use prefix []or [-]not [+]and [=]has feature [!]exclude feature ie. 'interleukin-6 -animal +phenotypic =protein !tumor'

Displaying 10 papers, 10 pages, start at 1, 1260 Hits
301 section matches
purpose of this study was to demonstrate the efficacy of, and suggest a regimen for, oral steroid in the treatment of CSU patients who were refractory to a high dosage of antihistamines. We conducted a retrospective chart review of all patients diagnosed with urticaria between Feburary 1, 2012, and December 31, 2014 . A total of 98 patients with CSU were included. Of these, 16 patients (16.3%) were antihistamineresistant and prescribed a 2-week course of steroid. Thirteen patients (81.2%) were successfully controlled with antihistamines only after stopping the first course. Second course of steroid induced remission additionally in two patients (12.5%). No adverse events and complications associated with oral steroid were observed over the study period. This study demonstrated the excellence of a 2-week course of oral corticosteroid in antihistamine-resistant CSU and propose standardized corticosteroid treatment regimen.


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.


Management of allergic disease exacerbations in pregnancy Yasunobu Tsuzuki Sapporo Tokushukai Hospital, Japan World Allergy Organization Journal 2016, 9(Suppl 1):A10 Introduction: Allergic disease exacerbations can affect maternal and fetal conditions in pregnancy. Some of allergic disease exacerbations may trigger pregnancy complications, life-threatening events of the mother and fetus. Eventually, it predisposes both them to the risk of severe damages. We report 4 cases of maternal allergic disease exacerbations (food allergy(FA) and anaphylaxis, bronchial asthma(BA), atopic dermatitis(AD), allergic rhinitis(AR), atopic eruption of pregnancy(AEP)), their management is discussed. Case report: Case1: a 31-year-old female in 32 weeks of gestation, with a medical history of BA in childhood, AD, AR, FA, was referred by an otolaryngologist because of persistent moderate-to-severe asthma symptoms, severe AR. We introduced long-acting β2-agonist plus inhaled corticosteroids, short term oral methylprednisolone and nasal corticosteroid. Case2: a 26-year-old female in 25 weeks of gestation, with a medical history of AD, but without a history of any FA or anaphylaxis, was brought to the emergency department because of dyspnea, generalized itchy rash, abdominal pain, and severe uterine contractions after having eaten dinner. She was diagnosed as anaphylaxis and threated abortion. She was immediately treated by epinephrine i.m injection 2 times and obsterician. We disclosed buckwheat allergy as the cause of anaphylaxis. Case3: a 30-year-old female in 27 weeks of gestation, with a medical history of AD, was referred by an obsterician because of her severe AD and AR. She had stopped the medication after her pregnancy, which developed severe AD and AR. We introduced local corticosteroids and nasal corticosteroid. Case4: a 34-year-old female in 31 weeks of gestation, with a medical history of AR and AD during her childhood, came to our hospital because of her severe itchy hives in her both arms and body. She was diagnosed as AEP and was introduced to use local corticosteroids. All mothers and their conditions improved immediately and the baibies of 4 cases were normally delivered without neurological deficiency or congenital malformations. Discussions: Allergic disease exacerbations may be common events during pregnancy, that reduce the maternal QOL and can even develop the potential risks of pregnancy complications, life-threatening events of mother and fetus, severe fetal brain damages. To prevent these situations, we should promote the appropriate therapies and educations to allergic diseases, and encourage the mothers to keep allergic medications, not only during pregnancy but prepregnant period. More investigations toward the pharmacologic management in allergic diseases are necessary to keep pregnant women and newborns healthy.

C) Results

Including present case, 9 cases (age 20~63, male 5, female 4) with anaphylaxis by ant siting have been reported in Japan since 1987. The numbers of ant stings just before the onset of anaphylaxis were 1 to 3. The intervals between ant stings and onset of anaphylaxis in most cases were less than 15 minutes, except 2 cases without description and 1 case, in which the onset was two hours after the ant sting. Symptoms include wheal and urticaria, diarrhea, dyspnea, and hypotension. As for diagnosis, the causal relationship between ant stings and anaphylaxis was established mainly based on their temporal order. The patients themselves or doctors in charge caught the ants on the same day or later, enabling determination of the ant species. In most cases, the ants were identified as B. chinensis. The proof of IgE antibody against ant protein was done by skin prick test only in 2 cases. Our present case is the first Japanese case in which IgE antibody against B. chinensis protein was directly proved. Epinephrine was used in 5 cases, while only anti-histamine and glucocorticoid were used in other cases with good prognosis. All patients had prior history Background: The etiology of chronic urticaria (CU) remains unknown in most patients. Possible causes in some cases include food, but the role of hypersensitivity to food antigens in patients with CU remains controversial. Objectives: The aim of this study was to evaluate the association between food hypersensitivity and CU in 350 Korean participants.


Dose optimizing study of a depigmented polymerized allergen extract of phleum pollen by means of conjunctival provocation test (CPT) Oliver Pfaar 1 , Angelika Sager 2 1 Center for Rhinology and Allergology Wiesbaden; 2 Leti Pharma Gmbh, Germany Correspondence: Angelika Sager -Leti Pharma Gmbh, Germany World Allergy Organization Journal 2016, 9(Suppl 1):A17
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.
Polyketide antibiotics including macrolides are known to affect signalling pathways of transcription factors and regulate a number of genes involved in their potential anti-inflammatory effects but these properties cannot be used in clinical settings due to a risk of bacterial resistance. The aim of our study was to assess the effect of colabomycin E, a new streptomycete-derived secondary metabolite *, on the mRNA expression and release of proinflammatory cytokines and chemokines from THP-1 monocyte/macrophage cell line and peripheral blood monocytes. Colabomycin E was isolated and purified from the natural producer Streptomyces aureus SOK1/5-04 by extraction of post-fermentation medias and mycelia with organic solvents and multiple subsequent liquid chromatography purification steps and crystallization. Monocytes/macrophages were cultured in RPMI1640 with 10% fetal calf serum and then stimulated with TNF-α (20ng/ml) under serum free conditions in the presence or absence of colabomycin E. The total mRNA was extracted from cultured monocytes/macrophages with RNAeasy Plus Mini Kit (Qiagen) and quantitative RT-PCR (SABiosciences) was used for the evaluation of 84 different gene expressions in TNF alpha and colabomycin E stimulated cultures and compared to unstimulated cells. The concentrations of cytokines and chemokines in culture supernatants of monocytes and THP-1 cells were measured by ELISA or Luminex.
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.


The effects of spirulina (Arthrospira platensis) dietary supplement as an adjunct therapy for children aged 7 to 14 years old with asthma: A randomized -double blind placebo controlled clinical trial Lou Ver Leigh Arciaga Manzon 1 , Pilar Agnes Gonzalez Andaya 2 kDa components of Ag5 and conformational epitope on these subunits. In addition, since the 57kDa component arise from the removal of the C-termainal portion of 22kDa subunit of Ag 5, thus IgE specifically recognized N-terminal of 22 kDa subunit which remain bounded to the other component, whereas IgG reacted with C-terminal of 38 kDa component of Ag5.
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.


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.


Objective: The purpose of this study is to evaluate the effects of Asian dust events on asthma by socioeconomic status using claim data. Methods: Case crossover design was used. This study is based on the national health insurance claim (ICD : J45, J46), air pollutants [PM 10 (μg/m 3 ), CO(ppb), SO 2 (ppb), NO 2 (ppb), O 3 (ppb)] and climate [temperature(°C), humidity(%), visibility(km), wind speed(m/s), air pressure(hPa)] data from 2007 to 2013 in Seoul and Incheon, Korea. The socioeconomic status was classified into health insurance group and medical aid group. The daily maximum value of air pollutants and daily average climate were calculated. The daily numbers of asthma cases on the 'Event' days were compared with 'Control' days. To select event days, 2 criteria were applied: 1) exclude weekends 2) excluded reoccurred Asian dust events on the 14 days before and after the Asian dust event. It was observed for 7 days after the events days. Control days is defined as the 7 days before and after the event days. Log poisson regression was used to estimate the ratio of averaged asthma cases using age, gender, region and climate between event and control days. Results: 7 event days were selected. On the event days, the average numbers of asthma cases were much more than the control days on the gender, age, region and socioeconomic status. However, there was no significant difference statistically. Humidity of the event days was lower (p=0.0950) but wind speed (p=0.0203) and PM 10 (p=0.0376) were higher than control days. The estimated ratio of averaged asthma cases on event days was 0.96 (95% C.I.: 0.95-0.98). According to the socioeconomic status, the ratio of asthma patients during 7 days from 'day +0' to 'day +6' were as follows: 0.96 (0.95 -0.97) on the day +0, 1.27 (1.26 -1.29 ) on the day +1, 1.11 (1.09 -1.13 ) on the day +2, 1.25 (1.23 -1.26) on the day +3, 1.13 (1.12 -1.15 ) on the day +4, 1.06 (1.04 -1.07) on the day +5 and 0.83 (0.81 -0.84) on the day +6 in the health insurance group. Also, in medical aids group, the estimated ratio of the each day were 1.00 (0.94 -1.07), 1.14 (1.06 -1.22), 1.15 (1.06 -1.25 ), 1.18 (1.11 -1.25 ), 1.08 (1.01 -1.15 ), 1.02 (0.94 -1.10) and 0.78 (0.74 -0.83). Conclusion: Asian dust events can worsen asthma and its effects on asthma appear differently by the socioeconomic status. Time lag analysis is needed in studying asthma effect on Asian dust event using claim data.


Purpose After I first joined at 1996 AAO-HNSF Annual Meeting in Washington, DC as residency, I became interested in high resolution nasal endoscopy and I planned study design for allergic rhinitis patients. Research diagram of DANYOUNG classification consist of the study design, with the three periods at 20 years strategic plan. Using digital HD 3chip endoscopy, digital HD Flexible videoendoscopy and 3chip endoscopy, DANYOUNG classification 2015 update is achieved by better objective visual data files. Method From Jun 2001 to Apr 2015, nasoendoscopic video data files were collected from allergic rhinitis patients. Nasoendoscopic video system is consist of stryker digital HD 3chip video camera system 1488 model, kay pentax digital HD Flexible videoendoscopy VNL-1190STK model and stryker 3chip video camera system 888, 988, 1088 model. Video data storage system is consist of stryker SDC-pro, SDC-HD, SDC3 recording system and NAS-LG system. Result DANYOUNG classification hypothesis based on surface change of allergic rhinitis patient's inferior turbinate mucosa.This classification consist of 3 stages. Stage 1 is hypertrophy state. Stage 2 is dimple state. Stage 3 is wrinkle state. A clear definition of stage is more characterized under digital HD endoscopic evaluation. Especially, irreversible change of nasal mucosa such as dimple and wrinkle shape is confirmed again.
Conclusion DANYOUNG classification has very simple, objective advantage and useful on early diagnosis of allergic rhinitis. When OMU-CT is using together for allergic rhinitis patient, this staging is clear more than. DANYOUNG classification 2015 update can related on ARIA 2010 update, can be one in the future. Background: Although many patients with allergic rhinitis have symptoms due to sensitization with more than one kind of allergens, and mixed allergen extracts are widely used for immunotherapy, there are few published trials. Methods: We performed a 1-year single-centre cohort study of subcutaneous immunotherapy using house dust mite extract, weed pollen extract, or mixed house dust mite/weed pollen extract in 44 allergic rhinitis patients. All the allergens responsible for the symptom of each patient were included in his immunotherapy. Quality of life was evaluated with the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) before and after 1-year immunotherapy. Results: After 1-year subcutaneous immunotherapy, RQLQ score of the house dust mite group 1.02±0.82(n=12)was significantly better than baseline RQLQ score 2.25±1.29 (p=0.024) ; RQLQ score for the weed pollen season of the weed pollen group 1.53±1.13 (n=21)was significantly better than baseline level 3.08±1.22 (p=0.000); RQLQ score for the weed pollen season of the mixed house dust mite/ weed pollen group 1.78±1.02 (n=11) was significantly better than baseline level 2.92±1.25 (p=0.004), RQLQ for ordinary times of the mixed house dust mite/weed pollen group 0.62±0.62 (n=11) was significantly better than baseline score 1.23±0.84 (p=0.002). The reduction of RQLQ score in the house dust mite group was 1.23±1.63, and 1.55±1.24 in the weed pollen group after 1-year treatment. In the mixed house dust mite/weed pollen group, RQLQ for ordinary times deceased by 0.60±0.47, with no difference compared to the house dust mite group (p=0.224); RQLQ for the weed pollen season decreased by 1.14±1.01, with no difference compared to the weed pollen group (p=0.358). Conclusions: There was no significant difference between the effect on quality of life of the mixed house dust mite/weed pollen extract immunotherapy and the effect of the house dust mite extract or the weed pollen extract immunotherapy. The efficacy of multi-allergen immunotherapy was not weaker than that of single-allergen immunotherapy. Background: Accumulating evidence suggests that desertification and climatic variability can contribute to increased desert dust formation in the air. Desert dust has been shown to exert adjuvant effects in animals. Objective: To examine if desert dust enhances allergic symptoms in real-life settings and to investigate its effect modifiers. Methods: We conducted a cohort study for 3,327 pregnant women during spring and fall in the period spanning October 2011 to May 2013 in three regions in Japan as an adjunct study of the Japan Environment & Children's Study. We timely acquired participants' daily symptom scores by sending a web-based questionnaire on high Background: There has been no nationwide population-based investigation of relationship between allergic rhinitis (AR) and mental health in Korea. Objective: To evaluate the association between AR and mental health status in the general adult Korean population. Also, to investigate relative burden of AR on mental health using Allergic Rhinitis and Its Impact on Asthma (ARIA) classification. Methods: A cross-sectional study was performed by using data of 11,154 individuals 19 years old or older, collected through the Korean National Health and Nutrition Examination Survey from 2011 to 2012. Univariate analysis was conducted on Healthy, AR groups with weighted prevalence of demographic characteristics, socioeconomic status and comobid diseases. Subanalysis classifying AR severity according to the ARIA classification was carried out to evaluate the relationship of AR severity with mental health. The odds ratios (ORs) for each components representing mental health status were estimated by multiple logistic regression analyses with confounder adjustment. Results: Univariate analysis with Chi-square test after adjusting age, sex, BMI, smoking status, alcohol use status and exercise status, components representing mental health status showed linear trend with the severity of AR according to ARIA classification. Stress, depressive mood, suicidal thought, psychological consultation factors were correlated with AR after adjusting demographic characteristics, socioeconomic status. Even after adjusting comorbid allergic diseases the correlation remained significant with stress, depressive mood, psychological consultation factors (OR [95% CI]; 1.227 [1.042, 1.445 ], 1.368 [1.095, 1.71 ], 1.804 [1.096, 2.969] ). Conclusion: Patients with AR appear to be at a higher risk for mental health disorders in the general adult Korean population. Moreover, persistent or severe AR was correlated with poor mental health. Therefore, better control of AR may be conducive to better mental health and more attention should be paid to the psychological status of AR patients.


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.


Background: To determine if EoE patients with concomitant seasonal or perennial allergic rhinitis improve with aeroallergen immunotherapy (IT). Methods: We present a case series of 3 Caucasian patients with a history of atopy and EoE based on characteristic clinical symptoms, EGD findings, and esophageal biopsy. One had oral allergy syndrome. None of the patients had peripheral eosinophilia. Two had seasonal exacerbations of their EoE symptoms. These patients were all started on aeroallergen immunotherapy for atopic disease other than EoE. Results: In this small group of aeroallergen and food sensitized adult patients, we demonstrated a lack of improvement in clinical symptoms of EoE with aeroallergen immunotherapy while making no modifications in diet or oral medications. It is difficult to ascertain improvement due to the lack of a validated adult symptom score and inherent restraints of repeat esophageal endoscopy due to cost and procedural risks. It is also unclear if the biopsy always accurately reflects disease activity. There are several limitation of this small sample which includes absence of a control group, no statistical validity, and possible selection bias. Conclusions: We would like to continue further evaluation of the prevalence of aeroallergen sensitized adults with EoE and will consider a similar evaluation of pediatric patients. We will review further data at an attempt to isolate a population in which improvement with aeroallergen immunotherapy may be successful in improving control of EoE without aggressive dietary modifications or medication management. Background Eczema herpeticum (EH) is a widespread herpes simplex virus infection, most often presenting as complication of atopic dermatitis (AD). Along with increased incidence of AD, the number of patients of EH seems to be increased over the years. However, population-based epidemiologic data on EH are insufficient because of its rarity. We aimed to evaluate the epidemiologic trends of EH in Korean during last 10 years, comparing those with prevalence of AD. Methods A retrospective analysis was carried out for patients diagnosed with EH between January 2005 and December 2014 at a single tertiary hospital in Korea. Variables of interest included age, sex, season of onset, treatment, outcomes, recurrence, and whether they had underlying AD or not. The prevalence of AD at the same period was investigated by the years.


Total 1,043 episodes of EH in 621 patients were diagnosed during ten years. The number of EH episodes per patient was 1.68 (range 1 -6) , with more than one episode in 288 patients. Mean age at onset was 23.4 years, and sex ratio was M:F = 1:1.4. The patients who had recurrent episodes tend to be older (25.9 years) than those with EH episode only once (21.3 years), and there was no significant difference of sex ratio between two groups. Seasonal variation of onset was not found. Duration of treatment was 7.8 days, and most of treatment (93.7%) included systemic antiviral agent. Eleven patients were hospitalized and improved by intravenous antiviral agent, but six of them showed recurrence after discharge. Majority of patients with EH had underlying AD except only four patients. At the same period, total 33,692 patients were diagnosed as AD in our clinic, with continuous increase of prevalence annually. The ratio of EH/AD was 1.83% in average, and it was steadily decreased by years: 2.52% in 2005, 1.36% in 2014. EH was more commonly complicated in old age, showing significantly increased EH/AD ratio above 30 years old. Conclusions EH is not a rare complication of AD, affecting about 2% of AD patients. While the prevalence of AD is increased over the years, total number of EH patients was little changed, leading to slight but continuous decline of EH/AD ratio. As patients getting older, EH could be more commonly complicated in AD, and show more recurrent course than in younger patients.


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.


To test use of jet nebulizers NE-C802 as a drug delivery system in the children with asthma Amit Agarwal 1 Background: Asthma is a chronic inflammatory disorder of the airway characterized by recurrent episodes of wheezing, breathlessness, chest tightness and coughing, particularly at night or early in the morning. These episodes are usually associated with variable airflow obstruction within the lungs that is often reversible either spontaneously or with treatment. Methods: Two hundred patients were initially screened in the outpatient clinic, Department of the Pediatrics, Post Graduate Institute of Medical Education and Research, Chandigarh. Out of the 200 patients, 30 were selected. Informed consent of one of their parents was obtained prior to enrolment into the study. Included patients were also be on daily Budesonide therapy for asthma control and Living in and around Chandigarh. The patients were then assessed every two weeks for symptomatic control of asthma and the participants and their parents were explained and demonstrated about the functioning of the nebulizers. PEFR, Height and Weight measurements were taken at every visit when nebulizer was used. Patients were assessed for improvement or deterioration of symptoms. The study was approved by Institute Ethics Commitee (PGI/IEC/2014/2337). Results: Seventy percent patients/parents/guardians preferred using nebulizer for one of the following reasons: Better symptom control, Decreased frequency of exacerbations or Management of exacerbations can be done at home by increasing the duration of drug delivery through the nebulizer. Thirty percent patients/parents/guardians preferred using spacer because they felt that their children could use a spacer easily as compared to nebulizer.


Effectiveness of premedication and rapid desensitization in hypersensitivity to l-asparaginase Hwan Soo Kim, Sul Mui Won, Yoon Hong Chun, Jong-Seo Yoon, Hyun Hee Kim, Jin Tack Background L-asparaginase is a crucial chemotherapeutic agent for the treatment of acute lymphoblastic leukemia. However, hypersensitivity to L-asparaginase is common which limits its usage. We aimed to evaluate the usefulness of premedication and desensitization in Lasparaginase hypersensitivity.


Angioedema with Eosinophilia: The First Report from Thailand Thatchai Kampitak Samitivej Sukhumvit Hospital, Thailand World Allergy Organization Journal 2016, 9(Suppl 1):A58 Background: Angioedema with eosinophilia (AE) is an uncommon form of angioedema. Although its pathogenesis remains unclear, it can be classified into episodic angioedema with eosinophilia (EAE) and nonepisodic angioedema with eosinophilia (NEAE). While EAE has been generally observed in the Western populations, almost all patients with NEAE were Asian, exclusively Japanese and Korean. Previously, AE has never been reported in Thai patients. Methods: A case series of 3 patients with AE from Thailand is described. Results: Three Thai patients with AE were identified during April 2014-March 2015. All but 1 patient were female. The mean age at the onset of symptoms was 32 years (27) (28) (29) (30) (31) (32) (33) (34) (35) (36) (37) (38) (39) . All patients presented with symmetrical swelling of distal extremities without systemic symptoms. No fever or weight gain was observed. Arthralgia and urticaria were present in 1 patient, respectively. No potential triggers were identified except 1 patient had preceding upper respiratory tract infection 1 week prior to the swelling. Previous history of significant medical or allergic diseases was unremarkable in all except 1 patient was hepatitis B carrier and had recurrent eczema. All patients had eosinophilia with the mean eosinophil count of 4,083/mm 3 (1, (6) (7) (8) (9) 420) . Blood chemistries, liver and kidney function tests, inflammatory markers (ESR and CRP) and immunoglobulin levels were within the normal ranges in all patients. Secondary disorders that might be responsible for eosinophilia were excluded. Recurrent episodes of angioedema were observed in 1 patient. Antihistamine was briefly prescribed in 1 patient with coexisting urticaria. All patients had complete spontaneous resolution of symptoms in parallel with the normalization of eosinophil count within few months after the presentation. Conclusions: AE should be considered in young Asian women whose presenting features include peripheral swelling and eosinophilia without constitutional symptoms, internal organ involvement and elevated immunoglobulin levels. Similar to previous reports from Japan and Korea, NEAE is more prevalent in Thai patients than EAE. No corticosteroid therapy is generally required since most patients have a self-limiting disease. Keywords: Hypereosinophilic Syndromes; Angioedema Background: Korean red ginseng (KRG) and ginsenoides have showed several biologic effects in various field including anti-inflammatory and anti-allergic effects. We aimed to investigate the anti-inflammatory and anti-pruritic effects of KRG on atopic dermatitis murine model. Material and methods: The atopic dermatitis-like skin lesions were induced by percutaneous challenge of 2,4,6-trinitro-1-chrolobenzene (TNCB) on the ear and back of NC/Nga mice. The KRG extract, evening primrose oil, cyclosporine and phosphate-buffed saline were administered orally by gastric tube. The effects of KRG and other drugs were assessed by measuring the clinical severity score, ear thickness, transepidermal water loss (TEWL), the number of scratching counts, total systemic IgE and IL-31 by ELISA, histologic changes of skin, and mRNA expression of TNF-α, IFN-γ, TSLP and IL-31. Each study group was divided into scratch-able and non-scratch-able subgroups to evaluate the impact of scratching behavior in atopic dermatitis. Results: Oral administration of KRG significantly reduced clinical severity, ear thickness, and TEWL elevation. The number of scratching counts was also effectively lowered in KRG administered group compared to other treatment groups. The clinical results were also revealed in serologic and histologic changes. In the KRG group, the systemic IgE and IL-31 level was significantly lowered on the last day of the experiment.
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.
Age group 19-54 years Mean age 29.7yrs • Duration of urticaria 6 months to 80 months • Associated conditions: -Eosinophilia -5 patients -Hypothyroidism -4 patients -Microcyctic Hypochromic anemia -2 patients -Autologous serum skin test +ve -11/24 serum group -7/17 saline group Urticaria activity score (UAS) came down form average 35.74 to 7 at the end of 9 weeks.Saline group did not show reduction in UAS. Daily requirement of antihistamines also came down in serum group. AST is a useful adjunct to antihistamines in CU. The effect persisted even four months after cessation of therapy and thus improves the quality of life. This therapy could be useful in India as cost effective & beneficial (a poor man's biologic!) for chronic urticaria patients. Background: Allergic bronchopulmonary aspergillosis (ABPA) is a lung disease that is caused by hypersensitivity reaction to the fungus Aspergillus fumigatus, where its colonization often found in chronic respiratory disease, either in bronchial asthma and lung tuberculosis. History of asthma in ABPA is often obtained from 5-10 years earlier. Lung tuberculosis is often difficult to distinguish with ABPA due to similar radiological features, often found as misdiagnosis in a previous study. Methods: Observational descriptive analytic with cross sectional approach, conducted in Prof. Dr.R.D. Kandou Hospital in Manado, from July-December 2013. Total 75 samples from 3 groups, each 25 samples: moderate-severe persistent asthma, Acid-Fast Bacilli (AFB) positive lung TB and AFB negative lung TB. Chest x-ray examination, skin prick test (SPT) using A. fumigatus antigen (rapid reaction/type I early and late/8 hours type III), total IgE, and IgG anti A. fumigatus are obtained. Greenberger assessment criterias are used for ABPA. Results: ABPA was found 1.55% (4/258) in moderate-persistent asthma, 0.64% (3/469) in FAB positive lung TB and 0.57% (6/1054) in AFB negative lung TB. Correlation between type I SPT and total IgE showed significant results (p<0.05) in moderate-severe persistent asthma and AFB negative lung TB, but is not significant in AFB positive lung TB, while the correlation between IgG A. fumigatus and type III SPT has very significant (p <0.001) results in all groups; Conclusion: ABPA is found either in asthma or lung tuberculosis patients. Significant correlation between IgG A.fumigatus and type III SPT may indicate SPT to replace IgG A. fumigatus examination which is currently a research kit. SPT examination may be considered as screening of suspected ABPA.


Methods: Human nasal epithelial cells (hNEC), RPMI2650 and A549 cell lines were used. Immunoblotting, immunofluorescence and immunohistochemistry were done to evaluate EMT markers and signaling molecules in vitro and in sinonasal tissues from CRS patients with or without NP. Boyden transwell system was utilized to measure the capacity of migration. Results: Four different cytokines, IL-5, IL-17, TNF-α and IFN-γ, were treated to both hNEC and RPMI2650 cells respectively, and EMT markers were traced. Among them, IFN-γ could most induce EMT, which was confirmed by the spindle-shape of cell morphology, modest cytoskeleton rearrangement, increased migration potential and EMT marker changes. Mechanistically, IFN-γ-induced EMT via ERK and p38 pathway, which were known as non-smad pathway of EMT. Next, we investigated whether p38 and ERK inhibitors could prevent EMT phenomenon. Actually, both p38 inhibitor (SB203580) and ERK inhibitor (PD98059) suppressed IFN-γ-driven EMT. Finally, we checked IFNγ and EMT marker levels in human nasal mucosa tissues. IFN-γ expression was upregulated in NP mucosa compared with tissues of control and CRS only patients. In addition, this IFN-γ expression was found to correlate with E-cadherin (an epithelial marker) loss and αsmooth muscle actin (a mesenchymal marker) expression. Conclusion: IFN-γ induce EMT in hNEC and this process is critically mediated by ERK and p38 pathway. This study shows that IFN-γinduced EMT is likely to contribute to nasal polyposis in CRS, and suggests that p38 and ERK inhibitors be viewed as a therapeutic target for nasal polyposis. We evaluate the relevance of management and education to anaphylaxis patients and emphasize the importance of education and understanding the disease.


One hundred and ninety five patients who visited ER were enrolled from three hospitals. We analyzed clinical features, prior history of anaphylaxis, management and education. For analyzing associated factors with injection of epinephrine, Pearson chi-square test was used by SPSS version 21.


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.


The relationship between sputum pentraxin 3 levels and childhood asthma Background: Pentraxin 3 (PTX3) is soluble pattern recognition receptor, and acute phase protein that has emerged as a new serological marker reflecting tissue inflammation and damage under diverse diseases. We determined whether sputum PTX3 levels are elevated in patients with childhood asthma. We also investigated the relationship between sputum PTX3 levels and airway inflammation, pulmonary function, and bronchial hyperresponsiveness in children.


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.


Methods: Study subjects included 15 non-asthmatic Der-p sensitized rhinitis (AR) patients with airway hyperresponsiveness (AHR) (AR +AHR+), 15 AR patients without AHR (AR+AHR-), 15 healthy control (HC) with Der-p sensitization (HC+DP+) and 15 HC without Der-p sensitization (HC+DP-). They underwent Der-p NPT. Nasal lavage and resistance, sputum induction, forced expiratory volume in 1 second (FEV 1 ) and airway responsiveness to histamine bronchoprovocation (PD 20 -FEV 1 ) and exhaled nitric oxide (FeNO) were performed before and 6 hours after NPT. Number of eosinophils in nasal lavage fluid and induced sputum eosinophils were determined. Results: The nasal airway resistance increased after NPT in subjects of all four groups (P<0.05). FEV1 % predicted decreased in AR+AHR+ patients after NPT (P<0.05). Eosinophils in nasal lavage fluid and sputum increased significantly after NPT in AR+AHR+ and AR+AHR-patients (P<0.001). PD 20 -FEV 1 was decreased and FeNO was increased significantly after NPT only in AR+AHR+ patients (P<0.05), wherease, no significant changes were observed in HC+DP+ and HC+DP-subjects after NPT. The number of eosinophils from nasal lavage was strongly correlated with the sputum eosinophils, the level of FE NO (r=0.737, p=0.000 and r=0.736, p=0.000), and was negatively correlated with FEV 1 , PD 20 (r=-0.287, p=0.026 and r=-0.436, p=0.000).


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.


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 normal lung function" (39%, Cluster 2), "atopy with impaired lung function" (14%, Cluster 3), and "non-atopy and high socioeconomic status" (15%, Cluster 4). Total serum IgE levels and serum eosinophil percentages were highest in cluster 3. Children in cluster 3 showed highest prevalence of new development of BHR during 4-year follow-up (P=0.039). Conclusions: From rhinitis phenotypes, rhinitis cluster with high atopy and impaired lung function in children is associated with new development of BHR. This finding suggests that identification of distinctive rhinitis phenotype will help to prevent the progression of new development of BHR in the aspect of allergic march. Background: Anaphylaxis to food, drugs and diagnostic reagents have been increasingly reported in adult patients; however, its pathogenic mechanisms or an efficient diagnostic test have not been settled. Basophil activation test (BAT) using two activation markers, CD203c and CD63, has been readily used to assess basophil activation status. Considering that mast cell/basophil play an important role in anaphylaxis, we evaluated the basophil activation status using CD203c and CD63 expressions in anaphylaxis patients compared to allergic patients without anaphylaxis. Method: 41 patients with various allergic diseases including asthma/ rhinitis, chronic urticaria as well as anaphylaxis and 23 normal healthy controls (NC) were enrolled in the study. Allergic patients were divided into two groups: anaphylaxis (n=13) and non-anaphylaxis groups (n=28), based on the presence of anaphylaxis to different drugs, foods and diagnostic reagents. BAT using CD203c and CD63 expression was performed in baseline and after stimulation with anti-IgE or calcium (Ca 2+ ) ionophore. The BAT is based on double staining with anti-CD123 and anti-HLA-DR and subsequent determination of the percentage of activated basophils by flow cytometry. Results: Baseline % expressions of both CD203c (30.28±23.10 vs. 13.76 ±14.60, P=0.036) and CD63 (17.67±20.48 vs. 3.31±3.73, P=0.028) on basophils were significantly higher in anaphylaxis group compared to NCs, while no differences were noted in non-anaphylaxis group. When the positive cutoff value for a positive BAT result was defined as mean +2SD of CD203c expression, positive BAT rate tended to be higher in anaphylaxis group (38.46%) than in non-anaphylaxis group (17.85%, P=0.20), while no differences were noted in CD63 expression levels. There were no significant differences in baseline % expressions of CD203c and CD63 or those induced by anti-IgE/Ca 2+ ionophore according to age, sex, atopic status, total IgE and ECP levels. Conclusion: These findings suggest that increased basal activation status of basophils may contribute to develop anaphylaxis in adult patients regardless of atopy status, serum total IgE and ECP levels. BATs with applying each allergen will be useful to confirm the causative agent.


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.


Total 60 patients were evaluated (mean age 55.7 years, range 7-96 years), 33 (55 %) were female. Twenty-eight patients (46.7%) had underlying diseases including hematologic malignancy, solid tumor cancer, HIV infection, or autoimmune diseases. Fifteen (25%) individuals were concurrently on systemic corticosteroids. The majority of subjects (49.1%) experienced maculopapular exanthems (MPE), while 36.7 % had severe cutaneous adverse reactions. The mean duration from drug intake to the onset of symptoms was 8 days and the mean interval from symptoms onset to the collection of peripheral blood mononuclear cells (PBMCs) was 9.5 days. In most cases, the number of drugspecific IFN-gamma secreting cells was later analyzed with ELISPOT by incubating PBMCs with the culprit drugs or potential alternative drugs. Beta -lactams occupied 70.8% of the analysis. Penicillins, cephalosporins and carbapenems were the most frequently suspected compounds. The number of drug-specific IFN-gamma secreting cells more than 20 spot-forming cells/10 6 (PBMCs) was considered a positive test. Among those examined for responsible drugs, 22 of 48 tests (45.8%) yielded positivity. The proportion of positive outcomes was 66.7% in acute generalized exanthematous pustulosis, 46.2% in MPE, 40.0% in drug rash with eosinophilia and systemic symptoms and lowest in Stevens Johnson syndrome (16.6%). Subsequently, twenty-four persons underwent drug challenges test. All were able to tolerate their alternative medications of which ELISPOT displayed negative results.


Providing excellent negative predictive value and favorable sensitivity in particular T cell-mediated reactions, IFN-gamma ELISPOT might be applicable to confirm antibiotic hypersensitivity in patients with a history of non-immediate reactions and reduce further allergic risk prior to receiving potential allergenic drug. March, 2006 to April, 2014 at Sagamihara National Hospital. The oral food challenge (OFC) was administered in either 2 divided doses in a 1 hour interval or 3 divided doses in 30 minute intervals. After each challenge, the patient was observed for at least 3 hours. At any sign of subjective or objective symptoms deemed clinically significant, the challenge was terminated and necessary treatment was provided. We had measured patients' almond specific IgE within one year of the challenge. Patient characteristics, positive rate of OFCs, and symptoms induced by OFCs were retrospectively analyzed. C) Results: The age range of the 145 subjects was from 1.0 to 16.0 years (median, 7.0 years). There were 103 male (71%) and 42 female (29%) patients. Median almond specific IgE ranged from less than 0.35 to 68.1 kU A /L (median, 2.84 kU A /L). Almond had been eliminated from the children's diet due to an immediate reaction to almond in 10 (6.9%) patients, due to a positive almond specific IgE in 117 (80.7%) patients, and for other reasons such as anxiety of parents in 18 (12.4%) patients. None of the 10 patients with a history of an immediate reaction to almond had experienced a case of anaphylaxis. Associated atopic disorders were atopic dermatitis in 72 (50%) patients, asthma in 35 (24%) patients, allergic rhinitis in 52 (36%) patients, and allergic conjunctivitis in 35 (24%) patients. OFC was positive in 7 (4.7%) of 145 patients. Symptoms in positive OFCs were oral mucosal symptoms in 5 patients, cutaneous symptoms in 3 patients, and gastrointestinal symptoms in 2 patients. There was no case of anaphylaxis. In the 4 patients who required treatment, only a dose of oral antihistamine was needed. In the comparison of OFC positive and negative patients, a significant difference was seen in history of an immediate reaction to almond (43% vs 5%, p=0.007). No significant difference was seen in other factors including almond specific IgE (1.38 kU A /L vs 2.84 kU A /L, p=0.33). D) Conclusions: The only risk factor of a positive almond challenge was a history of an immediate reaction to almond. OFCs should be performed in patients sensitized to almond to confirm the diagnosis, especially in those patients without a history of an immediate reaction to almond.


Effect of creatine supplementation in fish allergenic potential; A proteomics study Objectives: In this study we tested a specific formulated diet supplemented with creatine to decrease the expression of β-parvalbumin (main fish allergen) in the muscle of Sparus aurata (S. aurata). The effects of creatine in the muscle proteome were also analyzed. Methods: Aquaculture allows fish to be farmed under strict controlled conditions. However, knowledge on how farming practices can be used to modulate fish allergenicity is inexistent. Creatine is a nitrogenous organic acid that occurs naturally in vertebrates and helps to supply energy to cells, primarily muscle. Creatine was verified to reduce in 75% the expression of parvalbumin in rat skeletal muscle [1] . A trial was performed with S. aurata using 3 different concentrations of creatine (2%, 5% and 8%) that were added to a control diet (no creatine supplementation) and tested in tanks of 25 individuals in triplicate. At the end of the trial, plasma and muscle were individually collected for further analysis. Creatine levels in muscle samples were analysed. Cortisol was measured in plasma to address fish welfare/stress levels. Parvalbumin detection in muscle samples was studied using both proteomics and Western Blot techniques and an ELISA commercial kit (Bio-Check, UK). Comparative proteomics was performed on muscle samples to study differences in protein expression between the various treatments and further understand the effect of creatine in fish metabolism. To address this we used 2D Difference Gel Electrophoresis (DIGE). Differences in expression were analysed using the Samespots software (Totallab). Proteins with significant differences (P<0.05) were excised manually and identified by MALDI-TOF/TOF. Results: Cortisol levels are similar to basal levels reported for S. aurata, although the treatment with 8% creatine shows a significant reduction compared with the control diet (p=0.03). Parvalbumin concentrations show no significant differences between the treatments. Creatine concentrations in muscle show a slight decrease in fish fed with supplemented diets. Comparative proteomics in muscle show some differences in protein expression submitted to diets supplemented with creatine. The four protein spots identified as parvalbumins show no significant differences in expression. Proteins differentially expressed are currently being identified by MALDI-TOF/TOF. Conclusion and current work: No accumulation of creatine was found in muscle of fish fed with diets supplemented with creatine. The tested creatine percentages in fish diets did not significantly affect S. aurata allergenic potential. Current work involving new formulated diets and/ or different fish species is underway. We expect in a near future to develop a specific fish diet that will target the expression of fish parvalbumins in order to reduced its allergenic potential.


Flagellin modulates the function of invariant NKT cells via dendritic cells in asthma patients Jae-Uoong Shim 1 , Young Il Koh 1 , Joon Haeng Rhee 2 , Ji-Ung Jeong 1 1 Chonnam National University, South Korea; 2 Chonnam National University Hospital Correspondence: Jae-Uoong Shim -Chonnam National University, South Korea World Allergy Organization Journal 2016, 9(Suppl 1):A92
Backgrounds: Invariant natural killer T (iNKT) cells play a critical role in the pathogenesis of asthma. We previously reported the association between blood Th2-like iNKT cells and lung function in asthma patients and the suppressive effect of Toll-like receptor 5 ligand flagellin B (FlaB) on asthma in a mouse model. Objective: We investigated whether FlaB modulates the function of blood iNKT cells in asthma patients. Methods: Peripheral blood mononuclear cells (PBMCs) were treated with FlaB and then iNKT cells-derived and intracellular cytokines were determined by ELISA and flow cytometry, respectively, following the stimulation with a-galactosylceramide (a-GalCer). Foxp3 + iNKT cells were measured. To determine the effect of FlaB-treated dendritic cells (DCs) on iNKT cells, CD14 + monocyte-derived DCs and T cells from patients with house dust mite-sensitive asthma were co-cultured, in which intracellular cytokines of iNKT cells were determined. In some experiments, IL-10R mAb was used. Results: FlaB treatment reduced the productions of IL-4 and IL-17 from iNKT cells in PBMCs cultures, which effects were ameliorated following the addition of IL-10R mAb. FlaB-treated DCs decreased the frequencies of IL4 + and IL-17 + iNKT cells, which effects were eliminated after the addition of IL-10R mAb. In contrast, Foxp3 + iNKT cells were induced by FlaB treatment, which effect disappeared after the addition of IL-10R mAb. Conclusion: FlaB may inhibit Th2-and Th17-like iNKT cells and enhance Foxp3 + iNKT cells via DCs in an IL-10-dependent fashion in asthma patients. In patients with asthma phenotype in association with iNKT cells, FlaB will be the effective immunomodulator for iNKT cell-based immunotherapy. Background: Allopurinol, a xanthine oxidase inhibitor, has been used since the 1960s for gout, hyperuricaemia associated with treatment for malignancy and renal calculi due to hyperuricosuria. It is known as the leading cause of severe cutaneous adverse drug reactions (SCARs) comprising Stevens-Johnson Syndrome (SJS)/Toxic Epidermal Necrolysis (TEN) and HyperSensitivity Syndrome (HSS)/Drug-Rash with Eosinophilia and Systemic Symptoms (DRESS) (Halevy et al. 2008) . In Vietnam, we observed a high prevalence of allopurinol-induced SCARs, likely due to both its common use and the high prevalence of HLA-B*5801 (6.5% -Hoa et. al. 2008) . The role of viral activation in SCARs is well established. We reviewed patients with allopurinol-induced SCARs to reveal possible non-genetic risk factors. Methodology: The clinical history, examination findings and results of laboratory investigations in eighty-eight confirmed cases of SCARs caused by allopurinol seen between 2011 and 2014 were surveyed. Results: A total of 88 patients comprised 33 SJS (37.5%), 3 TEN (3.4%) and 52 HSS/DRESS (59.1%). The mean age was 59.9±14.4 years (median 57.5) (SJS/TEN: 57.92±15.02 vs HSS/DRESS: 61.33±13.887, p =0.284) and a male preponderance was noted (male: female =62:26). Indications for allopurinol were chronic gout (22.7%), acute gout (12.5%), asymptomatic hyperuricaemia (45.5%) and unknown (19.3%). 100% of patients commenced allopurinol at a dose of 300mg or above. Co-medications were diuretics (3.4%), anti-hypertensive agents (18.2%), colchicine (12.5%), digoxin and probenecid (1.1%). Co-morbidities consisted of hypertension (29.5%), renal insufficiency (13.6%), diabetes (9.1%), dyslipidemia (5.7%), cardiac diseases (4.5%) and liver diseases (4.5%). The index-day was 17. 5 Background: Specific allergen immunotherapy (SIT) is an effective treatment for IgE-mediated allergic disease and involve with specific IgG4 (sIgG4) level increase. Elevation of sIgG4 is accompanied by increase in IgG-dependent serum inhibitory activity for IgE-facilitated allergen binding (IgE-FAB) assay. Objectives: As this 'functional' assay of inhibitory antibodies may be correlate more closely with clinical outcome, we investigated the time course of serum inhibitory activity for IgE-FAB during different period of Dermatophagoides pteronyssinus subcutaneous immunotherapy (Der p-SIT) in rhinitis and/or asthma patient. Methods: This study involved 20 adult patients with allergic rhinitis and/or asthma receiving a 156-week course of Der p-SIT, and 20 adult patients with allergic rhinitis and/or asthma receiving drug therapy only as control. Symptom and medication scores, forced expiratory volume in one second (FEV1), Der p-sIgG4 levels and the serum inhibitory activity at weeks 0, 4, 12, 16, 52, 104 and 156 were analyzed. Results: Rhinitis and/or asthma symptom and medication scores, as well as FEV1% predicted showed improvement at week 52, 104 and 156 than 0 week with significant difference in SIT patients (p<0.05), and Background: Periostin, an extracellular matrix protein, has been known to play an important role in the process of tissue remodeling. Recently periostin has been discovered as a novel mediator in allergic diseases such as bronchial asthma and atopic dermatitis; however, the role of periostin in patients with chronic rhinosinusitis (CRS) remains unclear. Therefore, the objective of this study was to investigte the role of periostin in the pathophysiology of CRS patients. Methods: We investigated periostin expression and its cellular origins in uncinate process mucosa (UP) and nasal polyp (NP) tissues by immunohistochemistry (IHC), quantitative reverse transcription PCR (qRT-PCR), and enzyme-linked immunosorbent assay (ELISA). Correlations between periostin expression and other inflammatory markers, including of interleukin (IL)-5, IL-13, IL-17A, interferon (IFN)-γ, were also explored. Results: Periostin expression was upregulated in NP mucosa from patients with CRSwNP compared with the uncinate process (UP) tissue of control, CRSsNP and CRSwNP patients. Overexpression of periostin in eosinophilic NP compared to non-eosinophilic NP was confirmed by qRT-PCR, and ELISA. There was a positive correlation between periostin protein concentration and Lund-Mackay CT scores in eosinophilic NP. Double IHC staining showed that tryptase + cells were one of the main sources of periostin among immune cells. In addition, periostin mRNA expression was positively correlated with the expression of tryptase + cells and total IgE homogenate in eosinophilic NP. Overexpression of epithelial integrin αV was detected in NP mucosa from CRSwNP patients compared with UP from control and CRSsNP. Moreover, in eosinophilic NP, the expression of epithelial integrin αV was higher than non-eosinophilic NP and positively correlated with the concentration of periostin. Furthermore, periostin mRNA expression in eosinophilic NP patients was positively correlated with IL-5, IL-13 and negatively related with IL-17A; however, there was no association between those and IFN-γ. Conclusions: Our data suggest a role for periostin in the pathogenesis of nasal polypogenesis, especially in eosinophilic NP. Therefore, periostin protein might be a new treatment target for patients with CRSwNP.


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 and objectives: Cysteinyl leukotrienes C4, D4 and E4 mediate allergic inflammation by interacting with type 1 and 2 cysteinyl leukotriene receptors (CysLT1R, CysLT2R), G protein-coupled receptor (GPR) 99 and indirectly with purinergic receptor P2Y12 (P2Y12R). P2Y12R expressed on platelets and eosinophil granules are required for platelet activation, thus resulting in the recruitment of eosinophils in the lungs (1) , (2) . To understand the role of these leukotriene related receptors in allergic asthma, we compared the expressions of CysLT1R, CysLT2R, GPR99 and P2Y12R in an Ovalbumin-induced allergic asthma mouse model. Methods: BALB/c mice were injected intraperitoneally with ovalbumin (OVA) followed by nebulized OVA challenges, from which bronchoalveolar lavage fluid (BALF) cells and lung tissues were collected. Vehicle was treated as a control group. For platelet removal, mice were injected with anti-CD42b antibody. Western blot, immunocytochemistry and immunohistochemistry were applied to evaluate the expressions of these receptors. Results: P2Y12R, CysLT1R and CysLT2R signals were distributed in epithelial lining and lung parenchyma of platelet-depleted and nonplatelet-depleted mice, respectively. The expressions of P2Y12R, CysLT1R and CysLT2R were significantly higher in the lung tissue of OVA-sensitized mice than in vehicle-treated mice (P = 0.047; P= 0.04; P =0.045, respectively). The expression ratios of CysLT1R and CysLT2R to P2Y12R were 1.4 and 1.1 to 1 in vehicle-treated mice; 1.3 and 1.1 to 1, in OVA-sensitized mice. P2Y12R, CysLT1R and CysLT2R were localized to eosinophils from BALF and were elevated markedly after OVA challenges in OVA-sensitized mice, while GPR99 was found with the lowest level in BALF cells and lung tissue. Conclusions: Increased expressions of P2Y12R, CysLT1R and CysLTR2 were noted in the lung tissue of a mouse model of allergic asthma. Additional effects of P2Y12R antagonists on CysLTR1 antagonists should be investigated as a future therapeutic target.
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.

Materials and methods

We aimed to compare anxiety and depression levels of the patients with severe asthma before and after the omalizumab treatment. Patients' anxiety levels were measured with state trait anxiety inventory (STAI) and depression levels were measured with beck depression scale. Findings Five male (%25), fifteen female (%25) patients enrolled in study. The average age of the patients were 50,25. The average score of beck depression scale of patients was 25,35 and 8,55 before and after treatment, relatively. The score was higher before treatment, it was statically meaningful when it compared with after treatment scores (p<0.001). The STAI average score was 52,05 before treatment and 42.95 after it. There was a statistically meaningful difference between the anxiety score average before and after the treatment (p<0.0001). The anxiety score was higher before the treatment. Failure in symptom controlling in asthma can lead to depression. We think that these patients should be examined for psychological disor-Introduction & Objectives: Chronic spontaneous urticaria (CSU) is a common debilitating problem worldwide. Despite its prevalence in the Middle East, very little data is available on the economic impact of CSU on the public health system. This study evaluates the direct medical costs of treating refractory CSU patients in Kuwait. It also evaluates the budget impact of omalizumab (monoclonal anti-IgE antibody) use in these patients. Methods: Prevalence of CSU was estimated through the Delphi method. Data regarding drug utilization and health care system utilization was collected retrospectively from charts of refractory CSU patients who were followed at the Al-Rashed Allergy center in Kuwait. Costs were calculated from a health system perspective. One-way sensitivity analyses were conducted on the price and utilization of each cost component. Results: Before omalizumab use, the total direct costs of treating 1,293 refractory CSU patients was estimated to be 1, 072, 837 KD (US$ 3, 570, 185) per year, corresponding to around 829.7 KD per patient per annum (US$ 2,761). The total cost was principally generated by outpatient visits 1,072,837 KD; which corresponds to 82.45% of the total cost). After omalizumab use, the cost was estimated to be 4,654,800 KD (US$ 15,490,234) per year, corresponding to around 3,600 KD per patient per annum (US$ 11, 980) . The total cost was principally generated by omalizumab costs 4,762,895 KD; which corresponds to 97% of the total cost. All other direct costs of treating CSU patients were decreased after the use of omalizumab. Conventional medication costs and hospitalization costs were reduced by 90% and ER costs were reduced by 97%. Cost estimates were most sensitive to variations in the price and utilization of outpatient visits and the price of omalizumab. Conclusion: The economic burden of refractory CSU in Kuwait is high. The introduction of omalizumab on the health care system is costly because of its high price; however, omalizumab has proven to be effective and is driving all other direct costs down.


Maize is a major crop grown in India and is consumed in various forms. Although many patients report allergic symptoms to maize but a systematic study on its allergenic roperties has been lacking. The investigation was aimed at to find out maize sensitization in Indian patients of respiratory allergy and Characterize allergens of clinical significance by clinico immunologic evaluation. Methods Patients attending allergy clinic for respiratory allergy were screened for Maize sensitization by SPT and by allergen specific IgE by ELISA. The IgE binding epitopes were identified by Immunoblot after transferring SDS-PAGE separated proteins on to NC membrane. The 28kd major allergen was identified in Indian patients and was further subjected to in situ trypsin digestion and MALDI-TOF to determine the molecular masses of peptides and sequence similarity. Cross reactivity of maize seed extract was evaluated with extracts of pea nut, rice, and unrelated Putranjiva roxburghiipollen extract by Immunoblot inhibition studies.

D) Conclusions

Approximately 77% (27 out of 35) of the patients with DU was refractory to a standard dose of antihistamine. However, 85 % (23 out of 27) were satisfactorily treated by a higher dose of antihistamine and/ or a combination with other medications. The second line treatments suggested in the guidelines for urticaria are worth trying for DU refractory to antihistamines. Background: There have been only few reports of peanut allergy and peanut component-resolved diagnostics (CRD) in Korean children. In the present study we tried to establish the diagnostic decision point (DDP) of peanut-sIgE antibodies for predicting the outcome of oral food challenge (OFC). In addition, we evaluated the usefulness of IgE antibodies to recombinant peanut components (Ara h 1, 2, 3, 8, and 9) in diagnosing peanut allergy. Methods: Korean children aged over 12 months with suspected IgEmediated peanut allergy were enrolled. The diagnosis for peanut allergy was confirmed by an open OFC or through the presence of anaphylaxis history. The cutoff levels of sIgE for peanut and peanut components were determined by analyzing the receiver operating characteristic curves. Results: Forty-eight children (22 boys and 26 girls) with suspected peanut allergy were analyzed. The previously established DDP for peanut-sIgE antibodies (>14 kU/L) showed the sensitivity of 22.7%, specificity of 100%, PPV of 100%, and NPV of 60.4% in our study population. The median levels of peanut-sIgE (5.44 kU/L vs. 1.14 kU/L, P<0.0001) and Ara h 2-sIgE (0.8 kU/L vs. 0.0 kU/L, P<0.0001) were statistically significant higher in the peanut-allergic group than in the peanut-tolerant group. The peanut-sIgE concentration indicating a positive predictive value (PPV) of 100% was 10.3 kU/L. The Ara h 2-sIgE level of 4.03 kU/L showed PPV of 100%. Conclusion: Our result showed that the previously established DDP of peanut-sIgE level may be useful predictor for the outcomes of OFC in Korean children suspected of peanut allergy and Ara h 2 is the most important allergen in Korean children with peanut allergy. The cutoff levels for peanut (10.3 kU/L) and Ara h 2 (4.03 kU/L) might be helpful for the diagnosis of peanut allergy in Korean children. Background: The limited efficacy of topical tacrolimus may result from insufficient frequency of application or amount applied in eczema patients. Objective: To investigate the frequency of application and amount of use of topical tacrolimus in patients with various types of eczema. Methods: The frequency of application and the applied amount of topical tacrolimus were assessed over 2 weeks. Results: A total of 200 eczema patients completed this study. The average number of applications per day was 1.75 ± 0.53, despite instructions to apply the topical tacrolimus twice daily. With respect to the frequency of application, 147 (73.5%) and 122 (61.0%) of patients followed the prescription in the first and second weeks, respectively. The average amount applied per 2% of total body surface area was 0.54 ± 0.52 g. Only 53 (26.5%) patients applied between 80% and 120% of expected amount of topical tacrolimus. Limitations: The frequency of application was self-reported, possibly resulting in limited accuracy. Conclusion: Korean patients with eczema tend to apply topical tacrolimus less frequently and in inappropriate amounts. Clear instructions regarding both the frequency and amount of application are needed to improve the therapeutic outcome with treatment with topical tacrolimus.


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.


A total of 561 children (273 boys, 288 girls) aged 11-12 years were enrolled in this study. Serum periostin level was measured and the skin prick test was performed with 26 aeroallergens commonly found in Korea. Other information was collected, including sex, age, BMI, parental allergy history, and parental smoking status. Multivariate analysis was used to confirm the association between serum periostin level and allergic rhinitis.


The association between serum lead level and total immunoglobulin e according to allergic sensitization Yoo Suk Kim 1 Background: Lead exposure could cause various immunologic effects in humans. Several studies have shown that blood lead concentration is positively associated with total immunoglobulin E (IgE). However, no study has investigated whether allergic sensitization could be responsible for the association between lead exposure and total IgE. We investigated whether there was difference in the association between lead exposure and total IgE depending on the presence or absence of Dermatophagoides farinae (Df) sensitization, based on data from a large population-based survey. Methods: We used data from the Korea National Health and Nutrition Examination Survey (KNHANES) conducted in 2010. Serum levels of heavy metals such as mercury, cadmium, and lead were measured. Total and Df specific IgE were measured, and urinary cotinine level was investigated. Information about participant sex, age, body mass index (BMI), and household income were also obtained. Data from 2184 participants were analyzed. Multivariate linear regression analyses were used to determine the independent effects of these variables. Results: We found that serum lead concentration was positively correlated with total IgE using Spearman's correlation test (Spearman's rho = 0.150, p < 0.001). BMI, serum mercury level, and urine cotinine level was also positively correlated with total IgE. In an adjusted linear regression analysis, only serum concentration of lead among the three heavy metals was positively associated with logarithmic transformed total IgE [LogTIgE; coefficient (B) = 0.026, 95% confidence interval (CI) = 0.008-0.044]. When we performed the same analysis on groups divided by allergic Df sensitization status, we found a significant positive association between serum lead and LogTIgE in subjects with Df sensitization (B = 0.076, 95% CI = 0.003-0.150) but not in subjects without Df sensitization (B = 0.015, 95% CI = -0.008-0.039). Conclusions: Serum lead level was positively associated with total IgE level. However, this correlation was statistically significant in subjects with Df sensitization. This result suggests that the immunologic effects of lead exposure may be greater in people with allergic sensitization.


Clinical and laboratory characteristics of nasal obstruction dominant allergic sensitization Seung-No Hong 1 , Doo Hee Han 1 , Chae-Seo Rhee 2 1 Seoul National University Hospital, South Korea; 2 Seoul National University Bundang Hospital Correspondence: Seung-No Hong -Seoul National University Hospital, South Korea World Allergy Organization Journal 2016, 9(Suppl 1):A118 Background: Allergic rhinitis (AR) is defined clinically by the symptoms including nasal obstruction, rhinorrhea, nasal itching, sneezing with a positive allergen sensitivity test. However a positive skin prick test (SPT) does not always imply the occurrence of clinical symptoms. If an asymptomatic allergen sensitized patient is accompanied with septal deviation (DSN) which could cause nasal obstruction, it can be easily confused with a typical symptomatic allergic rhinitis patient. Objective: The aim of this study was to investigate the clinical and laboratory characteristics of nasal obstruction dominant allergic sensitizers (NODS) based on an allergic rhinitis cohort study. Methods: Patients from a nationwide allergic rhinitis cohort study (ARCO) which was conducted by 8 university hospitals were investigated. Allergic rhinitis was diagnosed when there were at least one rhinitis symptoms with a positive SPT result. The NODS group included patients who had severe nasal obstruction with less other symptoms and positive skin prick test with septal deviation. Clinical and laboratory characteristics were compared between the NODS group and the typical allergic sensitization group. Results: Total 695 patients were included. The average age was 32.6 and 68% of the patients had septal deviation. Laboratory test results reveal that the eosinophil level was lower in NODS group while total IgE level did not show any difference. SPT analysis showed that House dust mite was less sensitized to NODS patients. There was significant sex difference that the male to female ratio was higher in the NODS group. However, no statistically significant difference was found by age, family history and BMI. Conclusion: Asymptomatic allergen sensitized people with septal deviation can mimic allergic rhinitis. When we met the allergen sensitized people with nasal obstruction predominantly, septal deviation should be considered before diagnosis of allergic rhinitis.


Aspirin facilitates the intestinal absorption and oral sensitization of food allergens in rats Tomoharu Yokooji 1 , Taiki Hirano 1 , Hiroaki Matsuo 2 1 Hiroshima University, Japan; 2 Hiroshima University Hospital Correspondence: Tomoharu Yokooji -Hiroshima University, Japan World Allergy Organization Journal 2016, 9(Suppl 1):A120 Background: Aspirin-facilitated absorption of ingested allergens is considered to be an exacerbating factor in the development of food allergy. In this study, we examined the effect of aspirin on oral sensitization to an egg-white allergen, ovalbumin (OVA) as well as OVA absorption, in rats. Methods: To clarify the intestinal absorption mechanisms of OVA and the effect of aspirin, in situ intestinal re-circulating perfusion study was performed using OVA and fluorescein isothiocyanatelabeled dextran 40 (FD-40), a marker for non-specific-absorption pathways in the presence or absence of various endocytosis inhibitors and aspirin. In addition, plasma concentrations of OVA and FD-40 were measured after oral administration by gavage in rats. To investigate the effect of aspirin on the oral sensitization to OVA, rats were orally administered with OVA by gavage at 3 times a week every other day for 8 weeks. Aspirin or absorption enhancer, spermine was administered 30 min before or simultaneously with OVA, respectively. To evaluate the sensitization to OVA, plasma levels of OVA-specific IgE and IgG 1 were determined by ELISA at 2, 4, 6 and 8 weeks after initiation of OVA sensitization. Results: The absorption rate of OVA in the distal intestine was higher compared with that for a marker of FD-40. Colchicine (general endocytosis inhibitor), bafiromycin A 1 (inhibitor for receptormediated endocytosis) and phenylarsine oxide (inhibitor for clathrinmediated endocytosis) suppressed the OVA absorption whereas mehyl-β-cyclodextrin (inhibitor for caveolin-mediated endocytosis) exerted no significant effects at distal region, indicating that OVA is preferentially absorbed from the distal intestine via paracellular, and receptor-and clathrin-mediated endocytic pathways. Aspirin increased intestinal absorptions of OVA and FD-40 via the paracellular pathway and exhibited higher plasma levels of OVA-specific IgE and IgG 1 than those in control at 6 and 8 weeks. Spermine also increased the oral absorptions of OVA almost to the same extent of aspirin whereas the plasma IgE and IgG 1 levels exhibited no significant differences against those in untreated control. Conclusions: Facilitation of OVA absorption via paracellular pathway due to impairment of intestinal barrier function by aspirin is considered to be one of the reasons of enhanced oral sensitization with OVA by aspirin. However, our results have also shown that facilitated oral sensitization to OVA cannot be ascribed to increased absorption of OVA from the intestinal tract only. Background: Atopic dermatitis (AD) affects approximately 10% of children with rising tendency. The exact cause of AD is not known, but more than 50% of pregnant women are still exposed to secondhand smoke in Latvia and smoke exposure during pregnancy might increase the risk of AD in children. The aim of the present study is to investigate the mechanism of AD development in children, born of pregnancies affected with secondhand smoke. The objectives are in favour of the idea that N-glycosylation in keratinocytes cells is limited by Dolichyl Phosphate Cycle (DPC) intermediates, regulated by DPAGT1 (Dolichyl-phosphate (UDP-N-acetylglucosamine) Nacetylglucosaminephosphotransferase 1 (GlcNAc-1-P transferase). Dysregulation of DPAGT1 causes disturbances in filaggrin expression. In epithelial cells loss of filaggrin correlates with atopic dermatitis (AD) presence and activity. Methods: Two groups of mothers and children were compared. The samples were obtained from 154 women with self-reported secondhand smoke during pregnancy and their 156 children (group 1) and 180 women who did not have contact with tobacco smoke during pregnancy (group 2). Cotinine (Cot) and dolichol (Dol) were measured in blood and urine during pregnancy. Filaggrin expression was measured in skin biopsies in newborns with follow up for 2 years. Immunohistochemical and Western blotting methods were used to detect the changes in the expression levels of filaggrin and DPAGT1. Intermediates of DPC fractions were analysed by HPLC method. Results: In group 1 during the period of observation 117 (75%) of children were diagnosed with AD. Mothers of these children (92%) have had Cot in blood and elevated urinal Dol excretion in pregnancy. In group 2 during the period of observation 9 (5%) of children were diagnosed with AD and 16 mothers have had elevated urinal Dol excretion. Overexpression of DPAGT1 was 5-fold higher in AD skin biopsies than in normal skin biopsies and differ from normal one in filaggrin content lost by 3-4 times. Suspected urinary Dol level in pregnancy with positive Cot for AD risk in newborns is calculated as 18.0 mkg/mmol. Conclusion: Secondhand smoke during pregnancy could cause DPAGT overexpression and dysregulation of N-glycosylation in keratinocytes which leads to AD fenotype affecting the stability of tight assembly and adherence junctions in skin of newborns. There is a reason to suggest that elevated Dol correlated with detected Cot in urine in pregnancy may evidence of secondhand smoke related disorder of N-glycosylation. Dol appeared in urinary excretion in pregnancy affected by secondhand smoke is one of the first manifestation of AD risk for newborns. Dol detection in urine during gestational secondhand smoke exposure opens up possibilities for environmental control and for additional motivation to prevent AD in children.


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.
Background: Asthma and/or allergic rhinitis have been associated with sleep disorders. The aim of this study was to evaluate sleep disorders in Latin-American children (4 to 10 years) from 10 countries, with persistent asthma (A) and/or allergic rhinitis (AR) and in normal controls (C). Methods: Parents from 454 C and 700 A and/or AR children followed in reference clinics answered the Children Sleep Habits Questionnaire (CSHQ) that is an one-week retrospective questionnaire composed by 33 questions and divided in 7 subscales (bedtime resistance, sleep duration, sleep anxiety, night awaking, parasomnias, sleepdisordered breathing and daytime sleepiness). Total CSHQ scale and subscales were compared between C and A+AR, A (n=285) vs AR (n=390), and controlled A (CA, n=103) vs partially controlled/uncontrolled A (UA, n=182). Results: comparison between C and A+AR showed no significant differences in age (6.7 vs 7.0 years, respectively) and total CSHQ (53.3 vs 63.2, respectively) and subscales were significantly higher among A+AR group. Comparison between A and AR groups, except for sleep anxiety, show significantly higher values for total CSHQ (66.9 vs 61.0, respectively) and the other subscales. UA showed significantly higher values for total CSHQ and subscales in comparison to CA (71.1 vs 59.4, respectively Background: Epidemiological studies mainly from USA, the Europe, and Asia indicate a high prevalence of asthma. However, little is known about asthma among the population of the Afghanistan. In the patients with asthma have high levels of exhaled nitric oxide fraction (FeNO). We aimed comparing with respiratory symptoms and FeNO and lung function test in Afghanistan. Methods: Respiratory symptoms were assessed by a pulmonology physician (n=117). The FeNo was measured by NIOX MINO device (Aerocrine AB, Solna, Sweden). Lung function was examined by a portable spirometer and airway hyper-resposiveness. Asthma Control Questionnaire (ACQ), blood eosinophils were assessed at the same time.


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.


Atopic dermatitis and sleep disorders in latin American children Marilyn Urrutia Pereira 1 , Dirceu Sole 1 , Herberto Jose Chong Neto 2 , Alfonso Mario Cepeda 3 , Raúl Lázaro Castro Almarales 4 , Juan C. Sisul 5, 6, 7 Background: Atopic dermatitis (AD) has been associated with impairment of sleep. The aim of this study was to evaluate sleep disorders in AD Latin-American children (4 to 10 years) from 10 countries, and in normal controls (C). Methods: Parents from 454 C and 340 AD children followed in reference clinics answered the Children Sleep Habits Questionnaire (CSHQ) that is an one-week retrospective questionnaire composed by 33 questions and divided in 7 subscales (bedtime resistance, sleep duration, sleep anxiety, night awaking, parasomnias, sleep-disordered breathing and daytime sleepness). Total CSHQ scale and subscales were compared between C and DA groups. Spearman's correlation coefficient between SCORAD (Scoring atopic dermatitis) with all subscales and total CSHQ were also obtained. Results: C and DA groups were similar regarding age, however, significantly higher values for total CSHQ (62.2±16.1 vs53.3±12.7, respectively) and subscales were observed among DA children in comparison to C, and they were higher among those with moderate (54.8%) or severe (4.3%) AD. Except for sleep duration (r=-0.02, p=0.698), there were a significant Spearman's correlation index for bedtime resistance (0.24, p<0.0001), sleep anxiety (0.29, p<0.0001), night awaking (0.36, p<0.0001), parasomnias (0.54, p<0.0001), sleepdisordered breathing (0.42, p<0.0001), daytime sleepiness (0.26, p<0.0001) and total CSHQ (0.46, p<0.0001). Conclusions: Although properly treated, Latin-American children with AD showed to have sleep disorders evaluated by the CSHQ. Children with moderate to severe forms of AD were those who had the biggest changes in CSHQ. Background: The recently identified house dust mite (HDM) allergen Der p 23 has been considered as a major allergen, according to its high IgE reactivity which is quite similar to that measured for the major HDM allergens Der p 1 and Der p 2. Whereas the high IgE binding frequencies to Der p 1 and Der p 2 could be partially explained by the relative abundance of these proteins in the mite fecal pellets, there is a discrepancy between the IgE reactivity to Der p 23 and the very poor amount of intact Der p 23 in mite feces aqueous extracts. The goal of the study was to evaluate the release of Der p 23 from fecal pellets as well as the allergen sensitivity to proteases. Method: HDM enriched fecal pellets were extracted with PBS or 6 M Urea with 2% SDS and 10 mM DTT. The release of nDer p 23 in the extracts as well as in a commercial mite bodies extract (Greer) was measured by western blot. Recombinant Der p 23 (rDer p 23) and GST-Der p 23 were produced in P. pastoris and E. coli respectively. These two recombinant forms were incubated with activated natural Der p 1, trypsin or HDM extracts. The Der p 23 proteolysis was monitored by SDS-PAGE and western blot. Results: Very tiny amounts of nDer p 23 is released from fecal pellets upon incubation with PBS. Unexpected high molecular weight immunoreactive bands present also in very low amount were detected when extraction was performed under denaturing and reducing conditions. Intact nDer p 23 was not present in mite bodies extract. Recombinant Der p 23 can be degraded by Der p 1 but not by Trypsin. The Der p 23 O-glycosylation partially reduced the proteolysis. The Der p 23 sensitivity to cysteine proteases from HDM fecal pellets extracts was also demonstrated. Conclusions: Our results suggest that natural Der p 23, through probably its tight interactions with the peritrophic matrix, is very poorly released from the fecal pellets. According to nDer p 23 very low abundance in mite extracts and high sensitivity to proteolytic degradation, recombinant Der p 23 may be a valuable material for the diagnosis as well as the treatment of Der p 23 sensitivities. Background: Hypersensitivity reactions to corticosteroids are known to occur, but are an unexpected phenomenon. However, immediate hypersensitivity with severe anaphylactic reactions is scarce in literature. Methods: Diagnosis is confirmed using a patch test for suspected delayed type hypersensitivity. Skin prick and/or intradermal tests are for immediate type hypersensitivity to identify the responsible agent and potential cross-reactivity patterns [i] .

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.


We conducted this study on 27 pediatric patients with allergic rhinitis and adenotonsiller hypertrophy and 33 patients with adenotonsillar hypertrophy only. Demographic data, clinical examination including oral and nasal endoscopy, and skull lateral view were obtained. The mean age, Brodsky tonsil size, adenoid size, and BMI were similar between two groups. A follow-up evaluation, which included questionnaires of clinical scores, physical examinations and skull lateral view were performed 3, 6 months after adenotonsillectomy.


Methods: Data were obtained from our department in Athens, between October 1994 and September 2014 (240 months). We evaluated all AE occurring this period for patients allergic only to pollens, according to the results of skin prick testing. A positive SPT was defined as a wheal size at least 3 mm greater than the negative control. AE were defined as a deterioration in asthma resulting in an unscheduled visit (i.e patient-initiated) leading to change in asthma treatment or the need for oral steroids for>3 days and/or emergency room visit/hospitalization. Data are presented as monthly averages of these years of combined data, as a percent above (+) or below (-) the average monthly value (%) for the 240 months under study. pollens. An increase in AE occurred in three months (April, May, June) and a decrease in the rest of the months. It is of great interest to note that especially in May occurred a huge increase (peak) in AE (+476%) in patients allergic to pollens (May epidemic). This study suggests that aeroallergens (pollens) can exacerbate asthma, especially in May, in Greece and the results may offer significant opportunities for improved disease management.


The pathogenesis of nasal polyps is associated with the interaction between mucosal epithelial cells, extracellular matrix and inflammatory cell, and their chemical mediators. Fibroblasts are major structural components of nasal mucosa and play an important role as a source of chemical mediators and tissue remodeling. The aim of this study was to evaluate the effect of airborne fungi in the production of extracellular matrix from nasal fibroblasts with the interaction of activated eosinophils. Methods Nasal fibroblasts were isolated from nasal polyp and normal inferior turbinates. Nasal fibroblasts were stimulated with Alternaria alternate at 100 ug/ml and Aspergillus fumigatus at 50 ug/ml. Eosinophils from peripheral blood were extracted then stimulated with both fungi. Nasal fibroblasts were co-cultured with activated eosinophils with or without physical contact for 24 hours. Then α-smooth muscle actin (α-SMA), collagen type I, TIMP-1, MMP-9, fibronectin mRNA expression were determined with real time RT-PCR and protein production was determined with western blot method.


Respiratory syncytial virus (RSV) is the main etiologic agent of bronchiolitis worldwide and RSV bronchiolitis seems to be a more severe disease than that caused by other viruses. The aim of our study is to observe the clinical, pulmonary function and bronchodilator responsiveness differences between respiratory syncytial virus (RSV) and non-RSV bronchiolitis. Methods 96 bronchiolitis inpatients of Shengjing Hospital from November 2012 to March 2014 were enrolled. RSV detection was performed at enrollment and the patients were divided into RSV group and non-RSV group. Patient's information of demography, allergy and duration of onset were collected, infant pulmonary function, bronchial dilation test and serum total IgE were tested, and modified-Tal score and length of hospitalization were also recorded at admission. Results RSV bronchiolitis (n = 40 [46.17%]) were younger at hospitalization (5 ±3.97 vs 7.38±4.42 months, p=0.008) and disease severity defined by length of hospitalization and modified-Tal score was significantly worse in children with RSV bronchiolitis. There is no difference in sensitization between the two groups. The respiratory rate (RR) and respiratory system resistance (Rrs) were significantly increased, while the tidal volume per kilogram (VT/kg), ratio of time to peak tidal expiratory flow and total expiratory time (tPTEF/TE), ratio of volume to peak expiratory flow and total expiratory volume (VPTEF/VE), and respiratory system compliance per kilogram (Crs/kg) were significantly decreased as compared with those in non-RSV bronchiolitis. The plethysmographic functional residual capacity (FRCp) showed no statistically significant differences. With bronchodilators, VT/kg, tPTEF/TE and VPTEF/VE were significantly improved in RSV bronchiolitis. There were good correlations between disease severity and lung function.


In conclusion, this study supports that younger age is a risk factor for RSV bronchiolitis. The airway obstruction of RSV bronchiolitis seems to be more severe and have higher bronchodilator responsiveness. Infant pulmonary function may reflect disease severity, while we need to consider the affected factors when assessing the disease severity based on infant pulmonary function. Purpose: The role of PM 10 in development of allergic diseases remains controversial among epidemiological studies, partly due to the inability to control for spatial variations of large-scale risk factors. This study aims to investigate spatial correspondence between the level of PM 10 and allergic diseases at the sub-district level in Seoul, Korea, in order to evaluate whether the impact of PM 10 is observable and spatially varies across the sub-districts. Methods: PM 10 measurements at 25 monitoring stations in the city were interpolated to 424 sub-districts where annual inpatient and outpatient count data for three types of allergic diseases (atopic dermatitis, asthma and allergic rhinitis) were collected. We estimated multiple ordinary least square regression models to examine the association of the PM 10 level with each of the allergic diseases, controlling for various sub-district level covariates. Geographically weighted regression models were conducted to evaluate how the impact of PM 10 varies across the sub-districts. Results: PM 10 was found to be a significant predictor of atopic dermatitis patient count (p<0.01), with greater association when spatially interpolated at the sub-district level. No significant effect of PM 10 was observed on allergic rhinitis and asthma when socioeconomic factors were controlled for. Geographically weighted regression models revealed spatial variation of PM 10 effects on atopic dermatitis across the sub-districts in Seoul. The relationship of PM 10 levels to atopic dermatitis patient counts is found to be significant only in Gangbuk region (p<0.01), along with other covariates including average land value, poverty rate, level of education and apartment rate (p<0.01). Conclusions: Our findings imply that PM 10 effects on allergic diseases might not be consistent throughout Seoul. GIS-based spatial modeling techniques could play a role in evaluating spatial variation of air pollution impacts on allergic diseases at the sub-district levels, which could provide valuable guidelines for environmental and public health policymakers.
High in of respiratory virus is found in children with wheezing exacerbation. RV is the most important pathogen in recurrent wheezing patients. The RV induced wheezing is associated with high level of EOS, LYMP and WBC counts. It implies RV may associated with atopy and immunoreaction. The clinical symptom is not different between RV and other virus infection in short time. Background: Staphylococcus aureus is known to be the most frequent cause of skin infection or aggravating factor in atopic dermatitis patients. The colonization rate of S. aureus reaches to 90% of atopic dermatitis patients, which is much higher than in the healthy subjects. Until now, bacteria could be identified only through the bacterial culture technique, by which only 1% of total bacteria can be identified. Here, we performed metagenomic analysis to determine major colonizing bacteria in the skin of atopic dermatitis patients vs. healthy control subjects. Methods: Seventeen patients with atopic dermatitis and 6 healthy control subjects were enrolled. Skin washing fluids were obtained from the moistened gauze which loaded on the skin lesion in the cubital fossa of atopic dermatitis patients and on the same part of normal controls. After genomic DNA was extracted from the skin washing fluids, 16s ribosomal DNA was amplified using the universal primer, sequenced through the next generation sequencer, and then the sequenced data was analyzed using bioinformatics. Results: Staphylococcus spp. was dominant in the skin from atopic dermatitis patients, while it was undetectable in the control subject skins. The mean proportion of Staphylococcus in the total bacterial DNA of atopic dermatitis patients was 68%, however that was 0% in normal controls. Additional analysis for the species of Staphylococcus spp. revealed that most of Staphylococcus spp. was Staphylcoccus aureus. The following frequent bacteria were Pseudomonas and Streptococcus spp., and their proportions were 11% and 10% in the patients vs. 2% and 1% in the controls, respectively. On the other hand, Alcaligenaceae family and Sediminibacterium spp. were the most frequent bacteria in the skin of the controls, and their proportions were 39% and 13% in the controls vs. 0% and 0% in patients, respectively. Conclusions: Staphylcoccus aureus is the predominant colonizer in the atopic dermatitis skin through the metagenomic analysis of bacterial DNA. Background: The aim of this study was to estimate the efficacy and the safety of the combination of micronized cellulose powder and locally applied glucocorticoids on the symptoms of allergic rhinitis. Methods: This single blind controlled study was conducted in 120 subjects (2-60 years of age, mean age 38.5) with allergic rhinitis, 66 men and 54 women. All participants had a positive medical history for allergic rhinitis. They were randomized to 1 puff mometasone furoate followed by 1 puff of commercially available micronized cellulose powder in the morning, and only 1 puff micronized cellulose powder in the evening (test treatment, TT) or 1 puff mometasone furoate, Bid (reference treatment, RT). Participants were allowed to take oral antihistamine or eye drops they wished. The symptom scores were recorded before and after the treatment. Mean values for the sum of all scores were calculated. The pre-vs post-treatment differences were compared using t-test. Also the decrease of the symptom scores between groups were compared using t-test. The efficacies were analyzed using Chi-2 tests. Results: Both treatments could reduce the symptom scores significantly (P<0.001), and the improvement rates were similar (P=0.052). Total efficacies of RT and TT were 95% and 100% respectively without significant differences (P=0.244). There were no adverse reaction found in both groups. Conclusions: The combination of micronized cellulose powder and locally applied glucocorticoids could reduce the dose of glucocorticoids, and the treatment is safe.


New strategy for atopic dermatitis therapy with modulation of calcium ion channels Woo Kyung Kim 1 Background: Intracellular Ca 2+ signaling via various calcium channels, such as Orai1, Transient receptor potential (TRP)A1, TRPV1, and TRPV3, has been shown to directly modulate not only inflammation but also barrier homeostasis, and inflammation. Ca 2+ influx through these channels eventually generates intracellular Ca 2+ signaling that results in different outcomes dependent on the individual Ca 2+ channel type, for example, keratinocyte proliferation and migration through Orai1, epidermal barrier formation and keratinocyte differentiation through TRPA1, and keratinocyte cornification through TRPV3. Therefore, a specific agonist/antagonist for each calcium channel is required for maintaining skin barrier homeostasis and for the treatment of atopic dermatitis. Objectives: To identify applicable topical botanically derived chemicals for the treatment of atopic dermatitis. Method: Novel modulators of Orai1, TRPA1, TRPV1, and TRPV3 were identified were identified by screening the 70% methanol (MeOH) extracts (plus their fractions) of 30 medicinal herbs and their constituents. The potencies of the activating and inhibitory compounds of each channel were determined by an automated patch clamp system. The biophysical properties of channel modulation by hit products were re-analyzed using conventional whole-cell patch clamp and fluorometric calcium imaging. Results: We prepared 70% MeOH extracts of 30 medicinal herbs, performed bioassay-guided fractionation of the active extracts, and then isolated and identified the bioactive constituents. By performing the combination of automated and conventional whole-cell patch clamp studies, we found eight medicinal herb fractions for Orai1, four for TRPV1, two for TRPA1, and one for TRPV3 that showed >50% inhibition rates at 30 μg/mL. We also found three fractions with TRPA1 agonist activity. Further, we also identified chemical constituents that inhibit Orai1 (compound V: 95 ± 5% inhibition at 90 μM) and TRPV1 (compound M: 93.9 ± 2.45% inhibition at 90 μM; compound CYP: 61 ± 5% inhibition at 90 μM). Chemical constituents that showed agonist/antagonistic effects on TRPA1 and TRPV3 also will be discussed. Conclusions: Considering that most regional plants have not been investigated chemically or pharmaceutically, they remain as untapped potential sources of topical agents for drugs and other application. We found major active components and chemical constituents of plant extracts for the modulation of various calcium ion channels, which may have potential clinical applications for atopic dermatitis. Limitations: Extensive clinical studies of the lead compounds are needed to develop topical agents for atopic dermatitis that relate to skin barrier functions. Background: Microbial infection is one of the local factors that contribute to the pathogenesis of atopic dermatitis. However, many studies had been reported the systemic effect of the microorganism, especially of the lactic acid bacteria. Until now, they only have been studying the systemic effects of local microorganisms, not the systemic microbial distribution. No study has revealed that relationship between the systemic bacteria and atopic dermatitis. Here, we performed metagenomic analysis to determine systemic bacteria distribution of atopic dermatitis patients vs. healthy control subjects. Methods: Twenty-eight patients with atopic dermatitis and 8 healthy control subjects were enrolled. Urine was obtained in all subjects and serum was obtained in eighteen atopic dermatitis patients. After genomic DNA was extracted from the urine and serum, 16s ribosomal DNA was amplified using the universal primer, sequenced through the next generation sequencer, and then the sequenced data was analyzed using bioinformatics. Results: The bacterial composition was nearly identical between serum and urine. However, there was notable difference of bacterial composition in the urine of the normal control and the atopic dermatitis patients. In the control group, proportion of Lactococcus, Leuconostoc, Lactobacillus, Lactobacillales(o) were significantly higher than in the patients group, and that of Alicyclobacillus, Propionibacterium, Streptophyta(o) were increased in the patients group than in the control group. Pseudomonas was commonly found in the both groups. Before treatment, Alicyclobacillus and Comamonadaceae were frequently found, however their proportion were decreased and
Acinetobacter and Oxalobacteraceae(f) were increased after treatment in the urine of atopic dermatitis patients. Conclusions: We confirmed the systemic bacterial composition in the atopic dermatitis and normal controls through the metagenomic analysis of bacterial DNA in the urine and serum.


Occurrence and physiological function of immune complexes of food proteins and IgA in human saliva Hiroshi Narita 1 , Junko Hirose 2 , Kumiko Kizu 3 , Ayu Matsunaga 1 1 Department of Food and Nutrition, Japan; 2 Department of Food Science and Nutrition; 3 Department of Life and Living Correspondence: Hiroshi Narita -Department of Food and Nutrition, Japan World Allergy Organization Journal 2016, 9(Suppl 1):A141 A) Background: We have revealed the occurrence and physiological function of immune complexes (ICs) of food proteins and IgA in human breast milk (Ref. 1, 2) . Universality of these findings was examined this time in another exocrine fluid, human saliva. B) Methods: ICs of several food proteins in human exocrine fluids were determined with sandwich ELISAs constructed with antiindividual protein and anti-human IgA antibodies. The IC fraction obtained from human pooled saliva by ammonium sulfate precipitation and gel filtration was administered orally for successive 6 days to 8 weeks old BALB/c mice fed casein-based commercially available mouse diet. At day 8, they were immunized with egg white proteins in Freund's complete adjuvant and boosted at day 22 with egg white proteins in Freund's incomplete adjuvant. Blood was drawn from orbital vein and serum ovalbumin and ovomucoid specific IgG1s were measured at day 36. As the control, free ovalbumin corresponding to its amount in the IC fraction was administered. C) Results: Food proteins were detected as respective ICs in healthy human saliva. IgG1 production to ovalbumin and ovomucoid was significantly suppressed (p<0.05) in the IC administered mice in comparison with the control mice. D) Conclusions: ICs of food proteins and IgA could be determined in human saliva as well as in breast milk. Evidence indicating their physiological function as the inducers of oral tolerance was proved in mice. ICs of food proteins and IgA in human exocrine fluids are thought to be "Natural Drinkable Vaccine", functioning in the prevention of food allergy through induction of oral immune tolerance. E) References 1) Biosci. Biotech. Biochem., 65, 1438 -1440 , 2001 2) Food and Nutr. Sci., 6, [221] [222] [223] [224] [225] [226] [227] [228] [229] [230] [231] [232] [233] 2015 A142 Association between DNA hypomethylation at IL13 gene and allergic rhinitis in house dust mite-sensitized subjects Jingyun Li, Yuan Zhang, Luo Zhang Beijing Institute of Otolaryngology Correspondence: Jingyun Li -Beijing Tongren Hospital, China World Allergy Organization Journal 2016, 9(Suppl 1):A142 Background: Allergic rhinitis (AR) is a complex disease, in which gene-environment interactions contribute to its pathogenesis. Epigenetic modifications such as DNA methylation play an important role in the regulation of gene function. As IL13, a pleiotropic cytokine, may be important in conferring susceptibility to AR, the aim of the present work was to assess the relationship between a CpG island methylation status at the upstream of IL13gene and house dust mite (HDM)-sensitized AR in Han Chinese subjects. Methods: A total of 60 HDM-sensitized AR patients and 65 control subjects were enrolled as two independent cohorts from Beijing and Liaoning. MassARRAY EpiTYPER was used to systematically screen the status of DNA methylation in peripheral blood leukocytes. IL13mRNA expression was measured by real-time quantitative PCR. Results: The mean level of methylation was decreased in the AR patient-group compared with the control-group (P = 0.01). Two of a total of 33 IL13CpG units analyzed (CpG units 24:25:26 and 38:39) showed significant differences in methylation status between the AR patient-group and the control-group; with DNA hypomethylation at CpG38:39 significantly associated with higher risk of HDM-sensitized AR in both independent cohorts and a combined cohort ( Background and objective Recent data have shown that the prevalence of asthma and allergic disease continuously increase. Some diet can prevent asthma or allergic disease by epigenetic change, including DNA methylation. The aim of this study was to investigate the association between dietary methyl donors (folate, vitamin B2, vitamin B6) and the development of asthma and allergic sensitization in children. Methods Children aged 7-13 years in a Korean elementary school were surveyed in 2006 as part of the first Children's Health and Environmental Research (CHEER) survey and 2,333 children were included in this study. Korean version of the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire and food frequency questionnaire (FFQ) were done by their parents. The skin prick test was performed using 18 common allergens in Korea. Genotyping for MTHFR (rs1801133) polymorphism was performed by TaqMan assay.


These results indicate that dietary methyl donors decrease the risk of asthma and atopy, which may be modified by MTHFR polymorphism. Objective: Thymic stromal lymphopoietin (TSLP) is an epithelialcell derived cytokine that may be important in initiating allergic inflammation. This study aimed to investigate whether TSLP reduced airway inflammation in a murine model of asthma. Methods: BALB/c mice were sensitized and challenged with ovalbumin (OVA), and the effect of TSLP on airway inflammation and airway hyperresponsiveness (AHR) was evaluated. Furthermore, we measured changes in various cytokines in the bronchoalveolar lavage (BAL) fluid when treated with TSLP. Results: We observed that TSLP exert a negative regulation on OVA mediated allergic airway inflammation. TSLP treatment reduced total cell counts and eosinophil counts in BAL fluid and AHR to methacholine. The Th2 cytokines, such as IL-4, IL-5 and IL-13 in BAL fluid also decreased after TSLP treatments. Conclusions: These results suggest that TSLP has a therapeutic potential for allergic asthma through inhibition of Th2 cytokine production. Background and Objectives: FAspirin-exacerbated respiratory disease (AERD) is a clinical tetrad of nasal polyps, chronic hypertrophic eosinophilic sinusitis, asthma, and sensitivity to aspirin. Aspirin provocation test is the gold standard for diagnosing AERD. The aim of this study was to evaluate the clinical features and prognosis after surgical treatment in chronic rhinosinusitis (CRS) patients who have aspirin hypersensitivity. Subjects and Method: FWe conducted an analysis of 100 CRS patients who underwent endoscopic sinus surgery at the Department of Otorhinolaryngology of our hospital from October 2012 to March 2013. We measured nasal volume change and symptom change before and after the aspirin nasal provocation test (ANPT), and examined patient's asthma history, allergy, Lund-Mackay score (LMS), total immunoglobulin E, peripheral eosinophil percentage, and objective measurement relapse. Results: FChronic rhinosinusitis patients with nasal polyps (CRSwNP) were more likely to have a positive ANPT test results compared to patients without nasal polyps (CRSsNP) (21.4% vs. 5.5%). ANPT (+) group had higher LMS and required more revision endoscopic sinus surgery than ANPT (-) group. These results were similar to those of CRSwNP compared with CRSsNP. Conclusion: F LMS and recurrence rates were higher in ANPT (+) compared to ANPT (-). Especially, recurrence rates were higher in ANPT (+) regardless of nasal polyp. Thus, careful endoscopic examination is required at follow up if CRS patients showed positive ANPT results.


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.


Expression of muscarinic receptors and effect of tiotropium bromide on chronic asthma according to age in a murine model Background: The aim of this study was to investigate the expression of muscarinic receptors and resultantly the effect of muscarinic antagonist, tiotropium bromide depending on aging process in a murine model of chronic asthma. Methods: Different aged female BALB/c (6 weeks old, 9 and 15 months old) female BALB/c mice were sensitized and challenged with ovalbumin (OVA) about for three months. Tiotroipum bromide of 0.1 mM was administered via intranasal route before OVA challenge. We measured cell counts and Th2 cytokines in bronchoalveolar lavage fluid and airway hyperresponsiveness. Parameters of airway remodeling and the expression of muscarinic receptor subtypes, M2/M3, were assessed. Results: Airway resistance decreased in aged (9 and 15 months old) OVA group than young (6 weeks old) OVA group. Inflammatory cells including eosinophils had a decreased tendency according to age among the OVA groups. Administration of tiotropium showed the improvement of the infiltration of inflammatory cells and Th2 cytokines such as IL-4 and IL-13. Goblet cell hyperplasia and smooth muscle hypertrophy, pivotal markers of airway remodeling, ameliorated in the tiotropium treated group than OVA group in the three aged group. The OVA group had an increased expression of M3 subtype and a decreased expression of M2 subtype according to age. Conclusion: This study shows that tiotropium bromide could have the effect on not only airway inflammation but also remodeling regardless of age and the effect might be related with the pattern of expression of muscarinic receptors subtype. Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is classified as eosinophilic or non-eosinophilic CRSwNP depending on histopathological features. However, there are few useful markers for the differential diagnosis of CRSwNP. Therefore, we sought to investigate useful surrogate markers for CRSwNP endotyping in Asian patients.
Methods: A total of 81 patients (45 with non-eosinophilic nasal polyps and 36 with eosinophilic nasal polyps) were enrolled. Clinical information and computed tomography (CT), endoscopic, and histological findings were investigated. Tissue samples were analyzed for total IgE protein concentration levels and for mRNA expression levels of interleukin (IL)-4, IL-5, IL-13, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-17A, IL-22, IL-23p19, transforming growth factor (TGF)-β1, TGF-β2, TGF-β3, and periostin. Immunostaining assessment of Ki-67 as a proliferation marker was performed. Results: Non-eosinophilic CRSwNP showed greater localized and maxillary involvement but lesser olfactory involvement on CT in early stage disease compared with eosinophilic CRSwNP. In addition, ethmoidal/maxillary CT scores, indicating ethmoidal dominant involvement, were positively correlated with levels of T H 2 inflammatory markers, such as IL-5, periostin mRNA expression and total IgE levels in nasal polyp (NP) tissues, whereas scores were inversely correlated with levels of the T H 1 cytokine, IFN-γ. In non-eosinophilic NPs, Ki-67 expression was upregulated, especially in epithelia. Additionally, epithelial ingrowing patterns such as pseudocysts were more frequently observed in histologic and endoscopic evaluations of non-eosinophilic NPs compared with eosinophilic NPs. A criterion combining the cutoff level (2,167) of ethmoidal/maxillary CT scores and the presence of pseudocysts on endoscopic examination yielded a sensitivity of 100.0% and a specificity of 71.0% for the diagnosis of non-eosinophilic CRSwNP. Conclusion: We demonstrate that the combination of ethmoidal/ maxillary CT scores and the presence of pseudocysts by endoscopy may be used as a surrogate marker to distinguish non-eosinophilic CRSwNP from eosinophilic CRSwNP in Asian patients.


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.
Methods: A total of 975 patients who underwent skin test or MAST were included in this studies. We tested the serum ECP, total Ig E, eosinophil counts, datas of skin test, datas of MAST in all patients. Various parameters were compared to ECP using the Mann-Whitney U test. Pearson's correlation coefficient was used to analyze the relationship between variables and ECP in each datas. Results: In total, 975 patients (578 men and 367 women) were included in our study. Regression analysis showed that ECP was significantly correlated with the asthma (r = 0.76, p =0.023), the score of MAST for Dermatophagoides farinae (r = 0.144, p = 0.000), the score of MAST for mite, Dermatophagoides pteronyssinus (r = 0.123, p = 0.000), and the score of skin test for Der.f (r = 0.171, p =0.032). There were no difference between the ECP and other datas significantly. Conclusions: There might be positive relationship between the ECP and MAST for Dermatophagoides. Hydroclorothiazide (HCTZ) is widely used in the treatment of essential hypertension. It may be given alone or together with other antihypertensive agents in fixed combination preparations. The most frequent adverse reactions are hypotension and disturbances in the level of serum electrolytes. Nevertheless severe adverse reactions such as shock have also been described. We describe 5 patients that have suffered episodes of sudden-onset pulmonary edema immediately after the ingestion of HCTZ. Five female patients aged between 54 and 76 years-old presented with episodes of dyspnea, malaise, chills, dizziness, fever and, in two of the patients, loss of consciousness. Chest X-rays showed bilateral interstitial infiltrates suggestive of pulmonary edema. All the patients were admitted in hospital, three had a severe respiratory failure and two of them were intubated and mechanically ventilated. Common causes of shock and pulmonary edema were ruled out in all cases. All the patients had received a dose of HCTZ (12.5-50mg), 10-60 minutes before the onset of symptoms but all them were discharged without being diagnosed. Cutaneous (prick and intradermal) tests and patch tests to HCTZ were negative. The 5 patients were diagnosed in the Allergy Unit as having HCTZ-induced non-cardiogenic pulmonary edema. The close temporal relationship between the ingestion of HCTZ and the onset of symptoms, the clinical pattern, the fast recovery after-withdrawing the drug and the relapse with re-exposure, supported this diagnosis. According to Naranjo adverse drug reaction probability scale, in 4 of the patients the diagnosis was considered definite and in the fifth patient, the score indicated a probable relationship between the hypersensitivity reactions and HCTZ. We report a potentially fatal adverse drug reaction due to HCTZ that was not recognized during the patients' hospital stay. All the cases reported affected women according to female predominance in previously published literarure Doctors should consider this potentially life-threatening adverse drug reaction early and withdraw the drug in such an event.


In a multi-country, double-blind, randomised controlled study, 153 infants born by elective C-section were randomised to receive (1) an infant formula supplemented with scGOS/lcFOS (0.8g/100ml) and B. breve M-16V (7.5×10 8 CFU/ 100ml), or (2) a formula supplemented with scGOS/lcFOS (0.8g/100ml), or (3) a control formula from birth until age 4 months. As a reference group, 30 vaginally born, breast fed infants were studied in parallel. Stool samples were collected at day 3, day 5, week 4, week 8, week 12, week 16, and week 22 (6 weeks post-intervention). The proportion of bifidobacteria, different Bifidobacterium species such as B. longum and the probiotic strain B. breve M-16V were determined with molecular tools, pH and SCFA were also measured in the stool samples.


The data confirm the delayed colonization of Bifidobacterium in Csection delivered infants. The synbiotic supplementation resulted in a significant higher proportion of bifidobacteria from the first days of life (p=0.006) and this bifidogenic effect remained significant until 1 month of age (p=0.029) compared to the control group. The prebiotic group showed a significant bifidogenic effect at age 1 month (p=0.048) compared to the control group. In the synbiotic arm, B. breve M-16V was still detected in 37 % of the infants at week 22 indicating a persistence of the probiotic strain. A significant lower faecal pH and a higher acetate level were observed in the synbiotic group from the first days of life and this remained significant until 1 month of age compared to the control group. A lower number of subjects with adverse events of eczema/atopic dermatitis was reported in the synbiotic group (n=3) compared to the control (n=10), and prebiotic group (n=9), after correction for family allergy history.


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.


In 2014, a total of 627 Korean parents/caregivers of infants(48.6% boys) aged 0 till 18 months completed the internet-based expanded version of the Brief Infant Sleep Questionnaire(BISQ), which included specific questions of infants' daytime and nighttime sleep patterns as well as their sleep related behaviors.


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.


Ethnic differences in lifetime prevalence and indoor environmental factors for childhood eczema Hyo-Bin Kim 1 Parental history of allergic disease had a larger effect in HWs than NHWs (P for interaction=0.005). High maternal education level (OR=1.46, 95% CI=1.14-1.87), parental history of allergic disease (OR=2.21, 95% CI=1.78-2.76) and maternal smoking during pregnancy (OR=1.44, 95% CI=1.06-1.95) increased the risk of eczema. Indoor environmental factors (e.g., mold, water damage and humidifier use) increased the risk of eczema in NHWs independent to parental history of allergic disease, but in HWs, increased risks were observed primarily in children without parental history of allergic disease. Conclusions: HW children in southern California have a lower prevalence of eczema than NHWs and this ethnic difference is not accounted for by socio-demographic differences. The effects of parental history of allergic disease and indoor environmental exposures on eczema varied by ethnicity suggesting that the etiology of eczema may differ in HWs and NHWs. Among the various dermatological entities, toxic epidermal necrolysis (TEN) is a rare but potentially fatal delayed hypersensitivity reaction to numerous medications. Methazolamide is one of the rare culprit drug. We here report the patient who presented TEN after taking methazolamide.
He was managed with fluid supplements, total parenteral nutrition, daily dressing of the involved body surface. IVIG was administered as 0.6g/kg/day for 3 days in addition to methylprednisolone, acetylcysteine and moxifloxacin. Skin lesions started to improve after 2 weeks of management and fever was subsided. Cutaneous lesions were improved with minimal permanent sequele in 2 months later. HLA-B*5901 was found by high-resolution genotyping. Strong genetic association between HLA B*5901 and methazolamideinduced SJS/TEN has been suggested in Koreans. Screening for HLA-B*5901 may be useful for avoiding the methazolamide-induced SJS/ TEN. Therefore, methazolamide should not be prescribed for HLA-B*5901 positive patients.


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.

C) Results

Of the 71 patients 50 were male, 21 were female. Median age was 7.5 years with a range from 3.3 to 22.5 years. The reason for elimination of CN in 8 patients (including 2 with anaphylaxis) was a history of immediate reaction to CN. Fifty seven patients had eliminated CN due to a positive CN specific IgE. Atopic dermatitis was seen in 76% (54/71), asthma 45% (32/71), allergic rhinitis 36% (27/71), allergic conjunctivitis 17% (13/71). History of immediate reaction to nuts other than CN was seen in 23% (16/71) of the patients and history of immediate reaction to peanut in 31% (22/71). Eighteen % (13/71) of the patients were positive in OFC and 82% (58/71) negative. Of the 13 patients with a positive OFC, anaphylaxis was seen in 5 patients. Oral mucosal symptoms were seen in 9 cases, gastrointestinal symptoms in 9 cases, cutaneous symptoms in 7 cases, respiratory symptoms in 6 cases, neurologic symptoms in 3 cases and cardiovascular symptoms in 1 case. Seven patients were treated with antihistamine, 5 patients with steroids, 4 patients with inhaled β2 stimulant and 1 patient with adrenaline. In the comparison of OFC between positive and negative patients, a significant difference (p<0.01) was seen in a history of immediate reaction to CN and CN specific IgE. There was no significant difference in other factors including sex, age, history of immediate reaction to nuts other than CN, immediate reaction to peanut and anaphylaxis due to CN.

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.


Korean treatment guideline of atopic dermatitis Due to the recent advances in atopic dermatitis (AD) research and controlled clinical studies, establishment of updated evidencebased treatment guideline for Korean atopic dermatitis is demanding. B) Methods: Task force team convened by KADA collected database of references from relevant systematic reviews and guidelines of atopic dermatitis. They raised all the relevant key statements on the management of AD. Evidence of each statement was graded and classified the strength of recommendation for each statement. The evidence of each statement was graded using the classification of the Oxford centre for evidence-based medicine (level 1-level 5). The strength of recommendation was classified as follows; A, level 1; B, level 2 and 3; C, level 4; D, level 5. Fifty four council members of KADA were asked to vote on the statements of the draft guidelines. Participants indicated their level of agreement with each draft statement using a voting scale of 1-9 (where 1=strong disagreement and 9=strong agreement). Consensus was defined as ≥75% of participants scoring within the 7-9 range (agreement). After three rounds of votes, expert consensus of recommendations were established. C) Results: Updated guideline provides up-to-date evidence based systematic combined treatment algorithm including basic, proactive, induction and maintenance treatment. In addition, average agreement scores of experts panel were presented considering Korean healthcare system and patients' adherence. The guideline comprises of the topical management of AD via bathing and skin care, avoidance of exacerbating factors, education and psychosocial support, moisturizer and topical anti-inflammatory drugs, antibiotics, and antipruritic drugs and the systemic management of AD including antihistamines, antimicrobials, systemic immunomodulators, allergen-specific immunotherapy (ASIT), phototherapy, and complementary and alternative medicines. Clinical questions were focused on the therapeutic effect, action plans in detail, side effects, cost effectiveness, and measures to enhance patients' compliance of each treatment. D) Conclusions: To achieve high treatment efficacy and patient satisfaction, treatment decisions should be made jointly by the physician and patient. We expect this evidence-and experience-based treatment recommendations of AD experts will be a reference guide for physicians and AD patients choosing the appropriate treatment to improve quality of life and decrease unnecessary social medical costs. Background: Subcutaneous immunotherapy(SCIT) is one of the evidence-based treatment for allergic rhinitis. However, with the advent of sublingual immunotherapy(SLIT) SLIT is more preferred over SCIT because of the proven safety. Although it is reported SCIT showed some systemic reactions which can be fatal in some patients the fatality of SCIT still needs to be elucidated. Objectives: The objective of this study is to categorize the side reaction of SCIT into local or systemic one and identify correlations between antecedent local reaction and systemic reaction and between the dose, concentration of allergen and systemic reaction. Methods: Allergic rhinitis patients under SCIT over age of 4 were included. Retrospectively with the medical chart review we investigated the incidence of side reaction of SCIT, relationship between the doses, concentration of allergen. Results: 130 patients met criteria for inclusion, 80 patients (61.5%) had one or more side reactions. 59 patients (73.8%) had only local reaction, 9 patients (11.3%) had only systemic reaction. 12 patients (15%) had both local and systemic reaction. Among 21 patients who had systemic reaction 12 patients showed no antecedent local reaction. Among systemic reaction urticaria was the most common (57.1%) followed by aggravation of rhinitis symptoms (38.1%) and dyspnea (4.8%). 23.8% of patients showed systemic reaction over 30 minutes after the shot. The more concentration and dose were injected the more systemic reaction occurred. Conclusions: Although systemic side reaction was common severe symptom like dyspnea was very rare. Local side reaction cannot forewarn the systemic reaction. It is advised the caution is needed when administering high dose and concentration. Rationale: The clinical profile of Asian patients suffering from Chronic Spontaneous Urticaria (CSU) is relatively unknown. The demographic and baseline characteristics of Asian versus non-Asian patients of three randomized, placebo-controlled omalizumab trials (ASTERIA I, ASTERIA II and GLACIAL) are described and compared. Method: The pooled baseline data of Asian and non-Asian patients suffering from CSU that remained symptomatic despite anti H1antihistamines (ASTERIA 1 and ASTERIA 2) and anti H2-antihistamines and/or leukotriene receptor antagonists (GLACIAL) treatments were assessed in this post-hoc descriptive analysis. Demographic and baseline disease characteristics are described and compared. Results: Among 975 (mITT population) patients enrolled 32 (3.3%) were Asians. Most of the patients were enrolled in the United States and Europe. There were 22 (68.7%) females in the Asian group and 694 (73.6%) in the non-Asian. Mean age was 41.2 years; mean body weight was 70.3 kg and the mean BMI 26.9 kg/m2 in the Asian subgroup and 42.4 years, 83.2 kg and 29.7 kg/m2, respectively, in the non-Asian subpopulation. Mean duration of the disease was 6.7 years in Asians and 7.0 years in non-Asians. Baseline IgE levels were 163.2 and 169.8 IU/mL in Asians and non-Asians, respectively. Baseline mean urticaria activity score over 7 days (UAS7) was 30.7, weekly itch severity score 13.9, weekly number of hives score 16.8 in Asians and 30.9, 14.1, 16.8, respectively in non-Asians. Angioedema was present in 11 Asian (34.4%) patients and 449 (47.6%) non-Asian. Dermatology Life Quality Index (DLQI) was 11.12 and 13.29 in Asian and non-Asians, respectively. At baseline the Sleep Interference Score was 12.1, and the Daily Activity Interference score was 12.1 in Asians, while in non-Asian, they were and 12.1 and 12.8, respectively. Previous number of CSU medications, such as anti-histamines, LTRA and corticosteroids was 3.8 in Asian and 5.1 in non-Asians. Conclusions: With the exception of body weight and previous history of CSU treatment, the clinical profile of patients with refractory CSU is similar between Asians and non-Asians. Background: Recent metagenomic approaches succeeded in characterizing the microbial communities of airway diseases present in bronchoalveolar lavage and supernatants of induced sputum but those results were limited by small sample size and lack of microbial information from inflammatory cells and epithelial cells of airways. We investigated the use of terminal restriction fragment length polymorphism (T-RFLP) analysis, in conjunction with multivariate statistical methods, to examine the difference of micro biota in whole induced sputum (inflammatory cells and epithelial cells in addition to supernatant) between normal control and asthma. Methods: Induced sputum samples were obtained from 36 normal nonsmoker subjects and 89 patients with steroid naïve asthma.


Background: Eosinophilia in specific conditions such as allergic diseases, helminthic infection, and drug-induced reaction is well recognized. In the present study, we evaluated the clinical characteristics of eosinophilia and change in prevalence over 10 years in recipients of health screening program at a tertiary hospital of South Korea. Methods: We collected the data of health screening program recipients at the health promotion center of Chung-Ang University Hospital from 2004 to 2013. Eosinophilia was defined when the absolute eosinophil count exceeds 500/μL in the peripheral blood. We reviewed health-related questionnaires and laboratory findings of health screening program which might be related to eosinophilia. Results: The cumulative prevalence of eosinophilia was 4.0% (1,963 out of 48,858). Most of eosinophilia cases (96.6%) were in mild degree (500 to 1500/μL). Eosinophilic subjects were older and more male-predominant (P<0.001, respectively). Subjects with eosinophilia showed lower level of FEV1%, FVC% and FEV1/FVC than those without eosinophilia (P<0.001, respectively). Of note, annual prevalence was in decreasing trend from 2004 to 2013 (OR=0.942, 95% CI: 0.926-0.958, P<0.001). Eosinophilic subjects showed higher positive rate for common parasite ELISA (P<0.001). The positive rate for ELISA to parasites increased with advancing age in subjects with eosinophilia (P=0.002). Conclusions: Eosinophilia in general, healthy population was not uncommon and usually in mild degree. The prevalence of eosinophilia decreased from 2004 to 2013, which might be related to decrease in parasitic infection in young Korean population. Purpose: Toxocariasis is the most common cause of peripheral blood eosinophilia in Korea and produces eosinophilic infiltration into various organs, including the lung. However, the prevalence of toxocariasis in the general population is rarely reported. Methods: We investigated the seroprevalence of Toxocara larval antibody among asymptomatic people who attended Samsung Medical Center for a health checkup, including low-dose chest computed tomography (CT) between March 2012 and December 2013. A total of 633 people (400 men and 233 women) were recruited. Results: The Toxocara-seropositive rate was 51.2% using the current cutoff value based on Toxocara enzyme-linked immunosorbent assay (ELISA) (67.0% for men and 24.0% for women). In the multivariate-adjusted model, age (odds ratio [OR], 1.08; 95% confidence intervals [CI], 1.05-1.11), male sex (OR, 3.47; 95% CI, 2.26-5.33), rural residence (OR, 1.55; 95% CI, 1.05-2.30), and history of raw liver intake (OR, 8.52; 95% CI, 3.62-20.11) were significantly associated with Toxocara seropositivity. When subjects were divided into 3 groups using cutoff values base on weak positive and strong positive control optical densities (ODs), the ORs for peripheral blood eosinophilia and serum hyperIgEaemia were 0.31 (95% CI, 0.02-2.89) in the weakpositive group and 36.64 (95% CI, 11.73-111.42) in the strong positive group compared to the seronegative group. Similarly, ORs for the solid nodule with surrounding halo were 2.54 (95% CI, 0.60-10.84) in the weak positive group and 15.08 (95 CI 4.09-55.56) in the strong positive group compared to the seronegative group. Conclusions: The study indicated that the Toxocara-seropositive rate obtained by using the current cutoff value based on ELISA was high in the asymptomatic population in Korea. The results of this study suggest that active toxocariasis may be more frequently seen in the Toxocara-strong positive group than in the Toxocara-weak positive group. Since a large proportion of adverse drug reaction (ADR) affects the skin, investigations of cutaneous drug hypersensitivity reaction (DHR) are important to evaluate their impact in dermatology and health care in generals as well as their burden for affected patients. However, little is known about the characteristics of drug-induced cutaneous reactions in Korean children.


We analyzed Individual Case Safety Reports (ICSRs) of cutaneous adverse reactions kept in the Korea Adverse Event Reporting System (KARES). From January 2012 to December 2013, cases of cutaneous DHR were selected and analyzed regarding the age, gender, causative agents, and fatal cases. Based on the WHO-UMC causality assessment system, cases that assessed as 'unlikely' , 'unclassified' or 'unassessable' were excluded. Results A total of 2,577 cases were identified. 1406 cases were male (54.6%), and mean age was 5.97 ± 6.48 years. The most common agent was vancomycin (6.1%), followed by amoxicillin (4.0%), ampicillin (4.0%). The most common adverse reaction was rash (29.2%), followed by urticaria (20.8%), itching (14.0%). Among the 'certain' cases by WHO-UMC causality assessment system, the most common agent was acetylsalicylic acid (13.5%), followed by paracetamol (6.7%), iopromide (5.6%). There were 55 cases of serious ADR. Among the serious ADRs, Acute generalized exanthematous pustulosis (AGEP) was most common (37 cases), followed by Steven-Johnson Syndrome (SJS, 14 cases), Toxic Epidermal Necrolysis (TEN, 2 cases), and Drug reaction with Eosinophilia and Systemic Symptoms (DRESS, 2 cases). Paracetamol was most common causes of serious ADRs (5 cases).


The brief analysis of ICSRs-KARES ADR report reveals that the antibiotics and commonly used antipyretics were most common causative agent of cutaneous reaction. More active reporting about cutaneous DHRs should be encouraged to indicate unlabeled ADRs.


Comparison of clinical characteristics, quality of life and sleep in patients with allergic rhinitis when categorised as "sneezers and runners" and "blockers" Ashok Shah 1 , Kamal Gera 2 Since these two groups have distinct profiles, they were assessed and compared in terms of quality of life (QoL) and sleep disturbances. Methods: The study comprising 106 consecutive patients (males:60/ females:46), 18 to 60 years with AR, diagnosed as per ARIA guidelines, were enrolled from outpatients department of VP Chest Institute, University of Delhi. Patients were categorised into "SR" (group1) and "blockers" (group2) with the help of a visual analog scale (VAS) of 10 centimetres with 0 being "no symptoms" and 10 being "symptoms extremely bothersome". Scores for global VAS, sneezing, runny nose, nasal congestion, post nasal drip and loss of smell were recorded and patients classified as "SR" and "blockers". Impact on QoL was assessed with Sinonasal Outcome Test 22 (SNOT-22) and sleep was assessed by Nocturnal Rhinoconjunctivitis Quality of Life Questionnaire (NRQLQ), the Epworth Sleepiness Scale (ESS) and the Pittsburgh Sleep Quality Index (PSQI) instruments. Results: Just over two thirds (n=73:68.9%) of the patients, were categorised as "SR"(group1) while remaining third (n=33:31.1%) were categorised as "blockers"(group2). The significant features in group1 were: age at onset lower than 20 years (n=60:82.2% P=0.002); birth dates were between June and September (n=42:57.5% P=0.003); family history of atopy (n=59:80.8% P=0.001); itching of skin (n=25:34.2% P=0.002), eye (n=30:41.1% P=0.001), ears (n=28:38.4% P=0.002), and throat and palate (n=42:57.5% P=0.001); and aggravation with dust (n=65:89.1% P=0.001). History of breathlessness (n=28:84.8% P=0.002), mouth breathing (n=28:84.8% P=0.003), loss of smell (n=13:39.4% P=0.004), and prior nasal surgery (n=8:24.2% P=0.001) were significantly higher in group2. Patients in group1 were significantly more sensitised to seasonal allergens like pollens [Kigelia (P=0.045); Salvador (P=0.005)] while patients in group2 had more sensitisation to perennial allergens like house dust (P=0.001), house dust mite (P=0.044) and fungus including Aspergillus species (P=0.001). Mean SNOT-22 scores (group1:60.89;group2:61.66 P=0.763) and mean NRQLQ scores (group1:47.66;group2:50.91 P=0.238) were not significantly different between the groups, while mean ESS (group1:10.52;group2:12.30 P<0.001) and mean global PSQI scores (group1:9.71;group2:11.27 P=0.009) were significantly higher in group2. Conclusions: The two groups differ significantly in terms of their respective profiles, whether be demographic or clinical. Further, the sensitivity patterns to allergens differ significantly between the groups. "Blockers" experienced significantly more sleep disturbances as compared to "sneezers and runners". Background: S-nitrosothiols (SNOs) are potent endogenous bronchodilators. Genetic ablation of S-nitrosoglutathione reductase (GSNOR), which catalyzes the metabolism of SNOs, results in protection from airway hyperresponsiveness (AHR) in mouse. This study was performed to know whether activity of GSNOR of mice may explain the strain differences in AHR. Methods: Three different strains of mice -A/J, BALB/c, and C57BL/6 -were untreated (control, each n=5) or were sensitized and challenged with ovalbumin (asthma model, each n=5). AHR was measured using methacholine and activity of GSNOR was measured in whole lung lysate. Results: Persistent increase of AHR was observed in A/J compared to BALB/c or C57BL/6 control mice. GSNOR activity was significantly higher in A/J than BALB/c or C57BL/6 control mice (596.8±217.5, 400.0±184.8, 263.1±121.7; au, nmol/min/mg, p <0.05). In asthma model, AHR were also increased in AJ mice compared to other strains, and GSNOR activity was higher than BALB/c or C57BL/6 asthma model mice (749.7±192.5, 466.3±218.1, 474.4±24.0; au, nmol/ min/mg). Conclusion: GSNOR activity may contribute to the difference of AHR between mouse strains. Background: S-nitrosoglutathione reductase (GSNOR) is an important regulator for S-nitrosoglutathione (GSNO), the main source of bioavailable NO, and protects cells from nitrosative stress. We hypothesized that aerosol delivery of GSNO could reduce bronchoconstriction and pulmonary inflammation in a mouse model of asthma. Methods: To evaluate whether GSNO could ameliorate AHR and inflammation, we compared AHR and inflammation in the 6-week-old female BALB/c mice treated with 0.3 cc aerosolized 0-10 mM GSNO. Results: GSNO inhalation significantly decreased airway hyperresponsiveness with the increasing GSNO dose up to 0.03 ng/ml. But increasing the dose of GSNO more over than 0.03 ng/ml, there was absence of bronchoprotection or even aggravation of bronchocontriction. Conclusions: These results suggested that GSNO may be an important factor to control airway hyperresponiveness, and there might be a concentration threshold for an effective action of GSNO. Objectives: Exercise-induced asthma (EIA) is a significant burden for children with bronchial asthma because EIA often interfere with exercise activities of children if it is not properly treated and children with uncontrolled EIA may fall into inactive, sedentary life. We hypothesized that daily activity of children with EIA can be improved by controlling EIA. To test the hypothesis, we evaluated physical activity in children with EIA before and after EIA-targeted therapy. "Achieve Active life by Controlling EIA for asthmatic Kids (ACE kids) study". Methods: We enrolled 7-10 years old boys with untreated EIA. The patients were eligible if they had current history of exercise-induced symptoms, >12%reduction in FEV1 by treadmill exercise challenge at entry and had no anti-inflammatory treatment. Physical activity of the subjects were monitored using an accelerometer, Lifecoder EX®(Suzuken), during 2 weeks of run-in period and 8 weeks of treatment with salmeterol/fluticasone combination (SFC). Primary outcome was the length of strenuous activity in a day and secondary outcomes were %fall in FEV1 after exercise challenge, peak flow and exhaled NO. Results: Eight patients (mean 9.5 ± 0.6 years) were enrolled and 6 gave full dataset. The length of strenuous activity a day increased in 5 patients out of 6. Fall in FEV1 after exercise challenge was significantly smaller after treatment. Morning and evening peak flow significantly increased and exhaled NO significantly decreased after SFC. Conclusions: EIA-targeted treatment for boys with EIA improved their physical activity and measurement of physical activity with an accelerometer may be a surrogate marker for asthma control in children.


Wheezing as a clue to the diagnosis of cough variant asthma and nonasthmatic eosinophilic bronchitis Jin-Young Lee 1 , Sehyo Yune 2 , Byung-Jae Lee 3 , Dong-Chull Choi 3 , Mi-Jin Jang 4 , Jae-Won Paeng 4 , Young Eun Kim 2 Background: Clinical reports on cough variant asthma (CVA) or nonasthmatic eosinophilic bronchitis (NAEB) rarely suggest any symptom as an important diagnostic clue. The aim of this study was to investigate whether history of wheezing is useful in detection of CVA or NAEB among patients with chronic cough. Methods: Patients with cough persisting for more than 8 weeks were prospectively enrolled. They were divided into two groups according to the presence of wheezing in the past. Results of methacholine bronchial challenge and induced sputum examination were compared between two groups. Results: Four hundred sixty patients (165 men and 295 women) were enrolled and analyzed. Their mean age was 47.4 years and the median duration of cough was 13.5 months. Patients who had experienced wheezing were 164 (35.6%). The prevalence of CVA (36.4% vs. 5.8%, p<0.01) and NAEB (15.4% vs. 4.4%, p<0.01) were significantly higher in wheezing group compared to non-wheezing group. Conclusion: History of wheezing in the past significantly increases the chance of CVA or NAEB in patients with chronic cough. Careful history taking is important in diagnosing the cause of chronic cough.


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.


Two patients, aged 3 and 77, who suffered anaphylactic shock after contact with topical chlorhexidine were studied. The first case was a 3-year-old boy who underwent hypospadias surgery; among other drugs, chlorhexidine was used. He developed sudden hypotension, desaturation and facial swelling. The boy did not respond to adrenalin and efedrine; inotropic support at the Paediatric Intensive Care Unit was required. The second case was a 77-year-old woman who had a wound that was sutured at the Emergency Room (ER). She presented cough, dysphonia, palmar itching, universal erythema and hypotension that was refractary to intramuscular adrenalin. Mepivacaine was used as local anaesthetic and clorhexidine as disinfectant.


Allergic reactions to chlorhexidine are not common if we consider its widespread use in healthcare settings. However, these reactions can be life-threatening even after topical use so awareness is needed, especially at the ER and at perioperative environments. IgE determination and skin tests are useful tools to get an accurate diagnosis of these patients. Chlorhexidine can be used as an excipient of several medications and cosmetics, therefore a thorough information must be given to chlorhexidine allergic patients in order to avoid further contact with this agent. Background: Ambient pollution has been associated with adverse respiratory health effects. Although meteorological variables have been known to impact on respiratory hospitalization, few studies have investigated the effects of ambient pollution considering temperature or humidity. Here, we identified the effects of ambient particulate matter for daily respiratory admissions considering meteorological factors. Methods: We used daily hospital admissions for respiratory diseases in Busan from hospital records using the International Classication of Diseases (ICD-10) for the period 2007-2010. The respiratory allergic diseases used in our study are allergic rhinitis (J30) and asthma (J45-46). Age was categorized as group I (0-15), group II (16-64) and group III (≥65 yr). Hourly particulate matter < 10μm (PM 10 ) levels and particulate matter < 2.5μm (PM 2.5 ) levels were obtained from 19 monitoring stations in Busan, and collected by and made available from the Korean Ministry of Environment. The meteorological observation data in Busan provided by the Korean Meteorological Administration included temperature and relative humidity.
Results: The mean value of hospital admission for allergy rhinitis and asthma was 4.4±6.1 people and 3.3±3.3 people respectively. A dailyaverage value of PM 10 and PM 2.5 concentrations level was 49.6±20.5 μg/m 3 and 24.2±10.9 μg/m 3 respectively. The mean temperature was 15.1±7.9°C, relative humidity was 62.0±18.0%. Admission for allergic rhinitis was associated with increasing temperature anomaly (P=0.003) and decreasing relative humidity (P<0.001). When the relative humidity was constant, the increase in PM 10 levels was significantly associated with higher admission for allergic rhinitis. In asthma, hospitalization was correlated with decreasing relative humidity (P<0.001) and increasing PM 10 (P=0.008). Even after considering relative humidity, higher PM 10 levels still were associated with higher hospitalization rate. In subgroup analysis according to age, admission rate in group I and group III was more strongly affected by PM 10 levels than group II (IRR 7.4 and 6.4, respectively). Furthermore, it showed the association between higher PM 2.5 levels and admission for asthma, regardless of the effect of PM 10 levels.
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.


We retrospectively reviewed all children aged less than 18years who visited emergency department for acute urticaria or angioedema at Seoul national university hospital, Seoul, Korea, from July 1, 2014 through December 31, 2014. The diagnosis of urticaria and angioedema was made on clinical grounds. The review included a history based on a standardized questionnaires such as precipitating events (eg, food intake, drugs, insect bites or other factors), complete physical examination, further evaluations trying to find the etiology (skin-prick test, serum-specific IgE or multiple allergen stimulation tests) and treatment performed in emergency unit.
Results 212 consecutive infants, aged less than 18years, visited emergency department with a final diagnosis of acute urticaria (195 patients, 91.9%) and angioedema (17 patients, 8.01%). The causative event was identified in 112 patients (52.8%), the rest of patients are unidentified. Associated with foods were identified in 84 patients (39.6%), drug intake in 17 patients (8.0%) and others causes in 11 patients (5.1%). The other causes were vaccination, contact with a dog, insect bite or grass exposure. All patients were treated with oral anti-histamine. Anti-histamine injection was given in 134 patients (63.2%), systemic steroid in 25 patients (11.8%) and bronchodilator in 5 patients (2.3%). All the patients but one has discharged with oral anti-histamine, one children was hospitalized suspected of Stevens-Johnson Syndrome. The allergy test was performed in 19 patients (8.9%) at outpatient clinic and 16 patients (7.5%) showed positive results.


Discordance between sputum eosinophilia and exhaled nitric oxide Jin-Young Lee 1 , Byung-Jae Lee 2 , Dong-Chull Choi 2 , Jae-Won Paeng 3 , Mi-Jin Jang 3 , Jihye Result: Among the total of 591 patients, 76 (12.8%) patients were classified into discordant group. Among them, 67 (88.2%) showed high FeNO and low ISE, while only 9 (11.8%) showed low FeNO and high ISE. Comparison between concordant and discordant groups showed that male sex, absence of airway hyperresponsiveness, increased age, and increased neutrophil count in sputum were more frequently seen in discordant group. Current or previous use of corticosteroid, presence of atopy, and salivary contamination of induced sputum were not significantly different between the two groups. Conclusion: Discordance between FeNO and ISE was observed in quite a few patients. Most of the discordance results from high FeNO and low ISE. Further study is necessary to find a proper method to assess airway inflammation in this subset of patients.


The prevalence of gastroesophageal reflux disease in chronic unexplained cough Jin-Young Lee 1 , Jae-Won Paeng 2 , Mi-Jin Jang 2 , Dong-Chull Choi 3 , Byung-Jae Lee 3 , Yongseok Lee 4 , Young Eun Kim 4 , Sehyo Yune 4 Background: The common co-existence of cough and gastroesophageal reflux disease (GERD) is well established. Several respiratory guidelines for the management of chronic unexplained cough in adults advocate empirical treatment of GERD. In contrast, guidelines from some gastroenterological societies conclude that cough is unlikely to be related to GERD in the absence of heartburn or acid regurgitation. This study was performed to assess the prevalence of GERD in adults with chronic unknown cough.
Results: The prevalence of GERD in chronic unexplained cough, as evidenced by an abnormal impedance or pH profile, was 46.3% (68 of 147 patients). Among 49 patients who were given anti-reflux medication for at least 3 months, 39 patients (79.6%) achieved total or near-total elimination of cough. Conclusion: GERD, which is readily detected by 24-hour impedance-pH monitoring, is a common cause of chronic unexplained cough and can be successfully managed with anti-reflux therapy. The nature of allergic rhinitis (AR) in preschool children has yet to be clearly characterized. The aim of this study was to investigate the prevalence and its risk factors of AR and its relationship with FeNO in preschool children.


This is a population-based, cross-sectional survey of 1757 preschool children, aged 3-7 years in Korea in 2010. A modified International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire was used. In addition, skin prick tests (SPT), serum total IgE and specific IgE were assessed. Current AR was defined as having nasal symptoms within the last 12 months and diagnosed AR by clinicians. Atopy was defined who had one or more positive reactions on SPT.


The prevalence of current AR in preschool age was 23.0% (392 out of 1702) and atopic current AR was 9.65% (93 out of 964 Vitamin D deficiency has been declared a public health problem for both adults and children worldwide. The growing data suggests that vitamin D deficiency plays an important role in the development of childhood asthma. The objective of this study was to investigate the potential relationship between asthma exacerbation severity and serum 25-hydroxyvitamin D in children.


This study was conducted in Shengjing Hospital of China Medical University, from September 2013 to March 2014. A total of 49 children with asthma exacerbation, aged between 3 and 14 years, were enrolled. The children should not have underling diseases such as chronic lung disease, congenital heart disease, chronic renal disease, etc. and vitamin D supplement in recent 3 months. According to GINA assessment of asthma exacerbation, they were divided into mild, moderate and severe exacerbation group. Serum 25-hydroxyvitamin D were assessed in all 49 children.


The 49 patients were 28 boys and 21 girls, mean age 5.28±2.28 years old. According to GINA assessment of asthma exacerbation, 20 (40.82%) children were enrolled in mild exacerbation group, 15 (30.61%) children were enrolled in moderate exacerbation group and 14 (28.57%) children were enrolled in severe exacerbation group. There was no significant differences in age, height and weight among the three groups (p>0.05). The concentration of serum 25hydroxy vitamin D in mild, moderate and severe exacerbation groups was 35.77±13.64 nmol/L, 15.30±4.97 nmol/L and 13.87±3.33 nmol/L separately. The serum 25-hydroxyvitamin D of mild exacerbation group is significantly higher than moderate and severe exacerbation groups. But no significance was found between moderate and severe exacerbation groups.


Neutralization of stratum corneum accelerates the progress from atopic dermatitis to asthma-like lesion in flaky tail mice treated by house dust mite allergen Hae-Jin Lee 1 , Noo Ri Lee 1 , Bo-Kyung Kim 1 Background: A disrupted skin barrier of atopic dermatitis (AD) permits easier penetration and sensitization of external allergens and then induces the development of asthma and allergic rhinitis, so called the 'atopic march'. Maintenance of normal acidity in the stratum corneum (SC) is an important factor for normal skin barrier function. Elevation of SC pH accompanied by the increase of serine protease activity and TSLP expression provokes skin inflammation. Objective: We determined whether the neutralized SC environment can accelerate airway inflammation more easily in flaky tail mice, a representative AD murine model with congenital skin barrier abnormality, after the exposure of house dust mite (HDM). Methods: Dermatofagoides pteronyssinus (Dp), a HDM was applied on the dorsal skin of flaky tail mice twice a week, which accompanied by the application of neutral cream (pH 7.4) and acidic cream (pH 2.8) twice a day for 6 weeks. Intranasal inhalation of Dp was done daily during last 3 days. Gross findings, functional study for skin barrier, blood sampling, bronchoalveolar lavage and biopsies of skin and lung were done at 24 h after last treatment.


The number of patients with food allergies is increasing on a global level. The estimated prevalence in Japan is 5-10% among infants and 1-2% among schoolchildren. The use of oral food challenges (OFCs) is the gold standard for the diagnosis of food allergies. As of 2015, Japan is currently the only country in the world in which OFC testing is covered by health insurance. We performed a questionnaire survey to all specialist training facilities belonging to the Japan The total estimated OFC testing fill-rate in Japan for each year was 6.4%, 8.8%, 9.3%, 10.0%, and 17.1%, respectively. These results indicate that the increased percentage of non-allergists performing inpatient OFC testing lead to increase of total estimated OFC testing fill-rate in Japan.


The Gut Microbiome in the Food Allergic Host Jamie Kiehm, Punita Ponda, Sherry Farzan, Jared Weiss, Claudia Elera, Catherine Destio, Cristina Sison, Annette Lee Shore Long Island Jewish Health System, USA Correspondence: Jamie Kiehm -North Shore Long Island Jewish Health System, USA World Allergy Organization Journal 2016, 9(Suppl 1):A200 A) Background: Alterations in the diversity and composition of the human gut microbiota have been associated with a myriad of diseases including inflammatory bowel disease and metabolic syndrome. In our study, we explore the association of the host gut microbiome with food allergy. B) Methods: 12.5 ng of isolated DNA from fecal samples from 8 children with peanut allergy (peanut specific IgE >15 kUA/L) and 10 healthy, non-atopic controls were amplified using primers specifically for the V3-V4 region of the 16S rRNA gene which is unique to bacteria. Sequence differences within the V1-V9 variable region were used for bacterial classification. Once amplified, the amplicons were dual-indexed for multiplex sequencing. Pooled libraries were sequenced on the Illumina MiSeq using 300 cycle paired end reads. Sequence data was processed through the MiSeq Reporter Metagenomics 16S application and the Greengenes 16S ribosomal RNA gene database. Data regarding family history of atopic disease, history of breastfeeding, antibiotic treatment per year, medications, and history of other atopic disease was collected via questionnaires. The Mann-Whitney U-test was used for comparison of continous variables between the two groups. The Fisher's exact test was used to compare proportions between groups. All analyses were carried out using SAS V9.3. C) Results: The median age of subjects with peanut allergy was 6 years (average peanut specific IgE=75.1 kUA/L), and median age of healthy controls was 4 years. All of the patients with peanut allergy had a history of other atopic diseases. The phylogentic differences showed that peanut allergic subjects had an increased proportion of Firmicutes (median=71% vs 59%; p<0.03) and a decreased proportion of Proteobacteria (median=1% vs 3%; p<0.009) when compared to healthy controls. At the class level, Clostridia was more abundant in the peanut allergic subjects (median=69% vs. 57%; p<0.03). Clostridiales order was significantly more abundant in the peanut allergic subjects (median=69% vs. 56%; p<0.03). Alcaligenaceae family was found in 6/10 healthy controls and in none of the 8 peanut allergic subjects (60% vs 0%; p<0.013). 16 genera were identified in healthy controls while 12 genera were identified in peanut allergic subjects. The 12 genera identified in the peanut allergic subjects accounted for 82.76% of the total sequences and were all found in the healthy controls. The 16 genera found in healthy controls accounted for 79.97% of the total sequences. D) Conclusions: Analysis of the human gut microbiome in children with peanut allergy and healthy, non-atopic controls revealed differences in the specific composition and diversity of the microbiota that may contribute to the pathogenesis of food allergy. More studies with a larger sample size are needed to further investigate these associations.


This was a phase I, randomised, double-blind, placebo controlled, parallel group study with oral single and multiple doses that were administered to male and female healthy Japanese subjects from 20 to 45 years of age. Twenty seven subjects (nine per each cohort of dose) were randomised in a 3.5:1 ratio to rupatadine (10, 20 and 40 mg) or matching placebo. On Day -1, all subjects received a single dose of placebo, followed by one single daily oral dose on Day 1 and once single daily doses on Days 2 to 5. Plasma samples collected at different time-points throughout the study were analysed by means of a validated LC-MS/MS analytical method to determine rupatadine and UR-12790 and UR-12788 metabolites concentration. Pharmacokinetic parameters were evaluated by using a noncompartmental analysis, and regression models were used to assess dose linearity. Results PK exposure after rupatadine administration of single and multiple doses in Japanese subjects was found to increase in a dose dependent manner. Single and multiple oral doses of rupatadine were well tolerated. There were no serious adverse events in this study and no subject withdrew due to safety reasons or any other reasons.


At present the only available management for food allergy is avoidance but wheat avoidance results in dietary limitations and can affect the quality of life. Oral Immunotherapy (OIT) is a method that has been shown to increase tolerance to wheat in allergic patients.


Among 11 patients, 9 (81.8%) were male and the average age of patients at beginning of the study was 6.2 years old (range, 5-11 years). All patients completed buildup phase successfully. One patient discontinued the maintenance phase for personal reason. Ten patients completed maintenance phase successfully and became desensitized. They are now consuming wheat products freely without any complications. Threshold doses in the wheat DBPCFC was from 0.08 g to 1.3 g of wheat protein. Build up phase continued in 3 to 7 days. Eight of 11 patients showed symptoms (72.7%) during this period, the total number of doses were 101 in which 25 of applied doses (24.8%) showed symptoms which mostly were mild reactions. Number of epinephrine that we took advantage was 9 in total 101 applied doses (8.9%). During maintenance phase seven patients showed mild reaction in first month of maintenance phase. The total number of doses in maintenance phase was 900 in which 52 of applied doses (5.8%) showed mild symptoms.


Wheat OIT through this method could be simple, safe and effective in selected patients with wheat allergy, although it needs further investigations with more patients. Posttranscriptional control by RNA binding proteins (RBPs) of CD4 + T cell development is poorly understood. We previously demonstrated that the RBP HuR (elavl1) controls Th2 differentiation via increased stabilization of Gata-3, IL-4 and IL-13. HuR CD4 + T from transgenic mice which over-expressed HuR had significant increases in Th2 but not Th1 cytokines. IL-2 is the primary growth factor for activated T cells. When IL-2 engages its' low affinity receptor, IL-2Rα (CD25) this results in phosphorylation of stat5 which turns off IL-2 via prdm1, which encodes the IL-2 transcriptional repressor, blimp-1. p-stat5 also opens up accessibility of the IL-4 gene to transcription, leading to Gata-3 activation, which is essential for Th2 differentiation. We hypothesized HuR regulates CD4 + T cell differentiation and is required for normal IL-2 homeostasis. We generated a HuR conditional KO model to study effects of HuR ablation in CD4 + T cell activation (distal lck-cre-ROSA HuR fl/fl ). The ROSA gene expresses YFP which is used to track HuR KO cells. We sorted CD4 + T cells into YFP + and YFPgroups and activated them with anti-CD3/CD28. Activated YFP + CD4 + T HuR KO cells had profound defects in Gata-3, IL-4, IL-5 and IL-13 expression and could not shut off IL-2. Up to 97% of activated T cells were unable to turn off IL-2 expression. HuR KO T cells had defects in proliferation and JAK-STAT signaling with reduced p-stat5 and were unable to up-regulate CD25. We found significantly increased IL-2 but decreased Gata-3, prdm-1, IL-4 and CD25 transcription. We investigated whether HuR directly controlled CD25 expression. We verified HuR interacts with defined AU-rich elements (AREs) in CD25 3'UTR. CD25 mRNA stability was unchanged in HuR KO T cells but there were translational defects in recruitment of CD25 mRNA transcripts to heavy polysomes. To determine in vivo relevance, we used the ovalbumin challenge model of allergic airway inflammation. HuR KO mice had significant decreases in lung neutrophils, lymphocytes, eosinophils and IL-13. Remarkably, immunized HuR KO mice had comparable levels of total lung inflammation as un-immunized controls. We confirmed increased IL-2 and reduced CD25 phenotype in CD4 + T cells from immunized HuR KO mice. In summary, these data suggest that HuR plays a major role in CD4 + Th2 differentiation and normal IL-2 homeostasis by controlling CD25 mRNA translation. Furthermore, HuR KO in T cells completely abrogates allergen induced lung inflammation. Therefore, HuR-CD25 interactions are required for normal IL-2 homeostasis and Th2-mediated allergic airway inflammation. Method: This is a part of International Study of Wheezing in Infants (EISL), a population-based study, in infants aged 12-15 months, compares data from two surveys (S1 and S2) performed using the same methodology, in three large cities that participated in both surveys: Curitiba and São Paulo (Brazil) and Santiago (Chile). Results: The average prevalence of wheezing once or more during the first year of life decreased from 52.9% (95%CI 51.8-54) in S1 to 46.9% (95%CI 45. 2-48.07 ) in S2, p = 0.0001. There was a significant decrease in the mean prevalence of RW between S1 (23.3%, 95%CI 22.3-24.3) and S2 (20.4%, 95%CI 19.0-21.8), p=0.004. In infants with RW the mean prevalence of severity markers between S1 and S2 remained high (severe episode: 56.9% to 54.2%, p = 0.32); ED visits (68.1% to 70.9 %, p = 0.21), with a significant increase in admissions for wheezing (21.1% to 26.7%, p = 0.004).


The prevalence of RW and severity markers during the first year of life remained high between both surveys. The infants who suffer from RW have markedly high prevalence of severity markers as visits to ED and admissions for wheezing, indicating that an important group of these infants has a troublesome progression that certainly affect quality of life and put infants at risk of more severe complications. Background: Cyclophosphamide (CYC) is an alkylating agent used to treat malignancies and autoimmune diseases. It is often given with mercaptoethane sulfonate (mesna) to prevent bladder toxicity. Hypersensitivity to CYC has been well described in adult patients with malignancy. These reactions are typically IgE-mediated to CYC or its metabolites after a previous exposure. Most of these patients have tolerated subsequent treatments by desensitization. We report the first described case of anaphylaxis after initial exposure of CYC in a pediatric patient with systemic lupus erythematosus (SLE) who successfully tolerated subsequent CYC by desensitization. Method: Case description. Results: An 11-year-old girl with SLE and Class III/V nephritis was admitted for hematuria, anasarca, and uncontrolled hypertension consistent with SLE nephritis flair. Her treatment was switched from mycophenolate mofetil to monthly CYC (945mg, 0.75 gm/m2) intravenously (IV) with mesna infusions given 30 minutes prior and 3, 6 and 9 hours after CYC infusion. Immediately after completing her first CYC infusion, she developed increased erythema at her IV site, angioedema of the lips and tongue, facial flushing, shortness of breath, chest tightness, and wheezing. She was treated for anaphylaxis with intramuscular epinephrine, IV diphenhydramine, methylprednisolone, and famotidine with An hour later, she became hypotensive (BP 91/31 from BP 147/69). Antihypertensives were held and she continued receiving IV diphenhydramine and methylprednisone. She received her post-treatment mesna infusions without any adverse event. She had no history of allergies or exposure to alkylating agents in the past. CYC was the preferred therapy as her renal function improved after her first treatment and Allergy was consulted to evaluate whether her anaphylaxis was secondary to mesna or CYC and for possible desensitization. Allergy evaluation revealed negative percutaneous testing to mesna (10mg/ml skin prick; 0.01mg/ml and 0.1mg/ml intradermal). CYC skin testing was deferred by the patient's guardian. She was admitted to the intensive care unit to receive CYC via a 12-step desensitization protocol. Her daily prednisone 40 mg dose was increased to methylprednisone 1 gm at 45 minutes prior to desensitization. She was also premedicated with diphenhydramine 25 mg and famotidine 20 mg at 20 minutes prior to desensitization. She tolerated desensitization without any adverse reactions. Since then, she has received CYC by desensitization every month at an outpatient infusion setting without any adverse event.


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

Si-Heon Kim 1 , Gil-Soon Choi 2 , Su-Chin Kim 1 Background: It has been suggested that vitamin D deficiency has an influence on increase in the prevalence of allergic disease. A few studies have been reported that epinephrine prescriptions varied from latitude of the regions. The present study aimed to examine the regional differences in incidence of food-induced anaphylaxis (FIA) and serum vitamin D level in Korea. Method: Nationwide data on FIA from2011 to 2013 were obtained from the Health Insurance Review and Assessment Service. We used serum vitamin D levels from the Korea National Health and Nutrition Examination Surveys during the period corresponding to FIA. Regions were divided into 2 categories based on the latitude N36.2°(Region 1 for high latitude and Region 2 for low latitude). We examined the differences in incidence of FIA and serum vitamin D levels between 2 regions after adjusting for age. Results: The number of cases of FIA was 2,851, and serum vitamin D levels were obtained in 15,368 persons from 2011 to 2013. FIA incidence was significantly higher (2.00 vs 1.73 per 100,000 person-years, p=0.03), and serum vitamin D level was lower (16.5 vs 18.1 ng/ml, p<0.001) in Region I as compared with Region 2. For all age groups of <20, 20-59, and ≥60 years, serum vitamin D levels were significantly higher in Region 2 than in Region 1. The regional difference of FIA incidence was significant in persons aged <20 years (1.90 in Region1 vs 1.15 in Region 2, p<0.001), but insignificant in other age groups. Serum vitamin D level in Region 1 was higher than that in Region 2 for both males and females. However, there was no difference in FIA incidence between 2 regions according to gender. Conclusions: Overall, higher FIA incidence and lower vitamin D levels were found in relatively higher latitude region compared with lower region. After stratification by age groups and gender, FIA incidences and serum vitamin D levels were inconsistent in aspect of the regional differences. Further investigations are necessary to identify the relationships between FIA and vitamin D. Background: Atopic dermatitis is exacerbated by several triggering factors, which are allergens, stress, infections climates and so on. We investigated triggering factors for better control of atopic dermatitis in children.
Methods: Subjects were diagnosed as atopic dermatitis by pediatricians of allergy clinic of Busan St.Mary's Hospital from April, 2014 to March, 2015. We got history taking, allergy test (SPT, ImmunoCap), Skin culture, and physical examination for checking triggering factors. We also classified by severity (SCORAD score), and analyzed each group's triggering factors. Results: Subjects number was 301. (male 185, 3month to 18 years old, average 4.6). Triggering factors were skin infections, foods (immediate 29, delayed 10), itching (21), traditional medicine (18), and systemic infections (16). Skin infections were by bacteria (S.aureus(SA) 178, methicillin-resistant SA(MRSA) 77), Fungi (Malassezia 78, average IgE 7.1kUA/L), and virus(Kaposi varicelliform eruption 58). Mild groups were 157, (male 89, average age 4.1) and triggered by SA/ MRSA (77/31), malassezia (29, IgE 4.3), KVE (12), foods (immediate/delayed 14/6), itching (8), sweat (7), irritation (6), systemic infection (5), and environment(4) in order of frequency. Moderate group were SA/ MRSA (87/39), malassezia (37, IgE 7.2), KVE (34), foods (immediate/ delayed 12/4), itching(10), traditional medicine (10), systemic infection(9), topical ointment tolerance (7), and sweat (5) . Severe group were 22, (male 15, average 8.0) triggered by SA/MRSA (14/7), malassezia (12, IgE 13.4), KVE (12), traditional medicine (7), foods (immediate/delayed 3/0). itching (3), systemic infection (2), and irritation (1, dyeing) . Conclusion: Skin infections, traditional medicine are high proportions of triggering factors of atopic dermatitis in severe group. Mildmoderated group were mainly triggered by skin infection, foods, and itching. Background: Recently monoclonal antibodies (mAbs) are widely used in various clinical fields. Although their safety was demonstrated prior to approval, targeted pharmacovigilance is essential for the recognition and assessment of adverse drug reactions (ADRs). The purpose of this study is to identify the frequency and major clinical features of ADRs referred to mAbs in Koreaa. Methods: ADRs attributed to eighteen mAbs submitted spontaneously to the Korea Adverse Event Reporting System (KAERS) were extracted from the database for January 2000 to June 2014. We analyzed these reports for information related to patient's characteristics and types or ADRs. Results: A total of 17,346 ADRs were obtained from 8,591 patients. The most frequent symptoms of ADRs were abnormalities of leukocytes (9.0%), followed by infections (6.3%), drug eruptions (6.2%) and drug fevers (3.4%). Hypersensitivity reactions were reported almost ten percent. Furthermore mAbs induced total 5,545 serious ADRs from 2,862 patients, including severe infections (9.6%), neutropenia (9.3%), drug fever (4.1%) and visual dysfunctions (2.8%). 279 patients died due to ADRs of mAbs. The mAbs with the highest number of ADR reports were rituximab (20.3%), followed by adalimumab (16.7%), cetuximab (15.0%) and bevacizumab (13.9%). Conclusions: Near ten percent of the ADRs were allergic-like, and no previously unrecognized ADRs were observed. Increased awareness among healthcare professionals is required to signal and prevent the consequences of adverse reactions caused by monoclonal antibodies. Background: Food allergy has previously been associated with impaired growth in children, however this has not been investigated in a longitudinal study to investigate growth over time and previous studies have not accounted for the impact of co-existent eczema. We aimed to examine the association between IgE-mediated food allergy at 12 months of age and anthropometric measures at 1 and 4 years of age, and whether this association differed by eczema status.
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 Role of Vasoactive Intestinal Peptide in the Pathophysiology of Acute Asthma Olga Semernik Rostov State Medical University Russia World Allergy Organization Journal 2016, 9(Suppl 1):A217 Background: Previous research has shown neurohumoral factors to play an important role in the pathogenesis of asthma in children. The relationship between plasma levels of norepinephrine, vasoactive intestinal peptide and cortisol and clinical status and pulmonary function in patients with asthma during the period of exacerbation have been investigated. Method: 30 children (aged 6 to 18 years) with asthma were examined in accordance with the purpose of the study. The control group consisted of 30 healthy volunteers of the appropriate age and gender. We compared clinical severity, spirometry, and neuroendocrine factors at asthmatic patients and healthy volunteers. We used multiple analyses of variance (repeated measures) to interpret the data. In addition, we used the Pearson Product Moment Test to investigate correlations among the different variables. Results: The levels of vasoactive intestinal peptide, norepinephrine and cortisol were significantly higher in patients with asthma than in healthy volunteers (P < 0.001). It was found the concentration of VIP in serum at patients with asthma during the period of exacerbation to be 110.60 ± 11.89 nmol/l, that was significantly higher than the control group values -53.26 ± 16.08 nmol/l (p = 0.016). In patients with asthma during the period of exacerbation, the level of vasoactive intestinal peptide correlated positively with the clinical severity rating (r = 0.621, P < 0.01) and negatively with FEV1 (r = -0.768, P < 0.001). In patients with mild attack of asthma concentration VIP in blood was 88.81 ± 31.14 nmol/l, with moderate -100.27 ± 16.27 nmol/l, severe -107.34 ± 22.70 nmol/l. In addition, the clinical severity rating showed a negative correlation with FEV1 (r = -0.359, P < 0.01). It can be assumed that the mobilization of the body defense at a child in the acute period of the disease in the form of additional ejection neurotransmitter and it can lead to a more rapid relief of obstruction airway. Conclusion: It was found the vasoactive intestinal peptide to be the only neuroendocrine factor closely associated with clinical severity and pulmonary function suggesting this factor play an important role in the pathophysiology of acute asthma.


Objective: To compare the influence on the regulatory T cell (Treg) by different house dust mite specific immunotherpy route-subcutaneous immunotherapy(SCIT) versus sublingual immunotherapy(SLIT). Methods: All of 86 dust mite allergic asthma children with mild to moderate severity were enrolled (male63,female23) in asthma center of Beijing Children's Hospital from February in2012 to October in 2013. Among of them, 29 patients (male22, female 7) took sublingual dust mite specific immunotherapy (SLIT group),13 patients (male8,female 5) took subcutaneous immunotherapy (SCIT group), 14 subjects (male14, female 0) had completed the3-years treatment process (after SCIT treatment group), and the other 30 asthmatic children (male19, female11)without immunotherapy was enrolled as control group. Peripheral blood mononuclear cells (PBMC) were isolated from all the subjects and in vitro stimulated with HDM extracted (0μg/mL, 2.5 μg/mL, 5 μg/mL) for 48 hours, and then the relative percentage of Treg were measured by flow cytometry. Results: In the unstimulation condition(Der p1=0μg/mL), the the baseline relative percentage of Treg in each group was significantly higher than that under stimulated condition. Besides, the baseline Treg% in SCIT group was significantly higher than that in the control group and in the SLIT group,however,there is no significant difference in the Treg% between SCIT group and those had accomplished the 3-years SCIT treatment. Conclusion: It seemed that it is more likely and effectively to induce regulatory T cells in asthmatic children by SCIT when compared with SLIT, and this effect could remain for a period of time even after the whole specific treatment procedure. Background: Asthma remains a serious healthcare burden in Asia. Despite the availability of efficacious treatments, asthma control remains suboptimal. REALISE Asia aimed to identify treatment gaps by exploring patients' perceptions and attitudes on their disease and its treatment, as well as insights from physicians managing this disease. While the main objective is to provide a broad view of asthma in the region, country-specific variations are reported here.
Methods: REALISE Asia was conducted in two-parts in the following countries: China, Hong Kong SAR, Indonesia, Malaysia, Philippines, Singapore, South Korea, and Taiwan. Part 1 was an online survey which involved 2,467 patients with asthma (aged 15-50 years, with access to social media). Part 2 was done through face-toface and online interviews among 375 physicians involved in asthma patient-care. Results: The disparity in the proportion of well-controlled asthma between patient-reported and physician-perceived ranged from 18% (Malaysia) to 44% (Hong Kong). A significantly higher proportion of physicians in Hong Kong (40%) reported that they do not use guidelines to assess asthma control (versus < 17% in other countries). Length of consultations ranged from 11.5 and 4.9 minutes for initial and follow-up in Korea, and 24.3 and 14.9 minutes in the Philippines, respectively. The percentage of patients who agreed they had full discussion with their physician about the best medication to treat their asthma ranged from~60% (Korea) to over 80% (China, Indonesia, and Philippines). Almost 90% of physicians indicated they explain the purposes of inhalers on initial consultation, though this was significantly lower in China (62%). On average, 80% of physicians believed a combination (corticosteroid + long acting bronchodilator) inhaler can improve patient adherence, but this was significantly lower in Indonesia (53%). The proportion of patients who reported that they use controller inhaler daily ranged from 9% in Korea to 26% in Singapore. Only half of patients on inhalers said that their inhaler techniques were checked by a healthcare professional in the past 12 months, and this was lowest in Korea (42%) and Hong Kong (39%). Conclusions: While variations among the countries in perceptions and management of asthma exist, there are common aspects of care that need to be optimised (e.g. adherence to controllers, inhaler techniques, patient education). Understanding these differences in the context of healthcare systems in these countries can provide additional insights which will be useful in the development of relevant interventions to improve asthma control. Background Asthma is known a disease with many variations, and one of the subtypes is Aspirin Exacerbated Respiratory Disease (AERD). AERD patients experience severe bronchoconstriction to aspirin or other NSAIDs. AERD patients in general have relatively severe asthma with a high proportion requiring long-term oral corticosteroid (OCS). We aimed to classify AERD phenotype and its clusters. Method 302 AERD patients who followed up at least 1 year in Ajou university hospital from Jan 1996 to Jul 2013 were enrolled. To fracture AERD phenotype using atopy, chronic rhinosinusitis (CRS) and urticaria, we performed two step cluster analysis. Severe exacerbation was defined as patients having taken intravenous steroid treatment or at least 2 burst of OCS in a year. The mean follow up duration was 7.2±5.2. Clinical characteristics among clusters were examined by Fisher's exact test and ANOVA. The generalized estimating equation was applied for the possession rate of anti-asthmatics and severe exacerbation in a year.


The Oxidative stress plays a role in the pathogenesis of chronic obstructive airway diseases such as asthma and COPD. Thus, the regulation of both reactive oxygen species (ROS) and anti-oxidant defense is also critical. In general, major source of ROS is mitochondrial respiration of cells and some of the antioxidants exist as a mitochondria-specific form which is important for regulating the significant quantities of ROS. The peroxiredoxin6 (PRDX6), known as a dual function protein with GSH peroxidase and phospholipase A2 activities, is reported to be predominantly expressed in airway epithelium. Recently, PRDX6 knockdown was reported to induce mitochondrial dysfunction although it is well known that PRDX6 is mainly located in cytoplasm, secretory organelles, and lysosomes. The aim of this study was to investigate if PRDX6 have an influence on mitochondrial function through its cellular trans-localization to mitochondria under oxidative stress. Mitochondrial translocation from subcellular fractionation of human bronchial epithelial cell line and mouse lung tissue under oxidative stress were analyzed by immunoblotting. We evaluated changed mitochondrial function by measuring O 2 consumption, ATP synthesis, and ROS generation. PRDX6 expression was increased in oxidative stress inducer (paraquat and H 2 O 2 ). The lipid peroxidation and protein carbonylation were significantly higher in PRDX6 knock-down cells compared to PRDX6 overexpressed cells. The intracellular trans-localization of PRDX6 under enhanced oxidative stress was confirmed by immunoblotting of subcellular fractionation and confocal microscopic analysis of immunofluorescence probes. The results of this study demonstrated that PRDX6 plays an important role in regulating mitochondria under oxidative stress in the airway. Dysregulation of PRDX6 function might be critical in the development and perpetuation of chronic obstructive airway disease. Clarification of the precise functioning mechanism of PRDX6 may be valuable to understand pathogenesis of the disease. Background: Silica nanoparticles (SNPs) can be easily exposed via inhalation owing to their low particle weight and ease of dispersion. However, toxic and adjuvant effects of SNPs on the airway system according to their surface pattern are not well established. We evaluated these effects on the airway system in a murine model using 3 types of SNPs. Methods: Female, 6-week-old, BALB/c mice were intranasally administered 3 types of SNPs (spherical-type [S-SNPs], mesoporous-type [M-SNPs], and polyethylene glycol conjugated type [P-SNPs]) with or without ovalbumin (OVA), thrice weekly for 2 weeks. All mice were sacrificed 48 h after the last dose. We evaluated airway hyperresponsiveness (AHR), bronchoalveolar lavage fluid (BALF), cytokine levels, and histology of the lungs.
Results: In the model administered SNPs alone, only M-SNPs induced significant AHR as compared to sham group, whereas all SNP-treated groups showed a significant increase in total cell, macrophage, and neutrophil counts in BALF. S-SNPs and M-SNPs induced an increase in cytokine (interleukin [IL]-5, IL-1β, and interferon-γ) levels. In the model administered SNPs with OVA, S-SNPs and M-SNPs induced significant AHR as compared to sham group and those administered OVA alone. Overall, greater inflammatory cell infiltration in BALF, extensive pathological changes, and higher cytokine levels (IL-5, IL-13, IL-1β, and IFN-γ) were observed in the group administered SNPs with OVA than those administered SNPs or OVA alone. However, P-SNPs induced lesser inflammation than the other types of SNPs in both models. Conclusion: SNPs alone has significant toxic effectc on the airway system. Moreover, SNPs when administered with OVA cause adjuvant effects. We recommend the use of P-SNP because of its relative safety compared with S-SNP and M-SNP. Objective of study: To develop the procedure for assessment, diagnostic and treatment of children (Ch) with different immunopathogenetic phenotypes (IPP) of atopic dermatitis (AD). Materials and methods: The participants of study were 94 Ch aged 5 to 17 with moderate course of AD in the exacerbation phase. The control group was comprised of 30 healthy Ch of the same age. The patients underwent general physical examination, clinical assessment and immunoallergological assessment (IAA) aimed at detection of clinical and laboratory signs of allergen-induced inflammation. General physical examination included clinical blood and urine analyses and screening for parasitic and viral infections. IAA consisted of: immunogram determination of levels of pro-and antiinflammatory cytokines (by fluorescence immunoassay); skin testing, challenge or elimination testing (if indicated), total and specific IgE blood testing. House dust mite allergens (HDMA) were used as a cause-significant allergen. Clinical assessment was aimed at collection of allergic anamnesis and evaluation of severity of clinical symptoms according to SCORAD scale. Results: The integrated study conducted enabled us to divide Ch into two groups based on their principal IPGP of AD: IgE-mediated and non-IgE-mediated form of AD. Ch with non-IgE-mediated type of AD showed no IgE-sensitization to HDMA and lower parameters of macrophage-phagocytic component of immune system (MPCIS). IgEmediated AD phenotype included 3 forms of ADallergic form, mixed form (in combination with allergic rhinitis, bronchial asthma) and combined form. In studying allergic and mixed form of AD we proved the existence of sensitization to non-eliminated HDMA, which promote allergization and provoke development of symptoms in the course of AD, and in Ch with combined form of AD a decrease in parameters of MPCIS (such as phagocytic number, phagocytic index, NBT Reduction Test) was also found. On the basis of the revealed disorders, several multimodality immunotherapy (MIT) programs were developed. For IgE-mediated forms of AD we proposed a MIT including basic therapy (BT) + parenteral antigen-specific immunotherapy (ASIT) as an accelerated treatment regimen and immunomodulator (IM) selected on the basis of its capacity to affect the cells of monocytic-macrophagal nature, increase of macrophages' cytotoxicity toward bacterial antigens and viruliferous cells, as well as correction of imbalance in cytokine profile Th1/Th2 and intensifying the production of IFN-y, which would eventually contribute to lower rate of infectious complications of AD. For non-allergic form of AD, the BT + IM were used. Conclusion. The procedure of assessment and diagnostic of Ch with AD developed by us provides an opportunity to correctly select an adequate MIT in accordance with IPP of the disease taking into account the revealed immune disorders.

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).
Methods: MSCs were isolated from human palatine tonsil (T-MSC) and adipose tissues (ASC), and the surface markers were analyzed. The effect of T-MSCs was evaluated in 24 BALB/c mice that were randomly divided into 4 groups (negative control group; positive control group; T-MSC group and ASC group). MSCs were administered intravenously to OVA-sensitized mice (T-MSC and ASC groups) on days 18 to 23 and subsequent OVA challenge was conducted daily from days 24 to 28. Several parameters of allergic inflammation were assessed. Results: T-MSC and ASC had similar characteristics in surface markers. Intravenous injection of T-MSC significantly reduced allergic symptoms, eosinophil infiltration, serum total and OVA specific-IgE and the nasal and systemic Th2 cytokine profile. Further analysis revealed that nasal innate cytokines such as IL-25 and IL-33, and chemokines such as CCL11, CCL24 induction were suppressed in T-MSCs injected groups, explaining their underlying mechanism. Additionally, the T-MSC group had more inhibition of allergic inflammation than the ASC group, which might be attributed to the more proliferative activity of T-MSC. Conclusion: Administration of T-MSC effectively reduced allergic symptoms and inflammatory parameters in the mouse model of AR. T-MSC treatment reduced Th2 cytokines and OVA specific IgE secretion from B cells. In addition, innate cytokine (interleukin-25 and inteleukin-33) expression and eotaxin mRNA expression was inhibited in the nasal mucosa, suggestive of the mechanism of reduced allergic inflammation. Therefore, T-MSC treatment is potentially an alternative therapeutic modality in AR. Objective: Allergic rhinitis (AR) and asthma are a major global health problem in developed and developing countries like India. These diseases have an adverse impact on the patient's quality of life (QOL) and also pose a big socio-economic burden. Yoga has shown to have some beneficial effect on improving the sleep quality, lung function and quality of life in patients with asthma. But there is no scientific study on the effect of Yoga on airway resistance in patients with AR. The aim of this study was to assess the subjective and objective effects of yoga and also to see if Yoga can be adapted as a cost cutting intervention for better control of asthma and AR. Methods: The present study was conducted on 31 adult subjects with mild-moderate persistent AR with or without asthma. These patients were trained in specific Hatha yogasanas which are known to improve respiratory functions. The participants practised these asanas for 12 weeks. The subjective and objective outcome measures were assessed at baseline (Day 0) and at 12 weeks post yoga, using Rhinomanometry, Spirometry, Sino Nasal Outcome Test questionnaire and QOL Short Form 12. Results: There was a significant reduction in the Total Nasal Resistance (TNR) at 150 Pa/ml/s (p<0.001) and a significant increase in Total Nasal Airflow at 150 Pa/ml/s (p<0.01) after yoga as compared to the corresponding baseline values at day 0. Indices of pulmonary function such as FVC (p<0.001), FEV1 (p<0.05), Forced mid-expiratory flow at 75% of FVC (FEF 75%) (p<0.05) and PEFR (p<0.01) showed significant improvement. QOL questionnaire, Short Form 12 showed a highly significant improvement in both physical (p<0.001) and mental (p<0.01) composite score along with significant reduction in the Sino Nasal Outcome Test score (p<0.001) post yoga as compared to the corresponding baseline values. Conclusions: The direct cost of treatment such as medications and hospital visits etc., as well as the indirect cost due to loss of productivity is significantly high in patients with AR and asthma. The results of this present study conclude that the practice of yoga offers a significant advantage in patients with AR by reducing their nasal resistance, increasing nasal airflow, improving lung functions and their quality of life. Further studies are needed to analyze the immunologcal mechanisms involved in this form of therapy, the impact on acute exacerbations, the need for rescue medication and the long term effects of yoga. A true patient-physician partnership further empowers the patients compliance and adherence, thereby their function and health. Background and Objectives: Chronic urticaria (CU) is a common skin disorder characterized by hives and itching for at least 6 weeks. The QOL in CU can be substantially impaired due to its unpredictable symptoms and long-term nature. This study was aimed to evaluate the impact of CU on QOL by using the CU-specific QOL measurements, previously validated in Korea, and to identify the predictors of QOL in CU patients. Methods: We enrolled 390 adult patients with chronic spontaneous urticaria who were followed in the Allergy and Clinical Immunology Clinic in Ajou university hospital from March 2009 to December 2012. The CU-QOL questionnaires, urticaria activity score (UAS), the presence of angioedema, and serum total IgE levels were investigated. Results: The average CU-QOL scores was 70.6 of 100 points. The CU-QOL scores significantly correlated with the UAS, particularly with our 15-point UAS (UAS15, coefficient -0.532, P <0.01) than the 6-point UAS (-0.502, P<0.01). Total CU-QOL scores significantly decreased in patient with severe CU (UAS15 score≥13) than nonsevere CU (52.3 vs 72.1, P <0.001). In cases having angioedema, the urticaria symptom domain scores significantly decreased (37.4 vs 46.9, P = 0.004) than those with urticaria only. Multivariate analysis showed that severe CU, high log[total IgE], and the presence of angioedema were significant predictors of CU-QOL impairment (<85 points). Conclusions: It is important to consider QOL impairment and severe CU, log[total IgE], and the presence of angioedema are significant CU-QOL predictors in Korean patient with CU. Background: In house dust mite (HDM) allergic asthma, symptoms occur due to airway eosinophilia and Th2 cell activation. Budesonide is used to treat airway inflammation and hyper-responsiveness. We showed that dietary non-digestible galacto-oligosaccharides (GOS) suppress symptoms in a murine model for HDM-induced asthma. The aim is to study combined dietary GOS and budesonide treatment on allergic asthma in mice. Methods: BALB/c mice were intranasally (i.n.) sensitized with PBS in presence or absence of 1μg HDM and challenged i.n. with PBS or 10μg HDM on days 7 till 11 while being fed a diet containing 0, 1 or 2.5 w/w% GOS. On day 7, 9, 11, and 13 budesonide was either or not instilled oropharyngeally. On day 14, airway resistance to metacholine and inflammation were determined. Leukocyte subtypes were analyzed in the broncho-alveolar lavage (BAL) and in lung cell suspensions. Mucosal mast cell protease-1 (mmcp-1) was measured in serum and cytokines in lung homogenates. Results: HDM-allergy significantly increased airway responsiveness and BAL leukocyte numbers. Budesonide treatment suppressed this, which reached significance in mice fed GOS. Budesonide reduced the number of lymphocytes and eosinophils in the BAL. Feeding GOS in absence of budesonide treatment reduced the number of eosinophils as well. In addition, both GOS as well as budesonide reduced mmcp-1 serum concentrations. Interestingly, only in the GOS fed mice, budesonide treatment reduced IL-33 and IL-13 concentrations and the frequency of Th2 cells in the lung. Conclusions: Dietary intervention using GOS may be a novel way to improve effectiveness of anti-inflammatory drug therapy in asthma. This study was performed within the framework of Carbohydrate Competence Center (WP25).


Purified, recombinant Per a 1, Per a 2 and Per a 3 were physicochemically characterized and their ability to bind IgE was shown. By including all currently described Periplaneta americana allergens and testing diverse patients' cohorts from Europe, Asia and America, the sensitization pattern of these allergens can be elucidated. A) Background: Hand eczema is a common inflammatory dermatosis which influences the quality of life especially when it comes to accompanying itching. However, there is no research regarding the characteristics of itch and neurologic association in hand eczema so far. We performed this study to objectify the influence on quality of life in patients with hand eczema and to investigate the association with cutaneous nerve. B) Methods: we conduct a hand eczema severity scoring using HECSI score, a questionnaire contains Leuvin itch scale and dermatology life quality index(DLQI), and a neurologic exam using von-Frey filament and neurometer. C) Results: Forty-four patients were enrolled the study and 36 patients were also done neurologic examination. Itch occurred at least once daily in all study patients, and finger and palm were the most commonly affected itch areas (25.0%). The Leuvin itch scale was directly proportional to HECSI score (p=0.272), and DLQI was inversely proportional to it (p=0.019). The sensory threshold force measured by von-Frey filament was significantly higher in lesion than normal skin (p<0.05) and the pain threshold using neurometer was also significantly decreased in lesion (p<0.05). D) Conclusion: This study is a unique trial which describes the characteristics of itch experienced in hand eczema and investigates the relationship between hand eczema and cutaneous nerve. We thought it could be a good basis in development of future therapeutic modalities such as neurotransmitters in hand eczema. Drug-induced anaphylaxis is a big pitfall in patients receiving antineoplastic chemotherapy. We report a case of lung cancer patient who experienced two near-fatal anaphylactic reactions that resulted from paclitaxel and multivitamin, separately. Recurrent severe reactions to different agents led to further investigation to which material the patient was hypersensitive. The skin prick test revealed sensitization to cremophor, which is a commonly used emulsifying agent. This case emphasizes the importance of correctly identifying the culprit drug of anaphylaxis to avoid potentially fatal reaction. We aim to describe the epidemiology and triggers of anaphylaxis related Emergency Department visits in children and adults in Singapore.


There were 271 cases of anaphylaxis identified, making up 7% of all ED visits for allergy-related symptoms. The median age was 22 years (range 5 months-89 years). Children (below 16 years) made up 35% (94/271) of the cohort, with 139 males (51%). Patient ethnicity included Chinese (180 cases, 66%), Malay (44, 16%), Indian (18, 7%) and others (29, 11%). The most common trigger was food (n=126, 46%), followed by drugs (n=50, 18%) and stinging insects (n=14, 5%). The trigger could not be identified at initial presentation in 62 cases (23%). The most common food allergen was shellfish (n=36, 29%), followed by peanuts and other nuts (n=16, 13%). There were 2 new cases of galactooligosaccharide allergy that were confirmed on follow-up. Age distribution varied with the triggering factor. Those with druginduced anaphylaxis were older than those with food allergy (mean age 32.5 vs 24.5 years, p = 0.015). All cases of insect-related anaphylaxis occurred in adults (age range 22-68 years). The cases of shellfish anaphylaxis were older than those with peanut/tree-nut anaphylaxis [mean 29.7 years (range 6-75, SD 19.7 years) vs mean 14.2 years (range 2-51, SD 13.9 years); p = 0.006]. The hospitalization rate was 52%. On both univariate and multiple regression analysis, the only significant factor associated with hospitalization was the age of the patient (Spearman's correlation coefficient 0.169, p=0.006).


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.
Conclusions: Together, these results demonstrate that DON facilitates allergic sensitization and may thus serve as a model adjuvant. Our data therefore illustrate the possible contribution of food contaminants, like DON, in allergic sensitization in humans. Background: Lately, the evidence shows a huge epidemiological burden of chronic cough in general populations. However, the definitions of chronic cough varied, and no definitions were validated for clinical relevance. We examined existing epidemiological definitions in detail and investigated the operational characteristics. Methods: A systematic literature review was conducted for the epidemiological studies that reported the prevalence of chronic cough in general adult populations, which were published in the peerreviewed journals during the years 1980 to 2013. The operational characteristics of the most common definition were examined by meta-analyses of the male-to-female ratio in chronic cough prevalence. Results: The systematic review included 70 studies. The most common definition was cough ≥ 3 months (12-month prevalence) without specification of phlegm (n=50), which conflicts with the criteria in clinical guidelines of cough ≥ 8 weeks. Meta-analyses were conducted for the male-to-female ratio of chronic cough among 28 studies that reported sex-specific prevalence using the most common definition; however, the pooled maleto-female odds ratio was 1.26 (95% confidence interval 0.92-1.73) with significant heterogeneity (I 2 =96%, P<0.001), which was in contrast to previous clinical observations of female predominance in cough clinics. Conclusions: This study indicates two important issues in defining chronic cough in further epidemiological studies. A conflict between epidemiological and clinical definitions in duration criteria needs to be resolved. Another unexpected difference in the gender preponderance between the community and clinics warrants clinical validation of the existing definition. Background: The objective of this study is to investigate the physicians' approach to asthmatic or COPD patients, living in different areas of Turkey. In this report baseline demographics, risk factors, and adherence to therapy of asthmatic and COPD patients are compared. Methods: A total of 1892 newly diagnosed adult patients (1116 asthmatic, 776 COPD) from 136 secondary or tertiary centers of different geographic locations took part in this study, and a standard webbased questionnaire including items related with demographic, clinical, laboratory and pharmacological parameters was applied from July 2012 to May 2014. Results: Asthmatic patients were mostly female (64.4%), while the male patients were higher (88.1%) in COPD. The percentage of patients whose age is ≥65 years was significantly higher in COPD patients compared to asthmatic patients (30.4% and 7.1%, respectively) (p<0.001). Evaluation of the disease severity showed that nearly half of the asthmatic patients were in "moderate persistent" category (45.0%) and more than half of the COPD patients (54.4%) were in "GOLD B". More than half of both asthmatic and COPD patients had at least one accompanying disease (53.9% and 52.8%, respectively) and hypertension was the most seen disease in both asthmatic and COPD patients (13.9% and 21.1%, respectively) (p<0.0001). Nearly half of the asthmatic patients (45.5%) stated asthma and 13.7% stated COPD in their family history, while nearly ¼ of COPD patients stated COPD (22.2%) and 8.2% stated asthma. Evaluation of smoking anamnesis showed that there was a significant difference between asthmatic and COPD patients by means of "currently smoking" status; percentages were 27.9% and 56.3%, respectively (p<0.001). It is found that the percentage of COPD patients (37.0%) who have been exposed to dust, gas and/or vapor in work place was significantly higher than asthmatic patients (25.2%) (p<0.001). Evaluation of trigger factors showed that air pollution was the most common trigger in both asthma (54.1%) and COPD (54.6%) groups. Evaluation of adherence to the study visits showed that percentage of the patients coming to one control visit was higher in asthmatics compared to COPD patients (61.6% and 55.9%, respectively) (p=0.014). However, when groups were compared in terms of 3rd follow-up visit, adherence was low in both groups (20.3% and 18.7% for asthma and COPD). Compliance to the treatment in percentages of regular medication use was significantly better in COPD patients compared to asthmatic patients (p=0.021). Conclusion: COPD and asthma are associated with significant economic burden. Identification and reduction of exposure to risk factors are important in the treatment and prevention. Patient compliance may be the key to better disease management. We need new strategies to improve adherence in patients.


Changes in Pulmonary Function in the Treatment of Obesity in Children Keigo Kainuma Mie National Hospital, Japan World Allergy Organization Journal 2016, 9(Suppl 1):A247 Background: Associations between obesity and asthma in adults and children have been implicated but causal mechanisms, especially those related to respiratory physiology, are not well understood. We reported previously that obesity caused in abnormal reactance values in lung physiology. To further dissect the link, we analyzed changes in pulmonary function during the treatment of obesity in children. Methods: Eleven obese children (9 boys and 2 girls) from 8 to 15 years of age were enrolled in this study. 3 of them were hospitalized for more over 3months and the others were outpatients for 6 months. Eight had no asthma and 2 of them had asthma in mild intermittent severity without need of controller medications. Spirometry and two forced oscillation technique (FOT) tests (MostGraph® and Master Screen IOS®) were performed to assess lung function before and after treatment of obesity (diet and exercise). Patients were divided into two groups, the success group (n=5) and the failure group (n=6), based on outcome in weight loss. Success was defined as more than 10% improvement in percentage of overweight (POW) in the observation period.


The study was carried out in an accredited private medical laboratory in Mumbai, India. It involved retrospective data analysis on 545 sera, collected between 2013 & 2014, from patients with suspected allergic disease. Tests included Allergen specific IgE testing for 29 common food and inhalant allergens (ImmunoCAP, Ms. Thermofischer Phadia, Sweden) .335 sera had also been simultaneously screened using Adult Phadiatop TM (ImmunoCAP, Ms. Thermofischer Phadia, Sweden), while 210 were screened for Total IgE (Immulite, Siemens healthcare, USA). These were designated as Group I & Group II respectively. Both groups had similar age and gender distribution. Results 446/545 patients (81.8%) showed sensitization to at least 1 or more allergens. Multisensitization was common and seen in 73.2% sera. Most prevalent allergens were Housedust mite-D pternyssinus (58.5%), Cockroach (57.4%), Housedust mite-D farinae (56.8%), Shrimp (47.7%), House dust (45.13%), Weed Chenopodium album pollen (44.2%), Candida albicans (41.8%), Weed Artemisia vulgaris-Mugwort pollen and Wheat (32%).


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: This study revealed that ocular symptoms of Japanese cedar pollinosis are prevalent even in years with low cedar pollen dispersal, and that pollinosis patients with ocular symptoms were likely to have more severe nasal symptoms. Background: Adverse drug reaction (ADR) increases in-hospital stay, cost of care, and even mortality. Prevention of ADRs leads to marked socioeconomic benefits. We performed this study to investigate the incidence, actual reporting status and clinical features of ADRs, for improving ADR reporting system and preventing recurrent ADRs. Methods: A retrospective study was performed in a regional university hospital located in Jeju, Korea. ADR cases were recruited by review of medical records from 2009 to 2013. An ADR event was defined as either of ADR-related diagnosis in a patient or ADRs reported through in-hospital ADR reporting system. The incidence, culprit drug, clinical manifestation, source of reporting, severity, treatment, and recurrence rate were assessed. Results: In 1112 patients, 1375 ADR events were enrolled, estimated as 0.06% of total patient-visit during the study period. Diagnostic contrast agent (46.4%) was most common as culprit drugs, followed by antibiotics (22%), non-steroidal anti-inflammatory drugs (9.9%), and opioids (4.5%). Cutaneous involvement (67.5%) such as rash and hives was the most frequently observed manifestation. In two thirds of ADR cases, additional medical attentions were noted. In severity, 180 (13.1%) were categorized in severe ADRs. Nineteen (1.4%) experienced re-exposure to the culprit drugs, resulting recurrent ADR and 4 (0.3%) died of ADRs. Physicians were the most frequent ADR reporter using in-hospital ADR reporting system. Conclusions: Large proportions of ADR events might be omitted in medical records or in reporting system. ADRs due to re-exposure to the culprit drugs were not rare. To prevent avoidable ADRs, an effective reporting and alerting system is necessary. Background: To analyze related risk factors and features of food allergy in Korea children through a cross sectional survey. Methods: We used a stratified cluster sampling design and chosen from a random sample of 45 primary and 40 middle schools in South Korea between October and November 2010. Total 7,725 children aged 6-7 years and 13-14 years were involved. We acquired that the information of food allergy from the questionnaires and analyzed the mean value of continuous variable (Total Ig E and Eosinophil count) and the risk factors which were associated with food allergy using multivariate logistic regression.
Results: The prevalence of food allergy in this study was 13.4% and the mean age at the beginning of the first allergic symptoms was 58.4 ± 41.9 months . The most common food, cause of allergic symptoms, was egg (21%) and following order common cause for food allergies symptoms were fruits, shellfish, and milk in the sequence. The mean total Ig E level and eosinophil count was higher in food allergy group ( Background: "Allergy march" is a postulated progression of allergic disease in infants with food allergy associated atopic dermatitis (AD) to subsequently develop asthma and allergic rhinitis (AR), evidence of which were mostly from the European countries. It was unclear how it presents in Chinese children. In this pilot study, we aim to investigate the prevalence of allergic diseases in previous AD infants, to assess the children's sensitization profiles of inhalant and food allergens in pre-school ages.
Methods: During the year of 2008 to 2010, 69 infants were diagnosed with food protein allergy (FPA) associated AD in Beijing Children's Hospital through clinic. Follow-up of these subjects was performed in their pre-school ages. Medical histories related to allergies during toddler's and pre-school ages were acquired through questionnaires. Serum specific IgE levels were tested for both food and aeroallergens. Skin prick test of aeroallergens was also performed.
Conclusion: A considerable proportion (34.55%) of FPA associated AD infants develop AR or asthma by pre-school ages. Most of the food sensitized infants will outgrow it 4 or 5 years later, while tend to evolve to aeroallergens sensitization, usually from a negative result in infancy. By pre-school years, children with moderate to severe sensitization to aeroallergens are more vulnerable to respiratory allergic diseases than others. Persistent AD might be an independent risk factor for developing AR or asthma. Background: The function of innate receptors including toll like receptor (TLR), conventionally recognized for their antimicrobial effects, has recently been extended to include epithelial barrier regulation. TLR 2 activation was shown to aid tight junction (TJ) repair in atopic dermatitis (AD). However, the role of other TLRs in modulating epidermal barrier in vitro and in vivo remains poorly understood. We investigated the changes of TJ proteins following the activation of TLR 1 and 6 by house dust mite (HDM). Methods: Firstly, the mRNA levels of TLRs and TJ elements were assayed using real-time RCR in epidermal keratinocytes and a murine model with AD-like lesions activated by HDM allergens. The association between specific TLR activation and the changes of certain TJ proteins was studied in TLR deficient mice.
Conclusions: Our data demonstrate that the innate immune activation of the keratinocytes by HDM allergens may lead the preservation of TJ integrity. Rationale: As required by the EMA and the US FDA for pivotal trials involving allergen immunotherapy (AIT) products, clinical efficacy assessment is currently based on DBPC field studies with natural allergen exposure. Problems with the field studies include the variability of allergen exposure in different trial sites, the uncertainty of time exposure and confounding environmental factors. A novel mobile Allergen exposure chamber was designed to operate with stable and reproducible allergen exposure under standardized environmental conditions. To be accepted as an appropriate alternative to natural allergen exposure for clinical trials the clinical validation of the Exposure Chamber must document that the symptoms provoked in the chamber reflect the kind and severity of symptoms in real-life. Methods: To determine the pollen-induced allergic nasal, eye and bronchial symptoms and their severity in real life we used data from patients suffering on rhinitis reported by using an electronic "patient hay-fever diary" (PHD) since 2009-2011 in a public app (Pollen App 3.0). For each organ and their symptoms a severity score of from 0 -3 is possible, resulting in a total symptom score (TSS) of 12. Also, comparisons of symptoms with pollen concentration in their surrounding leading to a "symptom load index" (SLI) were used to define the severity of "real-life symptomatology" in pollen allergic patients. In the chamber birch and grass pollen allergic adults were exposed to different birch and grass pollen loads (4.000 to 8.000) for 90 -240 min outside the pollen seasons. Spirometry, FeNO and nasal secretion was measured before and after exposure. Nasal, conjunctival and bronchial symptoms were recorded each 10 min, peak-flow and peak nasal inspiratory flow every 30 min. Results: Using > 60.500 data sets from >1.600 PHD users the mean TSS for 2009 to 2011 in Germany was calculated with 3.0 to 5.4 for birch seasons and 3.9 to 4.4 for grass seasons. The SLI (TSS) was calculated on a total of 293,098 data entries ranging for birch season from 4.5 to 5.6 and for grass season from 3.4 to 4.7 points. The repeated exposures with birch and grass pollen with 4000 -8000 grains/m3 elicited reproducible symptoms on all 3 organs and significant differences between placebo and verum pollen exposure. Generally, the symptoms started to occur after 10 min and reached a plateau following 70 -90 min of continuous exposure. The TSS for birch pollen reached an average of 5.8 and for grass 6.5 points.


The study analyzed the histories of 79 patients with contact eczema: 61 women in age 18-83 years (mean age 46.5 years) and 18 men in age 22-80 years (mean age 54.3 years). The most common locations of contact eczema were hands (n = 28; 35.4%) and faces (n = 22; 27.8%). Positive patch tests results were obtained in 29 (36.7%) patients, the majority in patients with hands (n = 12; 42.8%) and faces (n = 6; 27.2%) contact eczema. The most common sensitizing haptens were nickel sulfate (n = 16, 55.1%), para-phenylenediamine (n = 13; 44.8%) and potassium dichromate (n = 12; 41.3%). Prick tests with inhalant allergens were performed in 65 patients and with food allergens were performed in 29 patients. In 27 (41.5%) patients were registered positive skin prick tests results to inhaled allergens, in the majority of patients with hands (n = 13; 20%), faces (n = 7; 10.7%) and the upper limb (n = 4; 6.1%) contact eczema. Food allergy was diagnosed in 6 (20.6%) patients, 2 (33%) of patients were with hands, faces and feet contact eczema. Among the inhaled allergens, the most sensitizing were D. Farinae, D. Pteronyssimus and grass, while the most sensitizing food allergens were celery, pepper and flour.


With this case, we wanted to point out that ornidazole, a commonly used anti-infection agent, can be the cause of fixed drug eruption in some cases. Also, it should be noted that fixed drug eruptions can occur for multiple drugs in the same patient. Background: Atopic dermatitis (AD) is characterized by skin barrier dysfunction. Few studies have used non-invasive skin measurement techniques to measure epidermis function in asymptomatic neonates. We therefore conducted a post-hoc analysis to determine whether skin barrier function in the first week of life predicted AD development and allergen sensitizationby age 32 weeks.


Methods: Data of 116 infants collected during our previous randomized controlled study were analyzed. Skin barrier function was measured through transepidermal water loss (TEWL), stratum corneum hydration (SCH), and pH. Study participants were divided into 2 groups based on the results of Cox regression analyses of skin measurement values and cumulative AD incidence by 32 weeks of age. A Kaplan-Meier analysis and log-rank test were used to analyze skin barrier function and cumulative AD incidence. Allergic sensitization based on IgE levels to egg white and ovomucoid at 32 weeks of age was assessed by a Chi-squared test.


The Certain tendencies depending on types of allergens were foundsensitization by indoor allergens were high but did not indicate age-based differences, while sensitization by outdoor allergens tended to grow with age. In addition, total lgE presented difference between age under 7 groups (≤3, 4~6) and age over 7 groups (7~9, 10~12, 13~15, 16~18) with statistical significance (p<0.001) and increased with age in general, with boys showing significantly higher lgE titer than girls (p<0.001). Conclusion: The sensitization in children with allergic rhinitis was changed with age in some allergens by CAP test. Results: Out of 19 children aged 2-20 years old, 9 (47%) tolerated baked milk product (50mL containing muffin) and 10 reacted. There were no significant differences in mean age, gender and history of milk-induced anaphylaxis between two groups. In children tolerated baked milk, specific IgE titers to milk, casein and alpha-lactoalbumin were significantly lower, but not to beta-lactoglobulin. Furthermore, each component-specific IgE/IgG4 ratio was significantly lower compared to children who reactive to baked milk.

Clinical Characteristics of Anaphylaxis in Korean Childrens

Taek Although, cardiovascular symptoms of anaphylaxis were rare in young children (7.7%), cardiovascular symptoms were increased with age. Cardiovascular symptoms were common in reactions caused by insect sting(50.0%). The mainstay of first-line treatment in hospital included antihistamine (61.2%), corticosteroids (42.2%) and epinephrine(34.0%). Epinephrine auto-injectors were prescribed for 26.6%. Conclusion: We identified differences in the symptoms of anaphylaxis according to age and triggers. Rate of use of epinephrine as the first-aid medication is too low, and prescription rate of adrenalin auto-injector is too low regardless of age of patients.


Immunological Results: Among a total of 2,140 subjects, five subgroups identified through k-means clustering include putative "near-normal (n=232)", "asthmatic (n=392)", "COPD (n=37)", "asthma-overlap (n=893)" and "COPD-overlap (n=586)" subtypes. Among five subgropus, near-normal subgroup showed the oldest mean age (72±7 years) and the highest FEV 1 (102±8% predicted), and asthmatic subgroup was the youngest (46 ±9 years). Asthma-overlap subgroup had the lowest FEV 1 (77±9% predicted). COPD and COPD-overlap subgroups were male-predominant (100% and 98%, respectively) and all current or ex-smokers. When applying the lower limit of normal FEV 1 /FVC as a criterion for airway obstruction, asthma group showed the highest prevalence of airway obstruction. While COPD, asthma-overlap and COPD-overlap subgroups showed high prescription rate of respiratory medicine, asthmatic subgroup had the lowest prescription rate despite the highest proportion of self-reported wheezing. Except asthmatic subgroup, comorbidities such as hypertension, diabetes mellitus, hyperlipidemia and coronary artery disease were frequently observed. Although COPD subgroup represents only 2% of total subjects, they showed the highest mean medical cost and health utilization, comprising 5% of the total cost. When calculating a ratio of total medical expense to household income, mean ratio was the highest in COPD subgroup. Conclusion: Subjects with mild to moderate airflow limitation exhibited clinical and epidemiological heterogeneity. Each subgroup may have a different level of demand for health resources. A 7-year-old boy with acute osteomyelitis in right distal tibia, was treated by the combination of intravenous (IV) vancomycin and cefotaxime. He was tolerable for the given treatment and rapidly improved. Persistent fever had occurred from the day 17th with pruritic, maculopapular rash on day 19 th . Laboratory test performed on day 20 th revealed marked eosinophilia. Under suspicion of DRESS syndrome, both IV antibiotics were stopped and oral prednisolone was given. Three days after the cessation of the antibiotics, fever and skin manifestations had rapidly improved. However, as soon as we retried IV cefotaxime, his skin manifestation had immediately flared up. Intradermal test performed at 6 weeks after complete-recovery, was positive for cefotaxime. Purpose: Asthma and atopic dermatitis are common chronic diseases and depression is an important comorbidity in allergic diseases. However, it is little known about the association between maternal depression and child allergic diseases. This study was performed to find the association between maternal depression and child allergic diseases. Methods: Data were acquired from 4695 family who participated in the Fifth Korea National Health and Nutrition Examination Surveys (KNHANES), which was conducted from 2010 to 2012.
Results: The prevalence of childhood asthma was 5.3 % and childhood atopic dermatitis was 14.1%. the prevalence of maternal depression was 3.6 %. In univariated analysis, maternal depressions was associated with single mother, low economic state, maternal asthma, atopic dermatitis, children's asthma. (p<0.05) but sex, age, education status and smoking were not associated with the presence of maternal depression. After adjustment, maternal depression were associated with lower house income, maternal asthma, maternal atopic dermatitis, children's asthma.


Purpose: Childhood asthma is common reason for the hospitalization and the deterioration of asthma accompanied with respiratory infection. The burden of treatment asthma is high around the globe also in Asia and the assessment of asthma exacerbation in children is difficult and limited. We aimed to investigate the factors associated to hospitalization period in those were inpatients of pediatric asthma. Methods: We conducted the chart review of subjects admitted with asthma exacerbation from 2009 to 2014, retrospectively. The subjects consisted of the patients at the age under 18 years visit a single tertiary Hospital. We investigated the characteristics of those patients including clinical symptom and laboratory tests (serum total immunoglobulin (Ig) E, eosinophil counts). We assess the severity of asthma by Pulmonary Score (PS). We assessed the duration of hospitalization to related factors by using bivariate correlation analysis and multiple linear regression analysis using SPSS 20.
Results: A total of 357 subjects with 232 (65.3%) boys and the median age was 5.77 ± 6.1 years old. The mean of hospitalization period were 4.0 ± 1.9 days. The rate of total IgE over than 45 IU/mL was 66.9% and eosinophil count over than 470 /μL was 26.6%. The mean PS was 3.5 ± 1.1 days. The infiltration of chest radiography were 74 cases (20.7%) and body temperature over 38.3°C were 91(25.5%). The duration of hospitalization was correlated with age (p=0.036, r=0.11). In simple linear regression, PS score positively related with the duration of hospitalization but was not significant (β=0.127, R 2 =0.037, p=0.16). In multiple linear regression model, the duration of hospitalization was positively related the infiltration finding of chest radiography (β=0.962, p=0.008) and age (β=0.082, p=0.03) with R 2 =0.052, independent of fever, c-reactive protein, PS, past history of allergy, family history of allergy, elevated IgE and eosinophil count, multiple allergen sensitization and past history of visiting or admitt from asthma exacerbation.
Conclusions: Hospitalization period in pediatric asthma patients has positively correlated with the infiltration finding of chest radiography and no association with PS, total IgE and eosinophil counts. It could be implied that the prediction of morbidity of asthma exacerbation in children has to include the findings on chest radiography that presents respiratory infection. Also, new asthma severity score system for hospitalization of pediatric asthma patients would be needed. Acute eosinophilic pneumonia (AEP) is a rare disease characterized by acute febrile respiratory insufficiency, marked eosinophilia in bronchoalveolar lavage fluid (BALF), diffuse bilateral and thickening of interlobular septa on chest radiographic findings. Pathogenesis is not well understood, however direct or indirect exposure to smoke has been repeatedly reported as a cause of AEP. We present a case of 16-year-old boy, who developed an idiopathic AEP with no peripheral eosinophilia, marked eosinophilia in BALF (36.6%), decreased DLco (75%), typical radiologic findings, and dramatically improved after corticosteroid treatment without use of antibiotics. Despite best efforts, no evidence of infection was found. Although he initially denied a current smoking, we repeatedly asked the previous history of smoking cigarettes. He finally told the truth that he had started to smoke 19 days before hospitalization in an enclosed area with friends, and gradually increased smoking-dose. Conclusively, we suggest that no peripheral eosinophilia does not exclude an AEP, and clinical suspicion with exact history taking and radiologic findings, and early BALF exam will be the best approach to avoid use of unnecessary antibiotics and for the proper management. Leukotriene receptor antagonists have been increasingly used in the treatment of a variety of allergic diseases such as asthma, allergic rhinitis, chronic urticaria, and others and they are generally considered safe drugs with few adverse drug reactions. Type I hypersensitivity to montelukast has been rarely reported, with only a handful of anaphylaxis cases being reported worldwide. There is a lack of information about the severe adverse drug reaction associated with pranlukast. We experienced an extremely rare case of severe hypersensitivity reaction associated with pranlukast. A 65-year-old woman developed anaphylactic shock presented with generalized urticaria, angioedema, collapse and loss of consciousness after taking pranlukast, and which was confirmed by oral challenge test and skin prick test. The present case reminds that pranlukast can induce anaphylaxis, which is mediated by IgE-dependent pathway. Obesity is a known risk factor for the development of asthma and obese asthmatics are prone to be severe and poorly controlled. Obesity is also associated with increased risk of various metabolic diseases but recent studies suggested that not all obese subjects are at increased risk of such diseases and the 'metabolically healthy obese' (MHO) phenotype may exist in the absence of metabolic abnormalities. Due to the paucity of data regarding asthma-related outcomes of obese asthmatics according to their metabolic status, we aimed to investigate the differences between MHO and metabolically unhealthy obese (MUO) asthmatics in terms of asthma-related clinical outcomes.


The Background: The effective management of atopic dermatitis (AD) adjusted to individual clinical courses and demands can be challenging for both patients and physicians. Understanding of actual situations, experienced and perceived by patients with AD and their caregivers, is essential to improve clinical outcomes and satisfaction in real practice.
Methods: This multi-center survey was conducted in patients with AD or their caregivers from 9 centers with questionnaires on diagnosis and management of AD. Results: A total of 324 patients and caregivers participated in the study. Initial diagnosis of AD was mostly made by physicians (80.6 %), followed by self-diagnosis. Patients and caregivers believe that allergic substances such as house dust mite, food, pollution are responsible for AD development. Allergy tests were performed for 194 patients (59.9%), but allergen avoidance strategy was instructed in only 81 subjects (25.0%). Regarding the measures of AD management, they thought that moisturization, environmental control, improvement of body constitution are important. Major topical medications are steroid (81.8%) and topical immunomodulators (34.3%), while systemic medications include systemic steroid (42.6 %), anti-histamines (36.4 %), and cyclosporins (2.8 %) . 181(55.9%) subjects have tried complementary alternative medicine including Oriental medicine. Many subjects wished for personalized management, use of specialized institutions for AD, and evidence-based, effective, and sustainable treatment to be incorporated in their sessions. Conclusion: Our findings suggest there is still an unmet healthcare need for patients with AD in real practice. Customized, evidencebased, and multi-disciplinary approach including therapeutic patient education should be implemented to achieve the best possible outcomes. A) Background: To evaluate the IgE reactivity profiles to purified house dust mite (HDM) allergen molecules (i.e. nDer p 1, rDer p 2 and rDer p 10) in Korean allergic rhinitis (AR) patients. Also, symptomatic and serologic changes after sublingual immunotherapy (SLIT) were analyzed according to positive IgE profiles. B) Methods: Sixty AR patients already diagnosed to have HDM allergy were analyzed for the presence IgE antibodies against nDer p 1, rDer p 2, rDer p 10 and native Dermatophagoides pteronyssinus (Dp). Symptom scores and laboratory tests were followedup after SLIT. C) Results: Prevalence rates of IgE for Dp, Der p 1, Der p 2 and Der p 10 were 100%, 98.3%, 93.3% and 8.3%, respectively. After one year of SLIT, symptom scores and laboratory findings improved but did not show significant difference between Der p 10-positive and -negative patients. D) Conclusions: In Korean AR patients, specific IgE to Der p 1 or Der p 2 presents in most of Dp-allergic patients, while reactivity to Der p 10 is very low. Changes in symptom and serology after SLIT (not containing the allergen Der p 10) did not differ much between Der p 10-positive and -negative patients. Background A history of beta-lactam (BL) hypersensitivity is one of the most encountered problems in clinical practice and limits its further use. Determining whether patients with BL allergy could safely receive beta-lactams can be a difficult task. We summarize data from patients with a presumed allergic history to BL who underwent drug allergy verification and report the actual allergic rate.


Patients with a history of an immediate reaction or undetermined allergic onset to beta-lactams, who underwent BL hypersensitivity evaluation at King Chulalongkorn Memorial Hospital, Bangkok between 2012 and 2015, were retrospectively reviewed. The verification process was conducted according to the updated parameter on drug allergy included skin testing with both major and minor determinants of penicillin, amoxicillin, clavulanate, and/or the culprit BL. Intradermal test (IDT) was performed after negative skin prick test (SPT), and oral challenge test (OCT) was then carried out in patients who gave informed consent. Serum penicilloyl-and amoxycilloyl-specific IgE levels have also been evaluated. Results A total of 86 patients (mean age 40.7 years) were included. Forty-eight patients (56%) were female and 42 patients (48.8%) had underlying medical illnesses. Most patients have allergic history to penicillin (45.4%) or amoxicillin (29.1%). Sixty percent of patients developed symptoms within 2 hours. The majority experienced skin symptoms; urticarial rash (24.3%), angioedema (21.4%), and maculopapular rash (20%), while 3 patients reported anaphylaxis. BL allergy was confirmed in 7 patients (8.1%); identified by positive skin tests in 2 patients, positive specific Ig-E levels in 3 patients, and positive OCT in 4 patients. For those with positive skin tests; one had positive SPT but negative Ig-E levels and another one had positive results for both IDT and specific Ig-E levels. Sixty patients (71.4%) were underwent OCT and 54 patients (90%) demonstrated negative challenge. Serum specific IgE levels were determined in 46 patients and 44 of them (95.7%) showed negative results. Mild non-immediate reactions developed in 4 patients upon OCT after negative skin tests.


The respondents were comprised of nurse teachers (44%), general education teachers (32%), nutrition teachers (5%), assistant principals (10%) and principals (10%). Those who were negative about administering AAI to students accounted for 10.8% of total. The percentage differed significantly between different specialties/positions; nutrition teachers had the highest percentage (16.7%), followed by general education teachers (15.9%), nurse teachers (10.6%), assistant principals (8.1%) and principals (2.7%). The most frequent factor behind the uneasiness about the use of AAI was "the timing of AAI administration" (69.4%). By teaching specialty/position, a greater number of nurse teachers were concerned about "collaborating within the school" and "collaborating with a hospital" than teachers in other specialties/positions. Comparing between the group with negative attitudes and the group with positive attitudes toward AAI administration, the former was significantly more worried about "how to use AAI" (odds ratio [OR]: 2.1), "the timing of AAI administration" (OR: 02.9), "collaborating with the parents" (OR: 01.6), "the act of injection itself" (OR: 3.1) and "violating the laws" (OR: 3.5).


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.
Conclusion: This provides evidence that heavily increased levels of traffic-related pollutant are associated with poorly controlled asthma among the adults during cold period. Results: A total 991 cases (66% male, mean age 5.89±5,24) were reported, with 36.6% below 2 years of age. Food was the most common cause (74.7%), followed by drugs and radiocontrast media (10.7%), idiopathic (9.2%), and exercise (3.6%). The most common offending food allergen was milk, followed by egg white, walnut, wheat, buckwheat, and peanut. Milk was the most common trigger of anaphylaxis in young children. In older children, seafood was the most common trigger of anaphylaxis. The rate of drugs in triggers of anaphylaxis was increased by age. Conclusion: Food was the commonest trigger of anaphylaxis in Korean children. The common triggers of food induced anaphylaxis have changed over time in Korean children. Background Acute bronchiolitis is a common cause of hospitalization in children and has been identified as a risk factor of respiratory failure in young infants. There are few studies for determines the severity of acute bronchiolitis that may be helpful in the initial assessment of these infants.


We enrolled 51 hospitalized infants, all under 12 months old (3.79±2.64 months of age) and 66% were male (n=34). Mean body weight at admission was 7.11±1.88 kg. The mean (±SD) duration of hospitalization was 5.67 ±2.2 days and it had positive relation with BSS (P<0.05). There were significant association between BSS and maternal allergy, height and age (p<0.05). However, no significant association was observed between BSS and body weight, amount of increased weight from birth and infected virus.


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,