vs. 2.31 pg/mg; p=0.03), while those of IL-33 and TSLP were not changed. There was a significant correlation between concentrations of IL-25 and aspirin induced -fall rate of FEV1 in total subjects (r 2 =0.172, p=0.037). Conclusions: Among the innate Th2 cytokines, IL-25, but not IL-33 and TSLP, is related with development of airway spasm after aspirin challenge, which suggest that IL-25 may be play roles in pathogenesis of AERD via modulation of Th2-type immune response. Objectives: Allergic and nonallergic rhinitis are very common disease for children, however, little is known about their natural courses. The purpose is to evaluate the natural course of allergic and nonallergic rhinitis in children. Study Design: Individual cohort study Methods: We analyzed data from Snoring Child Cohort of 208 children. The data encompassed questionnaire about chronic rhinitis, and the result of skin prick test (SPT) for 5 inhalent and specific IgE for 2 allergens. Children were classified into four groups, namely allergic rhinitis (rhinitis plus positive SPT), nonallergic rhinitis (rhinitis plus negative SPT), sensitization only (no rhinitis plus positive SPT), and control (no rhinitis plus negative SPT). Results: Finally, the data of 124 children were analyzed. Among 18 children with allergic rhinitis at 7 year, 13 (72.2%) became sensitization only after 2 years and only 5 (27.8%) were remained as allergic rhinitis. Five (26.3%) out of 19 with children nonallergic rhinitis at 7 year turned into allergic rhinitis at 9 year and 7 (36.8%) into control. Twenty six (86.7%) out of 30 children with sensitization only at 7 year were remained as same at 9 year. Among 59 control children at 7 year, 2 (3.3%) became those with allergic rhinitis, 7 (11.9%) with nonallergic rhinitis, and 16 (27.1%) with sensitization only at 9 year. Conclusion: The status of chronic rhinitis and allergen sensitization is very changeable in children. Background: Psoriasis juvenile idiopathic arthritis (PsJIA) is an autoimmune disease, which constitutes a small part of Juvenile Idiopathic Arthritis (JIA) and classified within the spectrum of JIA and psoriatic lesion. The onset often occurs between the ages 7-13 years, but some of them occurs under 5 years. Its morbidity, such as: leg discrepancy, irreversible joint damage, contracture, visual loss caused by chronic uveitis, and persistent pain can impact the life quality of the patient. It is important to make an early and precise diagnosis, and give the treatment as soon as possible in order to make the quality of life of the patient optimum. Methods: A six months longitudinal case report about a 3-year-oldboy with early onset psoriasis JIA and the result of the treatment. Results: A 3-year-old-boy presented with a year history of right knee swelling accompanied by inflamation sign, joint stiffness, dactylitis, skin redness, and also white scales that generalized over his body. At first he was diagnosed with Ichtyosis vulgaris, because of the persistent arthritis (>6 weeks), he was referred from Dermatology and Venereology Department to Pediatric Immunology-Allergy Department with the highly suspected of JIA. He was born at term, from P 1 A 0 mother by spontaneous vaginal delivery, with a birth weight 3400 grams. There is no history of JIA or psoriasis in his family. From the laboratory examination, there were anaemia, with a small increased of the erythrocyte sedimentation rate (ESR), but C-reactive protein (CRP), liver and kidney function were within normal limits. Antinuclear antibodies (ANA), rheumatoid factor (RF) and anti-ds-DNA were negative. Before the treatment, the patient looked stiff, could not stand up well and could not move his hands, fingers and feet. The fingers bent like claws. After 5 months therapy of methotrexate, NSAIDs, physiotherapy and also topical momethasone furoate 0,1%, he experienced laboratory and clinically remission of arthritis and psoriasis. Conclusions: The goals of therapy are to control pain and inflammation, prevent joint damage, preserve range of motion and muscle strength, strive for normal function, growth, nutrition, physical and psychosocial development and to control systemic manifestations. A multi-disciplinary team approach is essential in optimizing results. Physical and occupational therapy are important for some patients. Methotrexate (MTX) has been recognized as the most effective DMARDs and applicable in almost every countries. Genetic counseling and education about the disease is needed for every parents with affected child. Background: Histamine H2 antagonists are generally welltolerated. Severe hypersensitivity reactions to these are rare. However, an IgE-dependent mechanism has been suggested for hypersensitivity induced by H2-receptor antagonists. In addition, the possible cross-reactivity among H2-receptor antagonists has been existed. Objective: To investigate the clinical features of immediate hypersensitivity induced H2 antagonists and their cross reactivity. Methods: We retrospectively evaluated clinical characteristics of patients diagnosed as immediate hypersensitivity to H2 antagonists at 4 University hospitals in Busan, Korea and analyzed the data from skin test to various H2 antagonists. Results: A total of 12 patients were enrolled in this study. The mean age was 48 ± 4 years (rage 26-68) and 6 patients were female. Most common culprit drug was ranitidine (N=10, 83%) followed by cimetidine (N=1) and nizatidine (N=1). Half of patients had previously allergic reaction to H2 antagonists but were not diagnosed before. The mean latent time was 42.09 + 18.4 minutes (range, immediate~210). Background: Although there have been several studies reporting that rhizosphere cleaning effects of potted indoor plants (RCEIP) could decrease indoor pollutants (VOCs, particulate matter, etc.) and habitants' stress, impacts of RCEIP on allergic rhinitis (AR) have not been fully evaluated. Methods: Total 115 students (male=54, 11.9±0.3 years) from the two newly built elementary schools were included. Their demographic data and skin prick results (for 30 common inhalant allergens) were collected initially. For RCEIP, potted indoor plants of eight plantspecies were introduced to four classrooms (77 students) for three months, and the others were included to the controls. This process was done randomly and the single blinded (investigator) study scheme was kept until the completion. AR symptom-questionnaire (ARIA 2008 based), Korean Daily Hassles Scale for Children, Stress-Arousal Checklist, and Indoor Attractiveness Scale were surveyed before and after introducing indoor plants.
A 43-year-old male patient visited allergy department for evaluation of chest tightness, throat swelling and dyspnea 20 minutes after an ingestion of two strawberries. The patient had repeatedly suffered from multiple food allergies to peach, plum, apricot, raspberry, and apple since his childhood, which was presented as acute urticaria. Laboratory test results showed an elevated blood eosinophil count (1800 /mm 3 ) and an elevated serum specific IgE level to strawberry (measured by ImmunoCAP® [ThermoFisher Scientific, Uppsala, Sweden] system, 3.98 KU/L). Spirometry showed normal range. We assessed him as food allergy to strawberry and eosinophilia was thought to be resulted from the food allergy. After using systemic corticosteroid and antihistamines, blood eosinophil count decreased to normal range and the patient's symptoms were resolved. Five months later, he complained of acute urticarial, dizziness, dyspnea after ingestions of pineapple, celery, and sesame. Blood eosinophil count was 900 /mm 3 and serum specific IgE levels to pineapple, celery, and sesame were 0.68 KU/L, 0.93 KU/L, and 0.77 Ku/L, respectively. One month later, the patients visited emergency department for acute urticaria, dyspnea, general weakness, and numbness of legs after an ingestion of almond. Blood eosinophil count was 1,600 /mm 3 and serum specific IgE level to almond was 4.63 KU/L. Recurrent episode of anaphylaxis due to multiple food was occurred with eosinophilia and food avoidance strategy was failed because of allergic reactions to unknown food. Furthermore, sesame was widely used to various Korean food as a spice. Omalizumab was treated monthly to him to control the IgE-mediated food allergy. After the treatment, there was no episode of anaphylaxis to him and the patient performed his daily tasks without disturbances. When complete avoidance of food allergy is impossible, omalizumab can be an alternative treatment to control symptoms. Second-generation antihistamines are widely prescribed for the control of symptoms of allergic inflammation such as itchy hives, coryza, and itchy eyes. In rare circumstances, these drugs can provoke allergic inflammation. Hypersensitivity to bepotastine besilate, a second-generation antihistamine has never been reported. A 17-year-old schoolgirl, whose paroxysmal itchy hives had been controlled with bepotastine, experienced aggravation of the hives. An oral provocation test confirmed her hypersensitivity to bepotastine and cross-reactivity to levocetirizine. She showed no reaction to chlorpheniramine, ketotifen, or olopatadine among the 13 antihistamines tested. While searching for an antihistamine to control her itchy hives, we found that she also exhibited cross-reactivity to various antihistamines with different chemical structures from that of bepotastine, which is not predicted according to the chemical classification of antihistamines. We report on a case of hypersensitivity to bepotastine besilate in a patient with chronic spontaneous urticaria. Background. Optimal asthma symptom control cannot always be achieved in severe cases due to the risk of steroid resistance and lack of response to beta-agonists. Therefore, alternative approaches are needed to achieve reversal of pathological airway remodelling in steroid resistant severe asthma. IL-4 and IL-13 cytokines are critical for asthma pathogenesis as they modulate IgE synthesis, chemokine production, airway eosinophilia, smooth muscle hyperplasia, and mucus production during asthma. During the past decade, several nanoparticles approaches have been developed and tested for efficient drug and anti-inflammatory agents delivery at various body sites during cancer other chronic inflammatory diseases. The current study evaluated the anti-inflammatory responses following intratracheal instillation of functionalized and PEGylated nanocarriers containing blocking anti-IL4Rα antibodies to the inflamed lungs of asthmatic mouse model. Methods. Anti-IL-4Rα loaded nanoparticles were administered intrapulmonary to asthmatic mice. Particles distribution within the lungs were then examined and their targeting of specific IL-4R+ inflammatory cells was investigated using MRI and histological analysis (immunohistochemistry, immunofluorescence). Multiple gene expression studies (RT-PCR), flow cytometry, cytokine arrays (Luminex) and histological analyses were performed on treated asthmatic lungs tissue and cells to evaluate the anti-inflammatory responses of these nanocariers. Results. Targeting and localization of nanocarriers with Perl's (iron), PEG (anti-PEG antibodies), immunofluorescence (SPIO nanocarriers with FITC labelled antibody) confirmed their localization with anti-IL-4R+ lung inflammatory cells. Following treatment of asthmatic mice with anti-IL-4R nanocarriers, a significant decrease in BAL levels of IL-1β, IL-10, IL-6, IL-13, GM-CSF, IL-5, IL-2, IL-4, MCP-1, IP-10/CXCL-10, MIG and IFN-γ was observed compared to Ova-sensitized mice. BAL levels of lymphocytes, neutrophils and eosinophils decreased significantly (p<0.01) in mice receiving anti-IL-4Ra loaded nanocarriers. Lung inflammation was significantly decreased as observed in histological analysis as well as gene expression of inflammatory cytokines (genes). In addition, a significant decrease in activation and functionality of lung inflammatory cells was observed suing FACS analysis following treatment with the IL-4R-nanocarrier. Conclusions. Treatment of inflamed lungs with anti-inflammatory IL-4Rα-nanocarriers was safe and efficient in reducing lung inflammation and controlling asthma pathogenesis. This approach could be effective in attaining asthma control in severe cases where alternative approaches for steroids are needed. Background: Allergen specific immunotherapy(SIT) is able to significantly improve symptoms as well as reduce the need for symptomatic medication. The SIT acts on basic immunologic mechanisms, and has the potential to change the pathological allergic immune response. The immunologic changes by treatment are achieved for a certain period of time, usually over 3~5 years. By the way, some patients present reduced allergic responses through immunotherapy in early stage. Immunologic responses to allergen may affect favorable clinical outcome during 1 year treatment. Methods: From 2009 to 2014, the patients with allergic airway diseases who received subcutaneous SIT with house dust mites and both allergen skin prick tests before therapy and after it on time about 1 year period were investigated for retrospective analysis. The main parameters of immunologic changes were skin reactivities(wheal ratio of allergen/histamine in skin prick test) for house dust mites ongoing immunotherapy. The numbers of positive allergen skin responses and some blood tests for eosinophil count, total IgE, ESR were collected as well. Results: Total 58 patients were analysed, the mean ages at initial immunotherapy time were 23.3 year old (5~60), males were 34 (58.6%), allergic rhinitis only were 35 (60.3%), bronchial asthma only were 1 (1.7%), both were 22 (37.9%). The median numbers of strongly sensitized allergens among 45 aeroallergens were two items at initial phage. The mean skin reactivities for target allergens before and after 1 year immunotherapy were 2.44 (0.5~7.75) and 1.19 (0~2.92), respectively. The skin reactivity for target allergen of ongoing immunotherapy were significant reduced in younger age group(<40 years old) (p=0.45 ), the groups who had small numbers of total allergen sensitization (p<0.05), house dust mites(HDM) sensitization only rather than those of mixed with HDM and pollens(p<0.05) and high reactivity(≥2 on A/H ratio) of target allergens (p<0.001) at initial time. But, there were not significant different among initial immunotherapy methods(rush or conventional), underline allergic airway disease, eosinophil count, total IgE and ESR level. Conclusion: This study suggests some clinical factors associated favorable allergen reactivity change may affect good clinical outcomes in early phase of immunotherapy. Background: Acute rejection (AR) in kidney transplantation is one the most important causes of rejection in Iran and the world. Considering the role of inflammatory cytokines in this process and due to this fact that genetic polymorphisms can alter the function of these cytokines, we aimed to evaluate various single nucleotide polymorphisms (SNPs) related to TNF-α, IL-6, IFN-γ and IL-1β cytokine genes. Methods: Genomic DNA was extracted from whole blood of 56 patients with acute rejection, and 56 patients with a stable graft function (SGF). A Polymerase chain reaction with the sequence specific primers (PCR-SSP) was performed using related kits. The results were analyzed by statistical software SPSS and Epiinfo. Results: The frequency of A and G alleles related to -308 and -138 positions of TNF-α, and alleles C and G of the -174 position related to IL-6 showed a significant association in patients with a transplanted kidney (Both AR and SGF) compared to controls (P value<0.05). Data related to both TNF-α SNPs, and GG, CG genotypes of -174 position (IL-6) revealed a significant relationship between AR and healthy controls. In addition, results from the comparison of SGF and healthy controls in -238(TNF-α) and -174(IL-6) positions showed a significant correlation. Haplotype analysis among study groups also displayed statistically significant associations. Conclusion: This study found an association between TNF-α and IL-6 gene polymorphisms in kidney graft rejection or survival processes. More studies with greater samples of various populations are needed in order to confirm this finding. Phthalates are widely used in our daily lives, including flooring, toys, food wrapping, plastic ware, emulsifying agent, lotion and shampoo. Several studies reported the association between the exposure to phthalates and allergic disorders. Also, some conflicting results reported whether atopic dermatitis is associated with overweight or obesity. We evaluated the association of phthalate exposure and overweight/obesity in atopic dermatitis (AD) of Korean children and adolescents.


Conclusions: This study revealed a significant differences for the emotional functioning in QOL between obese-atopic disease and obese-non atopic disease groups, but no significant differences in other scales. Further studies is needed to understanding the relationship between obesity and atopic disease to the patient's QOL. Background: Exacerbations of asthma are most frequently attributed to upper and lower airway infections by respiratory viruses such as rhinovirus and influenza viruses. Host cells protect against these virus via innate and acquired immune responses. MicroRNAs act as key regulatory molecules in complicated interaction networks between viruses and hosts. However, a few studies have been performed on miRNA related with influenza infection. The aim of this study is to search for candidate miRNAs by in silico analysis, and validate the relation of the miRNAs in sputum with exacerbation of asthma. Methods and Materials: Information on sequences of mature human miRNAs was obtained using miRBase ( and applied to the whole genome sequence of influenza viruses A ( by searching complementarity. Viral RNA and miRNA were extracted from sputum of exacerbated asthmatics using Viral Gene-spin¢â kit (iNtRON Biotechnology, Seoul, Korea) and miRNeasy kits (Qiagen, CA, USA), respectively. RT-PCR and Real-time PCR were applied to the discovery of 7 respiratory viruses (adenovirus, human metapneumovirus, parainfluenza virus 1/2/3, influenza A/B virus, respiratory syncytial virus A/B and rhinovirus A) and the measurement of miRNAs, respectively. Results: Total 2578 human miRNAs were used for analysis. Among them, miR-23b-3p was predicted to match with 7 nucleotides in one location +1915-+1921 of polymerase basic protein 2 mRNA and to three locations +244-+251, +1446-+1453 and +1470-+1477 of haemagglutinin mRNA of influenza A. Respiratory viruses were identified in 21 patients out of total 37 patients and 5 patients were infected by influenza A virus. The levels of miR-23-3p were much lower in patients infected with influenza A and rhinovirus (n=9) than those of other virus-infected (n=7) or uninfected patients (n=16). The levels of miR-23b-3p in influenza A-infected patients were comparable with those in rhinovirus-infected subjects. Conclusions: Down regulation of miR-23b-3p expression may be associated with infection with influenza A virus and might exert a negative regulatory activity on the influenza A virus replication. Due to the high frequency of allergic diseases and its special growing rate among the world population, in medicine, the 21st century is called the century of allergy. It is known that allergic diseases (pollinosis, bronchial asthma), the highest percentage comes on the allergens-aeropolutants, that are represented in many plants and herbs in the form of dust (ragweed pollen, alder, birch, maple, walnut, mallow, cotton plant etc). Since 2006, Institute is actively working in this direction gradually after the World Allergy Organization (WAO) presented the apparatus -Burkhard Pollen Trap (UK) to the Institute. Research is actively continued in this direction and the results are published periodically in international journals and became public as the reports at scientific congresses. According to the all above-mentioned, the aim of the study at this stage is as follows: identification of specific aeropollutants and elaboration of annual calendar of plants blossoming for the reality of Imereti region. In this study have been involved 69 patients of different ages (among them 34 males and 35 females) with allergic rhinitis and asthma, who applying to the S/R Institute of Allergy, Asthma and Clinical Immunology of Academy of Sciences of Georgia (Tskaltubo, Georgia) for allegro-diagnostics, revealed increased levels for Phadiatop in blood, on the existence of atopic allergen only to the inhaled allergen. The study covered the following allegro-diagnostic stages: I stage -For precise verification of the allergen, patient's blood serum was examined on a particular specific-IgE antibodies by modern automated system -"Immuno CAP 100" (PHADIA, Switzerland). II stage -Monitoring of the concentration of aeropoluments was conducted by using aeropolinometer "Burkard Trap" (Great Britain). The analysis of the laboratory results, obtained through the automated system "ImmunoCAP 100"* showed that the studied patients had high titers of specific IgE on the weeds (Wx2) -ambrosia, plantain, absinth, atriplex 47 (68%); tree dust (Tx9) -alder, lactarius piperatus, nuts, oak, willow -21 (30%); cereals (Gx1) -festuca pratensis, lolium temulentum, timoti grass, poa -19 (28%). A specific IgE concentration was detected for each positive panel, to reveal the concrete allergen. The mentioned patients were provided with: the data of aeropolinometer-"Burkard Trap", annual calendar for distribution of aeroallergens reflecting concentrations of blossoming plant-trees and atmospheric aerosols in the air in Imereti region at a given period of time. Extracorporeal membrane oxygenation (ECMO) has been used primarily to treat respiratory failure due to acute respiratory distress syndrome that failed to respond to maximal medical therapy. The use of ECMO in status asthmaticus is limited to case reports. We present three cases of patients with near-fatal status asthmaticus not relieved by conventional treatment, in whom early administration of ECMO resulted in a good outcome. In case 1 and 2, ECMO was instituted because of sustained hypercapnia and respiratory acidosis within 2 hours after initiation of mechanical ventilation. Patient 3 was supported by ECMO at 10 hours after intubation because of severe hypotension and hypercapnia. The lung status in these patients was rapidly recovered within days, and they were extubated at 31, 67 hours and 4 days after initiation of ECMO, respectively. Successful weaning of ECMO was complete the next day after extubation in all patients. There was no significant complication related with ECMO in these patients. Mechanical ventilation for the patients with refractory status asthmaticus can have deleterious effects due to worsening dynamic hyperinflation and increase intrathoracic pressure. Early ECMO application is a useful treatment options for these patients failed to conventional therapy. Background: Atopic dermatitis (AD) is a complex and heterogeneous disease influenced by genetic and environmental factors. In the last decade, previous efforts in finding AD associated loci have identified unprecedented amount of associated loci. However, the previously reported genetic loci explain only a small proportion of the heritability. Thus, further analysis on unrevealed genetic component is required to solve the missing heritability problem. In this context, whole-exome sequencing analysis have gathered much attention to find functional variants with relatively high genetic effects. In the present study, we performed whole-exome sequencing study to identify functional variants responsible for severe AD in Korean childhood. Methods: The case-control samples of 32 severe AD patients and 20 normal individuals were recruited from the Childhood Asthma Atopy Center of Asan Medical Center, diagnosed by physician. The cases and controls were sequenced by Illumina Hi-Seq 2500 with Agilent SureSelectXT Human ALL Exon V4+UTR Kit. Sequence alignment was performed using Burrows-Wheeler Aligner. Variants were called using Genome Analysis Toolkit (GATK). We identified 233,254 single nucleotide variants (SNVs), of which 131,321 SNVs passed quality control criteria (HWE p-value<10-3, Missing rate >10%, Minor allele count <2). Of these, 34,991 variants were nonsynonymous SNPs. A Chi-square test was conducted to find disease-associated variants. Results: We identified three missense variants in a 112bp window at ZNF443(p-value<10 -4 ). For p-value<10 -2 , 137 missense variants were discovered. Among them, 2 variants at NLRP10 and CYP24A1 were located nearby previously reported AD associated regions. Functional enrichment analysis showed that 47 SNVs were related with immune related genes such as ZBP1, FBXO38, MTR, TTN. Conclusion: In summary, we identified 137 missense variants susceptible to AD and replicated 2 previously reported loci. To validate the genetic effect of discovered variants, the replication analysis in an independent cohort is required. Most cutaneous molluscum contagiosum (MC) infection occurs in children, but it may be found in adults, especially who have been infected with human immunodeficiency virus (HIV). A 37-year-old man presented with multiple pea-sized firm skincolored round papules, which first appeared on the arms and then quickly spread over whole body for last 2 months. He has been treated for severe atopic dermatitis with systemic immunosuppressive therapies for 2 years. Screening test for HIV was negative. The lesions were diagnosed as MC based on histopathologic findings of typical eosinophilic cytoplasmic molluscum inclusion bodies on the acanthotic epidermis as well as dermal inclusion cyst. This is a very unusual case because widespread MC infection in adults was reported in some HIV positive patients. We supposed that our patient's disseminated infection may be related with the combination of perturbed skin barrier and systemic immunosuppressive therapy under severe atopic condition. Backgrounds: Macadamia nut is a tree nut listed as a major allergen to be labelled on pre-packaged foods globally. At least 19 cases of macadamia nut allergy have been reported to date, however, the eliciting allergenic proteins have not been identified and consequently component resolved diagnosis has not been developed. This study aims to identify putative allergenic proteins in macadamia nut by combining patient IgE recognition with an allergenomics approach. The challenge is that macadamia nut genome sequence is only partially complete. Methods: The proteomic profile was studied using a label-free shotgun proteomics approach. As the genome sequence of macadamia nut allergens is not available, homologies to other known allergens and affiliations to protein families were determined. The results from the allergenomic screening method were used to predict potential allergenic proteins and cross-reactivity with other plants particularly. The molecular weight distribution of proteins was determined by gel electrophoresis. Following in-gel digestion with trypsin, proteins were subjected to liquid chromatography coupled tandem mass spectrometry. Based on the shared peptide evidence, the identified proteins were clustered and the allergenic proteins were identified. Immunoreactive proteins were identified by immunoblotting with three patient sera confirmed to exhibit IgE-mediated reaction. Results: Peptides matched to the sequences of 21 allergenic proteins belonging to different protein families such as seed storage proteins (conglutins and vicilins), rubber elongation factor proteins, phosphate binding proteins and detoxifying methylglyoxalases were identified. This included peptide sequence homologies to 5 conglutins, which are known allergens from Lupin angustifolius. Conclusion: Allergenic proteins were confirmed to be seed storage proteins belonging to 11S, 7S and 2S proteins. Significant number of peptide sequence homologies to conglutins from Lupin angustifolius was observed, suggesting that there may be cross-reaction between macadamia and lupin allergens Background: Immunoglobulin E (IgE) triggers multiple inflammatory allergic responses and cytokine release when it binds to high-affinity IgE Fc receptor (FcεRI) on mast cells in atopic dermatitis (AD) and asthma. Anti-FcεRI antibody is a new option for treatment that may block IgE-FcεRI binding and therefore may reduce inflammatory cascade in allergic diseases. However, the potential effects and mechanism of anti-FcεRI antibody remain poorly understood. Objective: We investigated the effect and mechanisms of anti-FcεRI antibody by blocking the combination of IgE-FcεRI antibody in allergic march (AM) mice model. Methods: We developed mice model of AM with three 1-week exposures (separated by 2-weeks interval) to an ovalbumin (OVA) or saline followed by OVA inhalation (challenge). In order to develop a mice model of AM, the day before sacrifice, all mice inhaled 1% OVA as the airway challenge. Anti-FcεRI antibody was administered to the mice intraperitoneally for 4 consecutive days before the end of study. Identification of interleukin (IL)-17 expression was performed by immunohistochemistry and real time PCR on skin and lung specimens. Results: Anti-FcεRI antibody treated AM mice had significantly decreased phenotypes (e.g., clinical score, airway hyperresponsiveness, and pathology) of AD and allergic asthma. In addition, the levels of total IgE, OVA-specific IgG1 and IL-13 in serum were significantly lower in AM mice treated with anti-FcεRI antibody. The level of prostaglandin D2 and the number of mast cells in skin were also decreased in the anti-FcεRI antibody treated with AM mice. Furthermore, the skin and lung expressions of IL-17 were reduced after the treatment of anti-FcεRI antibody. Conclusion: IgE-FcεRI blockade by Anti-FcεRI antibody can suppress the IgE-mediated phenotypes and inflammatory responses in AM. And its mechanism may be the decrease in IL-17 via the suppression of FcεRI-mediated mast cell activation. Background: Anti-thymocyte globulin (ATG) is an immunosuppressant derived from horse or rabbit-immunized with human thymus lymphocytes and commonly used for the prevention and treatment of acute rejection in organ transplantation and aplastic anemia. Hypersensitivity to ATG can be life-threatening but there are not many clinical data from the real practice. Therefore, this study aimed to investigate the clinical characteristics and outcomes of ATG hypersensitivity. Methods: Cases of hypersensitivity reaction to rabbit ATG were retrieved from a database of individual case safety reports in Seoul National University Hospital from 2010 to 2015. Clinical characteristics of hypersensitivity reactions were analyzed according to involved organ system and severity was assessed according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Results: Among 82 patients, male was 36 (44.4%). The average age was 21.5 ± 19.6. High fever (100%) was the most frequent symptom followed by chill (95%) and cutaneous symptoms (65%) such as itching sense, flushing, urticaria and rash. The following majority of symptoms is gastrointestinal symptoms such as nausea, vomiting, abdominal pain and diarrhea. The mean severity was CTCAE grade 2.7 ± 0.9. Although all patients were premedicated with antihistamine and steroid, 51.2% had grade 3 or 4 reactions including cases presented with profound hypotension (36.0%). After the development of ATG hypersensitivity, most patients were able to continue the following ATG infusion by increasing the doses of anti-histamine and steroid (76.5%) or by slowing infusion rate (13.6%), and desensitization (7.4%). Conclusion: ATG hypersensitivity reactions presented as a severe form in half of cases reported. However, most patients with ATG hypersensitivity were able to continue ATG infusion by increasing premedication or modifying infusion protocol. Background: Total serum Immunoglobulin (IgE) is known to be an essential diagnostic tool for atopy and allergic diseases. It is difference according to host factors including sex, age, races. We evaluated the distribution of total IgE levels in Korean children and utility in the diagnosis of atopy and allergic diseases. Methods: In this nationwide cross-sectional study, 3,753 elementary schoolchildren (6-7 yr olds) and 3,930 middle schoolchildren (12-13 yr olds) were enrolled. Total IgE levels were measured and skin prick tests were performed for 18 common inhalant allergens. Children and parents answered the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. We analyzed the diagnostic value of total IgE by using ROC (Receiver operating characteristic) curve and compared total IgE levels according to atopy and allergic diseases such as atopic dermatitis, bronchial asthma and allergic rhinitis. Results: The total IgE ranged from 1.5 to 4,523.1 kU/L in elementary schoolchildren and 1.5 to 3,000 kU/L in middle schoolchildren. The median total IgE level was 86.7 kU/L (75th percentile, 292.6 kU/L; 90th percentile, 698.5 kU/L; 95th percentile, 1,200.7 kU/L) in elementary schoolchildren and 94.7 kU/L (75th percentile, 284.3 kU/L; 90th percentile, 625.1 kU/L; 95th percentile, 990.7 kU/L) in middle schoolchildren. The median total IgE level was significantly higher in atopic group defined as any positive SPT (elementary schoolchildren, 246.5 kU/L; P<0.0001, middle schoolchildren, 206.1 kU/L; P<0.0001) and any allergic disease group (elementary schoolchildren, 108.3 kU/L; P<0.0001, middle schoolchildren, 141.2 kU/L; P<0.0001). In ROC analysis of total IgE for diagnosing atopy, AUC was 0.7835 (95% CI, 0.7688-0.7982) in elementary schoolchildren and 0.8165 (95% CI, 0.8032-0.8297) in middle schoolchildren. At the optimal cut-off value of 127.7 kU/L in elementary schoolchildren and 63.0 kU/L in middle schoolchildren, sensitivity, specificity, and positive and negative predictive values were 67.06%, 75.38%, 65.44%, and 76.70% in elementary schoolchildren and 81.91%, 66.63%, 75.01% and 75.08% in middle schoolchildren respectively. Conclusions: Total serum IgE level was higher in children with atopy or allergic diseases, but the value of total serum IgE as a diagnostic test for atopy is limited due to the low sensitivity and specificity. Severe immediate hypersensitivity reaction (IHR) to contrast media (CM) is one of the legal problems in the hospital. The overall prevalence of IHR was 0.16%-7.7% with nonionic CM. In order to reduce immediate drug adverse reaction and legal problem, prescreening skin testing has been before administration of antibiotics such as penicillin and cephalosporin. It may be important to avoid cross-reactive agent and to select the alternative safe drug. Clinical value of CM prescreening skin testing is controversy. CM prescreening skin testing might be useful for reducing the IHR. We aimed to evaluate the incidence of IHR to nonionic CM in two-step prescreening skin testing group. Method This is a retrospective study. We reviewed CT cases performed between Jan. 2008 and Dec. 2014. All patients were performed skin testing just before their pending nonionic CM-enhanced computed tomogram (CT). Skin testing and CT scan were performed through two-step process. One step; 1 st Skin test was performed with a common nonionic CM. If 1 st skin test negative, nonionic CM-enhanced computed tomogram (CT) was performed. Second step; If 1 st skin test positive, 2 nd skin tests were performed with two other nonionic CM and saline (negative control). If 2 nd skin test negative, 2 nd skin test negative nonionic CM-enhanced CT was performed. If 2 nd skin test positive, clinician gave patients premedication before enhanced CT or exchanged alternative radiologic test without CM. Results IHR were noted in 21 of total 26638 patients (0.08%). 5 of 26638 patients (0.01%) had severe IHR. Symptoms of IHR were nause/vomiting, erythema/urticaria/pruritis,dyspnea, chest tightness, angioedema, hypotension and syncope. Conclusion Nonionic CM prescreening skin testing through two-step process may be useful for reducing IHR and for selecting safe CM. The evaluation of trigger allergen is important for the treatment and prevention of allergic rhinitis (AR). Several nationwide studies revealed that there were regional differences in prevalence of allergy sensitization for individual allergens and allergen types. In this study, using MAST CLA, we evaluate the allergen in AR patients in state level; Gwangju, Jeonnam area. We evaluated the differences in allergic sensitization across the levels of urbanization. Methods A total of 873 patients from Gwangju-Jeonnam region with allergic symptoms underwent MAST. Total nasal score (TNS) and serum total IgE were evaluated. 39 panels were evaluated in MAST and allergens with results greater than class 2(≥0.7 IU/mL) in considered as positive. Prevalence and distributions of allergen-specific IgEs and their correlations to serum total IgE and TNS were analyzed according to levels of urbanization and age.


Methods: Clinical and demographic information of subjects with CU-AIGA consulted to our clinic was summarized retrospectively. Digital blood flow (tissue blood flow, blood volume, and flow velocity) was measured with laser tissue blood flow meter before and after the standing position. Quantitative sudomotor axon reflex test (QSART) was used to measure the sweat volume after administration of acethylcholine by iontophoresis. Results: All subjects with CU-AIGA failed to restore the digital blood flow after standing position indicating the impaired autonomic nerve abnormality. Results in QSART showed extremely decreased sweat volume after stimulation with acethylcholine. After therapeutic intervention (e.g. antihistamines, chinese herbal medicine, or steroid pulse therapy), improved these evaluation items was observed in some cases accompanied with urticarial symptom improvement. Conclusion: These results indicated the possible involvement of abnormal autonomic nervous function in cholinergic urticaria. The knowledge of possible causal relationship between CU-AIGA and autonomic nervous function may contribute to formulating the novel therapeutic strategies for this disease. Background: Interleukin 1 beta (IL-1β), which is produced by inflammasome activation, involves to the various processes of chronic inflammatory diseases. Recently, although inflammsome activation is observed in chronic inflammatory airway diseases, its role in asthma has not yet been studied. The aim of the study was to investigate the relation of sputum IL-1β with inflammatory phenotypes and severity of asthma. Methods: Hypertonic saline induced sputum was obtained from asthma in stable state (n=143) and in exacerbated state (n=48). Differential cell count of induced sputum was done. IL-1β was measured using sandwich ELISA in induced sputum. The levels were analyzed in terms of airway obstruction (FEV1%) and inflammation (neutrophil % and eosinophil % of induced sputum) and exacerbation frequency and lung function over 1 year or longer follow up. Results: IL-1β levels were significantly correlated with the neutrophil cell counts of induced sputum (r=0.186, p=0.010), but not with initial FEV1% in total asthmatics (p>0.05). The correlations of IL-1β levels with neutrophil % (r=0.188, p=0.025) and eosinophil % (r=-0.178, p=0.033) were observed in stable asthmatics. In the exacerbation group, IL-1β levels were inversely correlated with FEV1% (r=-0.326, p=0.024). In long term follow up of stable asthmatics (n=71) over more than 1 year, IL-1β levels were correlated with the follow up FEV1/FVC (r=-0.318 p=0.007). Annual average exacerbation rate was also well correlated with the IL-1β levels in the subjects with neutrophilic inflammation (>70%) in sputum. Conclusion: Sputum IL-1β may be related with neutrophilc inflammation. In exacerbated state and long -term follow up of asthma, sputum IL-1β may also be related with the extent of airway obstruction. These data suggest the IL-1β may participate to airway obsturction and exacerbation frequecy, especially in neutrophilic inflammation. Background: Neutrophilic airway inflammation is often observed in non-atopic adult asthma. Interleukin 8 (IL8) is a potent pro-inflammatory cytokine recruiting and activating neutrophils. The relation of IL8 has been revealed with exacerbation of asthma, however its role has not been revealed in terms of prognosis in asthma. The aim of the study was to investigate the relation of sputum IL-8with inflammatory phenotypes, severity and long -term prognosis of asthma. Materials and Methods: Hypertonic saline induced sputum was obtained from asthma in stable state (n=88) and in exacerbation (n=55). Differential cell count was done. IL-8 was measured using sandwich ELISA. The levels were analyzed in terms of airway obstruction (FEV1) and inflammation (neutrophil and eosinophil % of the airway) and exacerbation frequency and lung functions over 1 year or longer follow up. Results: IL-8 levels were significantly correlated with the percentages of neutrophils (r=207, p=0.012) and neutrophils count (r=0.277, p=0.001) in sputum, and inversely with the levels of FEV1% (r=-0.277, p=0.028) in total asthmatics. The correlations of IL-8 levels with percentages of neutrophils (r=0.312, p=0.003) and FEV1% (r=-0.252, p=0.018) were also observed in stable asthmatics. In the exacerbation group, IL-8 levels were inversely correlated with FEV1% predicted values (r=-0.272, p=0.045). In long term follow up over more than 1 year, IL-8levels were positively correlated with annual number of exacerbation (n=109, r=0.227, p=0.017). Conclusion: sputum IL-8 is related with neutrophilc inflammation rather than eosinophilc inflammation of asthma. In long -term follow up of asthma, increase of sputum IL-8 may be one of susceptible factors for frequenct exacerbation. Background: To know the major soluble factors responsible for immunomodulatory effects of adipose-derived stem cells (ASCs) in an asthmatic mouse, we evaluated the effects of ASCs on allergic inflammation in the indoleamine 2,3-dioxygenase knockout (IDO-KO) mice and mice treated with prostaglandin E2 (PGE2) inhibitor and transforming growth factor-β (TGF-β) specific neutralizing antibodies. Methods: ASCs were injected intravenously in wild-type (WT) and IDO-KO asthmatic mice. PGE2 inhibitor and TGF-β neutralizing antibodies were injected intraperitoneally on four consecutive days at the approximate time of ASCs injection. We investigated the immunomodulatory effects of ASCs between WT and IDO-KO mice, WT mice treated with and without PGE2 inhibitor, and WT mice treated with and without anti-TGF-β antibodies respectively. Results: In WT and IDO-KO asthmatic mice, ASCs significantly reduced airway hyperresponsiveness, total inflammatory cells and eosinophils in the bronchoalveolar lavage fluid (BALF), eosinophilic inflammation, goblet cell hyperplasia, and serum total and allergenspecific IgE and IgG1. ASCs significantly inhibited Th2 cytokines (IL-4, IL-5, and IL-13) and enhanced Th1 cytokine (IFN-γ) and regulatory cytokines (IL-10 and TGF-β) in the BALF and lung draining lymph nodes (LLNs). Furthermore, ASCs engraftment caused significant increases the regulatory T cells (Tregs) and IL-10 + T cells populations in LLNs. However, when treating mice with PGE2 inhibitor and TGF-β neutralizing antibodies, blocking PGE2 and TGF-β, but not IDO-KO mice, eliminated the immunosuppressive effect of ASCs in allergic airway inflammation. Conclusion: ASCs themselves are capable of secreting PGE2 and TGF-β, which may play a role in inducing Tregs expansion. Furthermore, PGE2 inhibitor and TGF-β neutralizing antibodies eliminated the beneficial effect of ASCs treatment in asthmatic mice, suggesting that PGE2 and TGF-β are the major soluble factors in suppressing the allergic airway inflammation. Recently, the number of patients suffering from allergic diseases such as asthma or rhinitis has increased especially in developed countries. The reason is unclear, but many study have demonstrated that particle pollutants such as diesel exhaust and sand dust may exacerbate allergic responses. Furthermore, several nanometer-to micrometer-sized tiny particulates, such as particulate matter 2.5 (PM2.5) that is less than 2.5 micrometers in diameter, could enter into the respiratory tract and settle deep in lungs, causing pulmonary chronic inflammation such as asthma. Most particulates including particle pollutants are considered to function as immune adjuvants to enhance allergen-specific type 2 responses. However, the basis for the adjuvanticity of these particulates and the mechanisms by which they elicit type 2 responses remain poorly understood. Here, we show that particulate induce inducible bronchus-associated lymphoid tissue (iBALT) in the lung as a consequence of cell death of alveolar macrophages and IL-1α release. Particulate, alum or silica, was administered by intratracheal (i.t.) instillation and then we analyzed the particulate-induced lung inflammation. A histological analysis showed that, in addition to the infiltration of inflammatory cells, many lymphoid clusters, with the size of 100-300 mm in diameter, were induced in the lung. These clusters were mainly composed of B cells, and were characterized by area of B220 + and CD21 + cells, that is inducible bronchus-associated lymphoid tissue (iBALT). These clusters contained germinal center (GC) B cell area and T cell areas and generated CD138 + cells (plasmablasts), indicating that alum-induced iBALT structures function as tertiary lymphoid organ in the lung. I.t. alum instillation induced IL-1α released in the lung by alveolar macrophage (AM) cell death, and the number of iBALT formation was clearly reduced in IL-1R-deficient mice. Interestingly, IgE responses were also attenuated in IL-1Rdeficient mice, coincident with decreased number of iBALT structure. Our findings suggest that particulates induce unique immune responses in the lung through AM cell death and tertiary lymphoid organ formation, and that AM-IL-1α-iBALT axis may be a unique therapeutic target of particulate-induced allergic inflammation. Background: The present study sought to investigate the association between smoking and allergic diseases including atopic dermatitis, asthma, and allergic rhinitis in the Korean adult general population. Methods: A cross-sectional study was performed using data from 33,943 subjects aged 19 years or more who participated in the fourth and fifth Korean National Health and Nutrition Examination Survey performed in 2007-2012, which represents the Korean general population. Multiple logistic regression analyses were conducted to estimate the odds ratios of each allergic condition according to the smoking status with adjustment for potential confounding factors including age, sex, region of residence, level of education, income, and alcohol consumption. Results: After adjusting for potential confounders, neither atopic dermatitis nor asthma was associated with the smoking status (p=0.385 and 0.340, respectively). In contrast, compared to never-smokers, the odds of allergic rhinitis was significantly lower in current smokers (odds ratio [95% confidence interval] 0.76 [0.66-0.87], p < 0.001), and higher in ex-smokers (1.16 [1.02-1.32 ], p = 0.028) after adjusting for confounders. Conclusions: The present results may suggest the complex relationship between smoking and allergic conditions. Backgrounds: We previously reported elevation of S100A9 protein in sputum of neutrophilic severe uncontrolled asthmatics compared with stable asthmatics [Annals of allergy, asthma, immunology on 2013 Oct;111(4):268-275] suggesting possible role of S100A9 in neutrophilic severe asthma. IL-1beta(IL-1β) and IL-18, which are released by activated inflammasome, exert neutrophil -activating activities. The aim of this study was to evaluate the temporal relationship of S100A9 with inflammasome activation in neutrophilicmurine C57BL/6 mice model using CFA/OVA-sensitization/challenge. Methods: Expression of S100A9, S100A8 mRNA and protein levels and activated caspase-1 were measured in the lung tissues of the CFA/OVA modelusing a RT-PCR, real-time PCR and western blot. Spatial expression of S100A9 protein and inflammasome -related proteins were visualized by immune fluorescent stain. To evaluate the relation of S100A9 on activation of inflammsome, temporal changes of neutrophil infiltration and activation of caspase-1 were analyzed after intra-tracheal administration of 10ug S100A9 protein.


Results: S100A9 and P20 -activated caspase-1 started to increase from day 14 and peaked at day 23,earlier than the number of total cells, macrophage and neutrophils significantly increased with concomitant increase of airway resistance at day 23. Neutrophil elastase, S100A9 and activated caspase-1 co-localized on peri-bronchially infiltrating cells and apical portion of bronchial epitheliumusing confocal microscopy. Intra-tracheal instillation of S100A9 protein induced rapid increase of activated caspase-1 in the lung tissue from 2 hr, peaked at 8 hr, then progressively decreased till 80 hr with concomitantincrease of neutrophilsin BAL fluids. Conclusions: S100A9 may induces neutrophilic inflammation via direct activation of inflammsome in the airway. Asthma is a heterogeneous disease and has been classified into several phenotypes on the basis of allergic, inflammatory and clinical manifestations, such as atopic or non-atopic, eosinophilic or neutrophilic, and severe or non-severe subtypes. Cluster analysis is the task of grouping a set of objects in such a way that objects in the same group are more similar to each other than to those in other groups. Cluster analysis is applied to development of asthma sub-phenotypes and demonstrated the differences in clinical response to treatment, distinct phenotypes of severe asthma, clustering in extended populations including both asthma and chronic obstructive pulmonary disease, and clusters using additional parameters such as inflammatory biomarkers and obesity. In the present study, we investigated clusters reflecting the prognosis of asthma in terms of exacerbation over one or more years.


The During the last decades, the prevalence of metal contact allergy has been high. Among Danish female patients as well as North American patients, the occurrence of metal sensitization has increased. The importance of metal exposure from fixed orthodontic appliance is under discussion as fixed orthodontic appliance contain metals including nickel, chromium, cobalt and mercury. As our knowledge, it would be the first report about relationship between metal allergy and orthodontics. We investigated the association with prevalence of metals including nickel, chromium, cobalt, and mercury by patch test and orthodontic appliance. Additionally we investigated the coincidence of resin and colophonium sensitization which is adhesive materials of orthodontic appliance with the patients with orthodontic appliance. In total, 150 patients were included and performed patch test. The patients characteristics including orthodontic appliance history were collected with a questionnaire and clinical investigation. The incidence of metal allergy was significantly high in the patients with experience of orthodontic appliance. Especially nickel and cobalt allergy were more significantly correlated with orthodontics history. In metal allergy, orthodontics could be an important role. The atopic triad of allergic asthma, allergic rhinitis, and atopic dermatitis are reaching epidemic proportions. Epidemiological studies show that 20-40% of the world population is afflicted with allergies. In local setting, more than 10 million Filipinos are reported to suffer from allergic diseases. Allergies are multifactorial immunological disorders that involve genetic and environmental factors in its development, chronicity and severity. The pathogenesis of allergic diseases involves complex interactions between well-characterized environmental allergens and poorlyunderstood genetic factors. In addition, the decline in the number of infectious stimuli during the development of the immune system may contribute to allergy pathogenesis, a paradigm called "Hygiene Hypothesis" that supports the steep rise of allergies in developed populations. In contrast to the effect of environmental allergens, pathogenic and non-pathogenic microoganisms or their structural components can exert pressure on the immune system to modulate the development of allergic responses. Furthermore, the effect of different polymorphisms may play important role in an individual's predisposition to allergic diseases. In recent years, findings on the combined effect of environmental allergens, genetic polymorphisms, the absence of infections and other environmental factors are starting to converge, producing fascinating results on gene-environment interactions that may explain the development of allergies. Understanding the biochemical nature of allergens and the identification of genetic polymorphisms implicated in allergies has advanced our knowledge on the disease prevalence, healthcare burden and pathogenesis of allergies. Elucidating the mechanisms of interactions between the genes and the allergens involved in the pathogenesis of allergic diseases will help enhance the present medical armamentarium for the diagnosis and therapy of allergies.


One hundred and twenty-six cases of anaphylaxis from PN, TNs and seeds were identified (64.3% in male patients) and the mean age was 4.9 years (0.8-18.9 years), with 81.7% of subjects under seven years old. The number of patients increased from 9 cases in 2009 to 57 cases in 2013. PN accounted for 32.5%, walnut (WN) accounted for 41.3%, pine nut accounted for 7.1%, and other TNs and seeds accounted for 19.1%. The most common system involved was cutaneous (96.0%), followed by respiratory (87.3%) and gastrointestinal (26.2%). The proportion of patients with cardiovascular symptoms was significantly higher in older patients than in younger children (p = 0.001). The time intervals between ingestion of triggering food and onset of symptoms were immediate in 19.0% and less than two hours in 42.9%. Among 104 cases (82.5%) in which serum levels of specific IgE (sIgE) to corresponding allergens were measured, the median values of sIgE to PN, WN and pine nut were 10.50 (0.39-100.00) kU A /L, 8.74 (0.04-100.00) kU A /L and 4.61 (0.60-4.61) kU A /L, respectively. Among 50 cases managed in the emergency department, patients were treated with intramuscular epinephrine in 52.0%, with systemic steroid in 66.0%, with antihistamine in 94.0%, with oxygen in 36.0%, and with bronchodilator in 48.0%. The overall percentage of patients prescribed an epinephrine auto-injector was 48.4%, with no significant differences between age groups. Conclusions Among anaphylaxis caused by PN, TNs and seeds in Korea, WN, PN and pine nut were the 3 most common triggers in order, and 9 other kinds of TNs and seeds were also identified as triggers. About 82% of cases were in children under the age of seven. The median levels of sIgE to PN and WN were 10.50 kU A /L and 8.74 kU A /L, respectively, and some of cases showed remarkably low sIgE levels, and < 0.35 kU A /L in three subjects. * This study was done by Food Allergy and Atopic Dermatitis Study Group in the Korean Academy of Pediatric Allergy and Respiratory Diseases. Perilla (Perilla frutescens) seed, also known as wild sesame seed is one of the popular spices in Asia but serious allergic reactions to perilla seed have been rarely reported. Herein we report two cases of anaphylaxis caused by perilla seed in children. A 25-month-old boy presented to the outpatient clinic at Ajou University Hospital with previous experiences of urticaria and facial angioedema immediately after ingestion of soup containing perilla seed powder at ages of 13 months and 21 months. He had past history of asthma and previous experience of lip angioedema after ingesting kiwi for the first time at 9 months old. As the specific IgE (sIgE) test to perilla seed is not commercially available, the sIgE to sesame seed, which belongs to Lamiales like perilla, was measured instead. The sIgE level to sesame seed was 2.98 kU A /L at 25 months, and was 3.37 kU A /L at 4 years of age. The sIgE level to kiwi was 1.42 kU A /L and multiple allergosorbent test chemiluminescent assay (MAST CLA) revealed no remarkable sensitization to inhalant allergens. To confirm the causal relationship, an open oral food challenge (OFC) with perilla seed powder was performed when he was 4 years old. Immediately after the contact of extremely small amount of perilla seed powder around his lips, he developed urticaria, facial angioedema, cough and rhinorrhea. He was treated with intramuscular epinephrine, after which his symptoms resolved completely. The second patient, a 5-year-old boy, presented to the outpatient clinic with a previous history of urticaria, lip angioedema, pruritis of tongue and hoarseness immediately after ingestion of seaweed soup containing perilla seed a few months before. He had past history of asthma, allergic rhinitis and atopic dermatitis and was previously diagnosed as allergic to egg white and peanut. He also had oral allergy syndrome to kiwi fruit. Moderate sensitization to alder, birch and white oak was noted in MAST CLA and sIgE levels to sesame seed, egg white, peanut and kiwi were 1.01 kU A /L, 1.47 kU A /L, 2.82 kU A /L and 3.19 kU A /L, respectively. The OFC test with perilla seed was not performed in this patient because his initial symptoms were compatible with anaphylaxis. For the etiologic confirmation, Enzyme-Linked ImmunoSorbent Assay (ELISA) and IgE western blot with crude extract of perilla seed produced in our own laboratory are in progress for both patients. To the best of our knowledge, this is the first report of anaphylaxis caused by perilla seed in children. Background: Particulate matter (PM) associated with more wheezing episodes, increased risk of asthma symptoms and respiratory tract infection in children. However, the impact of prenatal exposure to indoor PM on the health of children is poorly understood yet. Toll-like receptor 4 (TLR4) plays a critical role in responses induced by air pollution. Objective: To investigate whether prenatal exposure to indoor fine particulate matter (PM 2.5 ) affects susceptibility to wheezing in children, and to determine whether genetic factor modify this environmental effect. Methods: The study population consisted of the 323 children with indoor PM 2.5 data in a birth cohort. Recurrent wheezing was determined as 2 or more wheezing episodes diagnosed by physicians in the first 2 years of age. Indoor PM 2.5 was measured during pregnancy. Genotyping for TLR4 (rs1927911) was performed by TaqMan. Results: Prenatal indoor PM 2.5 exposure increased the risk of recurrent wheezing in 2 years of age (aOR 3.52; 95% CI 1.50-8.30). TLR4 CC increased the effect of prenatal indoor PM 2.5 exposure on recurrent wheezing (aOR 7.00; 95% CI 1.41-34.73; p for interaction 0.153). Conclusion: Indoor PM 2.5 exposure during the prenatal period increased susceptibility to recurrent wheezing. This effect was modified by polymorphisms in TLR4. Reducing PM 2.5 exposure from the prenatal period may prevent wheezing in susceptible children. Background B-lymphocytes (BL) play a critical role in Systemic Lupus Erythematosus (SLE). BL depletion therapy still remains an attractive option, despite the disappointing results of RCTs. Methods Twelve SLE patients [2 males, mean age 43.8 yrs (29-54)] with polyarthralgia and multiorgan involvement including class IV or III/V (ISN/RPS) glomerulonephritis (9 cases), skin lesions (9 cases, with necrotizing ulcers in3), polyneuropathy (7cases, with CNS involvement in 2), lymphoadenopathy (6) e polysierositis (5) have been treated withan IBLD protocol for intolerance to conventional immunosuppressive therapy (6 cases) or as a front line therapy (6 cases). Protocol: Rituximab 375 mg/sm on days 1, 8, 15, 22 , and 2 more doses after one and two months, associated with 2 IV administrations of 10 mg/kg of cyclofosfamide, and 3 infusions of methylprednisolone (15 mg/kg) followed by oral prednisone (0.8 mg/die, rapidly tapered to 5 mg/day in 10 weeks). No further immunosuppressive maintenance therapy has been given. Results IBLD obtained a complete depletion of CD20+ BL for 12-18 months. Patients had been followed-up for 48.9 (25-93) months. A significant decreases (p<0.05) were found in the levels of ESR (baseline mean value: 54.2 mm; 3 months: 33; end of follow-up: 14.9), anti-dsDNA antibodies (baseline: 192 U; 3 months: 112; end of follow-up: 17) and proteinuria (baseline: 4.9 g/24 hours; 3 months: 0.97; end of followup: 0.22). Conversely, C4 values (baseline 11 mg/dl) significantly increased (p<0.05) after 3 months (22 mg/dl) and at the end of the follow-up (20 mg/dl). Three patients relapsed after 36, 41 and 72 months, respectively. They showed again a complete remission after retreatment over 13-48 months of observation.


In preschool children, with the management of asthma after exacerbation, lung function assessed by impulse oscillometry improved in different degrees. R5, Fres and AX may reflect the ongoing improvements. Assessment of respiratory mechanics over time with oscillometry might offer useful insights into the response of asthmatic preschool children to therapy. Further studies should focus on longer term of management and the relationship between impulse oscillometry and airway inflammations. Sulfites are in widespread use as preservatives or antioxidants even in cosmetic products. It was published that sodium metabisulfite could be a marker for sulfite allergy in cometics. However contact allergy to sodium sulfite is less well recognized. The relationship with sodium sulfite and cosmetic contact dermatitis is rarely known. We sought to establish the prevalence of positive patch test reactions to sodium sulfite in our patient population with facial cosmetic contact dermatitis. 130 patients with facial contact dermatitis were included and performed Korean standard patch tests, some of cosmetic patch tests and sodium sulfite patch test. In result, positive allergic reactions occurred to sodium sulfite in 3.5% of the tested patients. Clinically the patients with sodium sulfite positive reaction showed aggravation of facial symptoms after using cosmetic products including sulfites. Interestingly these patients experienced aggravation after eating sulfite containing food including dried fruit, fried potato and canned food, etc.
The levels of sIgE to milk and casein were significantly higher in patients who failed CM OFC compared to those in cases who passed OFC. The cutaneous symptoms occurred in all patients who failed OFC, and 7 patients experienced anaphylaxis during OFC. The comorbidity of asthma was the only significant factor associated with increased risk of OFC failure in crude analysis. Background: Spatial and temporal variability in seasonal pollen concentrations can confound the results of field studies for new allergy medications. Allergen exposure facilities such as the Red Maple Trials Allergen Challenge Theatre™ (ACT) provide stable, controlled pollen concentrations year round and offer an alternative to field studies. A full scale validation of the ACT for ragweed (Ambrosia artemisiifolia) pollen challenge was performed. Methods: The ACT is a 4-zone facility holding up to 100 seats in a series of elevated rows. Pollen was injected into the air supply and blown into the facility through ducts located across the top of the front wall. Pollen concentrations in the ACT were measured using laser particle counters (LPC) and impact samplers (IS). For the technical validation, LPC were used to assess the long-term stability of pollen levels; IS were used to determine pollen uniformity at 15 locations in the room. For the clinical validation, thirty ragweed allergic subjects were exposed to ragweed for 4 hours on two separate days to assess the reproducibility of rhinitis symptoms. Pollen was monitored at 30 min intervals by 3 IS located in the patient seating area. Results: Three-hour stability results were comparable for LPC (5107 ± 244 g/m 3 ) and IS (4858 ± 414 g/m 3 ). Uniformity testing gave an average ragweed concentration of 4,622 g/m 3 ; with a front-to-back SD of ± 544 g/m 3 and a side-to-side SD of ±333 g/m 3 . For the subject challenges, the mean 4-hour pollen concentration was 3,929 g/m 3 for Day 1 and 4,099 g/m 3 for Day 2. Plateau (2-4 hour) nasal symptom scores were 6.28 ± 1.49 and 6.19 ± 2.14, p=0.74, respectively. Ocular symptom scores were 2.82 ± 1.4 and 2.93 ± 1.82, p=0.59, respectively. Conclusion: The validation studies showed that ragweed pollen levels in the ACT could be maintained stable over long periods. Subjects responded to the allergen challenge with reproducible rhinitis symptoms on different days. Facilities such as the ACT can provide a suitable means to test new allergy medications. Rationale: Allergen challenge chambers expose allergen-sensitive subjects to a predetermined concentration of allergen in a closed, controlled environment and provide a mechanism to induce clinical symptoms and measure the effect of medication. Methods: The Red Maple Trials (RMT) Allergen Challenge Theatre (ACT) is a 4-zone facility holding up to 100 seats in a series of elevated rows. Grass pollen (Phleum pratense) was injected into the air supply and blown into the facility through ducts located across the top of the front wall. A technical validation was performed to determine stability and uniformity of pollen concentrations in the room. Pollen counts were measured by a laser particle counter (LPC) positioned 5 ft above floor level and by impact samplers (IS) set at face level. IS were installed in 5 sections of a T-shaped quadrant and measurements taken every 30 minutes for 180 minutes. To evaluate the clinical response to grass pollen exposure, subjects with a history of grass allergy and positive skin prick test underwent two 3-hour challenges to grass pollen. Nasal and ocular symptom scores were recorded at baseline and every 30 min during the challenge. Results: For the technical validation, pollen counts measured by LPC were stable for 3 hours at 4,800 ± 500 g/m 3 . LPC pollen counts correlated well with IS counts over a range from 1,500 to 7,500 g/m 3 (LPC =0.849IS -269.0, r 2 =0.85). Mean pollen counts in each of the 5 sections of the quadrant ranged from 2,821 ±303 to 5,726 ±249. For the clinical validation, 17/32 patients had at least one Total Nasal Symptom Score (TNSS) ≥5 at challenge 1. In these subjects, mean change from baseline TNSS was 4.35±2.32 for challenge 1 and 4.94±2.41 at challenge 2, p=0.48. Total ocular symptom scores (TOSS) were 1.29±1.31 and 2.29±2.17, p=0.029, respectively.
Active vaccination surmounts the effects of passive antibody therapy in the mouse model, but the presence of IgE tops the antigenspecific experiments. This study therefore suggests that IgE antibodies may play a significant role in innate cancer surveillance as well as during active anti-cancer immune responses.


Results indicate there is an improvement in the nasal airway resistance after the practice of yoga. The quality of life improvement was understood with the help of the SF-12 and SNOT questionnaire. A healthy discipline of yoga as a lifestyle modification also helped the smokers to decrease the number of cigarettes and lead a better life. After detailed history. Clinical Examination of ENT, Routine blood counts, absolute Eosionophil count, Serum IgE estimation. Patient were off the antihistaminic for minimum of seven days. Allergy test by modified prick method was performed on upper limbs on palmer aspect of forearms. Glycerinated Histamine acid phosphate as positive control and Glycerinated buffer saline as negative control were used. Each patient was tested for same 140 Allergens. Wheal & flare response recorded. Result: In above study with 810 patients following were the percentage of different Allergens positive in above group. House dust mite 18% with D. Farinae 18%, Pollens 78.5% with Prosopis Juliflora 15.5%, Fungus 13.5% with Aspergillus Flavus 4.5%, Insects 64.5% with Cockroach female 35.5%, Dusts 38.5% with Grain Dust Rice 22%, Danders 21% with Human Dander 6.5%, Fabrics 5% with Silk 2%, Foods 50% with Milk 5%, Miscellaneous 7.5% with Parthenium Leaves 4%. Conclusion: The above study gave us the common Allergen pattern in Central part of India in cases of Severe Persistent Allergic Rhinitis as Pollens 78.5%, Insects 64.5%, Food 50%, Dusts 38.5% were mostly responsible for Chronic Allergic Rhinitis. Background and Objective: Pruritus or itch is defined as a cutaneous sensation that provokes a desire to scratch. Pruritus is one of the major symptoms in atopic dermatitis (AD), and is of great interest. Mechanisms of itch and its neuronal pathways are being investigated using different approaches; still they are not yet fully understood. The aim of this study was to achieve new data on the mechanisms of chronic pruritus by means of innovative neurophysiological methods of itch research. Methods: Short-latency and long-latency pain-related somatosensory electrically evoked potentials (SEP) as well as long-latency evoked potentials to thermal stimulation with the innovative Contact Heat Evoked Potential Stimulator (CHEPS) were studied in 38 AD-patients and 26 healthy volunteers. Quantitative Sensory Testing (QST) of thermal perception thresholds was performed in 22 AD-patients and in 15 healthy volunteers. Results: AD patients showed lowered motor and pain thresholds to electrical stimulation while SEP recordings as compared with healthy individuals (g=0.004). Brain hyperactivity to electrical stimuli, delayed thermal evoked potentials and elevated cold, warm and cold-induced pain thresholds were revealed in AD-group as compared with healthy controls (p=0.007).


The data indicate small nerve fibers dysfunction in ADpatients that may contribute to the pathogenesis of AD and chronic itch. This dysfunction may determine a predisposition to atopic dermatitis, the severity of pruritus and the tendency to its chronic course, although further evaluation is required. Overall, the neurophysiological data provide the evidence of an alteration in the central responses to afferent inputs in AD-patients suffering from chronic itch. The study demonstrates objective approaches to assess the function of small nerve fibers in patients with chronic pruritus. OBJECTIVE Is to test the efficacy and safety of a novel oral immunotherapy (OIT) protocol for peanut allergy.


The Effects of Antihistamine Drugs on on-Road Driving Performance Aurora Van De Loo, Johan Garssen, Joris Verster Utrecht University, Netherlands Correspondence: Aurora Van De Loo -Utrecht University, Netherlands World Allergy Organization Journal 2016, 9(Suppl 1):A637 Background: Antihistamines can cross the blood-brain barrier and thus may cause drowsiness. As a result, daily activities such as driving a car may be impaired. The purpose of this review was to compare the effects of different antihistamines on driving performance. Methods: PubMed and cross references were searched to identify double-blind placebo-controlled clinical trials. Studies were selected that used the standardized 100-km on-road highway driving test in normal traffic to examine driving performance. Patient studies were excluded. Subjects are instructed to maintain a steady lateral position and a constant speed (95 km/h). The Standard Deviation of Lateral Position (SDLP, cm), i.e. the weaving of the car, is the primary outcome measure of the test. The magnitude of driving impairment for antihistamine drugs was compared to SDLP increments seen at Blood Alcohol Concentration (BAC) 0.05% (ΔSDLP= +2.4 cm) and BAC 0.08% (ΔSDLP= +4.3 cm), i.e. the most common legal limits for driving. Results: Eighteen studies were included. Regarding acute effects, impairment greater than BAC 0.08% was found after single dosages of diphenhydramine, emedastine, and hydroxyzine. Impairment after clemastine, triprolidine, mizolastine, acrivastine, dexchlorpheniramine, and mequitazine was comparable to BAC 0.05%. Results for cetirizine were mixed. No significant impairment was found for terfenadine, loratadine, levocetirizine, desloratadine, ebastine, bilastine, fexofenadine and rupatadine. Regarding sub-chronic effects (4-8 days of daily drug treatment), significant driving impairment was found for emedastine, diphenhydramine, clemastine, triprolidine, ebastine, and hydroxyzine. Mixed results were found for cetirizine, terfenadine and loratadine. No significant driving impairment was found for levocetirizine, acrivastine, fexofenadine, dexchlorpheniramine, bilastine, and mequitazine. Discussion: Antihistamine drugs may significantly impair driving performance. Impairment is often seen with acute use of first-and second-generation antihistamines, and the magnitude of impairment is comparable to that seen at legal BAC limits for driving. Tolerance to the impairing effect after chronic daily use of antihistamines develops slowly. The newer antihistamines levocetirizine, fexofenadine and desloratadine did not significantly impair driving performance. Abstract Anahylactic shock and astmatic status are both serious complications of allergic diseases that might have deadly outcome. As known in the literature, it's very rare to occur together in the same time in one patient. A 29-year-old-male athlete was introduced to our intensive care unit for experiencing anaphylactic shock and asthmatic status after running through grass fields near home. Upon arrival of emergency unit team, he had low blood preassure of 70/50 mmHg, and low oxygen saturation in 82% with altered mental status. After immediate application of epinephrine, prednisolone and salbutamol, his vital functions turned normal. He had mild asthma in childhood, but for the last 10 years, he had been asymptomatic without medication. For the recent 4 yeas, he had hay fever to grass pollen treated with intranasal glucocorticoid occasionaly and urticaria when exposed to almond and pork. Ten days before the reaction, he had an episode of hives while eating cake decorated with almond and after few minutes he had shortness of breathing, which was resolved on antihistamines. While testing sIgE, we found strong sensitization to grass and wheat, but not to insects or food he claimed to be eating. He was prescribed a self-injectable epinephrine and asked to avoid running thrue grass fields. We report a case of a male athlete who suffered from hypotension and asthmatic attack, provoked by grass polen. Keywords: anaphylactic shock, asthmatic status, grass polen Tel: 0038631315042 Background It is known that respiratory viral infection in infancy cause asthma. But the detailed mechanisms underlying the induction of allergic inflammation by virus infection are is not fully understood. Many papers have shown that, not only pathogen-derived factors such as virus DNA and RNA, factors released from dying or stressed cells, damage-associated molecular patterns (DAMPs), are recognized by immune cells and contribute to inflammation. Interestingly, host DNA as a DAMP is known to induce type 2 immune responses and exacerbates allergic inflammation. Host DNA is recognized by intracellular DNA sensors and activates cyclic GMA-AMP synthase (cGAS). Then activated cGAS generates cyclic GMP-AMP(cGAMP) as a second messenger. We hypothesized that host DNA release from damaged cells by virus participates in allergic inflammation via the action of cGAMP. In this study, we investigated the effect of cGAMP on the onset of asthma. Methods House dust mite antigen (HDM) was administered intranasally to C57B/6J mice with or without cGAMP as an adjuvant, and then mice were challenged with intranasal administration of house dust mite antigen (HDM) on days 7, 9, 11, and 13. Twenty-four hours after last challenge, we collected blood, BALF, lungs. Serum antibodies were measured by ELISA, and cells in BALF were analyzed by FACS. We performed similar experiment using gene-knockout mice to evaluate the factors involved in this inflammation model.


The immune status was evaluated and retrospective data analysis was performed of 17 DM1 patients. Standard screening comprised a questionnaire about (recurrent) infections, frequent use of antibiotics and hospital stays due to infections. Standard laboratory tests comprised serum IgA, IgM, IgG and IgG subclasses, NK, B and T cell counts, granulocyte, leucocyte and monocyte counts by FACS analysis. Also a vaccination response test was performed.


The majority of the patients (71%) had hypogammaglobulinemia (IgG<7 g/L) ranging from 3.9 g/l and 6.5 g/l. Strikingly, IgG1 was selectively below normal range in fifteen out of sixteen patients (94%). None of the patients were on immune suppressive medication. The overall rate of pneumonia was 53%. Nine out of seventeen patients suffered from pneumonia at least once between January 2000 and October 2012, four of those patients had recurrent pneumonia or sinopulmonal infections. Other infections also occurred, e.g. recurrent urinary tract infection, recurrent facial herpes simplex and erysipelas. In the patients with hypoglobulinemia the rate of pneumonia was 58% compared to 40% in patients whose total IgG was normal (p = 0,52). Interestingly three patients with low IgG serum levels also showed insufficient vaccination responses for H. influenzae type B and/or S. pneumoniae. Two of which had recurrent infections, including pneumonia. These patients met the criteria for common variable immune deficiency (CVID).


Drug allergy (DA) is an immunologically mediated response to specific agent in a sensitized person. The clinical manifestations of DA are restricted to certain syndromes that are specifically accepted as allergic in nature, which may present as mild to life threatening reactions.


Sublingual immunotherapy with tablet form in elderly AR patients sensitized to HDM is worth trying and no safety issue has become a problem, but further investigation results are needed. This study was supported by Lofarma SpA, Milano, Italy. Background: World population, over the age 65 (usually defined as the elderly) has been steadily growing, reflecting general trends of ageing societies. With advancing age, chronic diseases become increasingly prevalent and contribute to the loss of independence, frailty and increased risk of death. Understanding the role of environmental factors, specifically respiratory infections, in the pathogenesis of chronic respiratory diseases in the elderly may help in decreasing morbidity and extending the lifespan of this population. Methods: Healthy Ageing Research Center (HARC) which is a multidisciplinary research platform established at the Medical University of Lodz, involves research groups with various basic biological (immunologists, biochemists, molecular biologists) and clinical (geriatricians, psychiatrists, cardiologists and pulmonologists) interests and devoted to conduct research addressing key issues related to pathogenesis of increased morbidity in the elderly population. Here we present the HARC platform as a vehicle for development of multidisciplinary research related to various aspects of respiratory infections in the elderly. Results: Preliminary study involving elderly subjects (n=157; mean age 68.2) allowed to establish risk factors associated with frequent infections. In a multivariate analysis polytherapy (more than 5 prescription drugs) has been determined as one of the most important risk factors for frequent (defined as more than 3 per year) respiratory infections (OR=1.93 (CI95% 1.11-3.36). The effect of comorbidities as risk factors for respiratory infections, will be further analyzed in crosssectional study involving 3000 subjects randomly selected from the local population of elderly subjects. In collaboration with psychiatrics the prevalence and spectrum of respiratory infections among patients with various psychiatric disorders is being studied. Although viral infections are considered to be important triggers in asthma exacerbation in children and adults, it is difficult to extrapolate infection rates and specific pathogens from these studies to older adults with asthma. The study currently developed with microbiologist is aiming at assessment of the role of viral and bacterial triggers asthma exacerbation in the elderly patients. In parallel, in vitro model to assess the peripheral blood leukocytes immune response to rhinovirus infection and miRNA expression in the elderly patients with and without asthma has been introduced . Conclusions: Collaboration within multidisciplinary research team ( HARC platform) has allowed for development of innovative approaches to study various aspects of respiratory infections in the elderly population. Project is supported by the European Commission RegPot-2012-2013-1. Background: Capture-recapture models allow one to estimate the number of actual cases by assessing the probability of overlap between cases from multiple sources. The Korea Work-Related Asthma Surveillance (KOWAS) is a scheme designed to collect information on WRA cases from multiple reporting sources, which are the Korea Workers' Compensation and Welfare Service, occupational physicians, allergy and chest physicians, and regional work-related disease surveillance systems. The purpose of this study is to estimate the number of actual cases of WRA using the capture-recapture analysis. Methods: Capture-recapture analysis was used to obtain a nearly unbiased estimator (NUE) of the total number of WRA cases reported to KOWAS from 2004 to 2006. To do this, the 4 reporting sources were stratified into 2 categories as follows: (1) the workers' compensation scheme (i.e. the Korea Workers' Compensation and Welfare Service), and (2) the other 3 reporting sources (i.e. physicians' reports). Capture-recapture analysis was performed on sex, regions and specific industries when the number of overlapping reports was ≥7.


The allergenic pollen seasons of representative trees, weeds and grasses during the 2000s across the CONUS have been observed to start 3.0 (95% Confidence Interval [CI], 1.1-4.9) days earlier on average than in the 1990s. The average peak value and annual total of daily counted airborne pollen have increased by 42.4% (95% CI, 21.9%-62.9%) and 46.0% (95% CI, 21.5%-70.5%), respectively. Changes of ragweed pollen season timing and levels were identified as functions of latitude, and associated with changes of Growing Degree Days, Frost Free Days and precipitation. Conclusion: These changes are likely due to recent climate change and particularly the enhanced warming and precipitation at higher latitudes in the CONUS. The observed pollen season start date, season length and airborne pollen level could be correctly predicted using Bayesian and machine learning models based on the locally observed meteorological factors. Background Specific subcutaneous immunotherapy (SCIT) with house dust mite (HDM) has been shown to improve clinical symptoms in patients with allergic rhinitis and asthma in China, while less data regarding efficacy, safety and immunological mechanisms of specific sublingual immunotherapy (SLIT) in allergic patients. The aim of our study was to evaluate the efficacy, immunological mechanisms of SLIT HDM compared to SCIT HDM in rhinitis patients with HDM during 1 year of treatment. Method Recruitment took place from November 2009 to September 2010. The study enrolled 67 patients aged 5. '55 years old with moderate-severe HDM induced allergic rhinitis with or without asthma. They were randomized (2:2:1) in three groups (SLIT group, n=27; SCIT group, n=26; Placebo, n=14, following the same schedule as SLIT group). The allergic rhinitis and asthma symptom and medication score collected from patient diary cards (from baseline to 1 year) were used for assessment of efficacy. Visual analogue score (VAS) were collected and skin prick tests, total-specific IgE were performed at baseline and 12 months after treatment. In addition, patients underwent Der p IgG4 and CD4+CD25+FoxP3+ Treg cells measurements. Results SCIT groups had a significant improvement for the change from baseline in mean total rhinitis symptom score compared with placebo after 1 year therapy (P=0.015), but between SLIT and placebo groups there were no significant difference(P=0.060). Both two groups had a significant improvement in mean rhinitis medication score compared with placebo (P<0.05), and the analysis of rhinitis VAS score change from baseline showed the same results. The mean asthma symptom or medication score did not show significant difference among the three groups. There was a trend toward upregulation in the rate of CD4+CD25+FoxP3+ Treg cells from baseline to 1 year in both SCIT and SLIT subjects compared with Placebo group(P<0.05). The level of Der p IgG4 showed a significant increase in both SLIT and SCIT compared with placebo (P<0.05), furthermore, the mean level of Der p IgG4 of SCIT group was almost thirty times higher than SLIT group after 1 year therapy (P<0.05). Conclusion Both SCIT and SLIT had the efficacy in patients with moderate-severe HDM sensitized allergic rhinitis after 1 year of treatment, and SCIT also afford significant therapeutic benefits with respect to rhinitis symptom score. Serum Der p IgG4 and CD4+CD25+ FoxP3+ Treg cells may play roles in modulate immunoresponse to specific immunotherapy, but their relationship between clinical efficacy needs further study.


Background: The aims of this study were to verify the association between autologous serum skin test (ASST) and laboratory markers for autoimmunity in the patient with chronic idiopathic urticaria (CIU) and to evaluate whether parameters like ASST, thyroid autoantibodies (TA), anti-nuclear antibody (ANA), and serum total immunoglobulin E (IgE) could predict CIU severity including urticarial activity and refractoriness. Methods: Total 878 CIU patients were performed ASST to identify autoreactivity. Further, serum antibodies to thyroglobulin (ATG) and thyroid peroxidase (ATPO), ANA, and total IgE were measured. Clinical severity of CIU was estimated by urticaria severity score (UAS) and maximum level of medication (1∼4) to abrogate wheal and pruritus. We analyzed association among ASST, laboratory markers and clinical severity in different subgroups based on ASST and laboratory markers. Results: A total of 255 (29.0%) patients were tested positive in the ASST and 28/192 (14.6%) patients were tested positive for ATPO or ATG. Positive percent of ANA was 18.6% (106/571) with female preponderance. Serum total IgE level was measured in 521 of the 878 patients and was found to be elevated in 258 (49.5%). When ASST was analyzed in relation to laboratory markers, inverse correlation between ASST and serum IgE level was observed but significantly higher percentage of positive ANA was found in patients with positive ASST (31.5%) compared to patients with negative ASST (13.4%). Correlations of ATPO and ATG with ASST had no significant statistical difference. The patients with positive ASST had significantly higher scores of UAS compared with the patients with negative ASST. However, there was no significant statistical difference between maximum level of medication and ASST. Maximum levels of medication in the patients with elevated IgE were significantly higher than those with normal IgE. Conclusion: Significant association between ASST and thyroid autoimmunity was not identified in this study. Patients with positive ASST Introduction Asthma, because of its chronic nature, may adversely affect the life quality of patients leading to mental disturbances. Anxiety and depression can be accure more than on these patients compared with the healthy population. Life quality survey can be used to evaluate effect of asthma in the terms of physical, psychological and social function on the patients life. In particular, the importance of emotional factors come to the forefront more in the case which symptoms can not be controlled. Anxiety is the most common psychological disorders among patients who have respiratory system disease.


(p<0.05) The amounts of nutrition weren't related to neonatal cord blood IL-4 and IFN-γ. D) Conclusions: This is the study about the relationship between maternal food intakes and exposure to HDM during pregnancy and fetal immunity. The study found that 1) infants had Th1/Th2 polarization at birth and that 2) Expression of IL-4 and INF-γ was related to maternal allergic disease.


Most of the factors behind the negative attitudes toward the administration of AAI in school settings were associated with technical concerns. Background: The relationship between atopic dermatitis (AD) and low vitamin D levels has been studied. Emerging evidence has implicated vitamin D as a critical regulator of immunity, playing a role in both the innate and cell-mediated immune systems. However, the effect of vitamin D on house dust mite (HDM) sensitization in patients with AD has not been established. We investigated the association between vitamin D levels and HDM sensitization according to AD severity. Methods: In total, 80 patients (43 men and 37 women) with AD were included. We classified AD severity using Rajka and Langeland scores. Laboratory tests included serum 25-hydroxyvitamin D3, total immunoglobulin E (IgE), and specific IgE antibody titer against Dermatophagoides (D.) farinae and D. pteronyssinus. Results: There were no differences in vitamin D levels between the mild or moderate AD and severe AD groups. In the severe AD group, high HDM sensitization group had lower serum vitamin D levels compared to low HDM sensitization group with statistical significance. In addition, a significant negative correlation was found between vitamin D levels and HDM sensitization in the severe AD group. These results did not depend on the type of HDM, D. farinae or D. pteronyssinus. Conclusions: Our results demonstrate that low vitamin D levels may link to high HDM sensitization in patients with the severe AD. Further elucidation of the role of vitamin D in HDM sensitization may hold profound implications for the prevention and treatment of AD. Objective: To investigate the effect of COPD on the skeletal muscles, particularly in patients with limb muscle dysfunction. The appendicular skeletal muscle mass index (ASMI), an index of sarcopenia, which was recently in the limelight, is an index of the limb muscle mass and is considered useful for predicting skeletal muscle abnormality in COPD patients. Thus, their relationships were examined.

Comparison of Methacholine and Mannitol to Predict Exercise-Induced Bronchoconstriction in Children with Asthma

Results: IFN-γ levels in the 2 groups were statistically similar (P=0.08). IL-4 levels were significantly higher in the RSV compared to HMPV group (P<0.0001). IL-13 levels in both groups were under detection level. IL-1β levels were significantly higher in the HMPV compared to the RSV group (P<0.0001). Conclusion: Our results suggest that HMPV and RSV have different inflammatory mechanisms. HMPV induces airway inflammation by the Th17 pathway through release of IL-1β, whereas RSV acts through the Th2 pathway. Background: Asthma is a chronic inflammatory disease of the airways, the potential link between microbial infections and asthma is now thought to be environment, immunity and genetic factors. The potential role of bacterial colonization or infection of the bronchial mucosa in the pathogenesis of asthma has been raised by several recent reports. The aim of this study was to examine alteration of airway microbiota among asthma phenotypes in Chinese adult patients. Methods: Induced sputum samples were obtained from 49 nonsmoking patients with stable asthma and 15 healthy subjects. Total DNA was amplified by using primers specific for the V3-V5 hypervariable region of bacterial 16s rRNA. Samples were barcoded, and sequenced with the 454 GS FLX sequencer. Sequences were assigned to bacterial taxa by comparing them with 16s rRNA sequences in the Ribosomal Database Project. Results: Asthmatics had lower FEV1% predicted (72.2% vs. 98.6%, p<0.001) and higher sputum eosinophil (13.0% vs. 0.5%, p<0.001) compared to healthy controls. There was no statistically difference in OTU numbers and diversity score between asthmatic and nonasthmatic subjects. At phylum level, the difference of OTU relative abundance remained non-significant. Subjects with eosinopihilic asthma (EA) are older and have shorter duration of asthma (9.6 vs. 19.2 years, p=0.041) as well as lower FEV1% (69.3% vs. 79.2%, p<0.001) compared to subjects with non-eosinopihilic asthma (NEA). The highest OTU numbers (183.9 vs. 142.7 vs. 127.2) and diversity scores, including chao index (318.6 vs. 203.1 vs. 190.8 ) and ace index (419.8 vs. 251.0 vs. 218.5), were found in NEA group, followed by healthy and EA group. At phylum level, EA subjects had higher abundance of Firmicutes (33.7% vs. 27.5%, p=0.099) but lower Proteobacteria (27.5% vs. 35.2%, p=0.090) compared to NEA subjects, although the differences were not significant. Conclusions: Patients with eosinophilic asthma have an altered microbial composition in the respiratory tract compared with subjects with non-eosinophilic asthma. The corresponding biological effect on airway inflammation remains to be determined. This study evaluated which clinical features may predict presence of SA colonization/infection, and reviewed antimicrobial sensitivity of SA in patients with AD. Methods: The associations between bacteriologic culture results of skin swabs (taken at the most severely affected area and at the antecubital fossa) and SCORing-Atopic-Dermatitis (SCORAD), skin hydration, transepidermal water loss (TEWL) and quality of life were evaluated. Results: Moderate-to-heavy growth of SA was present in 31% of the swabs of the most severe area and in 16% of the flexural (antecubital fossae) areas of 95 AD patients (12.5±4.8 years). Binomial logistic regression showed moderate-to-heavy growth of SA were associated with objective SCORAD (p=0.004) and lesion intensity [erythema (p=0.022) and lichenification (p=0.035)] in the severe area; and excoriation (p=0.024) and TEWL (p=0.009) in the antecubital fossa. The relative risk of isolating moderate-to-heavy growth of SA in the most affected area in patients with severe disease (Objective SCORAD >40) is 2.73 (1.43 -5.21, p =0.001) . Any growth of SA in either swab sites was associated with objective SCORAD and lesion intensity (p=0.001-0.019). SA had no association with quality of life and other clinical parameters. All specimens of methicillin-sensitive SA were sensitive to cloxacillin. All methicillin-resistant SA (5.7%) was sensitive to cotrimoxazole and fusidic acid. Conclusions: Clinical features, especially severity and lesion intensity, are useful in "predicting" presence of SA colonization/infection in AD patients. Cloxacillin has a favourable sensitivity profile for methicillinsensitive-SA, and cotrimoxazole and fusidic acid for methicillinresistant-SA. These findings will facilitate management of patients before bacteriology results become available. Background: Vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-β 1 , and platelet derived growth factor (PDGF) are known to be involved in the pathogenesis of inflammation and remodeling in asthmatic airways. YKL-40, a chitinaselike protein, and clusterin have been reported to be biomarkers for severe asthma. We examined serum levels of growth factors, YKL-40 and clusterin in 223children with acute asthma or stable asthma and investigated their correlation with clinical findings and lung function parameters. Methods: Forty-one children (≥6yrs of age) with asthma were enrolled and 2 groups were defined: 23 patients admitted with asthma exacerbation and 18 patients with stable asthma. Serum levels of VEGF, TGF-β 1, PDGF-BB, YKL-40, and clusterin were measured using ELISA, and assessed in relation to the clinical and spirometric parameters. Fifteen age-matched controls were also studied. Results: VEGF, TGF-β 1, and YKL-40 levels in children with acute asthma were significantly elevated compared to controls. VEGF and YKL-40 levels in stable asthma group were higher than in controls and not different from those in acute asthma group. VEGF levels in acute asthma group correlated significantly with asthma severity. TGF-β 1 levels in stable asthma group showed a significant inverse correlation with FEV 1 % and FEF 25-75 %. YKL-40 had no relationship with clinical and spirometric parameters. Conclusions: Our study suggests that increased VEGF and YKL-40 might affect asthmatic airways not only during acute exacerbation but also in stable state. It also suggests that serum TGF-β 1 might be a biomarker for airway obstruction in children with asthma.


Good's syndrome is an acquired immunodeficiency state associated with thymoma. It is characterized by recurrent infection, autoimmune disease, and immunologic abnormality. The insufficient immunity can be supported by intravenous immunoglobulin(IVIG) replacement therapy. We describe 2 patients who presented with cough and dyspnea caused by Pneumocystis jiroveci pneumonia and Cytomegalovirus pneumonia respectively after thymectomy for a thymoma. Immunologic study revealed hypogammaglobulinemia with very low B-cell count, consistent with Good's syndrome. They were successfully treated with trimethoprim/sulfamethoxazole and gancyclovir respectively, and now they are doing well without additional infections, having regular IVIG replacement. Background: Recently, it has been reported that cigarette smoke exposure during allergen sensitization period facilitates the development of house dust mite (HDM) sensitization and subsequent allergic asthma. However, the mechanisms remain elusive. Several researchers have recently shown that IL-23 is involved in antigeninduced airway inflammation. Therefore, we hypothesized that IL-23 is involved in this pathway. Objective: To evaluate roles of IL-23 in short cigarette smoke exposure-induced HDM-allergic asthma mouse model Methods: BALB/c mice were exposed to HDM and/or cigarette smoke extracts (CSE) during HDM sensitization period (day 1, 2, 3, and 14) . Anti-IL-23p19 antibody was given during the sensitization period. And we analyzed several asthmatic phenotypes after last allergen challenge. In addition, we also analyzed the change of DC activation in LDLN and cytokines profile after last sensitization. Results: CSE exposure during sensitization period promoted the development of HDM-allergic sensitization and asthma phenotypes. The proportion of innate lymphoid type 2 cells also increased by CSE and HDM co-exposure, compared to a single exposure. Anti-IL-23 antibody treatment during allergen sensitization period significantly diminished several phenotypes of allergic asthma. Anti-IL-23 treatment also reduced the recruitment of innate lymphoid type 2 cells. Along with, the activation of DC in LDLN was significantly reduced by anti-IL-23 after last sensitization. Conclusion: IL-23 may play a significant role in the development of short cigarette smoke-induced allergic sensitization and asthma.


One of the key strategic ways of allergic diseases treatment is the update of methodology and creation of new immunothropic drugs for sublingual immunotherapy or SLIT, that determine mucosal tolerance development process. Combination of allergic rhinitis and palindromic herpetic infection (HSV and/or ÑMV) is usually characterized by rapid mucosal immunity barrier function violation, mucosal barrier permeability change and inevitable progress of allergic disease. Taking in consideration high prevalence of herpetic infection spread among patients, suffering from allergic diseases, search of optimal SLIT treatment schemes is becoming significantly important. Purpose of the current study is to evaluate SLIT effectiveness among immunocompromised patients, suffering from allergic rhinitis, using up-to-date tableted allergen extract (produced in Kazakhstan).


Assessment result -excellent and good effect was stated among 73% (21) patients. Among them, 20 patients (68,9%) noted the decrease in pharmaco-medicine need when contacting corresponding allergen., overall health status improvement -21 patients (73%). None of the patients claimed main disease flow worsening. Cytokine profile research after treatment showed IL-4 and ϒ -INF content level normalization both in local and serum fractions. Among 5 patients (16,6%) rapid increase of IL-8 è TNF -α in local fractions was stated before treatment, and it was the key reason to change SLIT mode and to add immunomodulating therapy. 27 patients (93%) agreed to continue treatment next year. Conclusions Full SLIT course was successfully implemented to all patients using modern tableted allergen extract (produced in Kazakhstan), despite violations in virus defense system and mucosal immunity system. Stated change in α-TNF and IL-8 content level among a group of patients allowed to change SLIT mode and complete the course successfully. SLIT using modern tableted medicine among immunocompromised (problematic) patients, suffering from allergic diseases is a successful and high effective method and complies with all criteria of rational pharmacotherapy.


Results: After excluding subjects with insufficient test compound intake, 29 in placebo and 34 in FOS groups were analyzed. There were no differences of the characteristics between 2 groups. The concentrations of IL-27 in colostrum samples were significantly higher in the FOS group (range: <0.156-46.6 ng/ml; median: 2.4 ng/ml) than in the placebo group (range: <0.156-95.8 ng/ml; median: 0.2 ng/ml) (P<0.05). Fecal numbers of Bifidobacterium were significantly increased in the FOS group but not the in the placebo group and were significantly higher in the FOS group (range: 8.9-11.0 log 10 cfu/g; median: 10.4 log 10 cfu/g) than in the placebo group (range: 8.8-10.72 log 10 cfu/g; median: 10.1 log 10 cfu/g) after the intervention (P<0.05). The concentrations of IL-27 in colostrum showed weak correlation to the Bifidobacteriumnumbers of 36 weeks of gestation. Conclusions: Our data suggest that mother's intake of prebiotics increases IL-27 expression in breast milk by modulating gut microbiota. Objectives: Nintedanib (BIBF1120) is tyrosine kinase inhibitor of VEGFR1/2/3, FGFR1/2/3, PDGFRα/β. Recently, nintedanib showed beneficial effect on patients with IPF. However, little has been known regarding the effect of nintedanib on asthma. Since VEGF and PDGF are well known mediator in the pathogenesis of asthma, we aimed to evaluate effect of nintedanib on asthma in acute and chronic mouse model. Methods: Female BALB/c mice, 8-10 weeks of age, were used. We developed a mouse model of both acute and chronic asthma in which ovalbumin (OVA)-sensitized mice were repeatedly exposed to intranasal OVA administration. Mice were treated with nintedanib during the OVA challenge. Results: Compared with control mice, the mice exposed to OVA developed sustained eosinophilic airway inflammation and airway hyperresponsiveness (AHR). Administration of nintedanib significantly decreased total cell and eosinophilic count in bronchoalveolar lavage (BAL) fluid. Also the level of IL-4, 5, and 13 in BAL fluid was significantly lower in nintedanib group compared with control. In a histologic analysis, there were fewer inflammatory cell infiltration in nintedanib group. Nintedanib treatment significantly attenuated airway remodeling including fibrosis and smooth muscle thickening. The protein and gene expression level of VEGF, FGF, and PDGF were lower in nintedanib group. In vitro experiment showed that nintedanib significantly decreased fibroblast proliferation. Conclusion: These results suggest that nintedanib administration can attenuate airway inflammation, AHR, and remodeling in mouse model of asthma. The beneficial effect of nintedanib was via blocking of VEGF, FGF, and PDGF pathway. Background: Coronary angiography (CAG) is a standard method for diagnosing coronary artery disease. Iodinated contrast media (ICM) used in CAG can induce both immediate and delayed hypersensitivity reactions. However, studies on delayed hypersensitivity reactions to ICM are relatively few and the reported incidence varies greatly. Therefore, we aimed to investigate the incidence and clinical features of ICM-induced delayed hypersensitivity reactions following CAG. Methods: We prospectively monitored ICM-induced delayed hypersensitivity in patients who underwent CAG from February 2015 to May 2015 at the Seoul National University Hospital. The ICM agents used were iodixanol and iopamidol. Symptoms were monitored from one hour to three weeks after the completion of CAG. Results: A total of 265 patients received CAG during the study period (mean age 63.6 years, male 70.5%). Delayed hypersensitivity reactions occurred in 35 patients (13.2%). The most common manifestation was skin rash (88.5%), followed by chest discomfort and gastrointestinal symptoms. The majority (87%) of the skin reactions were mild (involving < 25% of the body surface), mostly occurring within 3 days of CAG (within 24 hrs: 40%, between 1-3 days: 42.8%; more than 3 days: 17.1%). Subgroup analysis by ICM agent used, gender, and age did not show any significant differences in the reaction incidence or clinical manifestations. Conclusions: The incidence proportion of delayed hypersensitivity reactions to ICM was 13.2%, which was higher than previously reported. To our knowledge, this is the first study in Korea to investigate the incidence of ICM-induced delayed hypersensitivity following CAG. Background: Chronic Idiopathic Urticaria (CIU) is a relatively common disease which accounts for up to 30% of office visits to allergists. Although designated idiopathic the pathophysiology and mechanism of disease is reported to result from immune activation due to variety of causes. CIU is a manifestation of immune activation with approximately 50% of CIU patients demonstrating autoimmunity as evidenced by presence of IgG antibody to the FceR1 receptor present on mast cells and basophils. Autoantibodies to thyroid tissue and many other cellular and cell surface receptors commonly coexist. Further elucidation is lacking at the genetic and molecular level. Ideally, a better understanding of the underlying biology could improve not only prognostic indicators, but also provide a background for generating predictor models of treatment responders. Methods: We collected peripheral blood mononuclear cells (PBMC's) from 21 patients with active CIU disease and 10 non-atopic healthy controls. RNA was extracted from PBMC's and prepared for Affymetrix GeneChip® Human Gene U133 plus 2.0 Array hybridization. The raw data were normalized and the gene expression of CIU patients was compared to that of normal controls. Results: We found 149 genes that predicted CIU from normal controls (FDR<5%). The genes in the predictor are differentially expressed (P<0.001) with a minimum 2-fold difference between CIU patients and controls. The predictor was 100% successful in distinguishing patients with CIU from controls, and tested using leave one out cross-validation. Additionally we found that the upregulated genes seen in CIU most strongly correlated with monocytes, identified as cells expressing CD14 cell surface marker (p<0.001, r >0.8). Gene set enrichment analysis of CIU patients further revealed activation of a specific arm of the MAP-Kinase pathway utilized by monocytes (p<0.001, r >0.8).


Recent studies emphasized the important role of follicular T helper (T FH ) cells, which contribute to B-cell differentiation, as well as antibody production. The aim of our study was to investigate the possible role of T FH cells in the pathogenesis of primary Sjögren's syndrome (pSS). In the first part of the study, we focused on the periphery by analyzing immune-competent cells and serological markers. We enrolled 50 pSS patients and 16 healthy controls in the study. Patients had elevated ratio of peripheral T FH cells, however, when dividing patients into two groups defined by the presence of extraglandular manifestations (EGMs), only patients with EGMs differed from controls significantly. Moreover, T FH cell percentages correlated positively with both activated T cell and Tr1 cell values, but T FH cell percentages showed negative correlation with both IgM and IgG memory B cell proportions. Elevated T FH percentages were observed in the anti-SSA/SSB positive patients. In the second part, we concentrated on the site of the inflammation, and determined the composition of lymphocyte infiltration in labial salivary gland (LSG) biopsies with special emphasis on T FH cells. We selected tissue blocks obtained from 10 patients at the time of disease onset. LSGs were graded based on the organizational level of periductal lymphocytic infiltrates. T FH cell markers occurred predominantly in more organized structures with higher focus scores. The co-expression of CD3 and Bcl-6 markers identified T FH cells close to Bcl-6 + B cells with the typical formation of germinal centers. Systemic features were developed later in the disease course only in patients with more structured infiltrates.


In THP-1 cells, Colabomycin E inhibited TNF alpha induced mRNA expression of several proinflammatory genes including IL-1β, IL-6, TLR8, and MyD88. The effect was evident after 4h and 8h cultures and in some of the genes persisted for 24h. Furthermore, colabomycin E downregulated TNF alpha induced IL-1β, IL-6 and chemokine CXCL8/IL-8 release in a dose dependent manner from 0.25μM concentration. The secretion of IL-18 from THP-1 cells was only slightly upregulated by TNF alpha and not affected by colabomycin E. Our data suggest that colabomycin E is a potent transcription inhibitor of proinflammatory cytokines in human mononuclear phagocytes. Supported by IGA MZCR grant NT/13012-4 and by MH CZ -DRO ("Institute for Clinical and Experimental Medicine -IKEM, IN 00023001"). Atopic dermatitis (AD) is one of the most common dermatologic diseases, affecting approximately 20% of children living in industrialized countries. Moreover, approximately 70% of cases of AD affect children less than 5 years of age. Most cases of AD are effectively treated with topical steroids, topical calcineurin inhibitors and intermittent use of immunosuppressive agents, including oral corticosteroids and cyclosporine. However, for recalcitrant AD, continuous use of systemic immunosuppressive agents is limited by severe adverse effects, especially for children. For this subgroup of patients, a few studies testing systemic immunomodulatory drugs have been reported, and high-dose intravenous immunoglobulin (IVIG) therapy has been also intermittently reported to be effective without strong evidences. Herein we report a case of intractable atopic dermatitis in a 5-year-old girl who had a significant clinical improvement after receiving 3 cycles of IVIG treatment (2 g/kg) without notable side effects. Since the first infusion of IVIG, the patient's skin lesions improved steadily and the improvement persisted until the 8-month follow-up. The EASI score decreased remarkably, while the immunologic parameters did not correlate with clinical improvement. IVIG monotherapy is considered especially useful for children with severe AD since its immunoregulatory function is more profound in the relatively immature immune system of children. The mechanisms of action of immunoglobulin may include cytolysis of target cells through complement or antibody-dependent cell-mediated cytotoxicity, induction of apoptosis of target cells, blockade of costimulatory molecules, and neutralization of pathogenic antibodies and soluble factors such as cytokines and their receptors, which ultimately lead to amelioration of the inflammatory process. This case suggests that IVIG therapy can be quite effective and safe for children with resistant atopic dermatitis.


Conclusion: Recognition of the specific binding site on the 57kDa subunit of Ag5 can lead to understanding the regulating mechanism of IgE/IgG production in some immune circumstances that IgE tends to be dominated, whereas in other IgG is predominated. allergic, local allergic and non-allergic rhinitis by evaluate different levels in RANTES, IL-5, and TNF-α between the nasal polyps and serum from them. Methods: We recruited total 38 adolescents with allergic rhinitis (AR) (n=15, mean age: 17.4±4.2 yrs old), local allergic rhinitis (LAR) (n=9, mean age: 15.9±5.5 yrs old), and non-allergic rhinitis (NAR) (n=14, mean age: 15.6±2.9 yrs old) undergoing polypectomy. Atopic status was defined as presenting a sufficiently high total IgE serum concentration (IgE > 200 IU/mL) and a positive skin prick test or serum allergen test such as MAST (Green cross MS, Seoul, Korea) or ImmunoCAP system (Pharmacia, Uppsala, Sweden). Immunoassays were performed using polyp tissue homogenates and sera to quantify the levels of RANTES, TNF-α, and IL-5, and with sera to assess total IgE, eosinophil cationic protein (ECP) produced by them. Results: RANTES levels were higher in LAR than in NAR, but there was no significant difference between AR and NAR. IL-5 and TNF-α levels were higher in AR and LAR than in NAR but IFN-γ levels did not differ. There was significantly correlated between concentration of RANTES between polyp tissue homogenates and serum (R2 =0.51, P<0.05, n=38). IL-5, TNF-α, and IFN-γ also demonstrated positive correlation between concentration of that between polyp tissue homogenates and serum, however, there were not significant. Conclusions: RANTES levels were higher in polyp tissue homogenates from LAR than in those from NAR. Therefore, RANTES probably involves in the pathogenesis of LAR. IL-5 and TNF-α levels were higher in polyp tissue homogenates and sera from AR and LAR than in those from NAR. So IL-5 and TNF-α probably play important role in the pathogenesis of AR and LAR.


Effects of anti-IgE on IL-4, and CD19, 20, 200 Aim: Netherton syndrome (NS) is associated with the mutation in the SPINK5 gene, which codes LEKTI (lymphoepithelial Kazaltype related inhibitor), a serine protease inhibitor. LEKTI is expressed in epithelium, mucosa, and thymus. It is localized in the stratum granulosum of normal skin. NS is a rare genodermatosis characterized by autosomal recessive inheritance pattern, unknown etiology, ichthyosiform cutaneous changes, atopic diathesis, and alterations in the hair shaft. As a result of aging coupled with immune deficiency, clinical symptoms may vary. Materials and methods: A 20-year-old white Caucasian male presented to our Allergy-Immunology Unit with pruritus of the face and feet, skin desquamation, and sparse and thin hair. Dermatological examination demonstrated brittleness and scaling of the hairs, eyebrows, and eyelashes; erythema and desquamation of the cheeks; pinkish-red macules with scales; hypopigmented macular lesions on the ichthyosiform skin involving the area beginning from the patella and extending to the distal part of the leg; and lichenified, erythematous plaques with patchy fissures in both antecubital and popliteal regions. Microscopic examination of the material collected from the nails showed no fungal components. Subungual hyperkeratosis, discoloration, and destruction were noted in the toe nails. Patient presented to our clinic with sparse and brittle hair along with pruritic, erythematous, and scaling cutaneous lesions. Patient underwent a clinical examination and laboratory analyses. Based on the clinical and laboratory findings, patient diagnosed with Netherton syndrome. Results: Laboratory analyses yielded normal results except for a leukocyte count of 7,300/μL, CRP of 25.6 mg/mL (normal range:0-5 mg/ mL) and a total IgE of 31700 IU/mL (normal range:0-100 IU/mL) and IgG of 20g/L(normal range:7-16), IgA of 4g/L(normal range:0.7-4), IgM of 0.9g/L(normal range:0.4-2.3) and cow's milk,mite,grass, egg, hazelnut, orange, wheat, strawberry allergy were detected in the specific IgE studies. Anti nuclear antibody, hepatitis markers, HIV and rheumatoid factor were negative in patient. Renal function tests, complement-4 (C4), C3 levels were within normal ranges. During omalizumab treatment and after a short-term (4 months) treatment with omalizumab, he had a decreased CRP, IL-4, IL-5, IL-17, IL-1β and CD19-20, CD200 and had an increased CXCL8 levels. Conclusion: NS, peeling skin syndrome type B, and skin dermatitismultiple severe allergies-metabolic wasting syndrome are 3 autosomal recessive disorder resulting from aberrant regulation of epidermal desquamation. To our knowledge, this is the first time an association between omalizumab use and NS has been documented. As a conclusion allergic skin symptoms (pruritus, erythema, desquamation) and mucosal symptoms were decreased in patient.


Infantile eczema is associated with campylobacter and roseburia subpopulations but not microbial diversity in stool samples of Chinese newborns Ting Fan Leung 1 , Jamie Sui-Lam Kwok 2 , Christine Kit-Ching Tung 2 , Man Fung Tang Background: Gut microbiota is increasingly recognised to play crucial roles in the pathogenesis of asthma, obesity and autoimmune diseases. Faecal microbiome is likely ethnic and diet-specific, but such data is lacking in Asians. This study characterised faecal microbial compositions of Hong Kong Chinese infants. Methods: Random stool samples were obtained from 4-week-old infants with eczema (n=15) and without any allergy (n=15) at 9 months. Genomic DNA extracted by PowerSoil DNA Isolation Kit (MO BIO Laboratories) was sequenced using Ion PGM Seqeuncing 200 Kit v2, Ion 318 TM Chip v2 on Ion PGM System (Ion Torrent). Reads from each patient were filtered for low quality (Phred <20). Microbial diversity was evaluated using Shannon-Weaver diversity index in Swedish (J Allergy Clin Immunol 2012; 129:434-40) . The taxonomic classification of the reads was assigned by BLASTn. Results: 5 controls had insufficient DNA for sequencing. No significant association was detected between eczema and any bacteria with ≥1% relative abundance, including Bacteroides, Escherichia, Klebsiella, Bifidobacterium, Streptococcus and Lactobacillus. Among the less abundant genera (relative abundance <1%), Campylobacter was more abundant in cases (median 0.008%, IQR 0.003-0.022%) than controls (median 0.001%, IQR 0.001-0.004%) while Roseburia was less abundant in eczema (median 0%, IQR 0-0.063%) than controls (median 0.055%, IQR 0.002-0.270%). Nonetheless, Shannon-Weaver diversity index of stool microbiota at 4 weeks was similar between infants with eczema and non-allergic controls at 9 months (median [IQR]: 1.28 [0.94-1.93 ] versus 1.47 [1.31-1.80] ; P = 0.698). Comparing microbial compositions in our newborns and Swedish, Escherichia coli was found among top 5 genera only in both our cases and controls whereas enterobacter only in Swedish newborns. Clostridium, parabacteroides and lactobacillus were found only in Chinese eczema and healthy Swedish newborns.


Methods: Genetic association analysis of one single nucleotide polymorphism (SNP) from each candidate region was performed in non-Hispanic white asthmatic subjects from SARP, CSGA, ACRN, and TENOR cohorts (n = 1,209 and 154 for atopic and non-atopic asthma, respectively) using logistic regression model. Expression quantitative trait loci (eQTL) analysis, using linear regression model, of the candidate SNPs was performed in cells from human bronchial epithelial biopsy (BEC, n = 107) and bronchial alveolar lavage (BAL, n = 94) from the SARP cohort (GEO series accession number GSE67940). Results: SNPs in seven genes (IL18R1, LPP, SLC25A46, WDR36, HLA-DQB1, C11orf30, and CLEC16A) were associated with general physician-diagnosed asthma in the GABRIEL study (P = 3.5x10 -12 -4.4x10 -3 ) (Moffatt, NEJM, 2010). In our study, SNPs in five genes (IL18R1, LPP, IL21, TLR6, and C11orf30) were associated with atopic status in asthma subjects (P = 4.6x10 -3 -0.05). SNPs in LPP and IL21 showed opposite risk alleles between asthma and autoimmune diseases. The gene expression pattern between BEC and BAL were distinct. In BAL, rs1464510, rs7696175, rs1043828, rs6906021, and rs7936562 were cis-correlated with mRNA expression levels of LPP, TLR6, TSLP, HLA-DQB1, and C11orf30, respectively (P = 1.1x10 -10 -0.04). Conclusions: Most of the genes associated with allergic sensitization or self-reported allergic rhinitis are also associated with general asthma, indicating shared genetic factors among allergic diseases. IL18R1, LPP, and C11orf30-LRRC32 are associated with atopic asthma and general asthma, however, the association effects (odds ratio) are stronger in atopic asthma. IL21 and TLR6 are associated with atopic status in asthma, but not associated with general asthma, indicating the importance to perform genetic analysis in more homogeneous asthma subphenotypes. Asthma and autoimmune diseases have shared immunopathogenesis pathways but in opposite directions. There is a tissue-specific gene expression regulation. Background: The transient receptor potential vanilloid 1 (TRPV1), identified as a molecular target for the activation of sensory neurons by various painful stimuli, was reported to play a role in signaling and activation of CD4 + T cells. However, the role of TRPV1 remains poorly understood in allergic rhinitis. Objective: To exploit the role of TRPV1 using TRPV1 antagonist such as N-(4-Tertiarybutylphenyl)-4-(3-cholorphyridin-2-yl)tetrahydropyrazine -1(2H)-carboxamide (BCTC) and TRPV1 knockout mice in allergic rhinitis mice models and using samples of patients with allergic rhinitis and to evaluate the molecular mechanism of TRPV1 in CD4+ T cell mediated signaling pathway in allergic rhinitis. Methods: TRPV1 expression was measured in CD4 + T cell and cytokine analysis and T cell receptor signaling pathways were evaluated in BCTC pretreated T cell lines and TRPV1 (-/-) T cells. Allergic parameters were evaluated using TRPV1 antagonists and TRPV1 knockout mice in OVA-challenged mice model. Additionally, TRPV1 expressions were assessed in patients with allergic rhinitis. Results: TRPV1 expression was localized in CD4 + T cell. BCTC pretreatment and TRPV1 knockout suppressed T cell cytokine production and suppressed T cell receptor signaling pathways, including NF-kB, MAP kinase and NFAT signaling in both Jurkat cell line and CD4 + T cells in vitro. TRPV1 antagonists (BCTC and theobromine) significantly reduced allergic parameters such as symptoms, totaland ova-specific IgE levels in the mice model of allergic rhinitis. In TRPV1 knockout and BCTC treated mice, nasal eosinophil infiltration and nasal mucosal cytokines transcriptional activities were decreased, when compared OVA-challenged wild-type mice. In human nasal mucosa, TRPV1+ inflammatory cells was frequently observed. TRPV1/CD4 double positive inflammaotry cells were increased in nasal mucosa in patients with allergic rhinitis as compared with non-allergic rhinitis and normal controls. Conclusion: TRPV1 activation on CD4 + T cells is involved in TCR signaling and could be a novel therapeutic strategy in allergic rhinitis. Background: Allergic rhinitis (AR) has a wide range of clinical aspects, and comorbid allergic diseases may accompany. We aimed to identify rhinitis phenotypes in school children and to predict the prognosis of developing bronchial hyperresponsiveness (BHR). Methods: As a part of Children's HEalth and Environmental Research (CHEER) study, a prospective follow-up study for 4 years with every 2 year interval, 2,491 children aged 6 to 14 years-old were enrolled in the first survey. Among them, 512 children had current rhinitis, defined as parental-reported doctor-diagnosed rhinitis and having rhinitis symptoms in the last 12 months. Variables including age, sex, body mass index, parental allergic history, income, maternal education level, AR treatment during the last 12 months, environmental tobacco smoking exposure, total serum IgE levels, eosinophil percentage, diagnosis of atopic dermatitis and asthma, lung function tests, BHR to methacholine and skin prick tests were used in the latent class analysis. Results: We identified 4 phenotypes of rhinitis as the best fit in this study. Cluster types were characterized as "non-atopy with low socioeconomic status" (33% of sample, Cluster 1), "atopy with norm