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Results

In phase 1, the questionnaires were distributed to 96 trainees. The response was 98% (94 responses), 55 females and 39 males. 84 trainees (89% ) reported knowing how to treat and a total of 44 (50%) claimed not being trained at all. Epinephrine was selected as a life saving drug by 89 (94%). IM as a route of administration was selected by 76 (80%). Correct Epinephrine concentration was known by 77 (83%). For phase 2, questionnaires were distributed to 94 trainees who responded to the stage 1 and the response rate was 89% (84). 84% claimed they heard about Epinephrine Autoinjector, 5 fellows claimed they never heard about it. 72% claimed knowing when to use it .23 (27%) did not know, 9 of them were Fellows. Anaphylaxis was the case of using it in 71%. Only 43 (51%) know the right location and the method of injection. Sub Cutaneous injection was selected in 20 (23.8%).

A99

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.

A122

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.

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.

Conclusions

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

A201

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

A207

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.

Conclusion

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

Conclusions

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

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

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

Conclusions

These findings reaffirm that HND is a clinical subtype of AD that needs distinction from classical AD. In the future, further investigation of skin microbiome and inflammatory factors involved in vasculatures of facial lesions in AD will lead to development of potential therapeutic targets. Background: MicroRNAs (miRNAs) modulate gene transcription in response to environmental stressors and other stimuli. A role for miRNAs in inflammation and immunity has been demonstrated and further evidence suggests that miRNAs also play a role in atopic dermatitis. In this study, we hypothesized the immune suppression using miR-432 would be induced therapeutic effects on atopic diseases. Methods: The Ig-E, Interleukin-4 (IL-4), CCL22 and interferon-g (IFNg) were examined after treatments with miRNAs in murine atopic model. In addition, atopic patient's blood samples were collected and examined for miRNA expression. Results: miR-432 reduced CCL22 chemokine gene in activated lymphocytes. In mice with a cutaneous disease similar to atopic dermatitis, Interleukin-4 was inhibited and interferon-γ was induced after treatments with miR-432. Furthermore, miR-432 levels were suppressed in the atopic patients. Conclusions: miR-432 suppressed Th1 immune responses and induced therapeutic effects in atopic mouse model. A) Background: Cross-reaction between food and inhalant allergens usually show mild symptoms. However, severe asthma symptoms, exercise-induced anaphylaxis, urticaria and "recall urticaria" at the site of immunotherapy injection may occur after ingestion of snails by patients allergic to house dust mites (1) . B) Methods: We report the case of a 23-years old woman who suffered from an acute severe asthma attack complicated by asphyxic evolution leading to cardiopulmonary arrest. Cardiopulmonary resuscitation was successful, subcutaneous emphysema occurred, left pneumothorax was treated by chest tube. The clinical course was benign, and the patient returned from hospital to home after a few days with no complication. Medical history revealed that she had had asthma for 10 years, with allergy to inhaled allergens (grass pollen, house dust mites, pets dander). She had been treated 9 years earlier by subcutaneous specific immunotherapy against house dust mites for 2 years. Medications taken included albuterol, beclomethasone, salmeterol and montelukast. She ate Norway lobsters and snails 5 hours before the beginning of acute severe asthma attack and had sexual intercourse with no condom 3 hours before. C) Results: Skin prick tests (SPT, diameters of the wheals and flares in mm) and serum specific Ig E (SSIg E, Pharmacia Unicap 1000) confirmed sensitization against snails (SPT = 7/30; SSIg E 7,37 kUI/l) but not against Norway lobsters (SPT = 0/0; SSIg E < 0,35 kUI/l) nor human seminal fluid (SPT = 0/0; SSIg E < 0,35 kUI/l). No Ig E sensitization was later found against prawn nor house dust mites tropomyosin (rPen a 1 < 0,35 kUI/l, Pharmacia Unicap 1000 ; rDer p 10 < 0,10 kUI/l, Phadia Immunocap 1000). No severe asthma attack did occur thirteen years after beginning of eviction diet and continuation of asthma treatment. More than 100 cases of allergic symptoms after consumption of snails among patients allergic to house dust mites were published. These allergic symptoms may occur after the first ever ingestion of snails and may be life-threatening. They begin usually 5 to 60 minutes and rarely 1 to 5 hours after the ingestion of snails (1, 2) . Cross-sensitivity between snails and house dust mites is probably due to common epitopes as haemocyanin. D) Conclusions: Allergic patients to house dust mites should be informed about the possibility of severe cross-allergy symptoms after eating snails. Background: Distinctive pattern and diversity in early intestinal colonisation are shown to influence immune maturation and potentially development of allergic disease. We recently demonstrated that prenatal supplementation with Lactobacillus rhamnosus GG (LGG) during late pregnancy can influence infant gut colonisation by particular Bifidobacterium species directing towards healthy infant-type microbiota. We investigated whether this early-life gut colonisation with Bifidobacterium species is associates with systemic immune responses at 12 months of age. Methods: Faecal samples were collected from infants during the first 3 months of life. Bacterial DNA was extracted from the faecal samples and Bifidobacterium longum, B. lactis, B. breve, B. angulatum, B adolescentis, and B. catenulatum were detected by real time PCR. Infants' peripheral blood mononuclear cells at 12 months were stimulated with ovalbumin (OVA), heat-killed LGG (HKL) (the probiotic used in the original study), tetanus toxoid (TT), anti-CD3 or without stimulus. Cells were analysed by flow cytometry for markers of dendritic cells phenotype and regulatory T cell (Treg) numbers. Culture supernatants were analysed for IL-4, IL-6, IL-10, IL-13, IFNγ and TNF-α by multiplex ELISA, while TGF-β1 and IL-12p40 were measured using ELISA. Results: Colonisation with B. longum at day 7 of life was associated with significantly higher (p < 0.01) levels of Th1 cytokine (IFN-γ) and pro-inflammatory cytokines (IL-6 and TNF-α) and increased (p < 0.05) secretions of Th2 (IL-13) and regulatory cytokine (IL-10) in infants at 12 months. However, colonisation with B. adolescentis at day 3 was associated with higher secretion of IL-4 cytokine. A significantly increased numbers of Treg were observed in infants colonised with B. adolescentis at 7 days of age.

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

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

A First Case of Lymphocytic Interstitial Pneumonitis in Healthy Child

Ji-in Jung, Ha-Su Kim, Hyun-a Kim, Jin-a Jung Dong-a University Hospital, South Korea Correspondence: Ji-in Jung -Dong-a University Hospital, South Korea World Allergy Organization Journal 2016, 9(Suppl 1):A445 Introduction: Lymphocytic interstitial pneumonitis(LIP) is an uncommon histopathologic entity characterized by infiltration of the interstitium and alveolar spaces of the lung by lymphocytes, plasma cells and other lymphoreticular elements. LIP in children has been most commonly associated with human immunodeficiency virus(HIV) infection. We report a first case of LIP in a HIV-negative healthy adolescent. Case Report: An 13-year-old boy represented with pneumonia on chest X-ray in routine health examination. He had no respiratory symptoms and there was no abnormal findings on physical examination, A chest CT showed multiple ill defined centrilobular nodules and peribronchial air space nodules with mild volume loss in RLL. There was no increase of IgG Mycoplasma pneumoniae antibody titer in 3 serial tests between 7 days interval. Tuberculin skin test and Tbc specific antigen induced interferon-gamma(IGRA) test were negative. Chest x-ray in regular intervals during 6 months showed improvement of pneumonic consolidation, but new pneumonic consolidation on other site. Therefore, open lung biopsy was performed, and it showed diffuse interstitial lymphocyte infiltrate. The lung tissue was negative for EBV by DNAPCR and EBV serology showed all-negative. Serum immunoglobulins were normal and autoimmune studies were negative. The total lymphocyte count and lymphocyte subset were normal. He was started on oral prednisone (1 mg/kg/day) for 2 months and the chest x-ray returned to normal. Then he was tapered oral prednisone for 2 months and follow-up chest CT showed no abnormal finding. He has been followed for 8 months after diagnosis without complications. Conclusion: We report a first case of HIV-negative, EBV-negative LIP in a healthy child. Background: Epidemiological data from cohort studies indicate associations between Caesarean section and development of allergy in infants. Besides the delayed colonization of commensal bacteria (which in turn affect the immune system development), the cytokine profile in C-section delivered infants could be different, which may be implicated in infant's immunity. Methods: A clinical study was conducted at KK Women's and Children's Hospital, where 55 cord blood samples from Caesarean section-delivered infants were collected to evaluate the response to allergens in the cord blood cells. Freshly isolated cord-blood mononuclear cells (CBMCs) were cultured in a 96-well plate at 100,000 cells per well (in triplicate per condition) and stimulated with the extracts from either one of major house dust mite species: Blomia tropicalis (BloT) and Dermatophagoides pteronyssinus (DerP). Phytohemagglutinin (PHA) and Lipopolysaccharide (LPS) were used as positive controls. The supernatants of these cutures were harvested after 5-day stimulation and were analyzed using the Bio-Plex Pro TM Human Cytokine assay. The production of IL-5, IL-13, IFN-gamma and TNF-alpha by the allergen-stimulated CBMCs were analyzed.

A457

Methods: We performed a randomized, placebo controlled trial in adult subjects meeting the research criteria for CRS, with low serum vitamin D levels (<40 ng/mL), and having no contraindications to vitamin D therapy. Subjects were randomized to receive vitamin D (n=12) or placebo (n=12) for 12 weeks in addition to their standard regimen. Peripheral blood mononuclear cells (PBMCs) and nasal epithelial cells (NECs) were collected at the beginning and end of the trial and we analyzed the upregulation of molecules involved in mucosal immunity by RT-PCR. Clinical response was analyzed using SNOT-22 and the SF-36. Results: The Levels of vitamin D in the serum were elevated in the vitamin D group and unchanged in the placebo group. Cathelicidin, human b-defensin and autophagy related protein light chain 3 alpha (LC3A, a molecule involved in autophagy) were upregulated after vitamin D administration in PBMCs with similar results observed in NECs. There was no significant change in the upregulation of these mediators in the placebo group. No symptomatic changes were observed in SNOT-22 or SF-36 scores in either group. There were no side effects or adverse events during the study. Background: Systemic contact dermatitis (SCD) is an inflammatory skin disease that may occur in persons with contact allergy when they are exposed to the allergens systematically including orally, transcutaneously, per rectum, intravesically, intravenously, or by inhalation. The most common causes of SCD are drugs used both topically and systemically. Other causes are ubiquitously occuring haptens, such as the metals nickel, cobalt, gold, and chromate, and aromatic substances such as spices. SCD from plants has been seen following ingestion of various rhus preparations. In Korea, Rhus has been used as a folk medicine to cure gastrointestinal diseases and as a health food, it is common to observe patients with accidental or occupational Rhus dermatitis, and also SCD caused by ingestion of Rhus. Objective: We investigated the clinical features of SCD caused by Rhus. Methods: We conducted a retrospective analysis of 11 patients with SCD caused Rhus in Dong-A University hospital and Haeundae Paik Hospital. Results: Nine (81.8%) were women, and average age was 58.91 ±10.29 years (range 45-75). The way of Rhus ingestion was boiled chicken with Rhus (n=9, 81.8%), Rhus vegetables (n=1), and Rhus sap (n=1). All patients experienced generalized pruritus and erythematous maculopapular rash. The patients developed erythema multiforme (n=2), vesiculobullous lesion (n=3), urticaria (n=3), and angioedema (n=1). Extracutaneous symptoms were duodenal ischemia (n=1), hypotension (n=2), fever (n=4), and oral mucositis (n=1). The mean latency period was 1.45±0.69 days (range 1-3), and mean recovery times were 12.27±3.77 days (range [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] . Systemic corticosteroid was administered in 10 (90.9%) for 18.09±15.44 days (range 4-47). Conclusions: SCD from ingestion of Rhus showed various cutaneous manifestation mainly erythematous maculopapuar eruption, and also extracutaneous symptoms. Most of the patients recovered well with the treatment of systemic corticosteroids. Background: Atopic dermatitis (AD) is currently regarded as an allergic inflammatory disease. Many studies have shown AD to have multiple causes that activate complex immunological and inflammatory pathways. However, aeroallergens, and especially the house dust mite (HDM), play a relevant role in the elicitation or exacerbation of eczematous lesions in many AD patients. Accordingly, allergenspecific immunotherapy has been used in AD patients with the aim of redirecting inappropriate immune responses. Sublingual immunotherapy (SLIT) is especially preferred because of its easy application and safety. The aim of this study was to describe the effect of SLIT in patient with AD. Methods: Patients with AD who allergic to HDM were evaluated. Patients who allergic to HDM have been treated with SLIT for over 1yr. The effect of patients on clinical course of SLIT with Dermatophagoides pteronyssinus and Dermatophagoides farinae in a standardized extract was assessed and the side effect of SLIT were recorded. Results: The records of 20 patients (13 males and 7 females) were studied. The mean age for starting SLIT was 16.3 years (aged 6-36 years, median age 13years). Treatment was deemed effective or very effective in 70% of the patients. The majority of the patients were satisfied with their treatment, which was well tolerated. There were no serious side effects except transient nausea, abdominal pain and oral itching sensation in the first few days. SLIT had to be discontinued in 2 patients (10%) because of exacerbation of asthma and dermatitis. Especially, the compliance of patients with AD and allergic rhinitis were better than patients with AD only. Conclusions: SLIT reduces symptoms of AD, the amount of drug consumption and the progression of the disease. Especially, SLIT is recommendable to patients with AD and allergic rhinitis. We believe SLIT can be an alternative, safe treatment option for allergic AD refractory to long-term conventional treatment. Background: Adverse drug reactions (ADRs) frequently occur in hospital setting, and serious ADRs (SAEs) may threaten the patient's life and lead poor clinical outcome. Early detection and urgent medical intervention is required to prevent development of SAEs. This study was conducted to investigate the clinical characteristics of SAEs in a single university hospital. Methods: ADRs reported to hospital Pharmacovigilance Center were collected from Jan 2012 to Dec 2014, and cases of SAEs were selected. Clinical information was collected from electronic medical records. Results: A total of 283 (3.7%) SAEs among 7,629 ADRs were identified through spontaneous reporting system. A gradually decreased tendency in the frequency and incidence of SAE was noted from 2012 to 2014. SAEs were reported by doctors (40.6%), nurses (11.0%), and pharmacists (48.4%). ADR related-hospitalization or prolongation of existing hospitalization (53.2%) was the most common cause of SAEs, and other medically important event was the second cause. SAEs were developed from the injections (54.4%), PO medications (44.9%), and the patch type agents (0.7%). Antineoplastic agents (40.9%), anti-infectives (16.8%), and anti-tuberculosis drugs (6.9%) were the drug class commonly involved. White cell and RES disorders (21.6%) were frequently involved system organ classes, and skin and appendages disorders (16.4%) were the next. Leukopenia and neutropenia were the most frequently noted SAEs. Conclusion: Antineoplastic agents, anti-infectives, and anti-tuberculosis drugs can elicit SAEs most frequently. A decreased tendency for the development of SAEs was noted, and this might be result at least partly from the pharmacovigilance activity and ADR monitoring. Comprehensive prophylactic approaches will be required to prevent development of predicted SAEs, and to reduce the chance of unpredicted SAEs. Background. Allergic contact dermatitis is a common diagnosis in eyelid dermatitis. Sensitization to metals are prevalent in eyelid dermatitis and color cosmetic products are frequently suspected as the source of metal exposure. This study was performed to investigate the recent contact allergens for eyelid dermatitis and to assess metal contents in eye shadow products. Methods. Data were collected in the department of dermatology of Ewha Womans University hospital from December 1998 to February 2014. A total of 983 patients were patch tested during the period and 67 patients had eyelid dermatitis among them. To examine metal elements in color cosmetic products for eyes, randomly selected 10 eye shadows were analyzed. Results. Frequent allergens were metals, thimerosal, and phenylenediamine in patients with eyelid dermatitis. The sensitization rates of individual allergens were not significantly different between patients with eyelid dermatitis and without eyelid dermatitis. All 10 eye shadow products contained more than 5 ppm of at least one element, nickel, cobalt or chromium. Conclusion. Metals were top-rank allergens in eyelid dermatitis and eye shadow products contained significant amount of nickel, cobalt or chromium to elicit allergic reactions. Patients with eyelid dermatitis and metal allergy should be informed that color eye make-up products can elicit or aggravate their symptoms. Background: Recent studies suggest that dietary change may influence programming of the immune system in favor of development of allergic disease. However, the results for the effect of fat status on development of allergic or respiratory disease in children are still conflicting. Methods: A total 426 children were included in this study from a birth cohort in South Korea. Data regarding the children's allergic and respiratory outcomes were obtained from standardized questionnaires completed by the mothers. Serum total cholesterol, triglyceride (TG) and high-density cholesterol (HDL) levels were measured in children at 24 months of age. Atopic biomarkers including total Ig E, IL-10 and eosinophil counts were also measured at 24 months. Results: Serum HDL cholesterol levels were inversely associated with the eosinophil counts counts (r = -0.221, P < 0.001). Total IgE, eosinophil counts, and IL-10 levels increased significantly in the group whose serum HDL cholesterol levels was above the median value (51mg/dL) compared to the other counterpart group (P = 0.014, P = 0.003, P = 0.040 respectively). However, there was no association between lipid levels and risks of respiratory outcomes and AD at 24 months in logistic regression analysis. Conclusions: We found that the HDL cholesterol levels were associated with lower atopic biomarkers in children at 24 months, but not with risk of allergic or respiratory diseases. Interleukin-32 (IL-32), first reported as an inducer of tumor necrosis factor-α, is a pro-inflammatory cytokine involved in various chronic inflammatory diseases. This study evaluated the relationship between sputum IL-32 expression and severity of asthma. Methods IL-32 was determined in induced sputum samples of patients with asthma (n = 137) using sandwich ELISA. Relationships among sputum IL-32, airway obstruction (FEV 1 ), inflammation (neutrophil and eosinophil % of the airway) and exacerbation frequency were evaluated.

A476

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

Background

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

Results

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

Conclusions

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

A3

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.

A17

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.

A22

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.

A28

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.

A34

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

A36

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

A54

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.

A62

Infantile eczema is associated with campylobacter and roseburia subpopulations but not microbial diversity in stool samples of Chinese newborns Ting Fan Leung 1 , Jamie Sui-Lam Kwok 2 , Christine Kit-Ching Tung 2 , Man Fung Tang Background: Gut microbiota is increasingly recognised to play crucial roles in the pathogenesis of asthma, obesity and autoimmune diseases. Faecal microbiome is likely ethnic and diet-specific, but such data is lacking in Asians. This study characterised faecal microbial compositions of Hong Kong Chinese infants. Methods: Random stool samples were obtained from 4-week-old infants with eczema (n=15) and without any allergy (n=15) at 9 months. Genomic DNA extracted by PowerSoil DNA Isolation Kit (MO BIO Laboratories) was sequenced using Ion PGM Seqeuncing 200 Kit v2, Ion 318 TM Chip v2 on Ion PGM System (Ion Torrent). Reads from each patient were filtered for low quality (Phred <20). Microbial diversity was evaluated using Shannon-Weaver diversity index in Swedish (J Allergy Clin Immunol 2012; 129:434-40) . The taxonomic classification of the reads was assigned by BLASTn. Results: 5 controls had insufficient DNA for sequencing. No significant association was detected between eczema and any bacteria with ≥1% relative abundance, including Bacteroides, Escherichia, Klebsiella, Bifidobacterium, Streptococcus and Lactobacillus. Among the less abundant genera (relative abundance <1%), Campylobacter was more abundant in cases (median 0.008%, IQR 0.003-0.022%) than controls (median 0.001%, IQR 0.001-0.004%) while Roseburia was less abundant in eczema (median 0%, IQR 0-0.063%) than controls (median 0.055%, IQR 0.002-0.270%). Nonetheless, Shannon-Weaver diversity index of stool microbiota at 4 weeks was similar between infants with eczema and non-allergic controls at 9 months (median [IQR]: 1.28 [0.94-1.93 ] versus 1.47 [1.31-1.80] ; P = 0.698). Comparing microbial compositions in our newborns and Swedish, Escherichia coli was found among top 5 genera only in both our cases and controls whereas enterobacter only in Swedish newborns. Clostridium, parabacteroides and lactobacillus were found only in Chinese eczema and healthy Swedish newborns.
Conclusions: Campylobacter and Roseburia appear to be less frequently detected in stool of 4-week-old Chinese infants who subsequently develop eczema. Microbial diversity is not associated with eczema susceptibility. This study confirms ethnic-specific early-life faecal microbial compositions. Background and objectives: Bakery workers are exposed to wheat allergens, bacterial endotoxins and fungus, which interact to induce allergic responses and work-related respiratory symptoms (WRSs). Our previous studies demonstrated that the WRSs of bakery workers were associated with TLR4 polymorphisms as well as Th2 immune responses, indicating a possible involvement of innate immune responses in the pathogenic mechanisms of baker's asthma. We hypothesized that Chitinase in wheat flour may involve in the development of WRS in bakery workers. We measured serum Chitinase level in bakery workers and analyzed associations with TLR4 polymorphisms in a single cohort of bakery workers. Methods: Three hundred eighty three bakery workers and as controls, 106 unexposed healthy subjects were enrolled. WRSs were evaluated using a questionnaire survey. Serum levels of Chitinase, IL-18, MPO and specific IgE/IgG antibodies to wheat flour extracts were measured by ELISA. The promoter polymorphisms of TLR4 at -2027AG and -1608TC were genotyped. Results: Serum Chitinase levels were significantly higher in bakery workers than in unexposed controls (P=0.026), however, no significant differences were noted according to the presence of WRSs and the prevalence of serum specific IgE or IgG antibodies to wheat flour (P>0.05, respectively). The workers carrying TLR4 -2027GG had significantly higher Chitinase levels than those with TLR4 -2027 AA/GG (P=0.021). Haplotype analysis indicated that the workers with ht1 [AT] had significantly higher Chitinase level that those without it (P=0.22). A significant correlation was found between serum Chitinase and IL-18 level (P=0.021), while no significant correlation was found with serum MPO level. Conclusions: These findings suggest that Chitinase may contribute to develop WRSs in bakery workers through the modulation of TLR4 function. Purpose: Nasal polyps (NP) imply a refractory clinical course in a case of chronic rhinosinusitis (CRS). Although, numerous etiologic factors including allergy, infection and hypoxia associate with nasal polyps (NP), the mechanism underlying NP is not fully understood. Previously, we reported that hypoxia-induced epithelial-to-mesenchymal transition (EMT) is frequently observed in Asian NPs, and HIF-1α could be a therapeutic target for nasal polyposis ( Ref 1) . However, the nasal epithelial cells in NP patients are not only exposed to hypoxia but also to diverse types or combinations of inflammatory milieu. So we hypothesized that specific immunologic endotypes could induce or accelerate EMT in nasal epithelial cells, and lead to nasal polyp formation.

A72

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.

A83

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.

Results

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.

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.

Conclusion

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

A125

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.

A141

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.

Introduction

Infants born by C-section miss the exposure to the maternal vaginal microbiota and this absence of microbial inoculation has been associated with a delayed colonization of commensal bacterial members such as Bifidobacterium. This compromised microbial inoculation may impact the health of the newborn. Epidemiological data from cohort studies indicate associations between C-section and, immune and metabolic disorders such as asthma, and obesity. The objective of this study was to determine the effect of a specific mixture of short-chain galactooligosaccharides and long-chain fructooligosaccharides (scGOS/lcFOS, ratio 9:1) and Bifidobacterium breve M-16V in restoring the delayed colonization of Bifidobacterium observed in term C-section delivered infants.
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.

Results

Filaggrin immunoreactivity was detected in epithelial cells and inflammatory cells. The number of Filaggrin+ cells in the epithelium of patients with NP was significantly higher than that in the nasal mucosa of the AR patients. The number of filaggrin+ cells in the lamina propria of patients with NP was significantly higher than that in the nasal mucosa of the AR patients. There was no difference in the number of filaggrin+ cells between nasal polyps from atopic and non-atopic patients. Periostin immunoreactivity was mainly detected in the basement membrane and the density of immunoreactivity of periostin in NP was significantly higher in NP than in the nasal mucosa of the AR patients. TSLP was detected in epithelial cells and in immune cells and greater in NP than AR mucosa. There was no difference in the density of immunoreactivity of periostin between NP from atopic and non-atopic patients. IL-13+ cells and IL-33 expression were also higher in NPs and there was a good correlation between the IL-13+ cells and periostin.

D) Conclusions

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.

A187

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.

Conclusion

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.

A193

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

A201

Cord blood cytokines and maternal environmental exposure during pregnancy Soo Hyun Ri, Chang Hoon Lim Korea University Medical Center, South Korea Correspondence: Soo Hyun Ri -Korea University Medical Center, South Korea World Allergy Organization Journal 2016, 9(Suppl 1):A201 A) Background: It has been suggested that initial priming of the T-cell system to environmental allergens may occur before birth. Cytokine expression in cord blood has been increasingly used as useful markers to assess the neonatal immunological development and future lifetime risk for various allergic diseases among offspring. The aim of this study is to evaluate the relationship between cytokine expression in neonatal cord blood and exposure to house dust mite (HDM) and food intakes during pregnancy. B) Methods: 405 pregnant women were recruited between April 2010 and November 2010. 111 women completed the study. The pregnant women with the genetic diseases, autoimmune diseases, and endocrinologic diseases were excluded. Parental allergic diseases, allergen sensitization, exposure to HDM, maternal diet during pregnancy, and cytokine expression in neonatal cord blood of all subjects were investigated. Information on physician-diagnosed allergic diseases of the subjects and/or their spouses had been gathered from the questionnaires and allergy specialist confirmed diagnosis after examining the subjects who declared to have allergic diseases on the questionnaires. Allergen sensitization was performed by using the skin prick test including Der p 1, Der p 2, tree mixture, grass mixture, weed, dog and cat. Dietary intakes and nutrition during the last 3 months of pregnancy period were assessed using the semi-quantitative food questionnaire and indoor environments of each household including exposure to dust mites were investigated by semi-quantitative rapid test. Expressions of IL-4, IL-13, and INF-γ of neonatal cord blood were examined by using quantitative real-time PCR. C) Results: Among subjects, the pregnant women with diagnosed allergic diseases were 54 and most common allergic disease was allergic rhinitis. (61.1%) 54 women were exposed to tobacco smoking and 5 women were living with pets. All subjects showed significant differences in expression of IL-4 and IFN-γ. (n=111, p<0.05) IL-4 /IFN-γ ratio was 4.63±8.72. (mean±SD) No significant relationship is observed between IL-4 and IFN-γ of neonatal cord blood and subject's environments including exposures to tobacco smoking, pet ownership, carpet use, detectable HDM and bedding for protecting HDM use. HDM was detected in 29 pregnant women's household, but significant difference between HDM detected and HDM non-detected was not showed. IL-4 and IFN-γ in cord blood of neonate with allergic mother had higher expression than those of non-allergic mother.

Conclusion:

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.
Conclusions: Hypersensitivity to CYC can be seen in pediatric patients with autoimmune disease. It can occur after initial exposure and can be as severe as anaphylaxis. Desensitization is one approach for continued treatment with CYC in pediatric patients with SLE which has been successful.

Conclusion

Severe exacerbation rate and the possession rate of major antiasthmatics were quite different among 4 clusters. Even AERD is recognized as a subtype of asthma, our results suggested that sophisticated therapeutic approach is needed for patients with AERD. Background. Concerns have been raised about the adverse impact of dusty air pollution (DAP) in Iran on human health; but there is no study showing the effect of DAP on immune system toward allergic diseases.
Methods. The effects of ambient DAP exposures (based on PM 10 ) on cytokine profiles and lymphocyte immunophenotypes in blood among 148 individuals of general population in hazardous (AQI >300) and good condition weather (AQI <50) was examined. We measured cytokine production (IL-4, IL-10, IL-13, IFN-γ) using ELISA as well as blood samples using a FACSort flow cytometer to determine phenotypes of T-lymphocytes (CD4+ and CD8+), CD19+ B-lymphocytes, CD25+ and CD4+ CD25+ cells. Results. The mean serum level of IL-4 (33.4± 2.9 vs 0.85± 0.65 pg/dl) and IL-13 (15.1± 4.4 vs 0.12± 0.7 pg/dl) in subjects who exposure to ambient DAP were increased significantly than individuals in good condition weather (P= 0.001 for both). In addition, CD19+ Blymphocytes (12.6± 4.9 vs 8.9± 3.2%) and CD4+ CD25+ cells (13.6± 4.6 vs 7.7± 3.8%) counts in peripheral blood were increased parallel with increased DAP exposure levels (P= 0.035 and P= 0.004, respectively). Conclusions. The study may suggest ambient DAP may affect immune system shifting allergic inflammation in general population. Key words. Dusty air pollution, immune system, allergic diseases, cytokine, lymphocyte Backgrounds: Antituberculosis drugs (ATD) are the major causes of drug-induced liver injury (DILI). Although genetic factors are known to play a role in the development of ATD-induced hepatitis, the genetic susceptibility to this condition is poorly understood yet. Methods: We performed a genome-wide association study (GWAS) to identify the genetic variants associated with the risk of ATDinduced hepatitis in a Korean population. DNA obtained from 40 patients with ATD-induced hepatitis and 119 ATD-tolerant subjects were genotyped on Affymetrix Genome-Wide Human SNP Array 6.0. After identification of genetic variants with significant associations, gene set enrichment analysis was done to find the relevant pathways associated with ATD-induced hepatitis. Results: In the case-control analysis, we found significant genetic variants at ID2 (rs345904, P=4.06 x 10 -7 , OR 8.03, 95% CI 3.34-19.35), PLXNA4 (rs156978, P=8.48 x 10 -6 , OR 12.78, 95% CI 3.31-49.36) and ZNF804B (rs2718306, P=8.26 x 10 -6 , OR 10.72, 95% CI 3.18-36.11). Pathway analysis identified several pertinent pathways including axon guidance, cGMP effects, developmental biology, signaling by Rho GTPases and interaction between L1 and ankyris. Conclusions: This GWAS identified genetic variants and pathways underlying the development of ATD-induced hepatitis. These results provides insights into the genetic susceptibility to ATD-induce hepatitis.

A224

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.

Conclusion:

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.

A275

Conclusions: Approximately a half of milk allergy children can tolerate baked milk product. Component-specific IgE and IgG4 titers could be useful as a predictor for tolerability of baked milk. Background: SP-D is a hydrophilic lectin and involves in a host defense mechanism against respiratory pathogens and modulates immune responses against bacteria or allergens.

Background

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

Conclusion

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

Methods:

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

Conclusions

The level of serum IL-13 and IL-17A of asthmatic children is higher than control. There is a positive relationship between serum IL-17A and the severity of asthmatic children. There is a positive relationship between the level of serum IL-17A and neutrophils in asthmatic children. There is a positive relationship between serum IL-13 and sIgE. In severe asthmatic children, there is a positive relationship between the level of serum IL-13 and the level of serum IL-17A. Purpose: Vitamin D is one of essential nutrients for immune modulator effector. Recently, epidemiologic studies have shown that the lack of vitamin D levels may be associated with high asthma prevalence. The purpose of this study was to examine the association of serum vitamin D levels with the prevalence of pediatric asthma in Korea. Methods: This study was conducted on 34 asthmatic children and 30 healthy controls aged 6-14 years. Serum 25-hydroxy vitamin D3 (25-OH vitamin D) levels were measured and compared between the two groups. Moreover, the relationship between serum 25-OH vitamin D levels and pulmonary function test and environmental factors for sunshine were examined in asthmatic patients. Results: Serum 25-OH vitamin D levels in asthmatic patients (16.63 ± 4.20 ng/ml) were significantly (p<0.05) lower than that in healthy controls (24.24 ± 6.76 ng/ml). Also, we found that when serum vitamin D level is 1 ng/ml decreases, the prevalence of asthma increase to 0.788-fold (OR, 0.788; 95% CI, 0.707-0.879; p<0.001). However, there were no associations with vitamin D level and pulmonary function and sunshine related factors, such as housing type, living floor, and indoor/outdoor activity time. Conclusion: These results suggest that serum vitamin D levels were associated with pediatric asthma in Korea. For prevention and treatment of asthma, an intervention study in asthmatic children with low serum vitamin D level, and a vitamin D study assessed the optimal delivery and safety of its supplementation is needed. Background: It is of great interest to develop validated, non-invasive methods for local measurement of IgE. This is however challenging, as IgE is the least abundant immunoglobulin isotype and present at low concentrations. We aimed to compare three methods for collection of NS for local measurement of IgE: Filter Disks (FD), Sinus Packs (SP) and Ear Packs (EP). We furthermore evaluated the suitability of using a fixed dilution instead of a fixed volume when processing. Methods: NS were collected with FD and SP in 15 house dust mite (HDM) allergic rhinitis (AR) patients and 15 controls. During processing, saline solution was added in order to mobilize the NS. For each sample, the volume to be added was calculated, based on the weight of collected NS, in order to obtain a fixed dilution. In a second experiment, NS were collected in two HDM AR patients (re-recruited from first experiment) with FD and SP on 4 consecutive days. This experiment was performed once with fixed volume and once with fixed dilution. In a third experiment, NS were collected with FD, EP and SP in 13 HDM AR patients (re-recruited from first experiment). During processing, a fixed volume of saline solution was added: 1 ml for FD, 2 ml for EP and 3 ml for SP. Total IgE and hx2-IgE were measured with the UniCap system. Results: In the experiment with fixed dilution, levels of total IgE and HDM IgE were significantly higher in HDM AR patients compared to controls. With the FD, total IgE and HDM IgE were below the detection limit (BDL) in 2 and resp. 6 out of 15 AR patients. With the SP, total IgE and HDM IgE were BDL in 3 and resp. 4 patients. When comparing FD and SP on 4 consecutive days, the reproducibility to measure IgE levels was better with SP. In the third experiment with a fixed volume, total IgE and HDM IgE were BDL in 3 and resp. 6 out of 13 AR patients when using FD and EP. With the SP, total IgE and HDM IgE levels were BDL in 5 and resp. 7 patients. Discussion: Each method has some advantages and disadvantages. The SP method seems to be more reproducible than the FD method, which makes it more suitable for repeated measurements and monitoring. However, SP are unsuitable for serial measurements on the same day, as they cause stimulation of the nasal mucosa. In this setting, FD are preferable. EP are intermediate in size to FD and SP and could be of interest in a pediatric setting. When comparing fixed volume to fixed dilution processing, the latter is more time consuming and prone to error. However, fixed dilution has the advantage of a fixed detection limit for all samples. Therefore, this method is recommended when measuring IgE or other mediators that are present at low concentrations and thus often BDL. The tight junction (TJ) protein, claudin 5 (CLDN5) is critical to the control of endothelial cellular polarity and pericellular permeability.In the past, the role of CLDN5 in asthma has had limited attention.

Conclusion

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

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

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

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

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

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

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

Conclusions

This study showed that most of children hospitalized with asthma in our setting were moderate exacerbation with frequent asthma, male, aged under 5 years old and first diagnosed at 2 years old, had history of hospitalization before, normal nutrition status, history of atopic in family, and cigarette smoking exposed. Keywords: asthma in children, hospitalized, characteristic Background: Allergic bronchopulmonary aspergillosis (ABPA) is known as type I and III allergic disease for Aspergillus. Clinical presentation of ABPA ranges from asymptomatic mucus plugs to severe asthmatic symptoms or destructive and fibrotic lung disease. The heterogeneity may reflect not only the different clinical stages of the disease, but also different phenotypes. We herein attempt to identify phenotypes in ABPA using cluster analysis. Methods: We analyzed the data of 332 patients with possible ABPA from national-wide survey in Japan executed between 2013 and 2014. Definition of possible ABPA were, (1) positive skin test or specific IgE for Aspergillus, and (2) either a) positive precipitation or IgG antibody for Aspergillus or b) mucoid impaction or bronchiectasis in chest computed tomography. Non-hierarchical cluster analysis using k-means method was performed. Results: Three clusters were identified. Cluster 1 (n=141) included the patients with later age at onset (mean ages, 68 years), femaledominance, and less frequent prevalence of asthma (76%). The patients in cluster 2 (n=95) were middle age at onset (55 years), female-dominant, and showed lower values of total serum IgE. Cluster 3 (n=96) was characterized with early-onset (37 years), maledominance, and frequent recurrences (59%). Conclusions: Three distinct clinical phenotypes were identified characterized by ages of onset, gender, asthma prevalence, total serum IgE levels, and the frequency of recurrences. Background: Chronic rhinosinusitis (CRS) is one of the most frequent chronic diseases, and little is understood about its pathogenesis. Eosinophils are considered to play a major role in its pathology, but we still know little which is causing chronic immune activation and persistent eosinophilic inflammation in CRS. Recently, type 2 innate lymphoid cells (ILC2s, lineage (-), CD45 (+), CD127 (+), CD294 (+)) were identified as a candidate, which produce highly levels of Th2 cytokines such as IL-5 and IL-13, which activates eosinophils. We hypothesized that ILC2s are enriched in blood and nasal polyps in patients with eosinophilic CRS (ECRS) and are associated with its pathology. Methods: FThe patients with CRS or pituitary adenoma (normal sinus) who underwent Endoscopic sinus surgery (ESS) in Jikei University Hospital were enrolled. We used PBMC and nasal polyps (NPs) from patients with CRS or normal subjects, and analyzed the amount of ILC2 by flow cytometry. We also investigated the distribution of ILC2s in NPs by immunohistochemistry. EDN and cytokines in NPs were measured by ELISA to investigate correlation with ILC2s. Lineage negative cells from nasal polyps were cultured in vitro with IL-33 or/and IL-2 to investigate the amount of cytokine produced by ILC2s. Results: EDN and Th2 cytokines are significantly higher in ECRS than non-eosinophilic CRS (NECRS). EDN had strongly correlated with the numbers of ILC2s in NPs. The counts of ILC2s in NPs were significantly higher in ECRS than NECRS. Immunostained ILC2 were showed accumulated in nasal polyps of ECRS, but not in NECRS or normal subjects. ILC2's CD25 surface expression in PBMC was significantly higher in ECRS than NECRS. ILC2's IL-17RB surface expression in NPs was significantly higher in NECRS than ECRS. Lineage negative cells from ECRS' NP, but not from NECRS' , produced IL-5 and IL-13 in both IL-2 and IL-33 stimulation. Conclusions: ILC2 are considered as candidate of the commander in ECRS, which strongly induce Th2 inflammation. There are possibility that ILC2s have several subtypes and the characteristic of ILC2s are differ from their environment.

Comparison of Some Vitamin Groups in Asthmatic Patients

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

Conclusions

Conclusions: Colonisation with specific Bifidobacterium species in early life can influence cellular immune function, namely cytokine profiles and Treg later at 12 months. This suggests that probiotic treatment during pregnancy may modulate infant immune function as late as 12 months of age, feasibly mediated by modulation of infant microbiota. However, the immune mechanism that might protect against allergic disease is still unclear. Background: Curry spice allergy in children is extremely rare in Japan. In addition, food-dependent exercise-induced anaphylaxis (FEIAn) as a manifestation of spice allergy against curry powder is quite uncommon. Methods: We report a case of FEIAn due to curry spice allergy in a 14-year-old boy. The boy had a history of several episodes of exercise-induced anaphylaxis since the age of 12 years, which were suspected to be FEIAn. He developed pollinosis in spring and autumn, and had increased levels of specific IgE antibodies against many different kinds of allergens such as food and pollens, including, celery, white birch, and mugwort. Among several different foods consumed before the last three episodes of anaphylaxis, we found that curry powder was the common ingredient in all of them. Since the curry powder did not induce symptoms without exercise, we suspected FEIAn caused by curry spices. Results: The results of the exercise challenge test conducted after ingestion of curry were positive and accompanied by skin flare, itching, urticaria, and bulbar conjunctival hyperemia. We recorded a 10.0% decrease in forced vital capacity, and a 13.5% decrease in forced expiratory volume in 1 s on respiratory function testing. The patient was diagnosed as having FEIAn in response to curry powder. The patient was found to be sensitized to coriander, a curry powder ingredient, on ImmnoCAP. Sensitization to several other spices was also detected with skin-prick testing. The patient was instructed to refrain from exercise for 2 h after ingestion of curry powder and has not shown any symptoms since then. Conclusion: Based on history and investigation results, we suspected that the celery-birch-mugwort-spice syndrome was caused by IgE cross-reactivity between pollens and spices. Background: Atopic dermatitis (AD) is a chronic, relapsing, inflammatory skin disorder characterized by multifactorial pathophysiologic aspects. Pruritus and sleep disturbance are cardinal symptom of atopic dermatitis. Several scoring systems are available, Eczema Area and Severity Index (EASI) is a tool commonly used to measure the severity of atopic dermatitis. Correlation between Visual analogue scale (VAS) of pruritus and loss of sleep (LOS) and the EASI score is not fully investigated yet. Objective: This study was designed to evaluate the association of pruritus and sleep disturbance in atopic dermatitis with objective disease severity and laboratory parameters.

Immune-Modulatory Genomic Properties Differentiate Gut Microbiotas of Infants with and without Eczema

Background: The gastrointestinal tract is the primary site of interaction between the host immune system and microorganisms. Studies have suggested that selective microbial targets may influence the development of the allergic diseases. But the difference in functional gene composition remains unknown. We aim to assess the structural and functional gene composition of stool microbiota of infants with eczema and their matched (for age, gender, mode of delivery, feeding) controls at the age of 1 month. Methods: Twelve children with eczema and their controls were selected from the placebo arm of a birth cohort of at-risk infants participating in a randomized double-blind trial on the protective effects of supplemental probiotics in early life on allergic outcomes. The four were caesarean delivery followed by formula feeding (eczema = 2 and healthy control = 2) and the eight were vaginal delivery followed by partial breast feeding mixed with formula feeding (eczema = 4 and healthy control = 4). Bacterial genomic DNA were extracted from fecal samples and prepared for Illumina Miseq and Hiseq sequencing. Data analysis such as sequence quality check, contigs assembly and gene annotation were carried out for the DNA sequences obtained from Miseq and Hiseq sequencing. Results: Phylogenetic analysis of metagenomic sequences revealed that four phyla dominated both microbial communities: Proteobacteria (54% and 63% for healthy and eczema communities, respectively), Firmicutes (26% and 18%), Actinobacteria (13% and 8%), Bacteroidetes (7% and 8%). Comparative metagenomic analysis showed that immune-regulatory TCAAGCTTGA motifs were significantly enriched in healthy communities, many of which were encoded by Bifidobacterium (38% of the total motifs in the healthy communities). Draft genomes of five Bifidobacterium species (B. longum, B. bifidum, B. breve, B. dentium, and B. pseudocatenulatum ) were recovered from metagenomic datasets. The B. longum BFN-121-2 genome encoded more TCAAGCTTGA motifs (4.2 copies per 1 million genome sequence) than other Bifidobacterium genomes and was significantly overrepresented (P < 0.05) in the healthy communities. Conclusions: Our results report distinct immune-modulatory genomic properties of gut microbiotas in healthy infants as compared to children with eczema and provide new insights into potential roles of gut microbiotas in affecting human immune homeostasis. Objective Allergic rhinitis occurs at 10-40% in the world's population and it cause runny nose, sneezing, itching and qualitative degraded sleep disorder which are causing the failure of social life. Allergic rhinitis can be associated with patient of obstructive sleep apnea. The aim of this study was to investigate the impact of allergic rhinitis on obstructive sleep apnea and the change of the symptoms of obstructive sleep apnea after allergic rhinitis treatment.

A428

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

A433

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

A444

Intravenous immunoglobulin (IVIg) is used as an immunomodulatory agent in various autoimmune disease and generally considered a safe therapy. Most of the adverse effects (AEs) associated with IVIg administration are mild and transient. The immediate (AEs) include headache, flushing, fever, and anaphylactic reactions, especially in IgA-deficient patients. Late AEs are rare and include acute renal failure, thromboembolic events, aseptic meningitis, and neutropenia. Patients with antibody deficiencies are more prone to develop acute netropenic episodes even during IVIg replacement. IVIG-induced neutropenia is transient and mild or moderate, and no severe infectious complications have been reported. We report a case of neutropenia in a patient with Guiilian-Barre syndrome (GBS) after infusion of IVIg. A 57-year-old female presented with a 4-day history of quadriparesis. She had no previous medical history. She developed myalgia and progressive descending weakness involving both upper and lower extremities. Electrophysiologic study showed motor dominant neuropathy. There were no abnormal findings on brain magnetic resonance imaging. A raised protein concentration but a normal cell count was observed in cerebrospinal fluid (CSF). No virus-specific antibodies, bacteria, and fungi were detected in CSF, blood, and urine. She was administrated IVIg (0.4g/kg daily) for GBS. She gradually recovered strength in her extremities after 2 days. On day 3 administration of IVIg, severe neutropenia (absolute neutrophil count < 1500 cells/mm 3 ) occurred. Tue infusion of IVIg was stopped, however, neutropenia lasted for 5 days. She developed a fever and was given granulocyte colonystimulating factor. She improved and was discharged with no infectious and neurologic complications on the 15 th hospital day.

Acknowledgement

This research was supported by a grant from Ministry of Food and Drug Safety to operation of the regional pharmacovigilance center in 2015. Background: Asthma traits are determined by complex interactions between predisposition genes and environmental influences. The GABRIEL consortium identified through meta-analysis of genomewide association study ten asthma loci. Nonetheless, the relevance of these loci on longitudinal changes in patients' lung function remains unknown. This prospective cohort study investigated the effects of these asthma loci on changes in spirometric indices among Chinese asthmatic children. Methods: 158 Chinese asthmatic children aged 6-12 years were recruited from our paediatric allergy clinic. These patients were prospectively followed for five years. Pre-bronchodilator spirometry was recorded at baseline and then monitored at least annually. Spirometric indices were compared with local references. Genomic DNA from these patients was genotyped for single-nucleotide polymorphisms (SNPs) on the 10 asthma loci by TaqMan genotyping assays. Generalised estimating equation was used to analyse effects of these SNPs on longitudinal changes in lung function parameters. Results: The mean (SD) age of patients at baseline was 10.0 (1.8) years, and 104 (66%) of them were male. Twenty-eight percent had passive smoking and 58% ever received inhaled corticosteroid (ICS) treatment during follow-up. About three quarters of these patients had family history of allergies. Rs3894194 and rs9273349 were not genotyped due to unavailable TaqMan assays. Adjusting for age, sex, passive smoking exposure, ICS treatment and presence of upper respiratory infection within two weeks, rs1342326 of IL33 was significantly associated with Conclusions: This is the first Asian study of genetic determinants for lung function growth. IL33 appears to be a candidate gene for longitudinal changes in several spirometric indices among Chinese children with asthma. Larger cohorts are needed to replicate our findings due to low frequency of risk allele in IL33_rs1342326 among our patients. A) Background: Usually rhinitis is classified simply allergic and nonallergic rhinitis according to the allergic reaction to airborne allergens. Ig E-mediated inflammation is confirmed with positive skin test or presence of specific IgE and the positive result from the one of the two tests is usually enough for the diagnosis do allergic rhinitis. We are interested in the diagnostic power of the allergen specific Ig E. Recently, during Korean National Health and Nutrition Examination Survey 2010, presence of rhinitis and the specific Ig E for major airborne allergens were checked in the population. Purpose of this study is to evaluate the significance of allergen specific Ig E in the diagnosis of allergic rhinitis. B) Method: The data were obtained from the 2010 Korean National HANES, which was a cross-sectional survey of non-institutionalized population all around the country. Presence of rhinitis was defined as "Have you experience the rhinitis symptoms" or "Have you diagnosed as have allergic rhinitis from doctor". Serum specific IgE was checked for Dermatophagoides farinae, cockroach and dog. Data was obtained from 1,922 adult (older than 18). The positive predictive values (PPV) of allergen specific IgE on the diagnosis of allergic rhinitis were calculated according to the level of the specific Ig E. C) Results: The specific Ig E higher than 0.34 kU/L(+) was found in 63.6 % in population with rhinitis and 39.7 %in the population without rhinitis. The PPVs were 61% with level of 0.35 kU/L and 66% with the level of 3.5 kU/L(+++). The prevalence of the allergic rhinitis increased with the increasing levels of the specific IgE, from 37.3 % to 77.4 % and the PPV also increased. However the positive predictive rate was 72.4 % with the level of 3.5 kU/L and 82.6 % with the level of 17.5 kU/L(++++). D) Conclusion: Diagnostic power of specific IgE on the classification of rhinitis is not high and the level of specific Ig E higher than 3.50 kU/L may be more clinically significant. Background: Allergen immunotherapy (AIT) is currently the only immune-modifying treatment for allergic disease. The clinical efficacy of AIT for the treatment of allergic rhinitis and bronchial asthma is well documented. However, many factors including inconvenience, cost, side effects, and adherence influence the initiation and persistence with AIT. We sought to evaluate the AIT practice pattern and patients' attitude and behavior about AIT.

Genetic Determinants for Lung Function Growth in Asthmatic Children

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

A457

Food allergy is one of the common allergic diseases in the world. Probiotics are shown to promote the endogenous host defense and modulate the host's immune responses to potentially harmful antigens. In this study, we first established a mouse model of food allergey by i.p. sensitization with OVA or β-lactoglobulin, and were orally challenged with protein allergen, OVA, or β-lactoglobulin in BALB/c mice. We found that the body weights and body temperatures immediately after food allergen challenged were significantly decreased as compared with the control mice. And the symptoms of food allergy, the levels of total IgE, allergen-specific IgE, IgG1, IgG2a, IgA of sera and the levels of IgE, IgA, IL-4 and IL-17 of intestine lavage fluids (ILF) of food allergen mice were significantly increased as compared with the control mice. After oral administration with 10 7 CFU Lactobacillus gasseri PM-A0005 (L. gasseri ) at the same time during food allergen sensitization and challenge, the body temperature, body weight, the levels of antigen-specific IgA of sera, and IL-10 concentration of the ILF, and the levels of IL-10, IL12, INF-γ, TGF-β of the culture medium and the cellular numbers of CD11c + CD103 + , CD11b -CD8a + dendritic cells (DCs), CD4 + FoxP3 + (Treg cells), CD4 + T bet + (TH1 cells) in the Peyer's patches and draining lymph nodes of L. gasseritreated mice were significantly increased as compared with the nontreated food allergy mice. In contrast, the food allergy symptoms, the levels of antigen-specific IgE, IgG1 of sera and the levels of total IgE, antigen-specific IgE, IgG1, α1-antitrypsin, IL-17, IL-6 of the ILF and the concentrations of TNF-α, IL-23, IL-6 of the culture medium and the cellular numbers of CD4 + RORγt + (TH17 cells), CD4 + GATA3 + (TH2 cells), lymphocytes proliferation and the intestinal inflammation of L.gasseri-treated mice with food hypersensitivity were significantly decreased as compared with the non-treated control mice. To further explore the anti-allergy effect of L. gasseri of dendritic cells (DCs) on food allergy development, bone marrow-derived dendritic cells (BMDCs) isolated from naïve mice were stimulated for 24 hrs with recombinant of L. gasseri. The PMA5P40-primed BMDCs were collected and adoptive transfer to mice sensitized and challenged with food allergens. These finding suggested that L. gasseri and recombinant of protein PMA5P40 have anti-allergy effect on the mice sensitized and challenged with food allergens, such as OVA and cow's milk. And this anti-allergic effect may be mediated through the tolergenic effect of dendritic cells that enhance immune-regulatory effect on T and B lymphocytes, which may have clinical application in patients suffered with food allergy. Background: Folate, a dietary methyl donor, is known to alter gene expression influencing immune system through epigenetic modification. However, the relationships between folate level and the risk of allergic and respiratory diseases in children are still unknown. Objectives: To investigate whether or not serum folate levels are associated with atopic biomarkers and also with the risk of allergic and respiratory diseases in children. Methods: Data of 462 children with complete information from a birth cohort in South Korea were available. Serum folate levels were analyzed at 24 months of age in children. Atopic biomarkers such as total Ig E, IL-10 and eosinophil counts were also measured at 24 months. Information on maternal demographic and obstetrical characteristics and that on children's allergic and respiratory outcomes was obtained from questionnaire. Results: Serum folate levels were inversely associated with eosinophil counts (r = -0.192, P < 0.001). Total IgE levels and eosinophil counts decreased significantly in the group whose serum folate was above the median value (17.6 ng/mL) compared to the other counterpart group (P = 0.013, P < 0.001 respectively). A multivariate logistic regression analysis revealed that folate level above the median value (17.6 ng/mL) was associated with a decreased risk for atopic dermatitis (AD) (adjusted odds ratio [aOR], 0.57; 95% confidence interval [CI], 0.34-0.95) at 24 months of age. However, no significant association was observed between serum folate levels and respiratory outcomes in children. Conclusions: Serum folate level is associated with a lower risk of developing AD in early childhood. Background: The dysregulated mucosal inflammation in chronic rhinosinusitis (CRS) is often difficult to control with pharmacotherapy alone. We sought to determine whether the immunomodulatory properties of vitamin D might have beneficial effects on CRS.

Conclusion

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

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

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

Conclusions

In addition to the initial test on textiles, as for medical devices of higher class, monitoring manufacturing processes certification is necessary to ensure the quality of the finished product, especially when using nonwoven fabric. Therefore, ISO 13485 certification is a relevant criteria for anti-mite covers quality and thus effectiveness. Subcutaneous immunotherapy is an effective treatment for allergy. It works by helping to re-balance an individual's immune response to allergens and the ability to drive an antibody titre response is greatly improved by the use of adjuvants, the most common being aluminium hydroxide. No data or preclinical model on the localisation kinetics of aluminium after subcutaneous injection, based on allergy formulations, currently exists. Methods Albino rats of the Crl:WI(Han) strain each received a single subcutaneous administration on 4 occasions with a 3 or 4 day intervals of a Birch concentrate formulated with either Alhydrogel or L-Tyrosine as the representative depot adjuvant. Dose sites were extracted and digested up to 6 months after final administration and aluminium (Al 3+ ) analysed via ICP-MS.

Background

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

Results

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

Conclusions

The ability of MCT to readily adsorb MPL compared to aluminium and calcium adjuvants supports a characteristic association based on both tyrosine's structure and MCT's physical properties. MCT is an effective depot candidate for allergy immunotherapy formulations and vaccines. Background: Inflammatory bowel disease (IBD) is an inflammatory disorder of unknown pathogenesis. Recent studies showed that interleukine-22 plays an important role in inflammatory processes during the disease. The purpose of this case-control study was to explore the association between IL-22 gene polymorphism (rs2227501) and susceptibility to IBD. Methods: 89 patients and 201 healthy individuals referred to the Namazi Hospital of Shiraz, Iran were entered in this study. Blood samples were collected and genomic DNA was extracted. Restriction fragment length polymorphisms polymerase chain reaction (PCR-RFLP) was performed, and data were analyzed using Chi-square and Bonferroni tests. Results: The frequency of the A allele was significantly greater, and the T allele was significantly lower in patients compared to controls (P value = 0.02). In addition, there was a statistically significant relationship between AA genotype and IBD (P value = 0.01). Conclusion: This is the first study of evaluating rs2227501 in Iranian patients with IBD. More studies are required in order to clarify the exact role of IL-22 polymorphisms in pathogenesis and susceptibility of inflammatory bowel disease. Background and Objectives: Several studies have demonstrated that adipose-derived stem cells (ASCs) can ameliorate allergic airway inflammation by shifting to a Th1 from a Th2-biased immune response. The ASCs secrete a variety of autocrine/paracrine factors, called secretome, that protect cells from apoptotic cell death and modulate immune system. In this study, we evaluated the effects of ASCs-derived secretome on allergic airway inflammation in ovalbumin (OVA) induced asthmatic mouse model. Materials and Methods: C57BL/6 mice were sensitized to OVA by intraperitoneal injection and challenged intranasally with OVA. To evaluate the effect of ASCs-derived secretome on allergic airway disease, 1 μl/ml of ASCs supernatant were administrated intranasally before OVA challenge. We evaluated airway hyperresponsiveness (AHR), the proportion of eosinophils in bronchoalveolar lavage fluid (BALF), lung histology, serum total and OVA-specific antibody, cytokine profile of BALF and lung draining lymph nodes (LLN), and T cell population of LLN. Results: ASCs-derived secretome significantly inhibited eosinophilic inflammation in the lung. AHR, total immune cell and eosinophils in the BALF, and mucus production were significantly reduced after ASCs-derived secretome administration. ASCsderived secretome significantly decreased the serum total and allergen-specific IgE and IgG1 level. ASCs-derived secretome significantly inhibited Th2 cytokines and enhanced Th1 cytokine (IFN-γ) and regulatory cytokines (IL-10 and TGF-β) in the BALF and LLN. In addition, CD25 + Foxp3 + and IL-10 + T cells in LLN were significantly increased after ASCs-derived secretome administration. Conclusions: ASCs-derived secretome ameliorated allergic airway inflammation and improved lung function through the induction of Tregs expansion. Secretome may be a promising candidate for a novel cell-free therapy for allergic airway diseases that has many advantages in overcoming the limitations and risks associated with the cell-based therapeutics. Alveolar hemorrhage with anti-neutrophil cytoplasmic antibody (ANCA) is a rare disease in children. ANCA is associated with certain diseases such as granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EPGA). This group of disease, characterized by necrotizing small-vessel vasculitis show autoantibodies in patients serum, directed against neutrophil cytoplasmic constituents, especially proteinase 3 (PR3) and myeloperoxidase (MPO). In these diseases, affected vessels have changed with focal necrosis in pathologic findings and patients suffer from pulmonary, cerebral, gastrointestinal, other hemorrhagic complication and also renal dysfunction represented by crescentic glomerulonephritis. A 8-year-old previous healthy girl presented with acute onset dyspnea, cough, hemoptysis, chest discomfort, fever and hypoxemia. Her chest CT scan showed diffuse consolidation and ground glass opacity in both lungs, hemoglobin was 3.9g/dL, hematocrit 12%, so she was diagnosed as diffuse alveolar hemorrhage. Bleeding diatheses were excluded by laboratory testing, and Anti nuclear antibody(ANA) and P-ANCA were positive. Myeloperoxidase-ANCA (MPO-ANCA) was positive but proteinase 3-ANCA was negative. Antiglomerular basement membrane antibodies(Anti-GBM) was negative. urinalysis showed RBC 21-30/HPF, creatinine 0.48mg/mL but there were no RBC casts or protein. This patient had been diagnosed for microscopic hematuria, but her kidney function was normal and other symptoms of ANCA associated vasculitis had never been appeared. The patient's alveolar hemorrhage recovered on immunosuppresive therapy with cyclophopamide and corticosteroids. We report 8-year old girl case, treated for severe alveolar hemorrhage and microscopic hematuria with positive ANCA. Background: The correct severity assessment is important for treatment of Atopic dermatitis (AD) Although the levels of serum Thymus and activation-regulated chemokine (TARC)/CCL17 is well known as a proper means for assessing severity of AD, the levels of TARC are different according to the month of age. We examined a correlation of serum TARC level and Severity Scoring of Atopic Dermatitis (SCORAD) index in patients with AD in early infancy.
The questionnaire proved to be a fast, cheap and reliable tool in allergy detection. It has been introduced in Wrocław,s schools for standard use. Rationale: Patients who have both food allergies and asthma are at increased risk for anaphylactic reactions and life-threatening asthmatic reaction. The aim of this study is to determine the asthma impact of on characteristics of children with food induced anaphylaxis adrenaline autoinjectors were prescribed. Methods: 90 patients (28female, 62male, range 2-11 year-old) with food allergy adrenaline autoinjector were prescribed between April and October 2013 were recruited. We excluded cases treated by oral immunotherapy. We evaluated causal food, symptom of recent anaphylactic reaction, serum mite-specific IgE, adrenaline treatment for anaphylaxis. Their factors of asthmatic group (n=53, asthma onset 2.7 years, 23 treated with inhaled corticosteroid) were compared with those of Non-asthmatic group (n=37). Results: Number of adrenaline treatment for anaphylactic reaction in asthmatic group was higher than those of Non-asthmatic group significantly (P<0.05). There was no significant difference in mite-specific IgE, symptom of anaphylaxis between asthmatic group and Non-asthmatic group. Forty three (81%) of anaphylactic reactions in asthmatic group induced by milk, wheat and egg were higher than 19(51%) in Non-asthmatic patients (p<0.01). In contrast, peanuts and nuts induced anaphylactic reactions in Non-asthmatic group more frequently than those of asthmatic group (30% vs.9%). Conclusion: In asthmatic children, anaphylactic reactions occurred frequently by accidental ingestion of daily foods, for example, milk, wheat and egg. Bronchial hyperresponsiveness may induce anaphylactic reaction easily by small amount of causal food. Background: Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are both immune-mediated disorders that can be life-threatening and frequently related to prior drugs consumption. Autoimmune disorders have been suggested to have a predisposing effect on SJS, SJS-TEN, or TEN; however, it is difficult to decide whether the eruption is induced by drugs or a manifestation of lupus itself.

A525

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

Conclusion

Background: Recent meta-analyses demonstrated a high global epidemiological burden of chronic cough in general populations. However, there is still a lack of nationwide studies on the epidemiology of cough in general Korean populations. Objective: We aimed to calculate the nationwide prevalence of current cough, and to explore the factors underlying the epidemiology in Korean general adult populations. Methods: We analyzed cross-sectionally the Korean National Health And Nutritional Examination Survey (KNHANES) database surveyed during 2010-2012. Presence and duration of current cough was defined by structured questionnaires, and classified as acute (<3 weeks), subacute (3-8 weeks), and chronic (>8 weeks). Demographic and clinical parameters were also examined in relation to cough. Weighted prevalence of cough according to duration was calculated, and risk factors with cough were evaluated by using multivariate logistic regression. Results: Among a total of 18,071 adults, 5.9% (n=1,076) had current cough. Among the subjects with current cough, proportions of acute, subacute, and chronic cough were 43.1%, 13.1%, and 43.8%, respectively. Of those with chronic cough, 65.4% had been coughing longer than 1 years. The epidemiology of cough significantly differed between age groups; acute cough was more prevalent in younger adults (18-45 years old), whereas chronic cough was significantly more prevalent in elderly subjects (≥65 years old). Prevalence of chronic cough increased with aging in both gender (in males, 2.4% in subjects aged 18-45 years, 3.4% in subjects aged 45-65 years, and 5.4% in subjects aged ≥65 years; in females, 1.2%, 1.9% and 3.9%, respectively; both p for trends <0.01). After adjusting for demographic and risk factors, several factors were associated with chronic cough independent of age: current smoking, chest X-ray abnormality, HbA1c and rhinitis or rhinosinusitis (all p<0.05). In female, menopause and estrogen replacement therapy were also related with chronic cough (all p<0.05). Conclusion: The present study indicates a considerable epidemiological burden of cough in Korean general adult populations. The epidemiology of cough significantly differed between age groups. These findings warrant further elucidation for various factors underlying a high burden of chronic cough in older adults. "memory"cells, associated with T cell development, T cell activation and IgE synthesis, were analyzed in BAL from WC and normals. Methods: We evaluated 18 WC with a minimum of 2 episodes of wheezing or prolonged wheezing ≥2 months in a 6 month period with BAL. WC were further sub-divided into children with history of RSV (WC+RSV)(n=10, median age 17.0 months) or without RSV (WC-RSV)(n=8, median age 9.3 months). Comparisons were made with normal controls (Control)(n=5, median age 19.5 mos). BAL cell counts and differentials were determined, and 10 6 cells were fixed in acetone and embedded in glycol methacrylate resin. Cell blocks were cut and immunohistochemically stained for the following T cell surface markers: CD3, CD4, CD8, CD25, and CD45RO. Co-expression of CD25 or CD45RO on CD3, CD4, and CD8 T cells was evaluated by an image analysis program on sequential sections. Comparisons between all the groups were first made using the Kruskal-Wallis test. In case of significant difference, individual groups were compared by using the Mann-Whitney U test. Results: The total number of CD3 cells was significantly elevated in the WC+RSV compared with the Control (p=0.008). WC+RSV had significant (p=0.003) elevations in # of CD45RO cells/1000 cells compared to Control and the total number of CD45RO was significantly elevated in the WC+RSV compared with the WC-RSV (p=0.033) and the Control (p=0.001). Although the % of CD4 T cells expressing CD45RO was greater in WC+RSV than WC-RSV, the elevation was only statistically significant compared to Control (p=0.005). Conclusions: These findings suggest that specific T cell profiles exist in WC+RSV which differ from WC-RSV and Control. Furthermore CD45RO cells may play a role in the immune processes of WC+RSV. Background: Obesity and atopic disease are two increasingly important population health issues. Obesity could be a risk factor for atopic disease. To have a full vision of the health condition of the patients with obesity and atopic disease, it is important for the pediatricians to make a Quality of Life (QOL) Questionnaire as part of the patient's follow-up. Few studies suggest that obesity decreases QOL in children with atopic disease such as asthma. The aim of this study was to evaluate the QOL in obese children with or without atopic disease. Methods: A cross-sectional study with an initial sample of 109 children (6-11 years old) recruited from some private elementary schools in Bandung, Indonesia. The subjects were divided into obese children with or without atopic disease and normal weight children with or without atopic disease. The standard definition for obesity and atopic disease in children was based on the World Health Organization. To determine the effect of obesity and atopic disease on QOL, the Pediatrics Quality of Life Inventory™ (PedsQL™) was applied to the subjects and also their parents. Mann-Whitney test was used to test the significance of categorical data and significance was determined by p < 0.05. Results: Out of 109 patients in the study, 54.1% were males and 45.9% females, with a ratio of 1.2:1 and a mean age of 9.4 years ± 1.58 (standard deviation). The results of the four scales evaluated in the questionnaire (physical, emotional, social, school functioning), showed significant differences for the emotional functioning in QOL between obese-atopic disease and obese-non atopic disease groups (p = 0.04), but no significant differences in other scales.
Conclusions: This study revealed a significant differences for the emotional functioning in QOL between obese-atopic disease and obese-non atopic disease groups, but no significant differences in other scales. Further studies is needed to understanding the relationship between obesity and atopic disease to the patient's QOL. Background: Exacerbations of asthma are most frequently attributed to upper and lower airway infections by respiratory viruses such as rhinovirus and influenza viruses. Host cells protect against these virus via innate and acquired immune responses. MicroRNAs act as key regulatory molecules in complicated interaction networks between viruses and hosts. However, a few studies have been performed on miRNA related with influenza infection. The aim of this study is to search for candidate miRNAs by in silico analysis, and validate the relation of the miRNAs in sputum with exacerbation of asthma. Methods and Materials: Information on sequences of mature human miRNAs was obtained using miRBase (http://www.mirbase.org) and applied to the whole genome sequence of influenza viruses A (http://www.ncbi.nlm.nih.gov/) by searching complementarity. Viral RNA and miRNA were extracted from sputum of exacerbated asthmatics using Viral Gene-spin¢â kit (iNtRON Biotechnology, Seoul, Korea) and miRNeasy kits (Qiagen, CA, USA), respectively. RT-PCR and Real-time PCR were applied to the discovery of 7 respiratory viruses (adenovirus, human metapneumovirus, parainfluenza virus 1/2/3, influenza A/B virus, respiratory syncytial virus A/B and rhinovirus A) and the measurement of miRNAs, respectively. Results: Total 2578 human miRNAs were used for analysis. Among them, miR-23b-3p was predicted to match with 7 nucleotides in one location +1915-+1921 of polymerase basic protein 2 mRNA and to three locations +244-+251, +1446-+1453 and +1470-+1477 of haemagglutinin mRNA of influenza A. Respiratory viruses were identified in 21 patients out of total 37 patients and 5 patients were infected by influenza A virus. The levels of miR-23-3p were much lower in patients infected with influenza A and rhinovirus (n=9) than those of other virus-infected (n=7) or uninfected patients (n=16). The levels of miR-23b-3p in influenza A-infected patients were comparable with those in rhinovirus-infected subjects. Conclusions: Down regulation of miR-23b-3p expression may be associated with infection with influenza A virus and might exert a negative regulatory activity on the influenza A virus replication. Due to the high frequency of allergic diseases and its special growing rate among the world population, in medicine, the 21st century is called the century of allergy. It is known that allergic diseases (pollinosis, bronchial asthma), the highest percentage comes on the allergens-aeropolutants, that are represented in many plants and herbs in the form of dust (ragweed pollen, alder, birch, maple, walnut, mallow, cotton plant etc). Since 2006, Institute is actively working in this direction gradually after the World Allergy Organization (WAO) presented the apparatus -Burkhard Pollen Trap (UK) to the Institute. Research is actively continued in this direction and the results are published periodically in international journals and became public as the reports at scientific congresses. According to the all above-mentioned, the aim of the study at this stage is as follows: identification of specific aeropollutants and elaboration of annual calendar of plants blossoming for the reality of Imereti region. In this study have been involved 69 patients of different ages (among them 34 males and 35 females) with allergic rhinitis and asthma, who applying to the S/R Institute of Allergy, Asthma and Clinical Immunology of Academy of Sciences of Georgia (Tskaltubo, Georgia) for allegro-diagnostics, revealed increased levels for Phadiatop in blood, on the existence of atopic allergen only to the inhaled allergen. The study covered the following allegro-diagnostic stages: I stage -For precise verification of the allergen, patient's blood serum was examined on a particular specific-IgE antibodies by modern automated system -"Immuno CAP 100" (PHADIA, Switzerland). II stage -Monitoring of the concentration of aeropoluments was conducted by using aeropolinometer "Burkard Trap" (Great Britain). The analysis of the laboratory results, obtained through the automated system "ImmunoCAP 100"* showed that the studied patients had high titers of specific IgE on the weeds (Wx2) -ambrosia, plantain, absinth, atriplex 47 (68%); tree dust (Tx9) -alder, lactarius piperatus, nuts, oak, willow -21 (30%); cereals (Gx1) -festuca pratensis, lolium temulentum, timoti grass, poa -19 (28%). A specific IgE concentration was detected for each positive panel, to reveal the concrete allergen. The mentioned patients were provided with: the data of aeropolinometer-"Burkard Trap", annual calendar for distribution of aeroallergens reflecting concentrations of blossoming plant-trees and atmospheric aerosols in the air in Imereti region at a given period of time. Extracorporeal membrane oxygenation (ECMO) has been used primarily to treat respiratory failure due to acute respiratory distress syndrome that failed to respond to maximal medical therapy. The use of ECMO in status asthmaticus is limited to case reports. We present three cases of patients with near-fatal status asthmaticus not relieved by conventional treatment, in whom early administration of ECMO resulted in a good outcome. In case 1 and 2, ECMO was instituted because of sustained hypercapnia and respiratory acidosis within 2 hours after initiation of mechanical ventilation. Patient 3 was supported by ECMO at 10 hours after intubation because of severe hypotension and hypercapnia. The lung status in these patients was rapidly recovered within days, and they were extubated at 31, 67 hours and 4 days after initiation of ECMO, respectively. Successful weaning of ECMO was complete the next day after extubation in all patients. There was no significant complication related with ECMO in these patients. Mechanical ventilation for the patients with refractory status asthmaticus can have deleterious effects due to worsening dynamic hyperinflation and increase intrathoracic pressure. Early ECMO application is a useful treatment options for these patients failed to conventional therapy. Background: Atopic dermatitis (AD) is a complex and heterogeneous disease influenced by genetic and environmental factors. In the last decade, previous efforts in finding AD associated loci have identified unprecedented amount of associated loci. However, the previously reported genetic loci explain only a small proportion of the heritability. Thus, further analysis on unrevealed genetic component is required to solve the missing heritability problem. In this context, whole-exome sequencing analysis have gathered much attention to find functional variants with relatively high genetic effects. In the present study, we performed whole-exome sequencing study to identify functional variants responsible for severe AD in Korean childhood. Methods: The case-control samples of 32 severe AD patients and 20 normal individuals were recruited from the Childhood Asthma Atopy Center of Asan Medical Center, diagnosed by physician. The cases and controls were sequenced by Illumina Hi-Seq 2500 with Agilent SureSelectXT Human ALL Exon V4+UTR Kit. Sequence alignment was performed using Burrows-Wheeler Aligner. Variants were called using Genome Analysis Toolkit (GATK). We identified 233,254 single nucleotide variants (SNVs), of which 131,321 SNVs passed quality control criteria (HWE p-value<10-3, Missing rate >10%, Minor allele count <2). Of these, 34,991 variants were nonsynonymous SNPs. A Chi-square test was conducted to find disease-associated variants. Results: We identified three missense variants in a 112bp window at ZNF443(p-value<10 -4 ). For p-value<10 -2 , 137 missense variants were discovered. Among them, 2 variants at NLRP10 and CYP24A1 were located nearby previously reported AD associated regions. Functional enrichment analysis showed that 47 SNVs were related with immune related genes such as ZBP1, FBXO38, MTR, TTN. Conclusion: In summary, we identified 137 missense variants susceptible to AD and replicated 2 previously reported loci. To validate the genetic effect of discovered variants, the replication analysis in an independent cohort is required. Most cutaneous molluscum contagiosum (MC) infection occurs in children, but it may be found in adults, especially who have been infected with human immunodeficiency virus (HIV). A 37-year-old man presented with multiple pea-sized firm skincolored round papules, which first appeared on the arms and then quickly spread over whole body for last 2 months. He has been treated for severe atopic dermatitis with systemic immunosuppressive therapies for 2 years. Screening test for HIV was negative. The lesions were diagnosed as MC based on histopathologic findings of typical eosinophilic cytoplasmic molluscum inclusion bodies on the acanthotic epidermis as well as dermal inclusion cyst. This is a very unusual case because widespread MC infection in adults was reported in some HIV positive patients. We supposed that our patient's disseminated infection may be related with the combination of perturbed skin barrier and systemic immunosuppressive therapy under severe atopic condition. Backgrounds: Macadamia nut is a tree nut listed as a major allergen to be labelled on pre-packaged foods globally. At least 19 cases of macadamia nut allergy have been reported to date, however, the eliciting allergenic proteins have not been identified and consequently component resolved diagnosis has not been developed. This study aims to identify putative allergenic proteins in macadamia nut by combining patient IgE recognition with an allergenomics approach. The challenge is that macadamia nut genome sequence is only partially complete. Methods: The proteomic profile was studied using a label-free shotgun proteomics approach. As the genome sequence of macadamia nut allergens is not available, homologies to other known allergens and affiliations to protein families were determined. The results from the allergenomic screening method were used to predict potential allergenic proteins and cross-reactivity with other plants particularly. The molecular weight distribution of proteins was determined by gel electrophoresis. Following in-gel digestion with trypsin, proteins were subjected to liquid chromatography coupled tandem mass spectrometry. Based on the shared peptide evidence, the identified proteins were clustered and the allergenic proteins were identified. Immunoreactive proteins were identified by immunoblotting with three patient sera confirmed to exhibit IgE-mediated reaction. Results: Peptides matched to the sequences of 21 allergenic proteins belonging to different protein families such as seed storage proteins (conglutins and vicilins), rubber elongation factor proteins, phosphate binding proteins and detoxifying methylglyoxalases were identified. This included peptide sequence homologies to 5 conglutins, which are known allergens from Lupin angustifolius. Conclusion: Allergenic proteins were confirmed to be seed storage proteins belonging to 11S, 7S and 2S proteins. Significant number of peptide sequence homologies to conglutins from Lupin angustifolius was observed, suggesting that there may be cross-reaction between macadamia and lupin allergens Background: Immunoglobulin E (IgE) triggers multiple inflammatory allergic responses and cytokine release when it binds to high-affinity IgE Fc receptor (FcεRI) on mast cells in atopic dermatitis (AD) and asthma. Anti-FcεRI antibody is a new option for treatment that may block IgE-FcεRI binding and therefore may reduce inflammatory cascade in allergic diseases. However, the potential effects and mechanism of anti-FcεRI antibody remain poorly understood. Objective: We investigated the effect and mechanisms of anti-FcεRI antibody by blocking the combination of IgE-FcεRI antibody in allergic march (AM) mice model. Methods: We developed mice model of AM with three 1-week exposures (separated by 2-weeks interval) to an ovalbumin (OVA) or saline followed by OVA inhalation (challenge). In order to develop a mice model of AM, the day before sacrifice, all mice inhaled 1% OVA as the airway challenge. Anti-FcεRI antibody was administered to the mice intraperitoneally for 4 consecutive days before the end of study. Identification of interleukin (IL)-17 expression was performed by immunohistochemistry and real time PCR on skin and lung specimens. Results: Anti-FcεRI antibody treated AM mice had significantly decreased phenotypes (e.g., clinical score, airway hyperresponsiveness, and pathology) of AD and allergic asthma. In addition, the levels of total IgE, OVA-specific IgG1 and IL-13 in serum were significantly lower in AM mice treated with anti-FcεRI antibody. The level of prostaglandin D2 and the number of mast cells in skin were also decreased in the anti-FcεRI antibody treated with AM mice. Furthermore, the skin and lung expressions of IL-17 were reduced after the treatment of anti-FcεRI antibody. Conclusion: IgE-FcεRI blockade by Anti-FcεRI antibody can suppress the IgE-mediated phenotypes and inflammatory responses in AM. And its mechanism may be the decrease in IL-17 via the suppression of FcεRI-mediated mast cell activation. Background: Anti-thymocyte globulin (ATG) is an immunosuppressant derived from horse or rabbit-immunized with human thymus lymphocytes and commonly used for the prevention and treatment of acute rejection in organ transplantation and aplastic anemia. Hypersensitivity to ATG can be life-threatening but there are not many clinical data from the real practice. Therefore, this study aimed to investigate the clinical characteristics and outcomes of ATG hypersensitivity. Methods: Cases of hypersensitivity reaction to rabbit ATG were retrieved from a database of individual case safety reports in Seoul National University Hospital from 2010 to 2015. Clinical characteristics of hypersensitivity reactions were analyzed according to involved organ system and severity was assessed according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Results: Among 82 patients, male was 36 (44.4%). The average age was 21.5 ± 19.6. High fever (100%) was the most frequent symptom followed by chill (95%) and cutaneous symptoms (65%) such as itching sense, flushing, urticaria and rash. The following majority of symptoms is gastrointestinal symptoms such as nausea, vomiting, abdominal pain and diarrhea. The mean severity was CTCAE grade 2.7 ± 0.9. Although all patients were premedicated with antihistamine and steroid, 51.2% had grade 3 or 4 reactions including cases presented with profound hypotension (36.0%). After the development of ATG hypersensitivity, most patients were able to continue the following ATG infusion by increasing the doses of anti-histamine and steroid (76.5%) or by slowing infusion rate (13.6%), and desensitization (7.4%). Conclusion: ATG hypersensitivity reactions presented as a severe form in half of cases reported. However, most patients with ATG hypersensitivity were able to continue ATG infusion by increasing premedication or modifying infusion protocol. Background: Total serum Immunoglobulin (IgE) is known to be an essential diagnostic tool for atopy and allergic diseases. It is difference according to host factors including sex, age, races. We evaluated the distribution of total IgE levels in Korean children and utility in the diagnosis of atopy and allergic diseases. Methods: In this nationwide cross-sectional study, 3,753 elementary schoolchildren (6-7 yr olds) and 3,930 middle schoolchildren (12-13 yr olds) were enrolled. Total IgE levels were measured and skin prick tests were performed for 18 common inhalant allergens. Children and parents answered the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. We analyzed the diagnostic value of total IgE by using ROC (Receiver operating characteristic) curve and compared total IgE levels according to atopy and allergic diseases such as atopic dermatitis, bronchial asthma and allergic rhinitis. Results: The total IgE ranged from 1.5 to 4,523.1 kU/L in elementary schoolchildren and 1.5 to 3,000 kU/L in middle schoolchildren. The median total IgE level was 86.7 kU/L (75th percentile, 292.6 kU/L; 90th percentile, 698.5 kU/L; 95th percentile, 1,200.7 kU/L) in elementary schoolchildren and 94.7 kU/L (75th percentile, 284.3 kU/L; 90th percentile, 625.1 kU/L; 95th percentile, 990.7 kU/L) in middle schoolchildren. The median total IgE level was significantly higher in atopic group defined as any positive SPT (elementary schoolchildren, 246.5 kU/L; P<0.0001, middle schoolchildren, 206.1 kU/L; P<0.0001) and any allergic disease group (elementary schoolchildren, 108.3 kU/L; P<0.0001, middle schoolchildren, 141.2 kU/L; P<0.0001). In ROC analysis of total IgE for diagnosing atopy, AUC was 0.7835 (95% CI, 0.7688-0.7982) in elementary schoolchildren and 0.8165 (95% CI, 0.8032-0.8297) in middle schoolchildren. At the optimal cut-off value of 127.7 kU/L in elementary schoolchildren and 63.0 kU/L in middle schoolchildren, sensitivity, specificity, and positive and negative predictive values were 67.06%, 75.38%, 65.44%, and 76.70% in elementary schoolchildren and 81.91%, 66.63%, 75.01% and 75.08% in middle schoolchildren respectively. Conclusions: Total serum IgE level was higher in children with atopy or allergic diseases, but the value of total serum IgE as a diagnostic test for atopy is limited due to the low sensitivity and specificity. Severe immediate hypersensitivity reaction (IHR) to contrast media (CM) is one of the legal problems in the hospital. The overall prevalence of IHR was 0.16%-7.7% with nonionic CM. In order to reduce immediate drug adverse reaction and legal problem, prescreening skin testing has been before administration of antibiotics such as penicillin and cephalosporin. It may be important to avoid cross-reactive agent and to select the alternative safe drug. Clinical value of CM prescreening skin testing is controversy. CM prescreening skin testing might be useful for reducing the IHR. We aimed to evaluate the incidence of IHR to nonionic CM in two-step prescreening skin testing group. Method This is a retrospective study. We reviewed CT cases performed between Jan. 2008 and Dec. 2014. All patients were performed skin testing just before their pending nonionic CM-enhanced computed tomogram (CT). Skin testing and CT scan were performed through two-step process. One step; 1 st Skin test was performed with a common nonionic CM. If 1 st skin test negative, nonionic CM-enhanced computed tomogram (CT) was performed. Second step; If 1 st skin test positive, 2 nd skin tests were performed with two other nonionic CM and saline (negative control). If 2 nd skin test negative, 2 nd skin test negative nonionic CM-enhanced CT was performed. If 2 nd skin test positive, clinician gave patients premedication before enhanced CT or exchanged alternative radiologic test without CM. Results IHR were noted in 21 of total 26638 patients (0.08%). 5 of 26638 patients (0.01%) had severe IHR. Symptoms of IHR were nause/vomiting, erythema/urticaria/pruritis,dyspnea, chest tightness, angioedema, hypotension and syncope. Conclusion Nonionic CM prescreening skin testing through two-step process may be useful for reducing IHR and for selecting safe CM. The evaluation of trigger allergen is important for the treatment and prevention of allergic rhinitis (AR). Several nationwide studies revealed that there were regional differences in prevalence of allergy sensitization for individual allergens and allergen types. In this study, using MAST CLA, we evaluate the allergen in AR patients in state level; Gwangju, Jeonnam area. We evaluated the differences in allergic sensitization across the levels of urbanization. Methods A total of 873 patients from Gwangju-Jeonnam region with allergic symptoms underwent MAST. Total nasal score (TNS) and serum total IgE were evaluated. 39 panels were evaluated in MAST and allergens with results greater than class 2(≥0.7 IU/mL) in considered as positive. Prevalence and distributions of allergen-specific IgEs and their correlations to serum total IgE and TNS were analyzed according to levels of urbanization and age.

A558

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

A569

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

A586

Allergen Sensitization in Zimbabwean Children with Atopic Dermatitis Jin-Kyong Chun 1 , Hilda Angela Mujuru 1 , Elopy N Sibanda 2 1 University of Zimbabwe, Zimbabwe; 2 Asthma Allergy and Immune Dysfunction Clinic Correspondence: Jin-Kyong Chun -University of Zimbabwe, Zimbabwe World Allergy Organization Journal 2016, 9(Suppl 1):A586
Background: The identification of food allergens implicated in the manifestation of atopic dermatitis is central to the prevention of serious hypersensitivity reactions and avoiding unnecessary and costly elimination diets. We investigated the profile of allergens sensitized in Zimbabwean children presenting with atopic dermatitis. Methods: Total 111 pediatric patients with atopic dermatitis attending an allergy clinic of Zimbabwe were evaluated with Euroimmun®immunoblotting assays from Jan. 2010 to Dec. 2014. The median age of subjects was 5 years of age (range: 0-16 years of age). Total of 14 allergens were tested in each patient. Results: 56.8% (63/111) were sensitized to at least one food allergen. Potato-specific IgE was detected with highest frequency as 32/111 (28%). Two-thirds 64.5% (40/62), of the tested children under 7 years of age were food allergen sensitized. Approximately half, 47% (23/49) of children older than 7 years were sensitized. There was no statistically significant difference between the two groups (relative risk: 1.39, 95%CI: 0.96-1.99). In terms of egg allergy, there was a statistically significant difference between the under and over 7 years of age groups (relative risk: 1.89, 95%CI: 1.47-2.50, P < 0.001). Among 63 patients who showed positive result, 40 patients (63%) showed multiple sensitizations to more than 3 allergens. 89% of patients who have wheat allergy also showed sensitization against rice as well. There was no concordance between milk allergy and soy allergy. Peanut sensitization was found in 27% of enrolled patients, 2/3 of patients with peanut allergy showed cross-reactivity with hazelnut. The most serious adverse effect of peanut allergy in this population was the oral allergy syndrome. There was no serious anaphylactic reaction in patients with peanut or potato allergy. Conclusions: Food allergen sensitization is common amongst children with atopic dermatitis. The highest sensitogens, potato and peanut were not associated with severe allergic reactions. Egg allergy is predominantly seen in children under 7 years of age. Background Vitamin D has important functions in the immune system. In recent years, several studies have reported an association between vitamin D levels, atopy, asthma and respiratory tract infections. Objective We aimed to investigate whether vitamin D insufficiency in asthmatic adults associates with atopy, poor asthma control, and more frequent respiratory tract infections, and whether these patients can benefit from vitamin D supplementation.

Conclusions

Active vaccination surmounts the effects of passive antibody therapy in the mouse model, but the presence of IgE tops the antigenspecific experiments. This study therefore suggests that IgE antibodies may play a significant role in innate cancer surveillance as well as during active anti-cancer immune responses.

A597

Failure to Recognize Lymphopenia in Newborn Leads to Undetectable Primary Immunodeficiency Endah Citraresmi Harapan Kita Women & Children Hospital, Indonesia World Allergy Organization Journal 2016, 9(Suppl 1):A597 Background Primary immunodeficiency (PID) has not been well known in Indonesia. Most physicians considered that PID is difficult to diagnose because the laboratory equipment in Indonesia is not complete. However, using simple laboratory tests such as CBC, a lot of data can be retrieved and be used as a clue in diagnosing PID. Case A baby girl, 7 days old, was referred to neonatology unit from other hospital due to thrombocytopenia with mark increased in AST and ALT. She received IVIG for 3 days in previous hospital. Her laboratory tests showed the percentage of lymphocytes ranged between 35.6 % -66 %. Retrospective calculation revealed total lymphocyte count ranged between 2760 -3830/uL (normal value >3400/uL). Neutrophil count within normal limits. Levels of IgM and IgG antibodies to rubella increased, accompanied by increased levels of IgG antibodies to toxoplasma, CMV and HSV1. She received PRC and TC transfusions. She was diagnosed as having rubella infection, discharged in good condition after 24 days of treatment. She then had Hepatitis B and BCG vaccination in outpatient clinic. At age 3 months, she experienced dyspnea, admitted to PICU for pneumonia that needed ventilator support. Her laboratory tests again showed lymphopenia. Further exploration found increased levels of IgM, with normal level of IgG, IgA and IgE, also decreased CD4 and C3 levels. HIV PCR was negative. IgM CMV was positive; she was treated with gancyclovir. She was died after 30 days of hospitalization. Discussion CBC test result does not automatically include the value of total lymphocytes; it included only the percentage of lymphocytes. Because the lymphocytes percentage were always within normal limits, the treating physicians were not concerned with the low value of total lymphocytes, reflecting the low levels of T and/or B lymphocytes. Unfortunately, the patient then underwent severe infection and further tests found low CD4 lymphocyte levels with increased levels of IgM. There should be an opportunity to explore PID, especially in this case the possibility of Severe Combined Immune Deficiency (SCID), in the first hospitalization during newborn period. If we were aware of PID, this patient could be treated and prevented for possible severe infections.

A608

Glatiramer acetate (GA) is a generally safe, effective and well tolerated drug, but discontinuation of treatment may be required in up to 10% of cases due to severe systemic postinjection reactions. Notably, there are only sparse data on desensitization protocols for patients with hypersensitivity to GA. We present 2 cases of successful desensitization to Glatiramer acetate (GA). A 51-year-old female with MS was treated with GA for the last four years without any adverse reaction. Suddenly, after GA injection she developed generalized urticaria. Skin prick (SPT) and intradermal (ID) testing to GA and mannitol (an inactive ingredient of Copaxone R with allergenic potential) was performed. Histamine and NaCl was used as positive and negative control. SPT showed a borderline reaction to GA (wheal diameter=3mm) at a concentration of 20mg/ml, while a positive reaction was shown on intradermal skin testing at a concentration of 0,002mg/ml. SPT and ID testing to mannitol, were negative. A procedure of desensitization to GA was carried out in an outpatient setting under close medical supervision. Increasing dosages of GA were administered subcutaneously every 15 minutes, at a starting dose of 20ng followed by gradual dose escalation up to 20mg. The entire desensitization procedure lasted 3 hours and 15 minutes. The desensitization procedure was well tolerated with no adverse events. The patient was able to resume GA treatment with no recurrence during a follow up period of 12 months. A 39 years old female was treated for MS with GA for 3 months without any adverse reaction until her last injection. Immediately after administration of Copaxone R she experienced, life threatening anaphylaxis with urticaria, angioedema, abdominal cramps, dyspnea, drop in blood pressure and loss of consciousness. The patient was referred to our department for further evaluation. Allergy testing, with the already described procedure, revealed positive ID test at 0,002mg/ml. We used exactly the same protocol of desensitization in an inpatient basis. During the process she experienced anaphylactic reactions were successfully treated. After 2 days the patient was able to tolerate 20mg of GA. The patient receives GA daily after 5 months without any adverse event. These 2 cases illustrates that rapid subcutaneous desensitization may allow continuation of GA treatment in patients with a history of systemic reactions. Background: Asthma exacerbations (AE) are caused for a variety of reasons including unrecognized disease, undertreated or unresponsive to conventional therapy asthma, recent exposure to triggers like viruses, usually rhinovirus or allergens. AE is defined as a worsening of asthma sufficient to require medical intervention and usually administration of oral steroids reflected objectively as a fall of PEF, FEV1 ≥20% or 30%. This study was performed to investigate the epidemics of exacerbations in mites monosensitized asthmatics. Seasonal variability of AE in such patients could be used as a tool for a convenient and preventive management. Non atopic asthmatic patients were used as a control group and this way we could understand how important trigger is the allergen comparing to virus. Methods: We have studied, from 1995 to 2014, AE in patients suffering from these two different phenotypes of asthma. Seasonal variation of AE in each phenotype separately and consequently comparison of them were evaluated by applying the x 2 -test and the null hypothesis. The null hypothesis is that there is not difference in the number of AE occurred in each month of the year. Results: Mite monosensitized patients (Month/AE number): Jan / 32, Feb / 41, Mar / 58, Apr / 59, May / 74, Jun / 55, Jul / 37, Aug / 10, Sep / 73, Oct / 67, Nov / 54, Dec / 30. By applying the χ2-test for 11 d.f we obtained χ2=84,319 (P-value<0,0001). Therefore the null hypothesis is not accepted and there is statistical significant difference in the number of AE occurred during the year (higher in spring and autumn months). Non atopic patients (Month/AE): Jan / 249, Feb / 239, Mar / 245, Apr / 237, May / 194, Jun/ 173, Jul / 124, Aug / 69, Sep / 249, Oct / 309, Nov / 283, Dec /. By applying the χ2-test for 11 d.f we obtained χ2=229,940 (P-value<0,0001). Therefore the null hypothesis is not accepted and there is statistical significant difference in the number of AE occurred during the year (higher in spring and winter months). Comparison of both time distributions revealed significant difference between them, χ2=62.042 and P-value<0.0. Conclusions: Our results showed that in Greece during 20 years (from 1995 to 2014) AE are seasonal variable in non atopic and mites monosensitized asthmatics but different between them. The results indicate that atopics react to viruses in a different way comparing to non atopics. Introduction: A large number of farmers work in paddy field around the world, suffering from asthma, allergy and systemic mycosis; however, it appears that adequate information on the fungal aerosols over the paddy field of 24-Parganas (North) and their allerginic effects of farmers are largely lacking. The aim of the study was to assess the concentration of the major airborne pathogenic fungal spore over paddy fields with an object to identify the fungal allergen which are causing respiratory allergy among farmers, by immune-clinical techniques. Method: Volumetric assessment of airborne culturable and nonculturable fungal spores was performed in the experimental site (North 24 Parganas, West Bengal, India) for 2 consecutive years (November 2011-October 2013) by using an Andersen Two Stage volumetric sampler and a Burkard Personal Slide Sampler for trapping culturable and non-culturable types of fungal spores. Culturable fungal spores were sub-cultured in medium for isolating and identifying individual species. The fungal antigens were prepared from the prevalent culturable types of selected fungal spores in Y-cell lysis reagent (buffer). The allergenic potential of the antigens were evaluated on atopic farmers by SPT (in vivo) followed by ELISA & IgE-specific Immunoblotting (in vitro). The antigens resolved in 11% SDS PAGE and IgE-reactive allergen were identified by western immunoblotting. Result: A total of 34 types of fungal spore and 24 types of viable colony-forming fungal spores were recorded. The major perennial cultured fungal spore types included Aspergilli group, Fusarium oxysporum, Cladosporium cladosporioides, Nigrospora oryzae, Helminthosporium oryzae, Alternaria alternata, Drechslera sp. etc. showed higher sensitivity in SPT. Among these fungal spores Aspergilli group (A.niger, A. fumigatus, A. flavus, A. clavatus, Penicillium claviforme) showed highest (23.7%) reactivity followed by Fusarium oxysporum, Helminthosporium oryzae, Alternaria alternate, Cladosporium cladosporioides, Nigrospora sp. in SPT carried out in 214 adult agricultural field workers with respiratory disorders. Total fungal protein of A.niger, A. fumigatus, A. flavus, A. clavatus, Penicillium claviforme, Fusarium oxysporum, Helminthosporium oryzae, Alternaria alternate, Cladosporium cladosporioides, Nigrospora sp. resolved into 11, 15, 17, 13, 16, 12, 10, 18, 13 and 12 distinct bands respectively in 11% SDS PAGE and in immunoblotting 5, 6, 4, 6, 7, 3, 4, 4, 5 and 3 IgE reactive allergens were identified respectively.

Results

Immunecheck human IgG (Proteometech Inc, Seoul, Korea) can detect IgG range from 1.2 to 40,000 ug/ml. To know the degree of agreement against other quantitative assay method, we compared our assay results of 30 human sera with an immunoturbidimetric assay using Cobas Integra 800 (Roche, Indianapolis, IN, USA). This comparison showed that Immunecheck human IgG had 74.2 -132.1% of degree of agreement and 0.9243 of coefficient of determination (R 2 ) against an immunoturbidimetric method. The detection limit of Immunecheck human IgE was 80 IU/ml of total IgE and their signals were increased depending on the concentrations of IgE.
The average of total IgE from 392 sera measured by ImmunoCAP and Protia Allergy-Q was 167.1 and 149.4 kU/l, respectively. Passing-Bablok regression analysis demonstrated that ImmunoCAP and Protia Allergy-Q exhibited almost perfect correlation (intercept, 5.6676 [95% confidence interval {CI} 4.3282, 6 .9388] and slope, 0.8676 [95% CI 0.8211, 0.9107]). Conclusions Protia Allergy-Q, a multiple allergy screening kit, is a low-cost screening test for patients with suspected allergy. It provides 60 kinds of specific IgE level but also total IgE level. Even though it is a semi-quantitative assay, total IgE concentration tested by Allergy-Q is nearly equal to that by ImmunoCAP. Therefore, it may be very convenient tool to measure not only specific IgE but total IgE concentration. A) Background: Asthma is considered as a common respiratory disease among farmers in many researches. In 13' International Journal of Hygiene and Environmental Health, farmers showed higher prevalence (8.0%) than all other population (6.7%). But there is no largescale research of the prevalence and current state of asthma among Korean farmers. B) Methods: Structured questionnaire was used to evaluate the demographic characteristics such as age, sex, place of residence, smoking, prevalence of asthma based on doctor diagnosis and possible risk factors like crop types, farming period, pesticide usage, indoor cultivation, respiratory protection usage. From 2013 to 2014, total 951 farmers answered the questionnaire. C) Results: Prevalence of asthma among male farmer was 5.2% and the prevalence among female farmer was 6.0%. Based on 2013 Korean national health and nutrition examination survey, prevalence of asthma among Korean male was 2.7% and the prevalence among female was 4.1%. The odds ratio of asthma for total pesticide use year (more than 20 years) was 2.07 (1.20-3.58 ) and the odds ratio for indoor cultivation was 0.97(0.49-1.90). D) Conclusions: The prevalence of asthma among farmers was higher than other population in Korea. Pesticide usage is considered as a risk factor of asthma. In further research, exposure measures and work-relatedness measures should be needed. Background: Dietary intake can have a positive or negative impact on both actual and perceived general health and immune status. The purpose of this study was to examine the impact of dietary intake of a variety of nutrients on perceived immune status in young adult women. Methods: A survey on dietary intake and perceived immune status was held among young Dutch women, aged between 18-30 years old. Perceived current immune status was scored on a scale ranging from 0 (very poor) to 10 (excellent). Subsequently, participants could indicate whether they perceived their immune status as normal or reduced. A food frequency questionnaire was completed recording past week food and beverage intake. From this data, the amount of various nutrients could be estimated, including fibers, sugar, tryptophan, beta-carotene, calcium, niacin, folate, thiamin, carbohydrates, riboflavin, vitamin A (retinol), vitamin B6, vitamin B12, vitamin C, vitamin D, and cholesterol. Non-parametric correlations (Spearman's r) were used to examine the association between perceived heath, immune status and nutritients. Dietary intake of those with normal and reduced perceived immune status was compared using the Mann-Whitney U Test. Results: N=329 young women (mean [SD] age: 20.7 [2.7] ) completed the survey. Significant correlations were found between immune ratings and consumption of tea (r= 0.124, p=0.023), sugar (r= -0.173, p=0.002), and carbohydrates (r= -0.125, p=0.022). N=109 women (33.1%) reported having a reduced perceived immune status. Women with a perceived reduced immune status reported consuming significantly more alcohol (p=0.025), and had significantly higher dietary levels of cholesterol (p=0.022), sugar (p=0.044), and vitamin B12 (p=0.021) when compared to women reporting a normal immune status. Discussion: The findings show that dietary intake is related to perceived immune status. However, some nutrients have a bigger impact on perceived immune status than others. Future studies, including objective measurement of immune biomarkers and nutrients, should confirm these findings.

A637

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

Methods

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

Results

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

Discussion

Our statistical data are limited due to the small number of patients included in this pilot study. However, the results are astounding with 94% having an IgG1 deficiency and 71% hypogammaglobulinemia. These results imply that screening for immune deficiency should be part of standard care for patients with DM1, however studies are warranted to investigate if IgG substitution therapy may lead to a decrease in infections and improving the quality of life.

Conclusions

Sublingual immunotherapy with tablet form in elderly AR patients sensitized to HDM is worth trying and no safety issue has become a problem, but further investigation results are needed. This study was supported by Lofarma SpA, Milano, Italy. Background: World population, over the age 65 (usually defined as the elderly) has been steadily growing, reflecting general trends of ageing societies. With advancing age, chronic diseases become increasingly prevalent and contribute to the loss of independence, frailty and increased risk of death. Understanding the role of environmental factors, specifically respiratory infections, in the pathogenesis of chronic respiratory diseases in the elderly may help in decreasing morbidity and extending the lifespan of this population. Methods: Healthy Ageing Research Center (HARC) which is a multidisciplinary research platform established at the Medical University of Lodz, involves research groups with various basic biological (immunologists, biochemists, molecular biologists) and clinical (geriatricians, psychiatrists, cardiologists and pulmonologists) interests and devoted to conduct research addressing key issues related to pathogenesis of increased morbidity in the elderly population. Here we present the HARC platform as a vehicle for development of multidisciplinary research related to various aspects of respiratory infections in the elderly. Results: Preliminary study involving elderly subjects (n=157; mean age 68.2) allowed to establish risk factors associated with frequent infections. In a multivariate analysis polytherapy (more than 5 prescription drugs) has been determined as one of the most important risk factors for frequent (defined as more than 3 per year) respiratory infections (OR=1.93 (CI95% 1.11-3.36). The effect of comorbidities as risk factors for respiratory infections, will be further analyzed in crosssectional study involving 3000 subjects randomly selected from the local population of elderly subjects. In collaboration with psychiatrics the prevalence and spectrum of respiratory infections among patients with various psychiatric disorders is being studied. Although viral infections are considered to be important triggers in asthma exacerbation in children and adults, it is difficult to extrapolate infection rates and specific pathogens from these studies to older adults with asthma. The study currently developed with microbiologist is aiming at assessment of the role of viral and bacterial triggers asthma exacerbation in the elderly patients. In parallel, in vitro model to assess the peripheral blood leukocytes immune response to rhinovirus infection and miRNA expression in the elderly patients with and without asthma has been introduced . Conclusions: Collaboration within multidisciplinary research team ( HARC platform) has allowed for development of innovative approaches to study various aspects of respiratory infections in the elderly population. Project is supported by the European Commission RegPot-2012-2013-1. Background: Capture-recapture models allow one to estimate the number of actual cases by assessing the probability of overlap between cases from multiple sources. The Korea Work-Related Asthma Surveillance (KOWAS) is a scheme designed to collect information on WRA cases from multiple reporting sources, which are the Korea Workers' Compensation and Welfare Service, occupational physicians, allergy and chest physicians, and regional work-related disease surveillance systems. The purpose of this study is to estimate the number of actual cases of WRA using the capture-recapture analysis. Methods: Capture-recapture analysis was used to obtain a nearly unbiased estimator (NUE) of the total number of WRA cases reported to KOWAS from 2004 to 2006. To do this, the 4 reporting sources were stratified into 2 categories as follows: (1) the workers' compensation scheme (i.e. the Korea Workers' Compensation and Welfare Service), and (2) the other 3 reporting sources (i.e. physicians' reports). Capture-recapture analysis was performed on sex, regions and specific industries when the number of overlapping reports was ≥7.
106 section matches
The small number of cases and the large variability in the parameters measured limited our ability to identify differences between groups. Despite the negative findings in this small, retrospective study, further study of the relationship between DOCP administration and CHF seems warranted. The oculocardiac reflex is the heart's physiological response to digital compression of the eyeballs, producing negative chronotropic and inotropic responses in healthy subjects. In this study, we investigated the autonomic imbalance in dogs with CHF due to myxomatous mitral valve disease (MMVD) by means of their individual response to that vagal maneuver. Fifty-two client-owned MMVD dogs (stages B1/B2/C/D) and twelve healthy dogs admitted for regular cardiac evaluation were recruited for a prospective observational study. Every dog had an ECG recorded for 5 minutes, and during the last minute both globes were compressed into the orbits using digital pressure until the 5 minute-recording was over. Twenty RR intervals were used to calculate the mean RR interval, the standard deviation of RR intervals, the root mean square of the successive differences in RR intervals and the vasovagal tonus index before eyeball compression and at approximately twenty seconds after compression started. The percent change of every surrogate was calculated. Although a significant difference was only documented for VVTI (P = 0.0419), the other surrogates did behave differently in stages C and D dogs as compared to B1 and B2 animals ( Figure 1 ). An explanation for this might be the parasympathetic withdraw in CHF, in addition to a subtle sympathetic activation due to discomfort, which was likely suppressed in dogs with preserved vagal response. Also, the sustained increased sympathetic activation rather than transitional sympathetic activation might be involved with the distinct response to OCR in symptomatic dogs as compared to the asymptomatic ones. In people, QT prolongation and instability are known to relate to ventricular arrhythmias. Since dogs with myxomatous mitral valve disease are prone to developing ventricular arrhythmias, this study investigated whether indices derived from QT interval could be used to predict an increased likelihood of arrhythmias regardless of clinical signs. 167 client-owned MMVD dogs (stages B1/B2/C) admitted for cardiac evaluation were recruited for a prospective cross-sectional study. Every dog underwent an echocardiogram and ECG recording. Fifty consecutive QT intervals were measured for each dog. QTs were corrected for heart rate and used to calculate the average QT (QTa), QT variance (QTv), total instability (TI), short term (STI) and long term (LTI) instabilities. A significant difference between asymptomatic and symptomatic animals was documented for every parameter (P < 0.0001),with higher values found for stage C dogs. Significant difference between B1 and B2 also existed for QTa. An AUC >0.5 was found when QTa and STI were used to discriminate dogs with or without ventricular arrhythmias (Figure 1 ). Dogs with QTa >310 (sensitivity:56%/specificity:71%), and STI >11 (sensitivity:56%/ specificity:85%) were shown to be slightly (15%) and moderately (30-45%) more prone to developing ventricular arrhythmias, respectively. Also, an AUC > 0.5 was documented when every QT index was used to distinguish animals with remodeled (B2/C) and non-remodeled hearts (B1). QTa and QTv best discriminated B1 from B2/C dogs and B1/B2 from C dogs, respectively. Because an increased QT instability was shown in symptomatic patients, QT indices might translate into prognostic surrogates for arrhythmias and CHF in MMVD dogs. Brachycephalic syndrome is characterized by primary and secondary upper respiratory tract abnormalities, which may result in significant upper airway obstruction. Cardiovascular and hemodynamic changes may also be present. However, unlike upper respiratory abnormalities which have been intensely studied, there is a paucity of information regarding cardiovascular and hemodynamic changes related to the syndrome.

C23

The evaluation of myocardial function through two-dimensional speckle tracking has been shown to be an effective method for the early identification of ventricular dysfunction, being safe and feasible for evaluation of myocardial function in dogs with suspected of some form of latent myocardial dysfunction not evidenced by conventional echocardiographic examination. Stress echocardiography with dobutamine is commonly indicated to detect cardiac dysfunction in asymptomatic patients, evaluating myocardial contractile reserve and viability. Pharmacological stress test was performed with dobutamine to evaluate the myocardial function via two-dimensional speckle tracking in healthy dogs and in different stages of the MMVM. The study included 15 Beagle dogs, distributed in 3 groups and selected according to the internal diameters of the left ventricle in diastole and the aortic ratio (DIVEd/Ao). The groups were constituted: Group I (Control) -5 healthy dogs without MMVD; Group II -5 dogs with MMVD (DIVEd)/Ao ratio lower than 2.8; Group III -5 dogs with MMVD and DIVEd/Ao ratio higher than 2.8. The animals were submitted to the echocardiographic examination performed by a single operator and evaluation was performed before and after dobutamine infusion. Dobutamine was diluted in 5% glucose solution, following the progressive scheme: 5 lg/kg/minute for 3 consecutive minutes; 7.5 lg/kg/minute for 3 consecutive minutes; 10 lg/kg/minute for 3 consecutive minutes. The images were analyzed using the Syngo Velocity Vector Imaging (VVI) algorithm optical flow algorithm (SIEMENS Ò ). Data were submitted to the normality test and to repeated measures analysis of variance and Tukey's test. The aim of this study was to evaluate the adaptations involving the left ventricle, across the gestational process and its diastolic function, using tissue Doppler echocardiography. Animals: 15 pregnant bitches, healthy aged 2-6 years and weighing between 5 and 15 kg. Heart rate and blood pressure clinical evaluation was performed, as well as echocardiography M-mode, spectral and tissue Doppler, in the estrous (EZ), every 15 days during pregnancy (PD 15, 30, 45 and 60) and 45 days post partum (PP). The variables from the evaluation were submitted to statistical analysis. Heart rate (HR) (P = 0.149) and systolic blood pressure (SAP) (P = 0.564) did not show significant changes during pregnancy. The parameters that have undergone significant changes were EF (P = 0.0016) and FS (P = 0.0019). AVVmax, PVmax, wave E'(s) S' (s) and S' (lat) being influenced by the gestational period (P < 0.05). These changes could be explained by cubic regression model. The E:A (P = 0.041) IVRT (0.044) relation and A '(lat) (0.023) also suffered influence of pregnancy, but had a nonparametric residual distribution. Pregnancy produces changes in maternal hemodynamics also influencing diastolic function. Myocardial contractility increases as a result of an improvement in systolic performance, while diastolic function changes significantly revealing a more compliant ventricle, which is the physiological response to increased volume and metabolic requirements due to gestation. Pulmonary hypertension (PH) is a hemodynamic and pathophysiologic condition defined an increase in systolic pulmonary artery pressure greater than 30 mmHg. Classically, this condition can lead to right ventricular dysfunction, which is associated to poor outcomes, especially in patients with chronic congestive heart failure. Unfortunately, right ventricular function in dogs with pulmonary arterial hypertension has been poorly investigated. Thus, the aim of the present study was to assess the right ventricular systolic function in dogs with tricuspid regurgitation and pulmonary hypertension by echocardiographic evaluation.

C30

The results confirm remodeling processes as a major component in the pathogenesis of canine DCM and suggest that cardiomyocytes at least contribute to the pathogenic processes. Atrial fibrillation (AF) is a common arrhythmia in dogs, usually associated with a rapid ventricular response rate, and typically managed with pharmacological rate control. This retrospective study aimed at assessing the effect of heart rate (HR) on survival time in dogs with AF. Forty-six dogs from 2 sites with AF and at least one 24 hours Holter recording were included from records reviewed between 2008 and 2016. The mean heart rate (meanHR, 24 hours average), minimum HR (minHR, 1 minute average), maximum HR (maxHR, 1 minute average) were recorded at the time when adequate rate control was presumed and no further adjustments of rate control therapy were made. Long-term outcome was ascertained and the primary study endpoint was all cause mortality.

N17

Neurologic signs included ophthalmoparesis/plegia (N = 13), reduced/absent pupillary light response (N = 11), mydriasis (N = 10), reduced/absent corneal sensation (N = 7), ptosis (N = 6), reduced facial sensation (N = 2), and enophthalmos (N = 1).
PC-3 is overexpressed in canine intracranial neoplasms and in high grade human astrocytomas relative to normal brain tissues. Immortalized canine, human, and murine glioma cell lines show in vitro sensitivity to PAC-1 and radiation monotherapies at biologically relevant exposures. Six dogs (3 gliomas 3 meningiomas) received PAC-1 combinatorial therapies and achieved objective responses (1 complete response, 3 partial responses, 2 with stable disease).

O02 DEVELOPMENT OF A HISTOPATHOLOGIC AND FLOW

Prognostic factors identified on univariate analysis as significant for median progression free survival time and/or MST included cell size on FC, presence of lymphocytosis, presence of hypercalcemia, need for dose reduction, experiencing complete remission as best response to therapy, and completing CHOP. Further studies are needed to determine factors that may allow for further patient stratification to eventually modify therapy to improve outcome. Canine osteosarcoma (OSA) is a highly aggressive mesenchymal cancer accounting for 85% of canine bone tumors. OSA commonly arises in the long bones of large breed dogs, and 95% of patients are thought to have micrometastases at diagnosis. Standard of care treatment for canine OSA consists of amputation followed by chemotherapy, with median survival times ranging from 207 to 366 days. Development of metastatic disease limits longterm survival, with 9.7%-28% of patients alive two years from diagnosis. Treatment of macroscopic metastasis is unrewarding and given this, therapy is focused on prevention of metastatic disease.
Serious complications were overall uncommon following resection of gastrointestinal lymphoma with the majority of cases found to survive the peri-operative period. Given the significantly longer survival times of cats with large intestinal lymphoma, it may be reasonable to recommend surgical removal for cats with solitary lymphoma tumors in this location. The purpose of this study was to solicit data regarding current clinical use of toceranib in dogs with gastrointestinal stromal tumors (GIST) to provide initial assessment of biologic activity. The American College of Veterinary Internal Medicine Oncology and Small Animal Internal Medicine listservs were used to solicit data pertaining to cases in which toceranib was used to treat canine GIST. Case data from 28 dogs with histopathogically confirmed GIST were received from 17 participating institutions. Dogs undergoing treatment other than surgical excision prior to toceranib were excluded. Clinical benefit (CB) was observed in 93% (26/ 28; 24 complete response [CR]/no evidence of disease [NED] , 1 partial response [PR] , 1 stable disease [SD] ). All dogs with microscopic disease experienced CB (21/21; 21 NED), while 71% (5/7; 3 CR, 1 PR, 1 SD) with gross disease experienced CB. Median duration of treatment in dogs experiencing CB was 36 weeks (1-159). At the time of data submission, 8/26 responding dogs were still receiving treatment and an additional 4/26 were experiencing continued NED following completion of prescribed therapy. In dogs with CB, the median toceranib dose was 2.6 mg/kg (0.5-3.5) and in 81% (21/26) was given three days per week. Treatment was well-tolerated with 57% (16/28) experiencing adverse events, a majority of which were Grade 1 or 2 gastrointestinal toxicities. Biologic activity of toceranib is evident in studied dogs; however, prospective studies are needed to refine the role of toceranib in treatment of GIST in microscopic and gross disease settings. Regulatory T cells (Tregs) play an integral role in suppression of inflammation and the maintenance of immunological tolerance. In addition, Tregs infiltrate into a variety of tumor tissues and thereby suppress antitumor immunity. However, data on the association between tumor-infiltrating Tregs and prognosis in dogs with various tumors are limited. The purpose of this study was to examine the number of tumor-infiltrating Tregs and their association with prognosis in dogs with solid tumors.
Minimal side effects were noted in the healthy dogs. Vitals showed normal variation during the study; gastrointestinal signs (most often noted as random emesis) were documented in three of four dogs. Pro-inflammatory cytokines (IL-6, IFNc, TNFa, and CCL2) and anti-inflammatory cytokine IL-10 were produced, although significant inflammatory-type symptoms were not noted in the healthy dogs. Both clinical patients were discharged the same day of the leukapheresis procedure. The only clinical patient who received ex vivo-activated T cells had not been pre-medicated and experienced a severe inflammatory response and became septic. The dog recovered and is still alive 11 months after diagnosis with no signs of metastasis and with no further cancer therapy.
Based on the encouraging safety data in our healthy canine patients, this adoptive T cell transfer approach has the potential to change treatment recommendations and outcome in dogs diagnosed with osteosarcoma. A phase I/II clinical trial is ongoing to determine if ECI-OSA-1 after amputation is indeed safe and results in similar or enhanced efficacy compared to surgery and chemotherapy. Exosomes are small lipid vesicles that mediate cell-to-cell communication. Cancer cells exploit exosomes to promote metastasis, evade host immune responses, and facilitate angiogenesis. Presently, the effects of osteosarcoma (OSA) exosomes on healthy osteoblasts have not been studied. This is the first study to investigate the proteomic composition of canine OSA exosomes and their impact on osteoblasts. We hypothesized that OSA exosomes carry a unique cargo which manipulates healthy osteoblasts, resulting in alteration of bone turnover.

O11

Based on this proof of target study, further investigation is warranted to determine clinical response of TCC to Palladia. Chemotherapy-induced vomiting and inappetence (CIVI) are common adverse events experienced by cancer patients. However the incidence and recommended treatment following administration of specific chemotherapeutics has not been established in dogs. The aim of this study was to assess perceived emetogenic and inappetence potential of chemotherapeutics and evaluate the clinical use of antiemetics and appetite stimulants in dogs receiving chemotherapy.
Eighty-five completed surveys were evaluated with responses from oncologists (83.5%) in private practice (73%) with >80% of their practice being medical oncology (70.6%). The oral chemotherapeutics evaluated were associated with a minimal/low (≤50%) risk of acute and delayed vomiting independent of VCOG grade. Injectable chemotherapeutics most associated with moderate/high (>50%) risk of causing clinically significant (≥Grade 2) acute or delayed vomiting included cisplatin, dacarbazine, epirubicin, paclitaxel and streptozocin. Of the nine antiemetics evaluated, maropitant and ondansetron were most frequently administered. Inappetence following chemotherapy administration was most commonly treated with maropitant and mirtazapine.
The perceived incidence and management of CIVI in dogs widely differs. Dogs receiving chemotherapeutics with currently perceived lower potential for CIVI may also benefit clinically from treatment with antiemetics and/or appetite stimulants. Further research to understand the true incidence and clinical impact of CIVI will contribute to development of guidelines to appropriately manage these effects in dogs. Cutaneous lymphoma represents 1% of skin tumors in dogs and is classified in epitheliotropic and nonepitheliotropic. Unlike the other anatomical forms of lymphoma, cutaneous lymphomas have a low response to the treatment, and dogs with nonepitheliotropic lymphoma have a lower survival time when compared to dogs with epitheliotropic form. The resistance of neoplastic cells to cytotoxic drugs is the major cause of failure of chemotherapy in cancer and one of multiple drug resistance mechanisms (MDR) is the active drug efflux mediated by ATP-Binding Cassette superfamily (ABC). Among these transporters is P-glycoprotein (ABCB1).The aim of this study was to investigate ABCB1 immunoexpression in cutaneous epitheliotropic and non-epitheliotropic lymphoma. Immunohistochemistry was performed in 18 paraffinembedded tumor samples of cutaneous lymphoma in dogs (11 nonepitheliotropic and 7 epitheliotropic) using CD20 and CD3 markers for immunophenotyping and ABCB1 antibody (C494 -Enzo Life Sciences Ò ). It was found 5 epitheliotropic T-cells and 2 B-cells and 10 nonepitheliotropic T-cells and 1 B-cell lymphoma. Two samples of epitheliotropic lymphoma were negative for ABCB1 and the median percentage of labeled cells was 20% (0-40%) whereas in nonepitheliotropic lymphoma, all cases were positive for ABCB1 and the median percentage of labeled cells was 50% (20-90%) and statistical analysis showed a significant difference expression of this marker (P = 0.0162). In conclusion, the majority of cases with cutaneous lymphoma expressed P-glycoprotein and the subtype nonepitheliotropic showed higher labeled cells than epitheliotropic. Intestinal lymphoma is the main anatomical form of lymphoma diagnosed in cats. Cell proliferation indicators as Ki-67 expression and mitotic index may be important in assessing the clinical behavior of the tumor and to determine the degree of malignancy. The objectives of this study were to determine the expression of Ki-67 and mitotic index in intestinal lymphoma of cats and its relation with overall survival time. Forty-seven samples of cats with intestinal lymphoma were studied and immunohistochemical was performed for: CD3, PAX5 and Ki-67. The analysis of Ki-67 was made by counting 1,000 infiltrating lymphocytes in the tumor microenvironment and mitotic index was ranked as mild, moderate or high, by the evaluation of 10 microscopic fields at 409. The results showed a significant difference in the immunohistochemical expression of Ki-67 in B and T-cell Lymphoma (P = 0.001) with a median of 47.2% and 8.5%, respectively. The same was observed when comparing the histological type (lymphoblastic and lymphocytic), with a median of 40.5% and 8.2%, respectively (P = 0.002). Regarding mitotic index, two cats with lymphoblastic B-cell and one with lymphoblastic T-cell lymphoma showed high expression, while three animals showed moderate expression and the majority of cases, 41 animals (87.2%) had mild expression. In conclusion, Ki-67 expression was a better proliferative marker when compared to mitotic index in cats with intestinal lymphoma. Higher expression of Ki-67 was observed in those animals affected by lymphoblastic or B-cell and is related to low therapeutic response and shorter survival time. is typically caused by a growth-hormone (GH) secreting pituitary adenoma and is thought to be a common cause of feline diabetes mellitus. Medical pituitary inhibition has been challenging in some humans and cats with this condition. This could be related to variable expression of somatostatin (SSTR) and dopamine (DR) receptor expression. There are five different SSTR subtypes (SSTR1-5) and five different subtypes of DRs, with D2R being the predominant DR subtype in the human pituitary. Pasireotide, a somatostatin analogue with high binding affinity to SSTR1, SSTR2 and SSTR5, is effective at controlling GH secretion in feline acromegalics but somatostatin analogues with high binding affinity to SSTR2 (octreotide and lanreotide) are not.
Feline GH-secreting adenomas expressed SSTRs are similar to human GH-secreting adenomas, having higher SSTR1, SSTR2 and SSTR5 expression than SSTR3 and SSTR4. However, the higher expression of SSTR1 and SSTR5 vs SSTR2 than in most humans may explain the greater biochemical response to pasireotide than octreotide. Decreased D2R expression in larger tumours may be a mechanism allowing unchecked adenoma growth. The receptor expression profiles of feline GH-secreting adenomas will help the search for improved medical management options of feline hypersomatotropism. The ACTH stimulation test, using cosyntropin at 5 mcg/kg IV, is the preferred method for diagnosis of hypoadrenocorticism. Previous studies have shown maximal stimulation of the adrenal glands using 1 mcg/kg cosyntropin in normal dogs. No studies have evaluated the efficacy of the lower dose in dogs suspected of hypoadrenocorticism. Our objective was to compare 1 mcg/kg (low-dose) to 5 mcg/kg (high-dose) cosyntropin IV to determine if both doses result in a similar adrenocortical response.
Therefore, the 1 mcg/kg IV dose of cosyntropin does not cause maximal adrenal response as does the standard 5 mcg/kg IV dose in dogs suspected of hypoadrenocorticism. The lower dose is not sufficient for ACTH stimulation testing in those patients suspected of hypoadrenocorticism. A veterinary-specific enzyme-linked immunoassay (ELISA) (SNAP Cortisol Test Kit, IDEXX, USA) is available to veterinarians for in-house diagnosis and management of canine hypo-and hyperadrenocorticism. However, analytical performance of the assay has not been reported in peer-reviewed literature. The purpose of this study was to investigate the precision of the ELISA, agreement of the ELISA with two chemiluminescence assays (CAs) at two reference laboratories, and the clinical implications of any identified bias.

EN03 PERFORMANCE EVALUATION OF

Our findings suggest that when using an AlphaTrak2, the accuracy and reliability of a glucose measurement obtained may be increased when using whole blood compared to serum or plasma. Thus, use of whole blood would allow for a more correct assessment and diagnosis which are necessary for appropriate therapeutic intervention. Optimal irradiation schedule for canine adrenocorticotropic hormone (ACTH) secreting pituitary tumors has not been defined and response evaluation criteria has not been established.
The aim of this study was to evaluate time-related clinical and magnetic resonance imaging (MRI) response in dogs suffering from pituitary hyperadrenocorticism with a measurable mass at MRI treated with stereotactic radiotherapy (RT).
A single institution prospective single arm observational study was conducted. Dogs naive of any endocrine treatment suffering from pituitary hyperadrenocorticism diagnosed by standard laboratory and imaging tests were irradiated with 6 MV LINAC using Volumetric Modulated Arc Therapy with a dose of 38 Gy delivered in 10 fractions on alternated days basis. Concomitant administration of trilostane were started. Tumor and endocrine response were evaluated by repeated MRI of pituitary and adrenal glands at 0-2-4-6-8-12-18-24 months. Basal and ACTH-stimulated cortisol were serially measured and the dose of trilostane to achieve eucortisolism was recorded.
The RT schedule used in this study allowed optimal tumor and endocrine control. A gradual progression in the response was observed, starting with a volumetric response of the pituitary tumor, delayed of several months after the treatment, than a response of the adrenal glands and ultimately a reduction of the serum cortisol levels was achieved. This pattern of response must be taken in consideration during follow up evaluation to adjust the dose of trilostane and to establish evaluation criteria. Insulin glargine 300 U/ml (Toujeo Ò ) and insulin detemir (Levemir Ò ) are synthetic long-acting insulin analogs associated with minimal intra-and inter-patient variability or episodes of hypoglycemia in people. Toujeo Ò is more predictable and longer acting compared to glargine 100 U/ml (Lantus Ò ) in people. The purpose of this study was to assess the pharmacokinetics or pharmacodynamics of Toujeo Ò compared to Levemir Ò in healthy dogs.
Thirty ACTH stimulation tests were performed on 15 dogs divided into 2 groups: 5 control animals (2 females and 3 males, healthy, mean age 2.5 AE 1.5 years) and 10 treatment animals (6 females and 4 males, previously hyperadrenocorticism diagnosed, mean age 11.7 AE 2.3 years). All animals were controlling them, in other words, first were challenged with Synacthen and then with Acthelea. For dogs on trilostano (1-2 mg/kg/day), ACTH stimulation tests were initiated 4-6 hours postpill administration as per manufacturer instructions. The first stimulation tests were performed using Synacthen as the drug of election to induce cortisol response and the second, which were separated by 15 days period, using Acthelea. Blood samples were obtained just before injection and 60 minute post-ACTH. The first to assess the cortisol basal concentration of control group (CSynbas and CEleabas) and Treated group (TtoSynbas and TtoEleapos) and the second collection for assessment of cortisol concentration post-ACTH in the control group (CSynpos and CEleapos) and treated group (TtoSynpos and TtoEleapos).The doses were: 0.04 mL/Kg for Synacthen and 0.08 mL/Kg for Acthelea, IV. Serum cortisol concentrations were measured at the PROVET/BR Hormone Laboratory using previously validated radioimmunoassay (MP Biomedicals).

EN21

This study found that dogs with AP exhibited decreased 25-(OH)D levels, which might be the result of inflammatory responses rather than a cause of AP. Moreover, alterations in serum 25-(OH)D concentrations might be associated with disease severity or mortality in dogs with AP. A high prevalence of cholestatic disease, including gall bladder mucocele (GBM) has been reported in dogs with naturally-occurring pituitary-dependent hyperadrenocorticism. Differences exist in the clinical features of dogs with PDH and concurrent cholestatic disease, and also is the management of these dogs with trilostane. In this study, 65 client-owned dogs with naturally-occurring PDH were analyzed. Each dog was treated with trilostane for at least 3 months before the study, and had a good clinical response, as determined by owners. Statistical comparisons of clinical signs, results of routine blood tests, basal and post-ACTH cortisol concentration, and optimal trilostane dosage were made after dogs were separated into the following 3 groups by ultrasonographic imaging: normal on ultrasound (NOU) group, cholestasis group, and GBM group. The GBM group had more severe clinical signs, and significantly different total serum cholesterol concentration and post-ACTH stimulation cortisol concentration at the time of diagnosis. Dogs that weighed <6 kg had a significantly higher prevalence of cholestatic disease than did the other dogs (P = 0.003). The optimal trilostane dosages for the GBM and cholestasis groups were 2.5 and 1.5 times the dosage of the NOU group, respectively (P < 0.001). Gall bladder disease associated with cholestatic disease is correlated with PDH in dogs, both in its clinical features and drug management. These findings may be associated with hypercholesterolemia, unidentified genetic factors, and the hydrophobic nature of trilostane. Hypothyroidism is a common endocrinopathy in dogs; however, the diagnosis of hypothyroidism may be difficult because nonthyroidal illness (NTI) and medication might affect the results of thyroid function tests. The objective of this study was to evaluate the usefulness of a thyrotropin (TSH) stimulation test for diagnosing hypothyroidism.
The results suggest that hypertriglyceridemia, hyperproteinemia, and decreased PCV can significantly affect the results obtained by various PBGMs. Clarification of the causes of errors in glucose measurements should lead to more accurate assessment of disease and appropriate glucose control and treatment for diabetic dogs. Previous studies have shown a relationship between mucosal bacteria and host responses in cats with inflammatory bowel disease (IBD) and lymphoma (LSA). However, these earlier studies have not investigated the specific microbial etiologic factors nor the selective recruitment of mucosal tumor-infiltrating immune (CD11b+) cells which may promote tumor progression. The objective of the present study was to investigate the relationship between pro-inflammatory microbiota (including Fusobacterium spp., Helicobacter spp., Enterobacteriaceae) and mucosal CD11b+ cells in cats with small cell LSA vs. IBD. A retrospective analysis of cats diagnosed with intestinal LSA (n = 14) or IBD (n = 14) from 2010-2015 was performed. Following detailed diagnostic evaluation and confirmation of a histopathologic diagnosis, the mucosal microbiota of endoscopic intestinal biopsies of IBD and LSA cats was evaluated by fluorescence in situ hybridization (FISH) targeting the 16S rRNA genes of select pro-inflammatory microbiota. Host responses to microbial dysbiosis were studied using immunohistochemistry to identify cells of the gastrointestinal mucosa expressing intestinal NF-kB (p65) and CD11b+. Results indicated that most IBD/ LSA cats were middle aged or older having chronic gastrointestinal signs of several months duration. Analysis by FISH showed that mucosal bacteria (EUB) were uncommonly observed in the duodenum of diseased cats. The numbers of mucosal Bacteroides spp. and Clostridium spp. were increased (P < 0.05) in IBD cats as compared to cats with LSA. Conversely, total numbers of Fusobacterium spp. were increased (P < 0.05) in colonic tissues of cats with LSA vs. IBD (LSA: median 30 [range 0-378]; IBD: median 9 [range 0-346]). Moreover, the numbers of Fusobacterium spp. found within adherent mucus of colons in cats with LSA were increased (P ≤ 0.05) relative to other mucosal compartments. Mucosal cells expressing NF-kB and CD11b+ were increased (P < 0.05) in intestines of cats with LSA vs. IBD suggesting the presence of a pro-inflammatory microenvironment. In conclusion, alterations exist in the composition of the mucosal microbiota in cats with LSA and IBD. The intestine of cats with LSA is selectively enriched with bacterial species, including Fusobacterium spp. These microbiota may trigger recruitment of tumor-infiltrating immune (CD11b+) cells contributing to a pro-inflammatory environment that is conducive for intestinal LSA progression. Diarrhea and other sequelae of gastrointestinal hyperpermeability are common complications of antibiotic therapy. Akkermansia muciniphila is a mucin-degrading bacterium, positively associated with gastrointestinal epithelial health and decreased permeability. The objectives of this study were to measure effects of Akkermansia administration on markers of gastrointestinal permeability following antibiotic administration.
In dogs with extrahepatic bile duct obstruction secondary to pancreatitis, age of 9 years or older, azotemia at admission, body temperature greater than 102.5°F at admission and lack of gallbladder distension on ultrasound are associated with an increased risk of death. Medical vs. surgical management, total bilirubin at admission, change in total bilirubin during hospitalization, and magnitude of increased liver enzyme activity were not significantly associated with outcome in this group of dogs. Canine Inflammatory Bowel Disease (IBD) is believed to be a multifactorial disease due to an abnormal immune response to intestinal microbes in genetically susceptible individuals. IL-1b, a pro-inflammatory cytokine, has previously been shown to be elevated in biopsies of dogs with food responsive disease in a small number of cases. The purpose of this study was to investigate duodenal levels of IL-1b protein in a larger number of dogs with different clinical severity of IBD. Duodenal biopsies from ten dogs each with mild IBD (Canine Chronic Enteropathy Clinical Activity Index, CCECAI 0-5), moderate IBD (CCECAI 6-8), severe IBD (CCECAI ≥9) and dogs with protein-losing enteropathy (PLE), as well as 10 healthy Beagle dogs were included in the study. Biopsy samples were weighed prior to manipulation. Samples were homogenized at 20 Hz for 2 minutes in 500 lL homogenization buffer (PBS containing 0.05% Tween-20) with protease inhibitor cocktail. Tissue homogenates were centrifuged at 12500 RCF for 2 minutes and the supernatants frozen at À80°C until the day of ELISA. Quantification of IL-1b protein expression was determined using a commercially available canine-specific IL-1b ELISA (Kingfisher Biotech Inc) following the manufacturer's assay instructions. All samples were analysed in duplicate. Median IL-1b expression (pg/ml/mg tissue) was 121.6 (range 38.3-219.4) in the severe IBD group; 19.7 (range 10.9-24.8) in the moderate severity IBD group; 13.3 (range 8.0-29.8) in the mild severity IBD group, 13.0 (range 8.0-27.9) in the PLE group, and 0.9 (range 0.3-1.4) in the healthy control dogs. There was a statistically significant difference in IL-1b expression between all IBD dogs and the healthy controls (p2 = 0.47, P < 0.001). The results of this study support previous findings that IL-1b may be involved in the pathogenesis of canine IBD. Criteria developed by the World Small Animal Veterinary Association (WSAVA) are commonly used for the assessment of feline intestinal biopsy specimens. However, the histological characteristics of intestinal biopsy specimens collected from healthy cats have not been well characterized using this scoring system. The aim of this study was to describe the histologic findings in endoscopically derived intestinal biopsy specimens from clinically healthy cats.

GI09

No global changes in the microbiome and metabolome were observed based on multivariant analysis (ANOSIM, P > 0.05). However, some bacterial genera were altered following omeprazole administration including an increased relative abundance of Streptococcus, Lactobacillus, Clostridium, and Faecalibacterium spp. and decreased Bifidobacterium spp. in all cats. The results of this pilot study suggest that omeprazole might have little impact on the feline fecal microbiome and metabolome when administered for 60 days or less. Larger studies are needed to confirm these results. There is evidence that oxidative stress plays an important role in the pathogenesis of IBD in human patients particularly in the initiation and perpetuation of inflammation and in subsequent tissue damage. Oxidative stress occurs when there is a marked imbalance between the production of Reactive Oxygen Species (ROS) and their removal by antioxidants. Recent publications suggest that oxidative stress could also represent a significant factor in the pathogenesis of IBD in dogs. The objective of this study was to compare a panel of various serum biomarkers evaluating both the antioxidant response and the oxidative damage in dogs with inflammatory bowel disease (IBD) and healthy control dogs. Eighteen dogs with IBD and 20 healthy dogs were enrolled in the study. Trolox equivalent antioxidant capacity (TEAC), cupric reducing antioxidant capacity (CUPRAC), ferric reducing ability of the plasma (FRAP), total thiol concentrations, and paraoxonase 1 (PON1) activity were evaluated in serum to determine antioxidant response. To evaluate oxidative status, ferrous oxidation-xylenol orange (FOX), thiobarbituric acid reactive substances (TBARS) and reactive oxygen species production (ROS) concentrations in serum were determined. Mean concentrations of all antioxidant biomarkers analyzed, with exception of FRAP, were significantly lower (P < 0.0001) in serum of dogs with IBD than healthy dogs. The oxidant markers studied were significantly higher (P < 0.0001) in serum of dogs with IBD than in healthy dogs. These findings support the hypothesis that oxidative stress plays an important role in the pathogenesis of IBD in dogs. L-lactate is generated from pyruvate via lactate dehydrogenase during normal cell metabolism. Lactobacillales (lactic acid bacteria) in the intestinal tract can synthesize both D-and L-lactate. Currently, serum lactate concentration is used as a marker of tissue hypoperfusion and hypoxia. Cases of D-lactic acidemia have been reported in dogs and humans with intestinal disease. Fecal lactate has also been shown to be increased in humans with short bowel syndrome and calves with diarrhea. Fecal lactate concentrations might serve as a marker of the microbial activity in the intestine. Therefore, the aim of this study was to analytically validate an enzymatic method for the measurement of both D-and L-lactate in canine feces.

GI33

Baseline fecal samples were collected from dogs with acute hemorrhagic diarrhea syndrome (AHDS, n = 22), food-responsive diarrhea (FRD, n = 10), steroid-responsive diarrhea (SRD, n = 24), and healthy control dogs (n = 82). In a subset of diseased dogs, follow-up samples were collected 2-3 months after the baseline sample (AHDS, n = 7; FRD, n = 6; SRD, n = 9). Diagnoses of FRD and SRD were based on response to therapy. All dogs with FRD were successfully managed with the same vegetarian diet. Feces were analyzed by gas chromatography/mass spectrometry (GC/MS) using an in-house assay. At each of the two timepoints, a Kruskal-Wallis test and the Benjamini-Hochberg step-up method to adjust for multiple comparisons were used to identify significantly altered compounds. Dunn's test was used to compare groups, and statistical significance was set at P < 0.05.
The most profound changes in fecal sterols observed were at baseline between dogs with AHDS and healthy control dogs, but many of these changes normalized rapidly. The observed differences between dogs with SRD and FRD at follow-up after 2-3 months may be largely due to the effect of diet. Future studies are required to evaluate the utility of these compounds as markers of disease phenotype or response to therapy. Cholesterol is the most abundant sterol in mammalian tissues, playing a critical role in cell membrane function and serving as a precursor molecule for hormones, vitamins, and bile acids. Structurally similar to cholesterol, phytosterols have been associated with anti-inflammatory effects in rodent models of colitis. Previous studies have shown altered fecal sterol concentrations in dogs with chronic enteropathy. Fatty acids are an important source of energy, and along with sterols, they are also critical for intestinal epithelial cell membrane structure and function. The aim of this study was to analytically validate a gas chromatography/mass spectrometry (GC/MS) assay for the measurement of several sterols (i.e., cholesterol, coprostanol, cholestanol, b-sitosterol, stigmasterol, campesterol, sitostanol, and fucosterol) and fatty acids (i.e., palmitic, oleic, linoleic, a-linolenic, stearic, gondoic, and erucic acids) in canine fecal samples.
These results suggest that the early low and then increase abundance of Proteobacteria could be related to overweight development. However, Proteobacteria have highly diverse metabolisms and further analyses at genus level and/or metagenomics analyses may explain the underlying link between the microbiota modulation and excessive weight gain. The gastrointestinal (GI) microbiota is considered to play a crucial role in the onset, progression, response to treatment, and outcome in many disease processes including chronic enteropathy (CE) in cats. However, only limited information on the fecal microbial composition in cats with CE is available. The aim of this study was to characterize the fecal microbiota in cats with histologically confirmed CE before and after treatment.
Serum IL-17 was measured in thirty dogs with primary IMHA at diagnosis (D0); and 2 (D2) and 4 (D4) days after initiation of immunosuppressive therapy as well as in 25 clinically healthy dogs. IL-17 was significantly increased at the time of presentation (D0) in dogs with IMHA (P = 0.0158) compared to healthy dogs as well at D2 (P = 0.0404). Over the course of hospitalization, IL-17 significantly decreased between D0 and D2 (P = 0.0146) and D0 and D4 (P = 0.0010) for the discharged patients (N = 19) . No changes in IL-17 levels were observed between D0, D2 and D4 among the dogs that were euthanized in hospital. There was no correlation between IL-17 concentration and bilirubin levels, lactate or any of the CBC parameters at the time of presentation or throughout the hospitalization. IL-17 is elevated in dogs with IMHA and seems to decrease when response to therapy is observed. Oxidative stress plays a considerable role in the pathophysiology of multiple diseases and has been well documented as a contributor to disease in both the human and veterinary literature. Oxidative stress results from the production of reactive oxygen species that cause cellular injury through direct and indirect mechanisms. One at-risk cell type is the erythrocyte, however, the role of oxidative stress in canine anemia has not been investigated. Oxidative stress is primarily assessed through the activity of antioxidant enzymes, the concentration of endogenous antioxidants, and byproducts of oxidative damage. The purpose of this study was to determine if oxidative stress is present in anemic dogs. We hypothesized that anemic dogs would have an alteration in the activity of glutathione peroxidase (GPx), a reduction of total antioxidant capacity (TAC), and an increased concentration of urinary F2-isoprostanes (F2IsoP, a byproduct of lipid peroxidation) when compared to healthy dogs.
Both markers of NETs increased during RBC storage and were higher in NLR than LR units (Figure 1 ). Isolated neutrophils did not form NETS in response to supernatant from stored canine RBC.
Survey data indicated 85.1% of respondents initiate glucocorticoid treatment at 2 mg/kg/d. 80.5% begin to taper glucocorticoids at ≥2 weeks, with each additional step at 2-4 week intervals (97%). 85.4% of respondents decrease by 25% of the original dose at each step, with 79% of responses indicating glucocorticoid treatment for greater than three months. Estimated relapse rates within six months of discontinuing immunosuppressive therapy was < 20% (85.7% of respondents).
In conclusion, WB PMP concentrations could be reliably quantified in cats in a clinical setting. The PMP concentration however, did not differ between healthy cats and cats with mild cardiomyopathy. The purpose of the study was to review cause and outcome of leukemoid response in dogs. A computerized search for dogs seen over the last 10 years with neutrophil counts ≥60,000 cells/lL at the University of Missouri was completed. Demographic data, hemogram, diagnoses and clinical outcome were extracted from records. Based on recorded diagnosis, leukemoid response was deemed to be due to focal or systemic infection or inflammation, immune-mediated disease, neoplastic disease, tissue damage/necrosis, or cause undetermined.
Magnitude of leukemoid response alone may not predict disease cause or prognosis. The use of infusion or syringe pumps during canine blood transfusion is controversial, because pumps can potentially damage red blood cells (RBC), rendering the transfusion less effective. A previous study in healthy dogs reported a complete absence of detectable biotinylated RBCs 24 hours post-transfusion in many animals when blood was given through syringe or infusion pumps. Complete loss of transfused RBCs within one day of transfusion is, however, inconsistent with anecdotal clinical experiences.
The majority of plasma transfusions were considered indicated based guidelines for human patients, however, 24% of transfusions were not considered indicated. Similar guidelines should be considered for companion animals. Cats with hypertrophic cardiomyopathy (HCM) are at an increased risk for formation of an aortic thromboembolism (ATE) due to blood stasis and platelet hyper-reactivity in enlarged cardiac chambers, among other prothrombotic factors. Anti-platelet medications are commonly used in cats considered at risk of developing thromboembolism. Clopidogrel bisulfate, a thienopyridine drug, causes irreversible inhibition of platelet aggregation in response to ADP and collagen, common initiators of clot formation. Trade name clopidogrel (Plavix Ò ) was previously investigated in healthy cats and was associated with a significant inhibition of platelet activity. In 2012, the FDA approved the generic form of clopidogrel, but its inhibitory effects on platelet aggregation have not been investigated. We hypothesized that generic clopidogrel is associated with equal anti-platelet effects to those associated with trade name clopidogrel in healthy cats, and that both formulations are associated with minimal oral/gastrointestinal adverse events.
All cats maintained a normal platelet count at each time point of the study. No adverse effects were noted with the administration of trade name or generic clopidogrel in any cat. Two cats reliably showed significant inhibition of platelet aggregation in response to both trade name and generic clopidogrel (full responders). One cat showed slight inhibition of platelet aggregation in response to generic clopidogrel, but not trade name clopidogrel (partial responder). Two cats did not show any inhibition of platelet aggregation in response to both trade name and generic clopidogrel (non-responders).
While we determined that both the trade name and generic formulations of clopidogrel are safe to administer in cats, there was not reliable inhibition of platelet aggregation in all cats. Cats tended to have a similar response to both formulations of clopidogrel implying that intrinsic factors affect the efficacy of the drug, as opposed to human or assay error. This variable response to treatment may be due to alterations in the cytochrome P450 gene coding for enzymes responsive for clopidogrel metabolism, as several polymorphisms have been identified in humans. This is the first study to investigate the effect of the generic formulation of clopidogrel on platelet aggregation, but due to the low sample size, meaningful conclusions cannot be made about the varying response to the drug. Further studies should aim to increase sample size, and investigate metabolic, genetic, and other intrinsic factors that could affect drug efficacy. The objective of this study is to evaluate the effect of 7.5% hypertonic saline solution (HSS) on whole blood coagulation in healthy dogs and to compare the effects of in vivo and in vitro dilution of HSS.

HP07 DEMOGRAPHICS AND HISTOLOGICAL CHANGES IN A COHORT GROUP OF DOGS WITH ABNORMAL HEPATIC COPPER CONCENTRATIONS. T. Ullal, D. Twedt. Colorado

Blood was collected from eight healthy, adult dogs and incubated with calcitriol (10 À7 M) or control for 24 h. Following incubation, LPS-stimulated leukocyte production of TNF and IL-10 were measured using a canine-specific multiplex assay and PMN phagocytosis of opsonized E. coli and constitutive TLR4 expression were evaluated using flow cytometry. In three dogs, a concentration response curve was performed to evaluate if the cytokine modulation was concentration dependent. Comparisons were made using paired T-test or Wilcoxon Signed Rank test, with a P < 0.05 considered significant.

IM02 URBAN ENVIRONMENT AND ODDS OF CANINE IMMUNE-MEDIATED DISEASE. U. Jeffery. Texas A & M University, College Station, TX, USA

These data indicate that nasal passages and the oropharynx in cats both contain a relatively abundant population of immune cells capable of responding rapidly to TLR activation, with the oropharynx containing a dense T cell population and the nose containing more neutrophils and likely B cells. Both sites responded rapidly to mucosal delivery of TLR agonists, with early appearance of innate immune cells and disappearance and then reappearance of T lymphocytes. These results indicate that mucosal administration of a liposome-TLR agonist rapidly activates local immune responses in the feline upper respiratory tract, which may be associated with non-specific protection from viral or bacterial pathogens. Idiopathic immune-mediated polyarthritis (IMPA) is an inflammatory non-infectious joint disease caused by immune-complex deposition in the synovium due to a type-III hypersensitivity reaction. Oral administration of immunosuppressive drugs is the standard treatment for this condition. The most commonly used drug is prednisolone, often in combination with other immunosuppressive agents. The benefit of combination immunosuppressive therapy introduced at the time of diagnosis has not been previously evaluated. The aim of this retrospective study was to compare outcomes for dogs with IMPA treated with prednisolone alone or in combination with other immunosuppressive drugs introduced at the time of diagnosis. We hypothesised that the use of combination immunosuppressants would not improve outcome in canine IMPA.
There was no significant difference between groups 1 and 2 for duration of therapy, relapse rate or mortality. Thus the hypothesis was accepted. The observations that dogs started on a multi-drug protocol from the outset required a shorter treatment duration, had lower mortality and a lower relapse rate may reflect a type II error due to low group numbers. A prospective study with greater numbers is ongoing to investigate this further. Previous studies have demonstrated the ability of liposome-TLR ligand complexes (LTLC) to potently activate innate immune responses in several species, but they have not been fully evaluated for activity in cats. There is currently an unmet need for a broad spectrum immune stimulant for prevention or early treatment of viral and bacterial respiratory tract pathogens in cats. The purpose of the present study was to investigate in vitro responses of cat lymphocytes and monocytes to stimulation by LTLC.

With flow cytometry, LTLC induced activation of B cells and T and monocytes, as reflected by upregulated expression of MHCII expression on B cells and monocytes and upregulated expression of OX40 on T cells and B cells. In addition, LTLC induced T cell proliferation.

In a companion abstract, we demonstrate the mucosal immune stimulatory properties of an LTLC-based immune stimulant administered to healthy cats. Therefore, taken together with the in vitro findings presented here, these results suggest that LTLC may be used as an effective non-specific immune stimulant for induction of anti-viral and anti-bacterial immunity in cats. Tumor necrosis factor-alpha (TNF-a) is a cytokine released mainly by macrophages in response to contact with infectious agents, tissue injury, tumor growth, and autoimmune conditions. Thus, measurement of TNF-a warrants evaluation as a diagnostic and prognostic marker in cats with inflammatory diseases. However, currently no analytically validated assay is commercially available for the measurement of this cytokine in cats. The aim of this study was to develop and analytically validate an electrochemiluminescent immunoassay for the measurement of TNF-a in cat serum.
This assay was shown to be sensitive, precise, and accurate for the measurement of TNF-a in cat serum. However, assay linearity was suboptimal. Further studies are needed to determine whether linearity can be improved with the current assay system. Also, the clinical implications of serum TNF-a concentrations need to be evaluated in this species. Canine atopic dermatitis (CAD) is a common, chronic, genetically-predisposed, and relapsing inflammatory skin disease. CAD is a multifaceted disease resulting from a complex interaction between environmental and genetic factors. Both of these factors can shape skin barrier function and the immunological response of predisposed patients. CD4 + CD25 + FoxP3 + Regulatory T cells (Tregs) become known to prevent excessive immune responses through their immunoregulatory properties and therefore play a leading role in the maintenance of immunological homeostasis. There was only few researches that was performed to analyze the relationship between CAD and proportion of Tregs in periphery blood. In the present study, the aims were to assess the proportion of circulating Tregs (CD4 + CD25 + FoxP3 + , CD4 + FoxP3 + ) in the healthy and the atopic dogs to analyze implication of Tregs to CAD and to investigate the correlation of Tregs with CAD severity and age.

ID19

EFFECT OF DOXYCYCLINE ADMINISTRATION ON ANTI-BODIES AGAINST DIFFERENT BORRELIA BURGDORFERI PEPTIDES. M.R. Lappin 1 , S. Moroff 2 . 1 Colorado State University, Fort Collins, CO, USA, 2 Antech Laboratories, Lake Success, NY, USA Borrelia burgdorferi is transmitted by Ixodes spp. and is associated with inflammatory arthritis or nephritis in some dogs (Lyme Disease). A number of diagnostic modalities have been evaluated to aid in the diagnosis of Lyme disease in dogs, with serological testing proving to be the most beneficial. Antibodies against outer surface protein A (OspA), OspC, OspF and antibodies against the C6 peptide are currently used most frequently in commercially available serological assays. Antibodies against OspC are often the first detected in serum after a new exposure to B. burgdorferi. In humans with Ixodes spp. infestation, doxycycline treatment has been shown to block progression of B. burgdorferi infection but whether this occurs in dogs is unknown. The purpose of this study is to report the effect of doxycycline administration on serological responses to OspA, OspC, OspF, and C6 peptide in dogs experimentally infested with wild-caught I. scapularis.
By Week 10 after I. scapularis infestation, 21 of 23 dogs had developed serological evidence of B. burgdorferi infection. Of the 3 dogs with OspC antibodies alone that were administered doxycycline for 28 days, 2 dogs never developed antibodies against the other peptides and were negative for OspC antibodies by Week 2 or Week 6 after starting doxycycline administration. The other treated dog became positive to the C6 peptide alone during week 1 of doxycycline administration, was positive for 2 of the next This model induced serological evidence of B. burgdorferi infection of 21 dogs with 17 of 18 untreated dogs developing serological evidence of chronic infection characterized by antibodies against OspF and C6 peptide. While only 1 dog may have spontaneously limited antibody production against all 4 peptides, all 3 dogs administered doxycycline during the acute phase limited antibody production. These results should be confirmed in larger numbers of dogs, but may suggest that treatment when OspC antibodies are first detected may block development antibody responses associated with chronic B. burgdorferi infection. A natural resistance of cats to leishmaniosis, primarily due to a cellular immune response, is widely suggested. Leishmanin skin test (LST) has been successfully used in humans and dogs and a positive LST result indicates exposure to Leishmania and a state of cell mediated immunity. A total of 96 cats, seronegative for FeLV and FIV, presenting to a Veterinary Teaching Hospital in an endemic area in Brazil, were evaluated by LST. Leishmania infection was confirmed in 56 cats by bone marrow qPCR, and 40 non-infected cats composed the control group. Among infected cats, 23/56 presented clinical signs and 33/56 were asymptomatic. Each cat was intradermally injected with a suspension of 4 9 10 7 L. chagasi promastigotes (inactivated in thimerosal solution), in the inner surface of the right thigh, and thimerosal solution was injected in the opposite limb. All control and infected cats tested negative to LST at any time reading (24, 48 and 72 h after inoculation). We expected that at least part of the 26 asymptomatic (and seronegative) cats presented a positive LST. In canine leishmaniosis (CanL) LST can detect a high proportion of asymptomatic dogs, although some of them have negative LST even in the presence of a cellular immune response. The method employed was previously used for CanL, and its potential immunogenicity was confirmed by promoting positive LST in five naturally infected and asymptomatic dogs from the same endemic area. However, the LST tested do not seem to be an adequate tool for the diagnosis of feline leishmaniosis. Transportation of blood from remote areas can be problematic. While DNA is generally stable and a number of studies have evaluated DNA extracted from dried blood of mammals, there is minimal information determining the sensitivity of different techniques using dog blood. The objective of this study was to determine the optimal technique for extracting DNA from filter paper dried blood spots using Ehrlichia canis DNA as the target.
In conclusion, the increase in SDMA correlated with histopathologic findings in patients with neoplasia. Thus, SDMA is a more reliable estimate of kidney function in cats and dogs with cancer. his study investigated water intake and hydration in healthy cats and evaluated a nutrient-enriched water on hydration. Domestic shorthair cats (N = 18; mean age 9.8 yrsAESD 2.5; BCS 5-7 on 9point scale) received either tap-water (W; N = 9) or test-water containing whey protein and glycerol (TW; N = 9) for 56 days. Prior to treatment, a 7-d baseline established daily W and food consumption using a 2-bowl monitoring system with ad libitum water and dry food. Blood and urine samples were collected on days À1, 8, 15, 30, and 56 for urine specific gravity (USG), creatinine, and osmolality measurements. Endogenous creatinine-based glomerular filtration rate (GFR) was calculated from sample collection on days 28-30 or 31-33. Baseline W and calorie intake were similar between groups. Although no difference was observed between groups during the treatment phase, TW group had a daily liquid increase of 52%, with a median intake across all days that ranged from 5% to 254% increase. Variance was controlled post hoc with cats characterized as responders (R:consumption >25%) and nonresponders (NR) (W: 2R/7NR versus TW: 7R/2NR; P = 0.02). Daily urine volume (mL/kg BW) was higher (P = 0.02) in TW (15.2 AE SE 1.8) versus the W treated cats (10.3 AE SE 0.7), but no difference (P = 0.60) between groups for GFR (1.8 AE SE 0.1 versus 1.9 AE SE 0.2, respectively). Baseline USG was similar between groups (1.052 g/mL), but declined (ANOVA P < 0.01) with TW (1.037 g/mL AESE 0.005) versus W (1.053 g/mL AESE 0.002). Serum osmolality was similar for both groups over the entire trial. This study suggests that specific nutrients added to a cat's water can improve liquid intake to significantly improve overall hydration, as determined by greater urine output and dilution, which may offer a health benefit to some cats in need of greater water consumption. Progressive interstitial nephritis (IN) is the primary cause of feline chronic kidney disease (CKD) which affects as many as 50% of elderly cats and prevalence increases with age. Vaccination has been shown to be a risk factor for development of feline CKD. The Crandell Rees feline kidney (CRFK) cell line is commonly used to grow viruses for use in feline vaccine production. Repeated administration of a vaccine containing CRFK remnants as a model for interstitial nephritis was shown to induce strong antibody responses against CRFK lysates and against alpha-enolase, an immunodominant glycolytic pathway enzyme found in all mammalian cells that has been studied as a marker of inflammatory diseases in people. The primary objectives of this study were to further evaluate this potential model for IN by assessing samples from the cats for cell-mediated immune responses to alpha-enolase, by evaluating serum cytokine concentrations using a commercially available kit, and by describing changes in renal alpha-enolase staining patterns.
Lymphocytes from hyperinoculated cats proliferated significantly more in the presence of alpha-enolase compared to the other three antigens confirming the induction of a cell-mediated immune response towards alpha-enolase contained in the vaccine. Glomerular and tubular alpha-enolase expression was significantly (P < 0.05) greater at week 16 (mean score 3.37 and 1.95, respectively) compared to week 0 (0.37 and 1.01, respectively). Increased cytokine concentrations over the hyperinoculation period were noted for GM-CSF (3 cats), IFN-gamma (5 cats), IL-1beta (3 cats), IL-4 (4 cats), SDF-1 (5 cats), IL-6 (4 cats), MCP-1 (3 cats), IL-13 (4 cats), IL-8 (5 cats), PDGF-BB (3 cats), RANTES (6 cats), IL-18 (3 cats), and TNF-alpha (3 cats).
Hyperinoculation with a market leading FVRCP parenteral vaccine induced both antibody and cell-mediated immune response towards alpha-enolase, increased alpha-enolase expression in both renal tubules and glomeruli, and led to elevations in select inflammatory cytokines and chemokines within this 16-week model. Although there has been no direct link made between parenteral FVRCP vaccines and feline interstitial nephritis to date, results of urinary cytokines and further assessment of alpha-enolase expression within feline kidneys will be used to continue evaluation of this potential IN model. Tamm-Horsfall Protein (THP) is exclusively synthesized by the distal nephron under physiological conditions. Therefore, it is expected larger amounts of this protein in the urine of healthy individuals. In chronic kidney disease (CKD) dogs, a few investigations have reported about the quantities of THP in urine. Lower urinary excretion of THP in CKD dogs might be associated with distal tubular injuries and/or to the loss of renal mass, and then, THP may act as a marker of disease progression. The aim of this study was to assess the role of THP as a marker of CKD progression in dogs. Nine clinically healthy dogs were recruited as control group. Forty CKD dogs were enrolled (IRIS staging, Stage 1, n = 10; Stage 2, n = 10; Stage 3, n = 10; Stage 4, n = 10). Western blotting of THP was performed, and the results of densitometry were expressed in mean AE SEM. Urinary immunodetection of THP was 100.0 AE 7.7% in control dogs, and 117.2 AE 10.8%, 86.0 AE 9.0%, 65.4 AE 8.7% and 46.7 AE 9.0% in CKD dogs in stages 1, 2, 3 and 4, respectively. Differences among all groups were observed, particularly between Stages 1 and 4 (P ≤ 0.0001). It is likely that progressive reduction in urinary excretion of THP may contribute to detect gradual loss of nephrons, and it may act as a marker of disease progression in CKD dogs. Infection with Angiostrongylus vasorum (Av) is an emerging disease in dogs with a wide range of clinical signs. To date, it is not clear whether Av is able to cause glomerular immune complex deposition or other renal damage.
Alpha-enolase expression decreases in damaged tubules and increases in the glomeruli of older cats prior to the development of detectable CKD when compared to young, non-azotemic cats. Further studies will be required to determine whether these findings relate to the pathogenesis of CKD or could be used as an early diagnostic test for CKD. Metabolomics may be used for providing description of endogenous metabolites present in biological samples in response to pathophysiological or external stimuli. The purpose of the present study was to use metabolomics to compare cats with feline idiopathic cystitis (FIC) or struvite plug (SP) with healthy cats.
In this study, the use of metabolomics was able to describe biochemical variations between urines of healthy cats and cats presenting FIC or SP. This novel application of metabolomics opens new hypothesis on pathophysiology and treatment in such cats. Monitoring the urine protein:creatinine (UPC) ratio in dogs with protein-losing nephropathy (PLN) to determine response to therapy can be challenging due to day-to-day variation in their UPC values. The purpose of this study was to determine if a single sample, averaged sample, or pooled sample are comparable for determination of the UPC ratio, regardless of the degree of proteinuria, in PLN dogs receiving medical therapy.

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Colorado State University Veterinary Teaching Hospital medical records (2006-2016) were retrospectively searched for cats that had been prescribed an oral potassium supplement for management of their CKD-associated hypokalemia. Data collected included signalment, bodyweight, age, supplement type, dose, directions, concurrent medications, diet, indication owner was unable to give the supplement, and serum chemistry and urinalysis values. For inclusion, laboratory work had to be available at the time of hypokalemia diagnosis, and at recheck within one to six weeks. Treatment response was defined in three ways: any increase in potassium, an increase in potassium to within the normal reference range, and an increase to greater than 4 mEq/L. Not all data was normally distributed thus Wilcoxon Sign Rank test was used to compare pre and post-supplementation values. Spearman Rank was used to assess correlation between dose and change in serum potassium and bicarbonate.