All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. J ALLERGY CLIN IMMUNOL Abstracts AB3 VOLUME 137, NUMBER 2

Psychosocial Associations with Life-Threatening Negative Skin Prick Test Predicts Asthma Remission in 6 Asthma in Inner City Children 8 Preschool Children

Mary E. Bollinger, DO1, Arlene Butz, ScD, CRNP2, Cassie Noppasorn Sitthisarunkul, MD1, Pasuree Sangsupawanich, MD, PhD2, Lewis-Land, MS2, Tricia Morphew, MSc3; 1Department of Pediatrics, Wanaporn Anuntaseree, MD2; 1Prince of Songkla University, Hat-yai, University of Maryland School of Medicine, Baltimore, MD, 2Johns Songkhla Province, Thailand, 2Prince of Songkla University, Hat-yai, Hopkins University School of Medicine, Baltimore, MD, 3Morphew Thailand. Consulting, LLC, Manhattan Beach, CA. RATIONALE: The goal of asthma treatment is to achieve remission. RATIONALE: Inner city children have high asthma related morbidity and Several studies have found an association between SPT results and asthma mortality. Previous studies suggest that psychosocial issues may increase remission in school age children, but few studies have directly examined the risk of near-fatal and fatal asthma, but detailed analyses of specific the relation of SPT results and asthma remission in preschool children. factors in high risk inner city children are scarce. METHODS: A retrospective medical records review was conducted on METHODS: Baseline survey data including measures of caregiver asthmatic children <_ 5 years of age during 2007-2013. Patients who used depression (CES-D), quality of life, social support and neighborhood inhaled corticosteroids [ICS] > 3 months with follow up time after ICS stress were collected from caregivers of inner city children with cessation >_ 12 months were included. Asthma remission was defined as uncontrolled asthma. All child subjects (N5150) were enrolled in a study free of asthmatic exacerbation that required re-starting ICS or admission evaluating the impact of a multifaceted preventive asthma care interven- within 12 months after ICS cessation. SPTs were performed before tion. Comparison of children with and without a prior intensive care (ICU) discontinuation of the ICS, and included standard aeroallergens such as admission for asthma was conducted using chi-square and logistic grass, house dust mite, cockroach, cat and kapok. regression. RESULTS: A total of 100 asthmatic children met the inclusion criteria. RESULTS: Subjects were primarily African American (95.3%) and young Fifty five percent had had negative SPT results. The overall remission rate (mean age 6.4yrs; 64% male); 31% of whom had a prior ICU admission. in the first year of ICS cessation was 65%. The remission rates of negative Caregivers were primarily mothers (92.7%), single (85.2%), employed and positive SPT patients were 82% and 44%, respectively. Multivariate (53.3%) and very poor (34.6% income <$10,000). Most caregivers analysis confirmed a negative SPT was a significant determinant in reported asthma related daily stress (64.7%), 29.3% had CES-D scores predicting asthma remission (odds ratio 5.4, 95% CI 2.1-13.7). >16, consistent with depression. Most reported some neighborhood related CONCLUSIONS: A negative SPT is a predictor of preschool asthma stress with low social embeddedness most commonly reported. There was remission after ICS cessation. a trend for children from very poor households (<$10,000/yr vs >$10,000/ yr) to have had a prior ICU admission (OR 1.96 (0.92, 4.17) p50.081). For Early Diagnosis of Asthma and Allergies Among caregivers reporting extremely high neighborhood stress, each unit in- 9 Wroclaw Children crease in depression (CES-D score) increased the odds of prior ICU admis- 1,2 3 3

sion by 20%, p50.031. Andrzej M. Fal , Dorota Kiedik , Agnieszka Muszynska , Iwona SATURDAY 3 1 2 CONCLUSIONS: Identifying and addressing caregiver depression and Pirogowicz ; Wroclaw Medical University, National Institute of Public 3 stress may help to decrease the high morbidity and mortality seen in inner Health, Wroclaw Medical University, Poland. city children with poorly controlled asthma. RATIONALE: The aim of the project to select children of greater risk of developing asthma or other allergic diseases. A specially prepared and pre- Prevalence of Asthma-Chronic Obstructive Pulmonary standardized questionnaire was used for this reason. 7 Disease (COPD) Overlap Syndrome in Brazilian Elderly METHODS: The survey was conducted in 8 and 9 year old children in Patients Wroclaw (Poland). In its first stage parents or guardians which were educated on asthma and allergy risk factors. The they were asked to Tamara A. de Freitas1, Antonio Godinho Netto1, Beatriz Aarestrup2, complete the questionnaire. Questions concerned inter alia: family history, Fernando M. Aarestrup, MD, PhD3; 1SUPREMA, 2Universidade Federal child’s exposure to potential asthma or allergy risk factors (tobacco smoke, de juiz de Fora- MG - Brazil, Brazil, 3Universidade Federal de Juiz de common allergens, humidity), presence of specific symptoms: recurrent Fora - MG- Brazil, Juiz de Fora, Brazil. bronchitis, coughing, wheezing, shortness of breath, runny nose or rash. RATIONALE: There are few studies in Latin America about the Then children, who scored above a fixed level were directed to an allergist prevalence of asthma-chronic obstructive pulmonary disease (COPD)- to confirm or rule out asthma. asthma overlap syndrome(ACOS) in elderly patients. RESULTS: During two school-years 5325 children entered the program. METHODS: An observational cross-sectional study was performed with Authors collected 3238 questionnaires. Nearly 30% (945) children 202 elderly patients (147 females and 55 males) who were subjected to the received more than 5 points (which was the cut-off level for possible asthma module of the International Study of Asthma and Allergies in asthma/allergy), of which 116 parents declared that their children are Childhood (ISAAC) test, which was modified for elderly patients, and already under an allergy clinic supervision. All other children (829) were evaluated by the Global Initiative for Chronic Obstructive Lung Disease sent to an allergy clinic for diagnosis but only 16% of them (131) appeared. (GOLD) routine in order to assess for COPD. Among those who underwent a full diagnosis in more than 80% (105 RESULTS: Of the 202 patients, 11.3% had definite asthma, 5.4% had children) the initial suspicion of asthma based on the questionnaire results probable asthma, 9.9%had COPD, and 6.4%had ACOS. In the elderly was confirmed. patients with ACOS, the incidence of pulmonary disease was higher in CONCLUSIONS: Our questionnaire is a reliable tool for initial screening patients who were 60 to 69 years old (10.6%) and in females (6.8%)than it for asthma diagnosis in children in their primary school. To increase the was in males (5.4%). percentage of children presenting at an allergy clinic more stress has to be CONCLUSIONS: The study group had a significant prevalence of ACOS, put on the initial parents/guardians education. which suggested that the methods that are used to diagnose ACOS need to be improved in order to provide a better quality of life to elderly patients with ACOS. All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. AB4 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2016

Spice Allergy: Asthma in the Food Industry The Association with Exercise Capacity and Anemia 10 12 in Chronic Airway Disease

1 2 1 1 2 Hyun Jung Jin, MD , Jin Hong Chung ; Yeungnam University College Mariangelica Bermudez Martinez , Ricardo Moreno-Borque , Paula 2 Sanchez-Lopez1, Pilar Gajate-Fernandez1; 1Hospital Rey Juan Carlos, of Medicine, Daegu, South Korea, Yeungnam University College of 2 Medicine, South Korea. Mostoles, Spain, Hospital Rey Juan Carlos, Spain. RATIONALE: RATIONALE: Sesame (Sesamun Indicum) is common ingredient in Anemia is frequently accompanied with many chronic cuisine around the world. In that sense, like other nuts, it can trigger diseases, which may contribute to dyspnea and exercise limitation in allergic reactions in some people but is not a common inhalant chronic airway disease patients. The aim of this study was to investigate the association of anemia and degree of dyspnea and exercise capacity in occupational allergen. METHODS: We studied the clinic case of a 28 years-old woman working COPD patients. METHODS: as a kitchen assistant; after preparing a chicken dish and incorporating the A total 87 male COPD patients were enrolled. Subjects were divided as anemic (n56) and non-anemic groups (n581) by the WHO use of several species, she reported a cough, dyspnea, sneezing and rhinorrhea. A deeper look into the ingredients used, it was determined she criteria, which meant that the Hemoglobin concentration was below 13 g/ had used sesame, black pepper, garlic, thyme, nutmeg, and parsley. The dL in men. We compared the clinical characteristics of two groups. We measured the shortness of breath using the modified Medical research

SATURDAY aforementioned symptoms manifested themselves immediately after using Council Dyspnea scale (mMRCs) and COPD assessment test (CAT). The the subject species. After obtaining the medical history and patient consent, skin prick testing exercise capacity was assessed by six minute walking distance (6MWD). is utilized to the most commonly commercially used spices (sesame, black The Saint George Respiratory Questionnaire was used to investigate pepper, garlic, nutmeg, thyme, oregano). In addition. Skin prick testing is HRQL. RESULTS: Anemic patients (7.4%) showed a significantly lower 6MWD also applied to determine the allergens effect of nuts (walnuts, almonds, 6 6 5 pistachios and peanuts). We measure specific IgE levels (ImmunoCAP, (293.17 82.60m, 380.15 91.97m, P 0.03). There were no differences Phadia) to each different spices. in age, smoking habits, dyspnea scales including mMRC score, CAT score, lung function and quality of life between the two groups. However, there RESULTS: Skin prick test results were POSITIVE to sesame and thyme. The weal diameter for the sesame was 13mm and for the thyme 8mm. was no significant correlation with Hemoglobin concentration and 6 The sesame specific IgE levels (ImmunoCAP, PHADIA) were above 2.71 MWD. CONCLUSIONS: KU/L. Anemia was related to a reduction of exercise capacity in COPD. Further studies about the relation of anemia and other parameter No specific IgE was detected with thyme. A methacoline inhalation challenge was positive with a 24% decrease in of exercise capacity including muscle strength and muscle mass are FEV1. needed. CONCLUSIONS: Our case confirms that sesame can be a sensitizing Retrospective Analysis of Allergy Skin Testing agent through inhalation in an exposed individual and might explain to a 13 Results and Relationship to Asthma in the Tucson large extend the increase levels to IgE mediated as an occupational disease. Adult Population

Characteristics of Asthma Exacerbations in the 1 1 2 1 Emergency Department at a Tertiary Hospital Ryan Buckley, MD , Snehal Patel, DO , Tara F. Carr, MD ; University 11 of Arizona, Tucson, AZ, 2Banner University Medical Center, Division of Beatriz Pola; La Paz Hospital, Madrid, Spain. Pulmonary, Allergy, Critical Care and Sleep Medicine, Tucson, AZ. RATIONALE: RATIONALE: There are few studies in Spain describing the clinical Numerous aeroallergens have been associated with the development of asthma, including alternaria, dust mite and pet dander. profile of asthmatic patients with asthma exacerbations attending the Emergency Department. Identifying the risk factors, recognizing severity Tucson, Arizona is located in the Sonoran Desert, which has the highest signs and starting an adequate and prompt treatment are essential tools to diversity of vegetation of any desert in the world. Given the unique pollen improve asthma control. profile in this region, we sought to identify the most common aeroallergens associated with allergic rhinitis and asthma diagnosis in the local adult METHODS: We included all patients aged 18 years or older who were attended during the year 2014 in the Emergency Department of our hospital population. METHODS: due to an asthma exacerbation. We performed an epidemiological, We conducted a retrospective electronic chart review of 226 retrospective, open and observational study. consecutive adult patients who underwent aeroallergen skin prick testing for rhinitis at the University of Arizona Adult Allergy and Immunology RESULTS: A total of 831 patients were included, with a mean age of 57 years, 67.7% were women, and 18% were active smokers. Higher number Clinic over the course of 1 year. All subjects were tested to a standard panel of asthma exacerbations were observed in January and May due to of tree, grasses, weed, mold, dust mite, animal dander, cockroach and feather extracts. Asthma was diagnosed using the Expert Panel Report 3 respiratory infections and exposure to seasonal allergens (pollen), respectively. 43% of the patients did not have a previous diagnosis of guidelines. Data was analyzed using descriptive statistics. RESULTS: asthma. Of the already diagnosed asthmatic patients 10% were not Skin testing was most commonly positive to Mesquite (54%), receiving any treatment and 13% had suffered an exacerbation the previous Bermuda (48%), Palo Verde (47%), Olive tree (43%) and Lambsquarters (43%). Compared with nonasthmatics, asthmatics were more often year. Of the study patients, 32% patients required hospital ward admission, 5 6 required admission into the intensive care unit and 3 patients died. 54 sensitized to molds (OR 2.25, CI 1.22-4.14, p 0.005), including 5 patients presented a relapse of the exacerbation during the following fifteen Alternaria alternata (2.58, 1.23-5.39, p 0.011), cat dander (2.13, 5 5 days. In our patients, blood eosinophilia was associated to higher rate of 1.24-3.69 p 0.006) and any tree pollen (1.85, 0.99-3.55 p 0.04). CONCLUSIONS: Regional pollens contribute significantly to allergic hospital admission. CONCLUSIONS: Asthmatic exacerbations are still a frequent cause of disease in this unique climate. Sensitization to Alternaria and other nonre- urgent medical assistance in the Emergency Department. Many patients do gional aeroallergens is related to asthma. This supports our current practice of testing and treating patients for allergy to both locally significant and not receive any therapy regularly. The hospital ward admission rate is high, 32% of patients could not be controlled with treatment in the Emergency ubiquitous aeroallergens. Department. All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. J ALLERGY CLIN IMMUNOL Abstracts AB5 VOLUME 137, NUMBER 2

Persisting Long Term Benefits of Smoking Abstinence [SD 14.7] and 54.6 years [SD 16.2]) and gender distribution (71.4% and 14 and Reduction in Asthmatic Smokers Who Have 64.9% female). High-OCS users had more chronic and respiratory-related Switched to Electronic Cigarettes conditions and were more likely Step 5/6. High-OCS users had higher odds of hospitalization (all-cause OR 1.81, 95% CI 1.25-2.62; asthma-related Davide Campagna, MD1,2, Jaymin B. Morjaria3, Pasquale Caponnetto4, OR 4.95, 95% CI 1.98-12.40). High-OCS users also had higher costs Massimo Caruso, PhD, FIT, AAAAI1, Maria Domenica Amaradio2, (all-cause $17,122 [SE $2,395; p<0.001]; asthma-related $3,728 [SE Giovanni Ciampi5, Cristina Russo, MD5, Riccardo Polosa, MD, PhD, $387; p<0.01] difference high vs. low OCS). FAAAAI1,4; 1Department of Clinical and Experimental Medicine, CONCLUSIONS: After adjusting for demographics, clinical character- University of Catania, Italy, 2Internal and Emergency Medicine, ‘‘Policli- istics and disease severity, patients with OCS fills >_30 days have higher nico - V. Emanuele’’, University of Catania, Italy, 3Dept of Academic healthcare resource use and cost than low-OCS users. High OCS exposure Respiratory Medicine, University of Hull, Castle Hill Hospital, may be a marker for poor asthma control and resultant increase in resource Cottingham, East Yorkshire, United Kingdom, HU16 5JQ, 4Centro per use/costs. la Prevenzione e Cura del Tabagismo (CPCT), ‘‘Policlinico - V. Emanuele’’, University of Catania, Italy, 5Accident and Emergency Lung Function, Allergic Sensitization and Respiratory Department, Garibaldi-Central Hospital, Catania, Italy. 16 Symptoms Among Children and Adolescents with RATIONALE: Improvements in asthma outcomes have been recently Sickle Cell Disease reported in asthmatic smokers who have substantially reduced their Gustavo Wandalsen, MD1,Maıra Moya2, Carolina Cobra2,Cıntia tobacco consumption by switching to electronic cigarettes (ECs); confir- 2 2 1 mation of these preliminary findings is necessary to reassure patients, Jonhston , Josefina Braga , Dirceu Sole, MD, PhD, FAAAAI , Fernanda C. Lanza2, Andrea Angel2; 1Federal University of S~ao Paulo, S~ao Paulo, healthcare professionals and policy makers. Here, we present findings from 2 long term prospective assessment of objective and subjective asthma Brazil, Federal University of Sao Paulo. outcomes as well as safety and tolerability in this group of EC users with RATIONALE: Sickle cell disease is a chronic disease that leads to asthma. frequent and severe pulmonary complications. Our objectives were to METHODS: We prospectively re-evaluated respiratory symptoms, lung evaluate lung function, allergic sensitization and respiratory symptoms function, airway hyperresponsiveness, asthma control, asthma exacerba- among children and adolescents with sickle cell disease. tions and tobacco consumption in adult daily ECs users with asthma who METHODS: Cross-sectional evaluation of 75 patients (36 females) with were previously studied in a retrospective study. Measurements recorded at sickle cell disease (6 to 17 years of age) that underwent the following tests: baseline prior to switching and at two consecutive follow-up visits at 6 and spirometry (pre and post bronchodilator), impulse oscilometry, skin prick at 12 months were compared with those obtained at the final follow up visit test and symptom questionnaire (ISAAC). at 24 months. RESULTS: Wheezing in the last year was reported by 11% of the patients, RESULTS: Eighteen ECs users with mild to moderate asthma were severe attacks by 5%, diagnose of asthma by 15% and nocturnal cough by 20%. Allergic sensitization was founded in 33 (44%) patients, mainly to followed up prospectively. Complete data was obtained from sixteen EC SATURDAY users and two relapsers. Significant and stable improvements in respiratory Dermatophagoides pteronyssinus (35%) and Blomia tropicalis(31%). 5 5 symptoms, lung function, AHR, ACQ, and tobacco consumption were Median values for spirometry were: FVC 94%; FEV1 91%; FEV1/ 5 5 _ observed in the 16 ECs users with asthma, but no significant changes in FVC 97% and FEF25-75 72%. Bronchodilator response (>12% exacerbation rates were reported. Similar findings were found in the dual FEV1) was noted in 16% of the patients and abnormal spirometry was users. identified in 35% of the patients with the predominance of obstructive CONCLUSIONS: This prospective study confirms that EC use amelio- pattern. Median values of resistance at 5hz (R5) and 20hz (R20) were rates objective and subjective asthma outcomes and shows that these 103% and 98%, respectively. No difference was observed in spirometry beneficial effects may persist in the long term. EC use can reverse harm and oscilometry values when patients were divided by the presence of hos- from tobacco smoking in asthma patients who smoke. pitalization, blood transfusion or acute thoracic syndrome in the last year. CONCLUSIONS: The prevalence of asthma and respiratory symptoms Cost and Healthcare Utilization in Asthma Patients among patients with sickle cell disease was not superior to those observed 15 with High Oral Corticosteroid Use in the general population. Allergic sensitization was found in almost half of the patients. The high prevalence of abnormal lung function reinforces the Karina Raimundo, BPharm, MS1, Ka M. Ngai, MD, MPH2, Eunice need for special attention to this group of children. Chang, PhD2, Michael Broder, MD, MSHS2, Noelle M. Griffin, PhD3; 1Genentech, Inc., South San Francisco, CA, 2Partnership for Health Ana- lytic Research, LLC, Beverly Hills, CA, 3Genentech, South San Fran- cisco, CA. RATIONALE: We hypothesized that high OCS use can be a marker of poor disease control. Our objective was to compare clinical and economic outcomes between high-OCS and low-OCS users. METHODS: We performed a cross-sectional retrospective study using commercial insurance claims from 2013. Moderate-to-severe persistent asthma patients were those with >_2 asthma claims, >_2 asthma medications, EPR3 Step 4-6, and either high-OCS (>_1fill>_30 days, or >_6 bursts of OCS, based on previous study) or low-OCS (no fills >_30 days and <2 OCS bursts) use. We excluded patients with COPD claims. We described demographics, comorbidities, medication use, healthcare utilization and costs. ANCOVA and Logistic regression models were used to adjust for between-group differences. RESULTS: 2,320 patients met the inclusion criteria 217 high- and 2,103 low-OCS users. High- and low-OCS users were similar in age (56.8 years All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. AB6 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2016

Risk of Developing Rheumatoid Arthritis in Adults use of asthma medications in Brazilian children, relating to higher 17 with Asthma: A Population-Based Case-Control Study prevalence of physician-diagnosed asthma.

Mary C. Rolfes1, Youn Ho Shin, MD2,3, Chung I. Wi, MD4, Cynthia S. The Association Between Pollutant Levels and Crowson, MS3, Richard S. Pendegraft3, Euijung Ryu, PhD3, Young J. 19 Asthma-Related Emergency Department Visits in the Juhn, MD, MPH4; 1Mayo Medical School, Rochester, MN, 2Department Bronx after the World Trade Center Attacks

of Pediatrics, CHA Gangnam Medical Center, CHA University School 1 2 3 3 Kunwar Ishan Sharma , Jennifer Toh, MD , Tulsi Desai , Mili of Medicine, Seoul, Korea, South Korea, Mayo Clinic, Rochester, MN, 4 3 2 4 Shum, MD , Priyank Patel , David L. Rosenstreich, MD, FAAAAI , Sunit Dept of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, 2 1 2 MN. P. Jariwala, MD ; Einstein/Montefiore, Albert Einstein/Montefiore Med- ical Center, Bronx, NY, 3Albert Einstein College of Medicine, Bronx, NY, RATIONALE: The relationship between asthma and the risk of systemic 4 inflammatory disease such as rheumatoid arthritis (RA) is poorly under- Montefiore Medical Center, Bronx, NY. stood. We determined whether asthma status is associated with the risk of RATIONALE: To examine the impact of the World Trade Center (WTC) incident RA among adults. attacks on asthma-related emergency department visits (AREDV) in the METHODS: We conducted a retrospective population-based case-control New York City borough of the Bronx. study, which enrolled a population-based incident RA cohort (2004-2007) METHODS: We used our institution’s Clinical Looking Glass software to SATURDAY and their 1:1 birth year- and gender-matched controls residing in Olmsted compare daily AREDV and pollutant levels from 1999 and 2002, a year County, MN. We performed comprehensive medical record reviews to before and after the WTC attacks. We obtained daily nitrogen dioxide ascertain asthma status of cases and controls using predetermined criteria (NO2), sulfur dioxide (SO2), and ozone (O3) values from the National for asthma. The frequency of a history of asthma prior to index date was Climatic Data Center’s collection station in the Bronx. Using a compared between cases and their matched controls. Data were fit to Mann-Whitney test, we calculated median values for each variable and logistic regression models to calculate odds ratios and the corresponding determined significant differences between the 1999 and 2002 values. 95% confidence interval (CI). We considered each season separately, such as Winter SO2 (1999) versus RESULTS: We enrolled 136 RA cases and 134 controls in the study, of Winter SO2 (2002), due to seasonal variations of AREDV and pollutants. whom 84 (31.1%) were male and 256 (94.8%) were Caucasians. The RESULTS: For median daily NO2, there were statistically significant median ages at the index date were 52.4 years for the RA cases and 53.0 increases from 1999 to 2002 in the spring (1999: 0.037 ppm; 2002: 5 years for controls. Of the 136 RA cases, 38 (28%) had a history of asthma, 0.046 ppm; p 0.039) and summer (1999: 0.033 ppm; 2002: 0.044 ppm; 5 whereas 21 of 134 controls (16%) had a history of asthma (adjusted odds p 0.0002). Significant increases for median daily SO2 and O3 values be- ratio [aOR], 2.16; 95% confidence interval [CI], 1.18-3.97, p50.013) after tween the years occurred in all four seasons (all p <0.0001). For median adjusting for age and sex. The similar trends were observed when a daily AREDV, significant increases occurred in the winter (1999: 11; physician diagnosis of asthma was used for ascertaining asthma status 2002: 17; p<0.0001) and spring (1999: 9; 2002: 12; p<0.0001). (aOR, 2.39; 95% CI, 1.27-4.50, p50.007). CONCLUSIONS: We observed an association between the WTC attacks and CONCLUSIONS: Patients with asthma as a T-helper 2 condition had a significant increases in O3 and SO2 for all seasons, and NO2 for the spring and significantly higher risk of RA as a T-helper 1 proinflammatory condition summer; AREDV significantly increased in the winter and spring following the than healthy individuals. fall WTC attacks. Multivariate analyses are necessary to examine the relation- ships between AREDV and pollutants before and after the WTC attacks. Treatment Patterns of Recurrent Wheezing in Infants: 18 Two Surveys Separated By Seven Years

Herberto J. Chong Neto, MD, PhD, FAAAAI1, Nelson A. Rosario, MD, PhD, FAAAAI1, Dirceu Sole, MD, PhD, FAAAAI2, Javier Mallol, MD, PhD3, EISL Study Group. 1Federal University of Parana, Curitiba, Brazil, 2Federal University of S~ao Paulo, S~ao Paulo, Brazil, 3University of San- tiago de Chile. RATIONALE: To determine the trends of treatment patterns of recurrent wheezing (RW) infants during the first year of life from two surveys seven years apart. METHODS: This is a cross-sectional study using standardized and validated questionnaire (EISL: Estudio Internacional sobre Sibilancias en Lactantes). Parents of infants, aged 12-15 months who attended to Health Centers for routine immunization were interviewed. This international, population-based study, compares data from two surveys (S1 in 2005 and S2 in 2012) conducted in three large cities that participated in both sur- veys: Curitiba and S~ao Paulo (Brazil) and Santiago (Chile). RESULTS: There was a significant decrease in the mean prevalence of RW during the first year of life between S1 (23.3%, 95% CI 22.3-24.3) and S2 (20.4%, 95%CI 19.0-21.8), p50.004. In infants with RW the mean prevalence of severity markers between S1 and S2 remained high (severe episode: 56.9% to 54.2%, p50.32); Emergency Department (ED) visits (68.1% to 70.9 %, p50.21), with significant increase in admissions for wheezing (21.1% to 26.7%, p50.004). Significant increase in the use of inhaled corticosteroids (1.7 and 2.9-fold) and leukotriene modifiers (5.1 and 5.3-fold) in Curitiba and S~ao Paulo, respectively. This was concomitant to a significant increase in the prevalence of physician-diagnosed asthma between S1 and S2. CONCLUSIONS: RW infants have higher prevalence of severity markers such as visits to ED and admissions for wheezing. There has been increased All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. J ALLERGY CLIN IMMUNOL Abstracts AB7 VOLUME 137, NUMBER 2

An Analysis of Obesity and Asthma Morbidity in at onset of wheezing > 5 years (adjusted odds ratio [OR] 3.87; 95% CI 20 Patients Managed at the Children's Hospital at 1.25-12.02), and sensitization to house dust mites (HDM) (adjusted OR Montefiore's Asthma Center 0.44; 95% CI 0.20-0.97). CONCLUSIONS: The probability of CR at 18 years of age was 80%. Gary K. Soffer, MD1, Jennifer Toh, MD2, Sunit P. Jariwala, MD3, Deepa Predicting factors for asthma remission were determined by age at onset of Rastogi, MD4; 1Children’s Hospital at Montefiore, Bronx, NY, 2Albert wheezing > 5 years and without HDM sensitization. Einstein/Montefiore Medical Center, Bronx, NY, 3Division of Allergy and Immunology, Department of Medicine, Montefiore Medical Center, Risk Factors for Asthma at Age 7 to 8 in Early Bronx, NY, 4Division of Pulmonology, Children’s Hospital at Montefiore. 22 Childhood Wheezers: Results from a Japanese RATIONALE: Previous studies suggest a relationship between obesity Asthma Cohort Study

and childhood asthma. We investigated the impact of body weight and 1 1 2 clinic visit compliance on asthma morbidity. Mayumi Furukawa, MD , Mari Sasaki, MD , Hiroko Watanabe, MD , Koichi Yoshida, MD1, Takao Fujisawa, MD, PhD, FAAAAI3, Motohiro METHODS: We reviewed 45 charts of children with moderate to severe 4 5 persistent asthma seen at the Montefiore Asthma Center (MAC), a Ebisawa, MD, PhD, FAAAAI , Hiroshi Odajima, MD, PhD , Akira- Akasawa, MD, PhD1; 1Division of Allergy, Tokyo Metropolitan multidisciplinary center comprised of Allergy, Pulmonary, and Asthma 2 Education services. Patients had 1 or more asthma-related emergency Children’s Medical Center, Tokyo, Japan, National Hospital Organization Kanagawa Hospital, Kanagawa, Japan, 3Allergy Center department (ED) visit or hospitalization or 3 or more steroid courses within 4 12 months of their first visit. Patients were categorized as obese/overweight and Institute for Clinical Research, Mie National Hospital, Japan. Clinical 5 5 Research Center for Allergy and Rheumatology, Sagamihara National (n 24) and normal-weight (n 21), based on CDC guidelines. Between- 5 group comparisons were done for compliance with MAC appointments, Hospital, Sagamihara, Japan, Fukuoka National Hospital, Fukuoka, asthma-related hospitalizations, and ED visits one year following the Japan. patient’s last visit. Compliance was defined as 3 MAC visits. RATIONALE: Previous studies have demonstrated that a proportion of RESULTS: Most patients lived in the Bronx (82%), were of children with wheezing episodes in early childhood do not have asthma at minority ethnicities (37% Latino, 35% African-American) and were school age. We sought to determine the risk factors for asthma at school age obese/overweight (53%). Visit compliance was similar between both among early childhood wheezers in a Japanese asthma cohort study. groups (50% obese/overweight vs 48% normal-weight.). However, more METHODS: A total of 632 children aged 0 to 3 with recurrent wheezing obese/overweight patients (45%) were hospitalized the year following their episodes were recruited in 2004 to 2006. Information including family last visit than normal-weight children (28%) with more hospitalizations history, environmental factors, wheezing symptoms and treatment were than normal-weight children (12 vs 2, p50.05). Similarly, 50% of obese/ collected by annual questionnaires. Among the 545 children with adequate overweight patients had asthma-related ED visits the year following their baseline information, we analyzed the 433 children followed up at 7 to 8 last visit compared to 23% of normal-weight children with more ED visits years old. Asthma at 7 to 8 years old was defined as having wheeze or the regular use of asthma controller medication in the past 12 months. than normal-weight children (30 vs 10, p 5 0.045). SATURDAY CONCLUSIONS: In spite of being compliant with asthma center RESULTS: Of the analyzed 433 children, 299 (69.1%) were boys and 350 evaluations, obese and overweight patients had more asthma-related ED (80.8%) children were on treatment of inhaled corticosteroids (ICS) or visits and hospitalizations, suggesting continued higher asthma morbidity. leukotriene receptor antagonists at recruitment. At 7 to 8 years of age, 276 This relationship requires further investigation as it may imply that obesity (63.7%) had asthma. Multivariate regression analysis showed that low birth interventions might play a substantive role in asthma management. weight, personal history of atopic dermatitis and food allergy at baseline, parental allergic rhinitis or pollinosis, the use of ICS at baseline were Predicting Factors for Asthma Remission in Children significantly associated with asthma at age 7 to 8 (each p<0.05). 21 CONCLUSIONS: Predisposition to atopy was a significant risk factor for asthma at school age in early childhood wheezers, similar to previous studies. Children with the early use of ICS had a high risk of asthma at Natcha Siripattarasopon, MD, Punchama Pacharn, MD, Orathai school age in our study population, probably due to the initial severity. Jirapongsananuruk, MD, Nualanong Visitsunthorn, MD, Pakit Vichyanond, MD, FAAAAI, Jittima Veskitkul, MD; Division of Allergy and Immunology, Department of Pediatrics, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand. RATIONALE: Factors contributing to outcome of childhood asthma are important for planning treatments and, potentially, in preventive in- terventions and advising on prognosis. Limited data are available on the asthma remission in Thai children. The objective of this study was to determine the predicting factors for asthma remission in children. METHODS: This is a prospective cohort study. Children who were diagnosed as having asthma during the period of 2004-2007 were reevaluated in 2015. The clinical characteristics and pulmonary function test were assessed. Clinical asthma remission (CR) was defined as having no asthma symptoms and no use of asthma medication during the past 12 months. RESULTS: One hundred and twenty children (63.3% male) with asthma were recruited. The median age at onset of wheezing was 2.0 years (range 0.2- 12.6 years), 95.7% had allergic rhinitis, 65.8% had aeroallergen sensitization and 20.8% had parental asthma. At reevaluation, 58 patients (48.3%) were in CR. CR rates at 15 and 18 years of age were 50% and 80%, respectively. Patients with CR had less significantly airway obstruction compared

with patients with persistent asthma (FEV1/FVC 97.667.3% VS 102.065.9%; p 5 0.004). Predicting factors for asthma remission were age All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. AB8 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2016

Impact of Asthma Exacerbations on Health Status in of 19 (p<0.01) and 21 (p<0.01) of having respective values <80% 23 Patients with Severe Asthma predicted over subsequent 4 years. CONCLUSIONS: Airflow obstruction persists in asthma children with Sarah Cockle1, Linda Nelsen2, Miriam Kimel3, Frank C. Albers, MD, early lung functions despite optimal guideline based therapy. PhD4, Paul Jones5; 1GlaxoSmithKline, Value Evidence and Outcomes, Stockley Park, United Kingdom, 2GlaxoSmithKline, King of Prussia, Characteristics That Distinguish Difficult-to-Control PA, 3Evidera, Bethesda, MD, 4GlaxoSmithKline, Research Triangle 25 Asthma in Inner-City Children 5 Park, NC, GlaxoSmithKline, Stockley Park, United Kingdom. 1 2 RATIONALE: Asthma exacerbations constitute a considerable part of Jacqueline A. Pongracic, MD, FAAAAI , Rebecca A. Zabel, MS , De- nise C. Babineau, PhD2, Edward M. Zoratti, MD, FAAAAI3, George T. disease burden in patients with severe uncontrolled asthma. However, the 4 5 impact of exacerbations is challenging to quantify. The St George’s O’Connor, MD , Robert A. Wood, MD, FAAAAI , Gurjit K. Khurana Hershey, MD, PhD, FAAAAI6, Carolyn Kercsmar, MD7, Rebecca S. Respiratory Questionnaire (SGRQ), a measure of health status in 8 9 obstructive airway disease, was measured at baseline and end of treatment Gruchalla, MD, PhD, FAAAAI , Meyer Kattan, MD , Stephen J. Teach, MD10, Samuel J. Arbes, Jr2, William W. Busse, MD, FAAAAI11, in a 32 week phase III clinical trial of mepolizumab for treatment of severe 12 13 asthma with a history of exacerbations (MENSA). Peter J. Gergen, MD, MPH , Alkis Togias, MD, FAAAAI , Cynthia Visness, PhD, MPH2, Andrew H. Liu, MD, FAAAAI14,15; 1Ann and Rob- METHODS: In this post-hoc analysis, we examined the impact of 2 SATURDAY ert H. Lurie Children’s Hospital of Chicago, Chicago, IL, Rho Federal exacerbations in 2 ways (1) baseline SGRQ scores by exacerbation history 3 <_ Systems Division Inc., Chapel Hill, NC, Henry Ford Health System, ( 2comparedwith>2) and (2) change in SGRQ scores for subjects with and 4 without exacerbations during treatment. All patients entering the trial had a Detroit, MI, Boston University School of Medicine, Boston, MA, 5Department of Pediatrics, Johns Hopkins University School of Medicine, history of at least two severe asthma exacerbations in the prior 12 months. 6 <_ Baltimore, Maryland, USA, Cincinnati Children’s Hospital, Cincinnati, RESULTS: Among subjects with a history of 2 exacerbations, mean 7 baseline SGRQ total score was 42.5 compared to 49.4 for those a history of OH, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, 8UT Southwestern Medical Center, Dallas, TX, 9College of Physicians >2 exacerbations (p<0.0001). Among patients not experiencing an 10 exacerbation during the study, SGRQ total score at 32 weeks was 28.5 and Surgeons, Columbia University, New York, NY, Children’s National Health System, Washington, DC, 11University of Wisconsin School of compared to 41.5 for subjects experiencing >1 exacerbations during study 12 treatment (p<0.0001) with changes of -15.4 and -8.0, respectively. Similar Medicine and Public Health, Madison, WI, AAIB/DAIT/NIH, Bethesda, MD, 13NIAID/NIH, Bethesda, MD, 14Children’s Hospital Colorado, patterns were observed for SGRQ domain scores. 15 CONCLUSIONS: The observed differences in SGRQ total and domain Aurora, CO, National Jewish Health, Denver, CO. scores for subjects with history of exacerbations at baseline or experi- RATIONALE: Because a significant proportion of inner-city children are encing an exacerbation during the study substantially exceeded the only partially responsive to guidelines-directed asthma therapy, we sought accepted minimum clinically important difference of 4. These differences to identify the clinical characteristics that distinguish difficult-to-control in SGRQ score demonstrate a substantial health impact of exacerbations. asthma. Funding: GSK (NCT01691521). METHODS: The Inner City Asthma Consortium enrolled children aged 6-17 years with asthma. After baseline assessment, participants had Persistence of Airflow Obstruction in Asthmatic bi-monthly guidelines-based asthma management visits over one year. 24 Children Difficult-to-control asthma (DCA) versus Easy-to-control asthma (ECA) were defined as daily controller therapy with inhaled fluticasone >500mcg Lori Banka, DO1, Yang Lu, PhD2, Lyne G. Scott, MD3, Salima A. +/-LABA versus <100mcg assigned on at least 4 visits, respectively. Thobani, MD4, Marilyn Li, MD5, Cindy Xi, MD6, Kenny Y. Kwong6; Forty-one baseline variables were used to compare DCA and ECA using 1LAC+USC Medical Center, Los Angeles, CA, 2Harbor-UCLA Medical univariate analyses. A variable selection algorithm was used to determine Center, 3University of Southern California, CA, 4University of Southern the most relevant features of DCA versus ECA. Generalized additive California, Los Angeles, 5University of Southern California, 6LAC+USC mixed-effects models were used to describe seasonal variation of Medical Center. symptoms, lung function, and exacerbations. RATIONALE: Chronic lung injury during early childhood may lead to RESULTS: Of the 619 participants, 40.9% had DCA and 37.5% had ECA. abnormal lung function persisting into adolescence. This study endeavors DCA was characterized by persistently low lung function, more frequent to determine whether children with asthma who initially present with low exacerbations in the spring and fall as well as greater daytime and lung function continue to have ongoing airflow obstruction despite optimal nocturnal symptoms in the fall and winter. Of the 41 variables, FEV1 asthma treatment. bronchodilator reversibility (BDR) was the most important characteristic METHODS: This is a 5 year retrospective study involving asthmatic distinguishing DCA. The other dominant features of DCA, in order of children, aged 6 to 14 enrolled in a pediatric asthma disease management importance, included: FEV1/FVC ratio, rhinitis medication score, FEV1 % program (Breathmobile). Patients had at least 1 spirometric assessment per predicted, rhinitis symptom score, mold sensitization, and total serum IgE. year and received asthma care in accordance with 2007 NHLBI-EPR-3 CONCLUSIONS: The phenotypic characteristics of DCA in inner-city asthma guidelines. Patients were divided into 2 groups, one with mean children include seasonal loss of asthma control, BDR, persistently low FEV1 and FEV1/FVC < 80% predicted and the second group with these lung function, rhinitis severity and atopy. These findings suggest that mean values > 80% predicted during the first year of treatment. Outcome baseline assessment of BDR and allergy-related factors, including rhinitis, was FEV1 and FEV1/FVC % predicted of these patients over subsequent 4 may predict future DCA. years. RESULTS: 621 patients were enrolled with 2711 visits. Mean age of patients was 9.3 years. 30%, 18%, 32% and 20% of patients had intermittent, mild, moderate and severe persistent asthma at initial evaluation. Patients with FEV1% and FEV1/FVC% <80% predicted during first year of enrollment was associated with increased odds ratio All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. J ALLERGY CLIN IMMUNOL Abstracts AB9 VOLUME 137, NUMBER 2

Income Is an Independent Risk Factor for Worse METHODS: This cross-sectional analysis used data from claims and 26 Asthma Outcomes electronic medical records (01/01/2007 – 08/31/2013) on asthma patients enrolled for >_1-year. Assessed outcomes included asthma-related health- Juan Carlos Cardet, MD1, Tonya S. King2, Margee Louisias, MD3, care usage (medications, office and emergency department [ED] visits, Mario Castro, MD, MPH4, Christopher D. Codispoti, MD, PhD5,6, Ryan hospitalizations) and asthma exacerbations. Outcomes for high-IgE vs Dunn, MD7, Brenda L. Giles, MD8, Fernando Holguin, MD, MPH9, low-IgE groups were compared using t-test or Chi-square tests as John Lima, MD10, Dayna Long, MD11, Njira Lugogo, MD12, Sharmilee appropriate. High IgE was defined as >_75 IU/mL, based on prior research. M. Nyenhuis, MD, FAAAAI13, Victor E. Ortega, MD14, Sima RESULTS: In the study population (n5652; mean age 52.4; 70.7% Ramratnam, MD15, Michael E. Wechsler, MD, MMSc16, Elliot female), 286 (43.9%) patients had high-IgE at least once. High-IgE Israel, MD, FAAAAI3, Wanda Phipatanakul, MD, MS17; 1Medicine, patients were more likely to have used allergen immunotherapy (18.2% vs Brigham and Women’s Hospital, Boston, MA, 2Penn State University, 10.9%; p50.008), chronic oral corticosteroids (OCS) (33.6% vs 26.0%; Hershey, PA, 3Brigham and Women’s Hospital, Boston, MA, 4Division p50.034), LABA (64.0% vs 56.0%, p50.040), and omalizumab (8.7% vs of Pulmonary and Critical Care Medicine, Department of Medicine, 3.6%; p50.005) and had received higher total annual prednisone- Washington University School of Medicine, Saint Louis, MO, 5Depart- equivalent dose (mean 738 vs 494 mg; p50.013); high-dose ICS usage ment of Immunology and Microbiology, Allergy/Immunology Section, did not differ between the groups (36.7% vs 35.5%, p50.753). Rush University Medical Center, Chicago, IL, 6Rush University Medical High- vs low-IgE asthma patients used asthma-related healthcare resources Center, Chicago, IL, 7National Jewish, 8University of Chicago, 9The at the following rates per 1,000 patient-years: office visits (2,197 vs 1,575; University of Pittsburgh Asthma Institute at UPMC and the University p50.008), ED visits (62 vs 5; p50.002), and hospitalizations (19 vs 14; of Pittsburgh School of Medicine, Department of Pulmonary, Allergy p50.141). Asthma exacerbation rates totaled 1,393 (high-IgE) vs 987 and Critical Care Medicine, Pittsburgh, PA, 10American Lung Assn, (low-IgE) per 1,000 patient-years, p50.144. Jacksonville, FL, 11University of California at San Francisco, 12Duke CONCLUSIONS: Patients with high-IgE levels had increased rates of University, 13MC 719, University of Illinois at Chicago, Chicago, IL, healthcare use, including emergency care and medications such as chronic 14Wake Forest University, 15Pediatric Pulmonary Clinic, 16National OCS, which providers seek to limit. Jewish Health, Denver, CO, 17Division of Pediatric Allergy/Immunology, Boston Children’s Hospital, Harvard University School of Medicine, Impact of a Mobile Health and Sensor-Driven Asthma Boston, MA. 28 Management Pilot Study on Symptoms, Control, and RATIONALE: Socioeconomic status (SES) and perceived stress Self-Management associate with increased asthma morbidity in observational studies. We 1 1 1 investigated whether SES and perceived stress are independent risk factors David Van Sickle, PhD , Meredith Barrett, PhD , Olivier Humblet, ScD , 2 1 3 1 for treatment failure and asthma exacerbations in a randomized clinical Jason Su, PhD , Kelly Henderson , Ted Smith, PhD ; Propeller Health, 2 3 trial (RCT) of vitamin D and asthma morbidity. University of California Berkeley, Louisville Metro Government

METHODS: The effect of household income (low defined as <$50,000/ Department of Economic Growth and Innovation. SATURDAY year), educational level (low defined as less than bachelor’s degree), and RATIONALE: We investigated the impact of a mobile health, sensor- perceived stress (high defined as score of >20 on a perceived stress scale) enabled asthma management program on rescue medication use, frequency of on asthma morbidity was analyzed in 381 participants utilizing Poisson asthma-free days, and asthma control among residents of Louisville, Kentucky. 5 regression models. The primary outcome was treatment failure (defined in METHODS: Adults and children (n 299) who reported a physician- the trial protocol as a significant clinical or airflow deterioration), and the diagnosis of asthma and a current prescription for short-acting beta agonist secondary outcome was asthma exacerbations requiring steroids. (SABA) were enrolled in a pre-post pilot study through community events, RESULTS: 54% of participants had low income, 40% had a low educational clinics, and retail pharmacies. Participants received an electronic inhaler sensor, level, and 17% had high levels of perceived stress. African American race and which tracked the date, time, and geographic location of rescue medication use. SES (income and education) were significantly associated (p<0.001) with Following a month-long control period to assess baseline levels of asthma each other. However, their level of association still met criteria for inclusion control and SABA use, participants received access to smartphone and in a regression model. After adjusting for study site, African American race, web-based applications that offered information about their asthma activity, ethnicity, number of people in household, and BMI, participants with lower personally-tailored education, and support based on national guidelines. income had a 1.5x higher rate of treatment failure [95%CI 1.05-2.25, RESULTS: By the end of the study rescue inhaler use declined by 75% and p50.026] and 1.9x higher rate of asthma exacerbations [95%CI 1.12-3.33, the proportion of asthma-free days increased significantly by 39% from p50.019]. African American race and vitamin D treatment were not effect intake to exit. A logistic mixed model showed that the proportion of modifiers of this association. Education and perceived stress were not asthma-free days during the intervention period was significantly higher significantly associated with treatment failures or exacerbations. than during the control period (p<0.01), while daily rescue use was lower CONCLUSIONS: In the context of a RCT, lower income associates with (p<0.01). The proportion of the participants with well-controlled asthma adverse asthma outcomes independent of race, education, and stress. improved over the course of the intervention, demonstrating a 33% increase from intake to exit (p<0.01). Survey results demonstrate an Higher Immunoglobulin E (IgE) Levels Are Associated increase in the percent of participants who reported having an asthma 27 with Greater Emergency Care and Other Healthcare action plan from intake (41%) to exit (57%). Utilization Among Asthma Patients in a Real-World CONCLUSIONS: A mobile health, sensor-enabled asthma management Data Setting program can help improve asthma management and outcomes within a community setting. Allan T. Luskin, MD1, Evgeniya Antonova, MS, PhD2, Michael Broder, MD, MSHS3, Eunice Chang, PhD3, Theodore A. Omachi, MD, MBA2; 1University of Wisconsin, Madison, WI, 2Genentech, Inc., South San Francisco, CA, 3Partnership for Health Analytic Research, LLC, Bev- erly Hills, CA. RATIONALE: IgE is a marker of allergic status in asthma, but there has been limited evaluation of whether higher levels of IgE might reflect poorer health outcomes, especially in a real-world setting. All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. AB10 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2016

Is Unrecognized Food Allergy or Aeroallergen hypertriglyceridemia (components of the metabolic syndrome, along 29 Sensitization Responsible for Emergency with obesity and insulin resistance), did not modify the obesity-asthma Department Visits Attributed to Asthma? association (P interaction50.68 and 0.45, respectively). CONCLUSIONS: In this large, nationally-representative sample, insulin Jennifer Dantzer, MD, Torie Grant, MD, Elizabeth Matsui, MD, MHS, resistance modified the association between obesity and current asthma in Corinne Keet, MD, PhD; Division of Pediatric Allergy/Immunology, adults. Clinical and basic studies are needed to better understand this Johns Hopkins School of Medicine, Baltimore, MD. important interaction. RATIONALE: Higher food IgE has been associated with asthma morbidity, but it is not known whether this is (a) independent of high- level aeroallergen sensitization and (b) related to allergen consumption among sensitized individuals. METHODS: 1170 individuals with asthma from NHANES 2005-6 were Identification of Pathways to Asthma Severity in included. IgE to cow’s milk, peanut, egg, shrimp, and 15 aeroallergens was 31 Inner-City Children measured. Allergen consumption was captured by questionnaires. Food sensitization was categorized as non-sensitized (IgE<0.35 kU/L), low Andrew H. Liu, MD, FAAAAI1,2, Denise C. Babineau, PhD3,4, Rebecca (>50.35–2kU/L), moderate (2kU/L-‘‘95% PPVs’’) or high (>’’95% PPVs’’). A. Zabel, MS4, Edward M. Zoratti, MD, FAAAAI5,6, Jacqueline A. SATURDAY Aeroallergen sensitization was defined as: (1) any aeroallergen IgE >_0.35, (2) Pongracic, MD, FAAAAI7, George T. O’Connor, MD8, Robert A. level of aeroallergen-specific IgE [non-sensitized, low (<2kU/L)orhigh Wood, MD, FAAAAI9, Gurjit K. Khurana Hershey, MD, PhD, (>_2kU/L)], and (3) number of different aeroallergen sensitizations. Logistic FAAAAI10,11, Carolyn Kercsmar, MD12, Rebecca S. Gruchalla, MD, regression models of Emergency Department (ED) visits included food-IgE PhD, FAAAAI13, Meyer Kattan, MD14,15, Stephen J. Teach, MD16, level, age, sex, race, income, and (a) magnitude of aeroallergen sensitization or Samuel J. Arbes, Jr3, Peter J. Gergen, MD, MPH17,18, Alkis (b) interaction of food-IgE level and relevant allergen consumption. Togias, MD, FAAAAI18, Cynthia Visness, PhD, MPH3,4, William W. RESULTS: Adjusted odds of an ED visit for asthma were higher in those Busse, MD, FAAAAI19; 1Children’s Hospital Colorado, University of with high food-IgE (OR: 8.4; 95%CI: 2.8-25). Adjusting for any Colorado School of Medicine, Aurora, CO, 2National Jewish Health, Den- aeroallergen IgE >_0.35 , level of aeroallergen-specific IgE , and number ver, CO, 3Rho, Inc., Chapel Hill, NC, 4Rho Federal Systems Division Inc., of different aeroallergen sensitizations attenuated but did not eliminate the Chapel Hill, NC, 5Department of Public Health Sciences, Henry Ford relationship between food-IgE and ED visits (OR: 6.6 [95% CI 1.2-4.3], Health System, Detroit, MI, 6Henry Ford Health System, Detroit, MI, 6.5 [2.1-20.4], and 4.4 [1.1-1.7], respectively). There was no increase in 7Ann and Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL, asthma ED visits among those with elevated food-IgE who reported 8Boston University School of Medicine, Boston, MA, 9Department of Pe- consuming that food (p>0.2). diatrics, Johns Hopkins University School of Medicine, Baltimore, Mary- CONCLUSIONS: Although high food-specific IgE predicts asthma land, USA, 10Cincinnati Children’s Hospital, Cincinnati, OH, 11University exacerbation independent of aeroallergen sensitization, allergen consump- of Cincinnati, Cincinnati, OH, 12Cincinnati Children’s Hospital Medical tion does not appear to modify this risk, suggesting that unrecognized food Center, Cincinnati, OH, 13UT Southwestern Medical Center, Dallas, allergy is not the likely cause of this relationship. TX, 14NewYork-Presbyterian/Columbia, New York, NY, 15College of Physicians and Surgeons, Columbia University, New York, NY, 16Chil- Insulin Resistance Modifies the Association dren’s National Health System, Washington, DC, 17AAIB/DAIT/NIH, Be- 30 Between Obesity and Current Asthma in Adults thesda, MD, 18NIAID/NIH, Bethesda, MD, 19University of Wisconsin School of Medicine and Public Health, Madison, WI. 1 2 Samuel Y. Ash, MD , Juan Carlos Cardet, MD , Tope Kusa, MBBS, RATIONALE: Pathways describing how host and environmental factors 3 4 1 MPH , Carlos Camargo, Jr, MD, DrPH , Elliot Israel, MD, FAAAAI ; lead to asthma severity have not been well defined in inner-city children. 1 2 Brigham and Women’s Hospital, Boston, MA, Medicine, Brigham and METHODS: Nine sites in the NIAID-funded Inner City Asthma Consortium 3 Women’s Hospital, Boston, MA, Harvard School of Public Health, Bos- enrolled 717 children aged 6-17 years with asthma. Subjects were evaluated 4 ton, MA, Department of Emergency Medicine, Massachusetts General every two months for one year, with adjustments in asthma and rhinitis Hospital, Harvard Medical School, Boston, MA. management made at each visit. An overall measure of asthma severity was RATIONALE: Insulin resistance potentiates the association between defined using longitudinal measures of asthma symptoms, exacerbations and obesity and pediatric asthma, but this relationship appears inconsistent in treatment. Twenty-two other variables measured at baseline or longitudinally relatively small studies of adults. We investigated effect modification in were used to define 8 domains: allergic sensitization, blood eosinophils and adults using a large, nationally-representative database. exhaled nitric oxide (Eos/FeNO), lung function, Vitamin D, stress, obesity, METHODS: Data were obtained from the National Health and Nutrition exposure to tobacco smoke (ETS), and rhinitis severity. A conceptual model Examination Survey 2003-2012. Insulin resistance and a history of of how these domains act through different pathways to explain asthma physician-diagnosed current asthma were obtained from 12,421 adults severity was tested using structural equation models. (ages 18–85 years). Logistic regression was used to determine associations RESULTS: This analysis included 579 participants with rhinitis who between obesity and current asthma, adjusting for age, sex, race/ethnicity, completed at least 4 follow-up visits. In an allergy pathway to asthma severity, poverty index ratio, and smoking status. We evaluated effect modification allergic sensitization strongly affected Eos/FeNO (p<0.001); and Eos/FeNO by insulin resistance of the obesity-asthma association. was indirectly associated with asthma severity via lung function and rhinitis RESULTS: As expected, obesity was positively associated with current severity (p<0.001). Additionally, ETS, lung function and rhinitis severity were asthma, with 97% greater odds of current asthma for obese participants directly associated with asthma severity (p<0.004). ETS was also indirectly (95% CI 1.64–2.36). Insulin resistance modified this association, with a associated with asthma severity via lung function (p<0.001). Our complete stronger obesity-asthma association among those with insulin resistance pathways model accounted for 50.9% of the variance in asthma severity. 5 (P interaction 0.03). Effect modification was also significant with obesity CONCLUSIONS: This is the first study to identify specific pathways and measured as waist circumference and waist-to-height ratio. Stratifying by their relative contributions to asthma severity in inner-city children with tertiles of insulin resistance, analyses of the relationship between obesity asthma and rhinitis, providing a strategic blueprint of pathogenesis and and current asthma showed an ordinal relationship, with OR increasing prioritized targets for preventive interventions. with greater insulin resistance (1.99, 2.69, 2.95, respectively). Subgroup analysis of participants not on insulin replacement therapy also showed a significant association (P interaction50.048). Hypertension and All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. J ALLERGY CLIN IMMUNOL Abstracts AB11 VOLUME 137, NUMBER 2

Association Between Asthma Symptom Scores and CI51.25–2.21), mold in the home (aOR52.01, 95% CI51.33–3.03), 32 Increased Perceived Stress and Trait Anxiety in and cost as a barrier to accessing asthma-related health care (primary care Asthmatic Adolescents aOR53.69, 95% CI52.25–6.05; specialty care aOR54.72, 95% CI52.63–8.45; asthma medication aOR53.23, 95% CI52.21–4.72). Cathryn J. Luria, MD1, Alexandra R. Sitarik, MS2, Suzanne CONCLUSIONS: Among older adults, asthma-related hospitalizations Havstad, MA2, Ganesa R. Wegienka, PhD2, Haejin Kim, MD2,3, Edward were associated with medical comorbidities, mold in the home, and M. Zoratti, MD, FAAAAI2,4, Christine L. M. Joseph, PhD2, Andrea- financial barriers to asthma-related health care. Interventions addressing Cassidy-Bushrow, PhD2; 1Division of Allergy and Clinical Immunology, modifiable factors could reduce asthma-related hospitalizations among Henry Ford Health System, Detroit, MI, 2Department of Public Health older adults. Sciences, Henry Ford Health System, Detroit, MI, 3Henry Ford Health System, Division of Allergy and Clinical Immunology, Detroit, MI, Influence of Depression on Asthma Outcomes in 4Henry Ford Health System, Detroit, MI. 34 Older Adults – Results from the National Health and RATIONALE: The relationship between asthma symptoms and perceived Nutrition Examination Survey (2007-2012)

stress and trait anxiety is not well understood. 1 2 METHODS: Adolescents ages 14-17 years were recruited to examine the Pooja M. Oza, MD , Minal R. Patel, PhD, MPH , Alan P. Baptist, MD, MPH, FAAAAI1; 1University of Michigan, Division of Allergy and effect of stress on health measures. They were included in the present 2 analysis if they reported current asthma, defined as self-reported clinician- Clinical Immunology, Ann Arbor, MI, University of Michigan School diagnosed asthma plus one or more episodes of asthma in the past year. of Public Health, Ann Arbor, MI. Asthma symptoms were assessed on a 7-point Likert scale using six asthma RATIONALE: Some of the highest asthma morbidity and mortality rates control questionnaire items targeting nocturnal awakening due to asthma, are observed in older adults. There are no nationally representative studies symptoms upon awakening, activity limitation, shortness of breath, time describing the influence of depression in older adults on key asthma spent wheezing, and short-acting bronchodilator (SABA) use. Stress was outcomes. This study investigated the influence of depression on asthma measured using the perceived stress scale (PSS), and trait anxiety was outcomes in older adults (age > 55) in National Health and Nutrition measured using the State-Trait Anxiety Inventory. Linear regression was Examination Survey (NHANES). used to associate asthma symptoms with PSS and trait anxiety. METHODS: Cross sectional data from the 2007-2012 waves of the 5 RESULTS: Of 335 adolescents recruited, 38 (11.3%) reported current asthma. NHANES were analyzed (n 7,256). Bivariate analyses and multivariate Four of the six asthma symptom assessments had significant associations with Poisson regression models were used to examine associations between PSS: symptoms upon awakening (b54.8, p-value<0.001), nocturnal awak- depression and asthma outcomes (asthma symptoms, sleep disturbances, ening due to asthma (b54.47, p<0.001), activity limitation (b52.78, activity limitation, urgent health care use, missed work days, health-related p50.005), and shortness of breath (b51.73, p50.014). These associations quality of life (QOL), and spirometry). 5 remained significant after adjusting for gender, race, and BMI percentile. Time RESULTS: 5.5% (n 402) of the sample reported a physician diagnosis of asthma. Older adults with asthma and depression (n 5 196) had increased spent wheezing and SABA use were not significantly associated with PSS. Trait SATURDAY 5 anxiety had significant associations with nocturnal awakening (b59.28, ED/ urgent care visits (PR 2.04, P <0.03) and sleep disturbances due to 5 p50.002) and symptoms upon awakening (b58.74, p50.002). asthma (PR 2.16, P<0.001) compared to those without depression. They CONCLUSIONS: Asthma symptoms are associated with increased also reported worse health-related QOL measures including number of 5 perceived stress and trait anxiety. Asthmatic adolescents may represent a unhealthy days (PR 1.93, P<0.001), days mental health was not good (PR population that is particularly vulnerable to perceived stress and anxiety, 5.16, P< 0.001), and inactive days due to health (PR 2.51, P< 0.001). No highlighting the importance of considering these factors in asthma significant differences in spirometric values were observed. counseling. CONCLUSIONS: Older adults with asthma and depression are twice as likely to have an ED/urgent care visit for asthma compared to those without Risk Factors Associated with Asthma-Related depression. They also suffer from decreased health-related quality of life 33 Hospitalizations Among Older Adults and sleep disturbances due to asthma. Screening for depression and providing supportive resources may decrease the morbidity and mortality Joy Hsu, MD, MSCI1, Jessica Chen, BA2, Maria C. Mirabelli, PhD3; rates among older adults with asthma. 1Centers for Disease Control and Prevention, Atlanta, GA, 2Emory Uni- versity, 3Centers for Disease Control and Prevention. RATIONALE: Asthma morbidity is elevated among the growing number of older adults in the United States. Targeted interventions to improve asthma control in this population are not well-described. METHODS: We investigated risk factors for asthma-related hospitaliza- tion using a sample of older adults (>_65 years) with active asthma from 40 states, the District of Columbia, and Puerto Rico who participated in the Behavioral Risk Factor Surveillance System Asthma Call-back Survey, a random-digit dialing survey. We conducted weighted logistic regression analyses using 2006–2010 data to compare older adults with and without asthma-related hospitalizations in the past year with respect to clinical, environmental, and financial measures. We controlled for sociodemo- graphic and clinical characteristics. RESULTS: Among 14,076 older adults with active asthma (representing >2.6 million persons), 5.7% (95% confidence interval [95% CI]55.0– 6.4%) reported >_1 asthma-related hospitalization in the past year. Compared to older adults without asthma-related hospitalizations, the adjusted odds were higher among older adults with >_1 asthma-related hospitalization for chronic obstructive pulmonary disease (adjusted odds ratio[aOR]54.88, 95% CI53.36–7.09), coronary artery disease (aOR51.92, 95% CI51.46–2.51), depression (aOR51.66, 95% All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. AB12 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2016

Retrospective Observational Study to Evaluate Long- only once after the first 7 months of treatment. He was considered for a dou- 35 Term Effectiveness and Safety of Omalizumab ble lung transplant, but after 1 year of treatment, transplantation and home Treatment in Real-Life Setting in Allergy Centre of oxygen were no longer indicated. Spain CONCLUSIONS: Omalizumab had a dramatic steroid sparing effect, reduced hospitalizations, and O2 requirements in this CF patient with Dorkas Margarita Marquez Hernandez, Jose A. Bastidas, Lys Herraez, ABPA and prednisone-induced diabetes. Further prospective studies using Elena Mederos, A. Enriquez Matas, MD, Ruth Mielgo Ballesteros, MD, a larger cohort are necessary to make clinical recommendations. Consuelo Fernandez; Hospital Universitario 12 de Octubre, Madrid, Spain. Effectiveness of Omalizumab in Asthmatics with RATIONALE: Few studies have evaluated long-term and progressive 37 Baseline Serum IgE>1500 IU/Ml Using a Novel beneficial effects of omalizumab uninterrupted treatment for > 5 years in Method for Assessing Response: Reality Study

real-life practice. 1 2 1 The aim of this study was to evaluate the clinical and functional Joseph D. Diaz, MD , Jay Peters, MD , Yogeet Kaur, MS , Harjinder Singh, MD1; 1Allergy, Asthma and Immunology Associates of South improvement of patients with persistent severe asthma treated with 2 omalizumab for 5 years. Texas, San Antonio, TX, Univ. Texas Health Science Center San Anto- METHODS: A retrospective, observational study based on medical nio, San Antonio, TX. SATURDAY record reviews of patients treated with omalizumab for minimum 5 years RATIONALE: Omalizumab has been approved for asthmatics with IgE was addressed. Annual asthma exacerbations (AE), emergency visits (EV), levels of 30-700IU/mL. It has even been used with IgE>1500IU/mL, hospital admissions (HA), systemic corticosteroid bursts (SCOb), inhaled although few studies have confirmed the efficacy at these levels. A standardized criterion for assessing response to omalizumab is needed. corticosteroids daily dose (ICS/d) and lung function (FEV1% predicted) were collected during the pre-treatment year and compared after 1 and 5 Study is designed to apply a novel method using multiple independent years of uninterrupted therapy. Adverse reactions (AR) were also modules comparing response to omalizumab in patients with IgE<700 vs reviewed. IgE>1500 IU/mL. RESULTS: 14 patients were evaluated. The average age was 41.64, nine METHODS: Retrospective analysis of response to omalizumab in patients were female and 13 had allergic asthma. Mean values before patients with elevated baseline IgE after one year of treatment. Response to therapy (one-year pre- to one-year post-treatment) was defined by omalizumab treatment were total IgE 767.37 KU/L, FEV1 77%, ICS/ d 1000 mcg (Fluticasone), SCOb 5.5, AE 7.14, EV 3.57 and HA 0.86. multiple modules:[Module1,M1]-complete control or marked improve- AER, ERV, SCOb reduced by 65%, 80%, 73%, respectively at year 1 ment in asthma-symptoms based on Global Evaluation of Treatment Effectiveness(GETE) scores; [Module2,M2]-improvement in at least three and 92%, 96%, 83%, respectively at year 5 of treatment. Mean FEV1 increased up 87% at year 1 and up 105 % at year 5. Pre-treatment ICS/ of six of the following:50% reduction in asthma exacerbations, steroid- _ d dose reduced by 28 % at year five and only one patient suffered 1HA bursts, ER-visits, hospitalizations; improvement in FEV1(>200c), _ at year five. Only 2 patients experienced mild headache and no serious improved ACT-score>3; [Module3,M3,True responder]-patient that meets AR were documented. both M1 and M2 response criteria. _ CONCLUSIONS: Omalizumab showed an excellent tolerability and a RESULTS: 157 patients with baseline IgE>30IU/mL received omalizu- progressive long-term effectiveness over 5 years in real-life practice, mab for one year: G1[30-700IU/mL],G2[701-1500IU/mL] and G3 although the most improvements were experimented within the first year of [>1500IU/mL]. Number of patients per group were: G1[101(64.3%)]; treatment. G2[20(12.7%)] and G3[36(22.9%)]. Mean (SD) for baseline IgE:G1 [278(194)]; G2[1,054(165)] and G3[3,486(2,661)]. Overall true response Efficacious Use of Omalizumab in the Treatment of (M3) was 64.3%. Response rate for G1 vs G3 are respectively 82.2% and 36 Cystic Fibrosis 86.1% by M1, 68.3% and 80.6% by M2, and 61.4% and 69.4% by M3. Using M3 response for G1 and G3, statistical p-value is 0.083. Diana Pham1, Hoang Pham, MD 2016, BSc, BA2, Ena Gaudet, RN3, CONCLUSIONS: After one year, there was no significant difference in Shawn Aaron, MD3,4, Stephanie Santucci, RN1, William H. Yang, true response to therapy (M3) between patients with baseline IgE<700 MD1,4; 1Ottawa Allergy Research Corporation, Ottawa, ON, Canada, compared to those with baseline IgE>1500. Positive response by subjec- 2University of Ottawa, Faculty of Medicine, Ottawa, ON, Canada, 3Divi- tive physician’s assessment was consistently higher than response by sion of Respiratory Medicine, The Ottawa Hospital, Ottawa, ON, Canada, clinical parameters. 4University of Ottawa Medical School, Faculty of Medicine, Ottawa, ON, Canada. RATIONALE: Cystic fibrosis (CF) is a genetic respiratory disease associated with airway obstruction and chronic lung infections. 7-9% of CF cases are complicated by allergic bronchopulmonary aspergillosis (ABPA). Few studies suggest omalizumab may be effective in CF. Here we report a 25-year old male CF patient with concomitant ABPA complicated with numerous hospitalizations and steroid side effects who responded well to omalizumab. METHODS: A retrospective chart review was performed. Evaluation jointly occurred at The Ottawa Hospital’s CF Clinic and a tertiary care Allergy & Asthma Clinic in Ottawa. RESULTS: CF was diagnosed at 5 months old. Patient had a positive skin prick to Aspergillus fumigatus and a total serum IgE of 111.7 IU/mL. Corticosteroid-induced diabetes developed at age 19. Given his poor health and high IgE levels, a decision was made to trial omalizumab. After 8 months of omalizumab, he successfully weaned off of prednisone. After 18 months, he no longer needed insulin to treat his prednisone-induced dia- betes. After 20 months, his quality of life improved. During the twelve months prior to treatment he was hospitalized 8 times, but was hospitalized All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. J ALLERGY CLIN IMMUNOL Abstracts AB13 VOLUME 137, NUMBER 2

Impact of Visit Compliance on Response to is some evidence demonstrating efficacy in ABPA and fewer adverse ef- 38 Omalizumab Therapy in a Real-Life Clinical Setting: fects than long-term corticosteroids. Reality Study METHODS: A retrospective chart review was performed on ABPA patients receiving omalizumab from 2007-2015 at our tertiary care Allergy Harjinder Singh, MD1,2, Jay Peters, MD1, Yogeet Kaur, MS2, Joseph D. & Asthma Clinic and The Ottawa Hospital Chest Clinic. Data was Diaz, MD2; 1Univ. Texas Health Science Center San Antonio, San Anto- collected on demographics, skin prick testing, inhaled /oral corticosteroid nio, TX, 2Allergy, Asthma and Immunology Associates of South Texas, use, asthma exacerbations/hospitalizations and quality of life (QoL). San Antonio, TX. RESULTS: Ten patients were evaluated (59.7613.9 years, 7 females, 3 RATIONALE: Omalizumab is indicated for patients with poorly males). By month 16, the average dose of inhaled corticosteroids dropped controlled allergic asthma. Compliance and impact on response to by 24%.There was an 89% drop in prednisone intake from baseline in three omalizumab therapy has not been studied. To evaluate visit compliance oral-steroid dependent patients. Nine subjects reported exacerbations 12 and investigate impact on response rate to omalizumab therapy in a real- months prior to treatment, but none reported exacerbations once they world clinical setting. started omalizumab. QoL scores improved from baseline. METHODS: A retrospective review of patients who received omalizumab CONCLUSIONS: Our retrospective study provides compelling evidence therapy for a minimum of two years during 2004-2011. Visit compliance that supports the hypothesis that omalizumab may be an effective low-risk and response rates to therapy were evaluated at three time-periods: P1(16- treatment for ABPA patients, a much underserved patient population. wk), P2(1-yr) and P3(2-yr). Compliance was calculated by comparing number of recommended injections to injections actually received. Patients Rapid Lung Function Improvement with Lebrikizumab were grouped based on compliance rates: C1(<50%, non-compliant); 40 in Patients with Uncontrolled Asthma >_ C2(50-75%); C3(76%-89%) and C4( 90%, high compliance). A positive 1 2 response was identified by combination of complete control or marked Jonathan Corren, MD , Nicola A. Hanania, MD , Phillip E. Korenblat, MD, FAAAAI3, Julie K. Olssen, MD, MS4, Nikhil improvement by Physician’s GETE (Global Evaluation of Treatment 5 6 7 Effectiveness), AND improvement in asthma symptoms pre- and post- Kamath, MD , Sarah Gray, PhD , Nicolas Martin , Cecile T. J. Holweg, PhD6, John G. Matthews, MB, BS, MRSCP, PhD6, Susan L. omalizumab therapy in three or more of the following six parameters: 4 7 1 >_ Limb, MD , Stephan Korom ; Asthma and Allergy Research Foundation, Decrease by 50% in asthma exacerbations (AE); steroid-bursts; ER- 2 >_ Los Angeles, CA, Pulmonary, Critical Care and Sleep Medicine, Baylor visits; hospitalizations; improvement in FEV1( 200cc); increase in ACT 3 score (>_3). College of Medicine, Houston, TX, The Clinical Research Center LLC, St. Louis, MO, 4Genentech Inc. (a member of the Roche Group), South RESULTS: Visit compliance and response rates were evaluated for 124 5 patients at P1, P2 and P3. Overall compliance: P1[98.4%]; P2[89.5%] and San Francisco, CA, Roche Products Limited, Welwyn Garden City, United Kingdom, 6Genentech, Inc. (a member of the Roche Group), South P3[87.1]. Overall response rate: P1[33.0%]; P2[62.9%] and P3[63.7%]. 7 Responder-rate for C2[P2(70.0%); P3(71.0%)] and C3[P2(64.0%); San Francisco, CA, F. Hoffmann-La Roche Ltd, Basel, Switzerland. RATIONALE: Interleukin-13 is a pivotal cytokine within Type 2 asthma P3(66.7%)] is higher than C4[P2(60.7%); P3(62.5%)]. Number of SATURDAY Patients with very high compliance (C4) drastically drops from P1 pathophysiology, driving airway hyperresponsiveness, mucus production [89(72%)] to P2[56(45%)]. Response rates for C1 and C4 are not and remodeling. Here, we assess the improvement in FEV1 with lebrikizu- statistically different (p-value,0.257). mab therapy. CONCLUSIONS: In this analysis, visit compliance does not statistically METHODS: We conducted a pooled analysis of three trials impact response rate to omalizumab therapy. Compliance to omalizumab (NCT00930163/NCT01545440/NCT01545453) including 565 patients therapy decreases over time. Higher compliance does not correspond to with moderate-to-severe uncontrolled asthma receiving ICS (200–2000 m _ high response rate. g/day fluticasone propionate or equivalent), >1 additional controller _ (>90% LABA), pre-bronchodilator FEV1 40–80% predicted and >12% Omalizumab Can be Effective in Patients with FEV1 reversibility. Lebrikizumab (125 or 250 mg) was administered sub- 39 Allergic Bronchopulmonary Aspergillosis cutaneously every 4 weeks to 337 patients, and 228 patients received pla- cebo. Change in FEV1 at Weeks 1 and 12 was assessed according to John W. O’Quinn, MD1, Diana Pham1, Hoang Pham, MD 2016, BSc, baseline serum periostin level (>_50 ng/mL vs <50 ng/mL). BA2, Gonzalo G. Alvarez, MD3,4, Istvan T. Bencze, MD3,4, Krishna B. RESULTS: In patients with baseline serum periostin levels >_50 ng/mL, 3,4 4 3,4 Sharma, MD , Mark Smith, MD , Shawn Aaron, MD , Jennifer the mean (SD) absolute increase in FEV1 from baseline was 208 (361) mL Block, MD4, Tara Keays, MD4,5, Judith Leech, MD3,4, David in lebrikizumab-treated patients versus 67 (262) mL with placebo at Week 4,5 1 6 Schneidermen, MD , Jodi Cameron, RPN , Jennifer Forgie, RN , Alicia 1. Week 12 FEV1 improvement from baseline was 292 (390) mL in lebri- Ring, RPN1, Stephanie Santucci, RN1, William H. Yang, MD1,4; 1Ottawa kizumab versus 94 (280) mL in placebo-treated patients. Lebrikizumab- Allergy Research Corporation, Ottawa, ON, Canada, 2University of treated patients with serum periostin <50 ng/mL at baseline showed a 3 Ottawa, Faculty of Medicine, Ottawa, ON, Canada, Division of Respira- smaller FEV1 improvement at Weeks 1 and 12 of 143 (326) mL and 180 tory Medicine, The Ottawa Hospital, Ottawa, ON, Canada, 4University of (298) mL, respectively versus placebo 86 (266) mL and 106 (293) mL. Ottawa Medical School, Faculty of Medicine, Ottawa, ON, Canada, CONCLUSIONS: In patients with moderate-to-severe uncontrolled 5Division of Internal Medicine, Monfort Hospital, Ottawa, ON, Canada, asthma with high serum periostin, a single dose of lebrikizumab led to a 6 Ottawa Allergy Research Coproration, Ottawa, ON, Canada. rapid, clinically meaningful increase in FEV1 within 1 week that was sus- RATIONALE: Allergic bronchopulmonary aspergillosis (ABPA) is a tained to Week 12. These data illustrate the efficacy of lebrikizumab on complex respiratory disease with significant morbidity and mortality. improving airway function in patients with moderate-to-severe Type 2- ABPA occurs in 10% of patients with severe asthma. Patients usually mediated asthma. demonstrate positive skin prick test to Aspergillus, decline in lung function, elevated total IgE levels, elevated Aspergillus fumigatus specific IgE anti- body, and central bronchiectasis. Symptoms are often persistent despite conventional asthma therapy. Serious adverse effects from long-term use of high dose inhaled and oral corticosteroids include immunosuppression, adrenal insufficiency, osteoporosis, and many others. Antifungals are also problematic due to drug interactions and monitoring requirements. Some studies suggest that omalizumab may be a better therapeutic option as there All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. AB14 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2016

Biomarkers Associated with Response in Patients calculated the Pearson correlation coefficients between WPAI and ACT 41 Initiating Omalizumab: Baseline Levels Among scores. Patients in the Prospective Observational Study to RESULTS: Well-controlled asthma patients consistently reported less Evaluate Predictors of Clinical Effectiveness in productivity impairment (mean WPAI-A scores [SD; n]) than those with Response to Omalizumab (PROSPERO) Study poorly-controlled asthma: baseline (6.9 [12.5, n53429] vs 37.4 [28.6, n53902], p<0.001), year (Y)1 (6.4 [12.1, n53953] vs 37.7 [27.8, n53378] Bradley E. Chipps, MD, FAAAAI1, William W. Busse, MD, FAAAAI2, p<0.001), Y2 (6.3 [11.9, n54019] vs 37.7 [27.4, n53312] p<0.001), and Allan T. Luskin, MD3, Robert S. Zeiger, MD, PhD, FAAAAI4, Benjamin Y3 (6.3 [12.0, n54050] vs 38.2 [27.5, n53281] p<0.001). Similar results Trzaskoma, MS5, Hooman Pazwash5, Theodore A. Omachi, MD, MBA5, were obtained when patients were stratified by their omalizumab status Thomas B. Casale, MD, FAAAAI6; 1Capital Allergy & Respiratory Dis- (continuous users, new starts, and no-users). ACT/WPAI correlation varied ease Center, Sacramento, CA, 2University of Wisconsin, Madison, WI, between -0.707 and -0.750 across timepoints. 3HealthyAirways, Madison, WI, 4Departments of Allergy and Research CONCLUSIONS: Asthma control demonstrated strong negative correla- and Evaluation, Kaiser Permanente Southern California, San Diego, tion with work/school productivity impairment: poor asthma control was CA, 5Genentech, Inc., South San Francisco, CA, 6University of Southern consistently associated with higher productivity impairment. Florida, Tampa, FL. RATIONALE: Biomarkers of type 2 inflammation in patients with Long-Term Safety and Efficacy of Mepolizumab in SATURDAY allergic asthma include fractional exhaled nitric oxide (FeNO), peripheral 43 Patients with Severe Eosinophilic Asthma

blood eosinophils (EOS), and serum periostin (PERI). Biomarker relation- 1 2 3 ships were explored using baseline data from an ongoing 48-week study of Frank C. Albers, MD, PhD , Njira Lugogo , Martyn J. Gilson , Robert Price4, Steven W. Yancey1; 1GlaxoSmithKline, Respiratory Medical Fran- omalizumab clinical effectiveness. 2 5 chise, Research Triangle Park, NC, Duke Asthma, Allergy and Airway METHODS: Baseline values in adult patients (N 737) with allergic 3 asthma who subsequently initiated treatment with omalizumab and had not Center, Duke University Medical Center, Durham, NC, GlaxoSmithK- received omalizumab within the preceding year were analyzed. Spearman line, Respiratory Research and Development, Uxbridge, United Kingdom, 4GlaxoSmithKline, Clinical Statistics, Uxbridge, United Kingdom. correlation coefficients (rs) of biomarkers between one another and with RATIONALE: To describe the safety profile of long-term mepolizumab FEV1 were determined. treatment and its effects on markers of asthma control in patients with RESULTS: Mean baseline FEV1 was 74.7% of predicted value, n5728. Median and geometric mean baseline biomarker values were: FeNO, severe eosinophilic asthma. 22.0 and 23.6 ppb, n5722; EOS, 230 and 220/mL, n5662; and PERI, METHODS: Following completion of MEA115588 and MEA115575 48.3 and 48.9 ng/mL, n5660. Biomarkers were weakly correlated with (both double-blind studies), 651 patients with severe eosinophilic asthma entered a 52-week open-label extension study (MEA115661), receiving one another at baseline. FeNO correlations were: EOS, rs50.35 (95% CI mepolizumab 100mg subcutaneous every 4 weeks adjunctive to standard 0.28, 0.41; p<0.0001; n5650); and PERI, rs50.27 (95% CI 0.20, 0.34; care. p<0.0001; n5648). Correlation between EOS and PERI was rs50.24 RESULTS: On-treatment adverse events (AEs) and serious AEs were (95% CI 0.17, 0.31; p<0.0001; n5636). FEV1 was very weakly correlated reported in 558(86%) and 94(14%) patients, respectively. Asthma with FeNO, rs520.10 (95% CI 20.17, 20.03; p50.0079; n5716); EOS, exacerbation 38(6%) was the most common serious AE. No fatal AEs rs520.12 (95% CI 20.19, 20.04; p50.0028; n5659); and PERI, were reported. Systemic and local site reactions were reported in 13(2%) rs520.08 (95% CI 20.16, 20.01; p50.0360, n5657). CONCLUSIONS: This analysis provides information on the biomarker and 29(4%) patients, respectively, with no reports of mepolizumab-related characteristics of allergic asthma patients before they initiated treatment anaphylaxis. Rates of AEs during MEA115661 were similar to placebo with omalizumab in a real world setting. It also highlights the heteroge- during the double-blind studies. For patients commencing mepolizumab in neity of biomarker profiles and the potential value of assessing more than a MEA115661, ACQ-5 scores were improved at Week 4 (mean change from single biomarker of type 2 asthma status. baseline: -0.28) and maintained through Week 52. For patients continuing mepolizumab, ACQ-5 scores were maintained. In a post-hoc analysis Poor Asthma Control Is Associated with Overall Daily combining MEA115588 and MEA115661, exacerbation rate/year re- 42 Activity Impairment: 3-Year Data from the EXCELS mained low in patients continuing mepolizumab (Weeks 0–32 [double- Study of Omalizumab blind]: 0.91; Weeks 32–52: 0.92; Weeks 52–84: 0.92). For patients previously treated with placebo, exacerbation rates decreased over time, Evgeniya Antonova, MS, PhD1, Benjamin Trzaskoma, MS1, Theodore from 1.94/year to 1.04/year when switched to mepolizumab. A. Omachi, MD, MBA1, Michael Schatz, MD, MS, FAAAAI2; 1Genen- CONCLUSIONS: The safety profile of mepolizumab over 52 weeks tech, Inc., South San Francisco, CA, 2Kaiser Permanente Southern Cali- open-label treatment was similar to previous studies. Improvements in fornia, San Diego, CA. markers of asthma control during MEA115588/MEA115575 were main- RATIONALE: Poor asthma control may reduce a patient’s overall daily tained during MEA115661, supporting long-term treatment in patients activity. Little is known about productivity limitations in patients with with severe eosinophilic asthma. Patients initiating mepolizumab in well- vs poorly-controlled asthma. We compared overall daily activity MEA115661 demonstrated similar improvements to those in impairment in well-controlled vs poorly-controlled asthma patients MEA115588/MEA115575. Funding: GSK (NCT01842607). enrolled in a longitudinal observational cohort study. METHODS: EXCELS was a 5-year prospective observational cohort study of ;5000 omalizumab (OMA)-treated and 2500 non-OMA-treated moderate-to-severe persistent allergic asthma patients, aged >_ 12 years. Patients reported asthma control via the Asthma Control Test (ACT; well- controlled [ACT>19] vs poorly-controlled [ACT<_19]) and productivity impairment via the Work Productivity and Activity Impairment-Asthma (WPAI-A) questionnaires at baseline, every 6 months through Month 24, and then yearly. WPAI-A ratings were summarized as the percent activity impairment due to asthma. Higher ACT scores reflect better asthma control, and higher WPAI numbers reflect greater productivity loss. We All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. J ALLERGY CLIN IMMUNOL Abstracts AB15 VOLUME 137, NUMBER 2

Improvements in Asthma Quality of Life significant reduced airway hyperactivity (PENH response) and resistance 44 Questionnaire (AQLQ) Domains with Reslizumab in (RI), pro-inflammatory cytokines like IL-5, IL-13, goblet cell hyperplasia Patients with Inadequately Controlled Asthma and and also collagen accumulation in the lung compared to no DOX treated Elevated Blood Eosinophils allergen challenged IL-15 bi-transgenic mice. CONCLUSIONS: Taken together, we first time report that IL-15 Jorge Maspero1, Joshua Jacobs2, Margaret Garin3; 1Allergy and Respira- immunotherapy may be a novel therapeutic strategy to improve airway tory Research Unit, Fundacion Cidea, Buenes Aires, Argentina, 2Allergy obstruction and resistance in food or environmental allergens induced and Asthma Clinical Research, Inc, Walnut Creek, CA, 3Teva Pharmaceu- chronic asthma. ticals, PA. RATIONALE: Results of two duplicate 52-week, placebo-controlled tri- The Extent of Serum Periostin Reduction in Asthma als indicate that patients with asthma and elevated blood eosinophils 46 Patients Treated with Lebrikizumab Is Related to (>_400cells/ml) who were inadequately controlled on at least medium- Baseline Periostin Levels: A Pooled Analysis of dose ICS, achieved significant improvements from baseline in the AQLQ Phase II Studies score with reslizumab versus placebo (p<0.0001) (Castro et al., Lancet David F. Choy1, Cecile T. J. Holweg, PhD2, Fang Cai3, Joseph R. Arron1, Resp Med. 2015). This analysis further investigates the AQLQ subdomains 2 1 driving the response in these two studies. John G. Matthews, MB, BS, MRSCP, PhD , Heleen Scheerens, PhD ; 1Genentech, Inc., South San Francisco, CA, 2Genentech, Inc. (a member METHODS: Patients received reslizumab 3mg/kg[IV] (Q4W) or placebo. 3 We assessed all four AQLQ domains (activity limitations [AL], symptoms of the Roche Group), South San Francisco, CA, Genentech, Inc. [S], emotional function [EF] and environmental stimuli [ES]) for change RATIONALE: Serum periostin has been used as a biomarker of Type 2 from baseline at week 52, and for the proportion of patients with a airway inflammation in asthma and may identify patients most likely to minimally important difference (MID) of >_0.5 improvement within each benefit from treatment with the anti-IL-13 mAb lebrikizumab. In this study domain. we investigated the effect of lebrikizumab on serum periostin levels over RESULTS: Except for ES in one study, significant changes from baseline time in relation to baseline levels. in all AQLQ domains were seen at week 52 with reslizumab versus METHODS: Serum periostin was measured (clinical trial version of the Ò placebo. AL: diffs 0.335(study1) and 0.219(study2), p<_0.05(both studies); Elecsys Periostin assay) in samples from 228 placebo- and 453 lebriki- S: diffs 0.393(study1) and 0.383(study2), p<_0.05(both studies); EF: diffs: zumab-treated moderate-to-severe uncontrolled asthma subjects from 3 in- 0.411(study1) and 0.375(study2), p<_0.05(both studies), and ES: diffs dependent Phase II trials MILLY (NCT00930163) LUTE and VERSE 0.419(study1) and 0.013(study2), p<_0.05(study1)/NSD(study2). The pro- (NCT01545440 and NCT01545453). The studies were pooled for this portion of patients with a MID from baseline for each AQLQ domain were: analysis. The percent change in serum periostin measurements at weeks AL: 67% reslizumab(both studies), 59% and 61% placebo groups 4, 12, 20, and 24 was estimated by a generalized linear model, in relation (p5NSD); S: 79% and 77% reslizumab groups and 68% placebo (both to treatment, week 0 periostin levels, and week of serum periostin measurement. studies; p<_0.05); EF: 72% reslizumab(both studies) and 61% and 60% SATURDAY placebo groups(both studies, p<_0.05); ES: 76% and 60% reslizumab and RESULTS: Serum periostin levels were reduced as early as one week after 67% and 63% placebo groups (p<_0.05 [study1]/p5NSD[study2]). treatment with lebrikizumab, reduced further over time and reduction was CONCLUSIONS: Reslizumab consistently improved AQLQ domains at sustained through week 24. The mean placebo corrected percent reduction 52-weeks. Clinically significant results were supported for S and EF of serum periostin in lebrikizumab-treated patients ranged from -2.6 to domains, with less robust results for AL and ES domains. -4.7% during weeks 4 through 24. The reduction of serum periostin was proportionately greater in lebrikizumab-treated subjects with increased Interleukin-15 Overexpression Protect Mice from the baseline periostin levels during all assessed timepoints (P<0.05 interac- 45 Allergen-Induced Airway Obstruction tion test). CONCLUSIONS: In three independent lebrikizumab trials, serum Sathisha Upparahalli Venkateshaiah, PhD, Murli Manohar, Chandra- periostin levels decreased as early as week 1 after initiation of treatment shekara Puthanapura Mahadevappa, PhD, Anil Mishra, PhD, FAAAAI; with lebrikizumab. The greatest reduction of periostin was observed in Department of Medicine, Pulmonary Diseases, Tulane Eosinophilic Dis- patients with the highest baseline levels of periostin. This observation order Center, Tulane University School of Medicine, New Orleans, LA. supports the link between IL-13 and periostin in asthma. RATIONALE: Diagnosis of chronic obstructive pulmonary disorder is associated with asthma in older patients suggesting that long-standing asthma may lead to irreversible airflow obstruction. Recently, we developed our interest in interleukin IL-15 in age associated asthma pathogenesis. Since, IL-15 protein levels decline progressively with advanced age in mice and IL-15 association and its deficiency is reported in human asthma. Therefore, a great need to continue with innovative fundamental studies to uncover new possibilities for the therapeutic interventions for airway hyperactivity/obstruction. METHODS: Airway hyperreactivity in allergen challenged rIL-15 treated, non-treated mice and IL-15 overexpressed mice were measured by whole body plethysmography and resistance (RI)/compliance (cdyn) by using AeronebÒ Lab nebulizer system. The cytokines levels were measured by performing ELISA analysis. RESULTS: rIL-15 delivery to the lung in murine model of asthma protects airway hyperreactivity (PENH response), improves airway resistance (RI), compliance (cdyn) and also downregulates the levels of pro-inflammatory cytokines like IL-4, IL-5, IL-13. In addition, we observed that DOX- inducible CC-10-IL-15 bi-transgenic mice were protected from the induction of Aspergillus extract-induced experimental asthma. The 3 weeks DOX exposed allergen challenged IL-15 bi-transgenic mice show All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. AB16 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2016

Response to Omalizumab Therapy Based on Level of benefits on AQLQ exceeded the minimal clinically-important difference 47 IgE: A Two Year Observational Study (REALITY Study) (>_0.5) and demonstrated statistically significant improvements in both EOS-high strata: EOS>_300 (n524) 0.55, p50.0001; EOS>_150 (n5310) Jay Peters, MD1, Harjinder Singh, MD2, Yogeet Kaur, MS2, Joseph D. 0.53, p<0.0001. The benefit on AQLQ was most apparent in the EOS>_150/ Diaz, MD2; 1Univ. Texas Health Science Center San Antonio, San Anto- IgE>75 stratum (n5231): 0.59, p<0.0001. nio, TX, 2Allergy, Asthma and Immunology Associates of South Texas, CONCLUSIONS: This analysis is among the first to examine a combi- San Antonio, TX. nation of biomarkers to assess response to omalizumab in SAA patients. RATIONALE: Omalizumab is indicated for patients with an IgE level They suggest that subgroups with a combination of increased IgE and EOS between 30-700 IU/mL, but is often used in patients with levels outside may experience a greater clinical benefit. However, caution must be used in recommendations. Observational study is designed to assess response to interpreting these results given their post-hoc nature. anti-IgE therapy based on serum IgE levels, and comparison of response based on physician’s clinical assessment vs objective changes in asthma Steroid Sparing Response with Mepolizumab: control. 49 Durability of Steroid Reduction in Severe Asthma METHODS: Asthmatics patients who have received omalizumab therapy Charlene M. Prazma, PhD1, Elisabeth H. Bel, MD, PhD2, Neil C. for two years were assessed retrospectively for response. Subjects were 3,4 5 1 6 5 5 Barnes, MD , Robert Price , Frank C. Albers , Steven W. Yancey ; grouped by their baseline IgE level: [G1(n 80):30-700; G2(n 17):701- 1 2 SATURDAY 5 GlaxoSmithKline, Research Triangle Park, NC, University of Amster- 1500; and G3(n 26):>1500]. Response rate was identified by two 3 categories: Positive response by Physician’s Global Assessment(PGA), dam, Amsterdam, Netherlands, GlaxoSmithKline, Uxbridge, United Kingdom, 4The London School of Medicine and Dentistry, London, and by Objective Assessment (OA) based on a 50% reduction in at least 3 5 of the following parameters: asthma exacerbation(AE);steroid-bursts;ER- United Kingdom, GlaxoSmithKline, Clinical Statistics, Uxbridge, United Kingdom, 6GlaxoSmithKline, Respiratory Medical Franchise, Research visits;hospitalizations;increase in FEV1>200cc; and improved ACT score>_3. All assessments were compared at three time points:16 Triangle Park, NC. weeks(P1), 1-year(P2), and 2-years(P3). RATIONALE: Steroid dependent asthma patients are at risk of compli- RESULTS: During P1, response-rates were:[G1(54%);G2(71%) and cations associated with use of oral corticosteroids (OCS). Reduction in G3(46%)] by PGA and [G1(51%);G2(77%) and G3(62%)] by OA. At dose and duration of OCS use are a major goal for physicians and patients. one-year(P2), the response-rates were:[G1(81%);G2(94%) and G3(89%)] METHODS: Upon completion of the MENSA or SIRIUS study by PGA and [G1(64%);G2(71%) and G3(89%)] by OA. At 2-year (P2), the participants were offered the option to enter MEA115661; a 52-week response-rates were:[G1(80%);G2(82%) and G3(89%)] by PGA and for open-label extension study where all subjects received open-label OA these were:[G1(69%);G2(71%) and G3(77]. Overall response rate at mepolizumab 100mg administered subcutaneously every 4 weeks as 1-year and 2-year were 85% and 82 respectively by PGI and 70% and 71% adjunctive therapy. The study objectives were to describe the safety profile by OA. of long-term mepolizumab treatment and to evaluate the effects of long- CONCLUSIONS: Overall, 70 to 80% of subjects treated with omalizu- term dosing on clinical markers of asthma control. This post-hoc analysis mab had a good clinical response independently by both subjective and evaluated the durability of steroid reduction following open-label mepo- objective assessments. At both 1 and 2-years after initiation of omalizu- lizumab treatment among the subset of subjects from the SIRIUS study that mab-therapy, the overall response-rate was higher in patients with an IgE completed MEA115661. MEA115661 was sponsored by GSK. 5 level >700 IU/mL than patients within recommended dosing range. RESULTS: Ninety-three percent (n 126) of SIRIUS subjects entered the open-label study MEA115661; 65 subjects previously received mepolizu- Blood Eosinophils and Serum IgE Predict Response to mab and 61 subjects previously received placebo, with 57 and 58 subjects 48 Omalizumab in Patients with Severe Allergic Asthma: completing MEA115661 respectively. For placebo subjects from SIRIUS Innovate Trial Post-Hoc Analysis the median OCS dose achieved at the end of SIRIUS was 10mg/day and following 52 weeks of mepolizumab treatment in MEA115661 was Volkan Manga, MD1, Marc Humbert, MD, PhD2, Ratko Djukanovic3, reduced to 5.0mg/day. For subjects who continued mepolizumab the Steve Greenberg, MD4, Theodore A. Omachi, MD, MBA5, Benjamin median OCS dose achieved was 2.5mg/day at the end of SIRIUS and was Trzaskoma, MS5, Roland Buhl6; 1Novartis Pharma AG, Basel, 2.5mg/day at the end of MEA115661. Switzerland, 2Hospital Antoine Beclere, Unversite Paris-Sud, Clamart, CONCLUSIONS: This open label extension study adds evidence that the France, 3University of Southampton, Southampton, United Kingdom, steroid reduction achieved in the 24-week double-blind SIRIUS study was 4Novartis Pharmaceutical Corporation, East Hanover, NJ, 5Genentech, sustained. Additionally subjects initiating mepolizumab treatment in Inc., South San Francisco, CA, 6University Hospital Mainz, Mainz, MEA115661 demonstrated improvements similar to that seen in SIRIUS. Germany. RATIONALE: Response to biologic therapy differs among severe allergic asthma (SAA) patients. Biomarker-guided therapy may help to identify subgroups who demonstrate greater clinical benefits from omalizumab than the overall SAA population. METHODS: A post-hoc analysis of INNOVATE trial data (Humbert et al. Allergy 2005) was performed to determine the impact of treatment on exacerbation rates and health-related quality-of-life (AQLQ) of SAA patients stratified by peripheral blood eosinophils per mcl (EOS) and serum IgE (IU/ml). Negative binomial regressions were utilized within biomarker strata to estimate response to omalizumab vs placebo, controlling for potential confounders. RESULTS: An exacerbation reduction was observed among omalizumab- treated patients vs placebo in EOS-high strata: EOS>_300 (n5245) 38.98%, p50.0399; EOS>_150 (n5316) 39.01%, p50.0178. Exacerbation reduc- tion increased further upon enriching these strata according to increased IgE (>75 IU/ml): EOS>_300/IgE>75 (n5184) 53.88%, p50.0018; EOS>_150/IgE>75 (n5235) 53.75%, p50.0005. Mean placebo-subtracted All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. J ALLERGY CLIN IMMUNOL Abstracts AB17 VOLUME 137, NUMBER 2

Omalizumab and Severe Alergic Asthma : Assessment showed portal and lobular hepatitis with granulomas and few EBER+ cells. 50 after 1 Year of Treatment Blood EBV PCR detected at 29038 copies /ml. She received Rituximab and azathioprine. Pulmonary nodules and HSM markedly improved. 1 year Rita Aguiar, MD, Ana M. Mendes, MD, Ana Celia Costa, MSc, Fatima later B cells had not recovered. At age 11 years genetic testing revealed a Duarte, MD, Estrella Alonso, Anabela Lopes, MD, Elisa Pedro, MD, novel homozygous variant in RAG1 (c.1514T>G; p.L154R). Manuel Pereira-Barbosa; Hospital de Santa Maria - Immunoallergology CONCLUSIONS: As previously described, children with hypogamma- Department, Lisbon, Portugal. globulinemia and granulomatous lesions merits genetic testing for leaky RATIONALE: Omalizumab is associated with improvement in asthma SCID, independent of age. Rituximab therapy may provide clinical benefit symptoms and quality of life in patients with severe asthma. Our aim is to in patients with leaky SCID in the setting of lymphoproliferation and EBV. evaluate clinical improvement and quality of life of patients treated with omalizumab in our Department. Anti-GAD65 Positive Stiff-Person Syndrome: Novel METHODS: Patients with severe asthma under Omalizumab treatment 52 Association with Common Variable Immune for 12 months were included. They signed informed consent and responded Deficiency

to the questionnaires: ACT (Asthma Control Test), CARAT (Control Test 1 2 2 Asthma and Allergic Rhinitis) and AQLQ (Quality of Life Questionnaire Jack G. Ghably, MD , Mark Guido, MD , Sara Atwater, MD , Guha Krishnaswamy, MD, FAAAI, CC-D, ABIHM3; 1University of Alabama on Asthma). FEV1 was evaluated at T0 and T12. Data were analyzed using 2 Ò at Birmingham, Birmingham, AL, Wake Forest Baptist Medical Center, SPSS version 17, p-value <0.05 was considered significant. 3 RESULTS: 31 patients were included: average age of 36 years-old, 22 Wake Forest Baptist Medical Center, Winston Salem, NC. females, all non-smokers. At T12, 16 patients (51.6%) obtained a ACT RATIONALE: Stiff-person syndrome (SPS) is a rare neurological disor- score of 25 (fully controlled asthma); 13 patients (42%) a CARAT score of der characterized by progressive muscle stiffness, rigidity, and painful 24 and 22 pts (71%) a score> 8 in the sum of the items 1-4 of CARAT (good spasms affecting the axial muscles eventually impairing ambulation. control of upper airways). The AQLQ average score was 6.4 (high quality Majority (60%) of SPS patients are found to have autoantibody targeting of life) with symptoms domains presenting the lowest scores. Inferential glutamic acid decarboxylase (GAD), an enzyme involved in synthesis of analysis showed that quality of life of patients was significantly influenced GABA neurotransmitter. Some cases are idiopathic or neoplasm-related by the level of asthma control. with no antibody detected. In recent studies, serum containing high titer 16 patients (51.6%) showed an increase in FEV1 and 15 maintained anti-GAD65 antibodies induced motor dysfunction in rats, suggesting overlapping values at T0 and T12. FEV1 at T0 was an average of 1.96 6 antibody functionality. SPS is known to be associated with various other 0.80 L/min, 73%of predicted and 2.10 6 0.82 at T12, 77% of predicted (p autoimmune conditions (notably type 1 diabetes mellitus) but association 5 0.04). with a primary immune deficiency disorder has not been described. CONCLUSIONS: Our data showed that omalizumab is associated with a METHODS: Here we report a case of a middle aged female patient with a good asthma control, improvement in lung function and high quality of life. history of common variable immunodeficiency well managed on subcu- taneous immunoglobulin (SCIG) therapy who subsequently developed SATURDAY Use of Rituximab in Late Onset Leaky SCID stiff-person syndrome. EMG findings were indicative of SPS and she tested 51 positive for GAD65 antibodies. RESULTS: Her SPS symptoms responded to treatment with clonazepam and later levetiracetam. The patient was placed on higher doses of SCIG Diana X. Nichols-Vinueza, MD1,2, Hung S. Luu, MD2,3, Norberto Rodri- and her symptoms were greatly ameliorated and physical functionality guez Baez, MD1,2, Yadira Rivera-Sanchez, MD1,2, Kenneth S. restored. Chen, MD2,4, Lee-Jun Wong, PhD5, Hui Yu, PhD6, M. Teresa De La Mor- CONCLUSIONS: More studies of neurological complications of PID and ena, MD7,8; 1Department of Pediatrics, 2University of Texas Southwestern their management are essential. Medical Center Dallas, TX, 3Department of Pathology Children’s Health, 4Center for Cancer and Blood Disorders Children’s Health, 5Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 6Baylor Miraca Genetic Laboratories, Houston, TX, 7The Division of Allergy and Immunology, 8Department of Pediatrics and Internal Medi- cine, University of Texas Southwestern Medical Center Dallas, TX. RATIONALE: At 9 years, a female with hypogammaglobulinemia, was diagnosed with EBV-encoded RNA (EBER) positive interstitial granulo- matous lymphocytic lung disease in the setting of generalized lymphade- nopathy and hepatosplenomegaly. Clinical improvement was noted after rituximab. METHODS: Severe-Combined-Immunodeficiency (SCID) comprehen- sive panel by Massively Parallel Sequencing was performed by Baylor Miraca Genetic Laboratories, Houston, TX. RESULTS: The patient had been diagnosed with common variable immunodeficiency after recurrent sinopulmonary infections and one episode of septic arthritis at 4 years and treated intermittently with intravenous immunoglobulin. At 9 years of age, she was noted to have failure to thrive, transaminitis, cholangitis, lymphadenopathy, hepatosple- nomegaly, bronchiectasis and pulmonary nodules. IgG <140 mg/dL, IgA <25 mg/dL, IgM 130 mg/dL; CD3 74%/2831 cells/mL, CD4 43%/1658 cells/mL, CD8 22%/837 cells/mL; NK 8%/309 cells/mL and CD19 17%/ 667 cells/mL; Normal response to phytohemagglutinin, pokeweed mitogen and tetanus. No mutation in activation-induced cytidine deaminase was detected. Lung biopsy demonstrated granulomatous lymphocytic intersti- tial lung disease with scattered EBER+ cells; lymph node biopsy showed an atypical lymphoid hyperplasia but rare EBER+ cells and liver biopsy All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. AB18 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2016

The Effect of Immunoglobulin Levels on CVID immunodeficiency, long after discontinuation of the anti-CD20 antibody, 53 Enteropathy Pathogenesis and Clinical Severity supports this supposition. As the utilization of immunomodulatory therapy increases, it will be important to perform baseline serum immunoglobulin Meng Chen, MD1, Edith Schussler, MD2, Mabel Ko, MD2,PaulJ. levels and B cell population analysis prior to starting B-cell specific Maglione, MD, PhD2, Charlotte Cunningham-Rundles, MD, PhD2; biologic therapies. 1New York University Langone Medical Center, New York, NY, 2Icahn School of Medicine at Mount Sinai, New York, NY. 31 Year Old Caucasian Male Presenting with RATIONALE: Mechanisms leading to enteropathy in common variable 55 Hypogammoglobulinemia and T/B-Cell Lymphopenia

immunodeficiency (CVID) are not well understood, and treatment 1 1 guidelines are yet to be defined. As immunoglobulin (Ig) replacement Nicholas L. Hartog, MD , John Chrisinger, MD , H. James Wedner, MD, FAAAAI2; 1Washington University School of Medicine, Saint Louis, MO, therapy has unclear penetrance into intestinal mucosa, we hypothesized 2 that Ig levels noted at CVID diagnosis may impact progression of Washington University School of Medicine, St. Louis, MO. enteropathy. RATIONALE: Lymphocytopenia in adults has a variety of etiologies METHODS: We conducted a retrospective review of all patients at our and a broad differential diagnosis. Here we present a 31 year old male with institution with CVID enteropathy confirmed by intestinal biopsy showing T/B-cell lymphocytopenia, hypogammoglobulinemia, and a unique characteristic pathology of plasma cell depletion (PCD) and/or intra- immunologic phenotype that has been previously unreported in SATURDAY epithelial lymphocytosis (IEL). We then compared Ig levels at CVID sarcoidosis. diagnosis with pathologic findings, clinical symptoms, and B cell METHODS: Flow cytometry, TCR gamma by PCR, and gene sequencing. phenotype quantification. RESULTS: Our patient presented after hospital evaluation for pneumonia RESULTS: Fourteen CVID patients with intestinal biopsies were revealed elevated ACE level, calcium, and hypogammoglobulinemia. CT identified for inclusion and divided into two groups based on IgG levels: of chest showed multiple calcified lymph nodes, bronchiectasis, pneuma- (1) IgG <200mg/dL at CVID diagnosis (n58, IgG range 9-149 mg/dL) and tocele, scoliosis, and fibrosing mediastinitis. Axillary lymph node biopsy (2) IgG >200 mg/dL at diagnosis (n56, IgG range 250-393 mg/dL). Group showed multiple non-caseating granulomas. Chart review revealed abso- 1 had more pathologic evidence of enteropathy as 100% of patients had lute lymphocyte count of 400-600 for the past 7 years. Lymphocyte PCD and 75% had IEL, versus Group 2, in which 50% had PCD and 50% subpopulation showed markedly decreased absolute counts of CD4+, had IEL. Mean weight loss in Group 1 was also greater than Group 2 (10.7 CD8+, CD19+, and CD20+ cells with normal NK cells. Aberrant T-cell € kg vs 3.4 kg, P50.002). Though not statistically significant, Group 1 had development was indicated by absence of naıve CD4+ T-cells, markedly fewer class-switched CD27+IgM-IgD- memory B cells (2.15% vs 5.38%, decreased TREC, skewing of T-cell receptor (TCR) repertoire from alpha/ P50.21) and lower average IgA levels than Group 2 (4.43 mg/dL vs beta to gamma/delta subset, and a clonal population of TCR gamma cells. 14.17 mg/dL, P50.086). Antibody responses to streptococcus, tetanus and diphtheria were normal. CONCLUSIONS: The extent of IgG deficiency at CVID diagnosis may Lymphocytes proliferated to mitogens was normal. Bone marrow biopsy be predictive of symptom severity and pathologic findings in CVID revealed non-caseating granulomas with lymphocytopenia (1%) but enteropathy. Further analysis is underway investigating the effect of Ig normal distribution. replacement on disease course. Genetic sequencing of RAG1, RAG2, STAT3, and DOCK8 did not reveal any pathogenic mutations. Patient was started on prednisone 60mg daily An Older Gentleman with Common Variable with decrease in pulmonary symptoms and normalization of calcium. 54 Immunodeficiency (CVID): A Question of Primary CONCLUSIONS: Here we present a case of a 31 year old caucasion male Immunodeficiency Versus Secondary Belimumab- with sarcoidosis who presented with hypogammoglobulinemia, severe Induced Immunodeficiency prolonged lymphocytopenia, hypercalcemia, and pneumonia/bronchiec- tasis. Further evaluation revealed granulomas in multiple locations and a Amy B. Schiffman, MD1, Laurianne G. Wild, MD, FAAAAI2; 1Tulane unique T-cell immunophenotype that has not been completely described University School of Medicine, New Orleans, LA, 2Tulane University, before in sarcoidosis. New Orleans, LA. RATIONALE: CVID is the most common symptomatic primary immu- nodeficiency, with perhaps 5% presenting with inflammatory or autoim- mune disease without recurrent infection. We present a case of CVID diagnosed subsequent to limited treatment of systemic lupus erythemato- sus (SLE) and suggest that belimumab, a monoclonal antibody that binds to B-cell activating factor (BLyS), inhibiting B-cell stimulation, accelerated the presentation of immunodeficiency in this patient. METHODS: A retrospective chart review was performed of a patient who received 2 doses of belimumab, for SLE poorly responsive to anti-malarial and corticosteroid treatment, which was discontinued due to development of acute pancreatitis. An immune evaluation 2 years after receiving the BLyS-specific inhibitor, fulfilled diagnostic criteria for CVID and immunoglobulin replacement was initiated. RESULTS: Two years after limited treatment with a humoral immuno- modulator, an evaluation due to continued severe symptoms, without reported recurrent infections, revealed hypogammaglobulinemia, and sub- protective levels of pneumococcal and tetanus antibodies. Immune evaluation prior to therapy was not conducted, complicating the diagnosis of CVID as delayed diagnosis versus a secondary immunodeficiency. CONCLUSIONS: Although a small extension of a phase II study of belimumab demonstrated modest decrease in memory B cells and plasma cells, the possibility of provoked B-cell dysfunction exists. A case series identifying 11 patients with secondary rituximab-induced All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. J ALLERGY CLIN IMMUNOL Abstracts AB19 VOLUME 137, NUMBER 2

An Unusual Presentation of Cutaneous development. This case provides an opportunity to review the role of the 56 Leukocytoclastic Vasculitis to Subcutaneous but beta-catenin signaling pathway and the contribution of desmoplakin gene Not IV Insulin in a Patient with Common Variable transcription in B cell differentiation. Investigation of pathway Immunodeficiency (CVID), Type I DM (T1D), and dysfunction may provide opportunities for targeted therapy in Autoimmune Enteropathy (AIE) hypogammaglobulinemia.

Julie J. Kim-Chang, MD1, Patricia L. Lugar, MD MS2; 1Duke University Three Cases of Elevated IL-1beta in Common Variable Medical Center, Durham, NC, 2Medicine, Duke University Medical Cen- 58 Immunodeficiency (CVID) with Autoimmune ter, Durham, NC. Complications RATIONALE: CVID patients have a higher incidence of autoimmunity Jennifer Toh, MD1, Tatyana Gavrilova, MD2, Arye Rubinstein, MD, and immune dysregulation. Here we present a patient with CVID, T1D, and 3 1 AIE who developed cutaneous leukocytoclastic vasculitis (CLV) to FAAAAI ; Albert Einstein/Montefiore Medical Center, Bronx, NY, 2Allergy and Immunology, Montefiore Medical Center, Bronx, NY, subcutaneous insulin. 3 METHODS: We performed a biopsy of the skin lesion. We also performed Albert Einstein College of Medicine and Montefiore Hospital, Bronx, intradermal skin challenge with two different volumes of saline control NY. (0.03 mL, 0.06 mL) and three different basal insulin formulations: RATIONALE: Altered cytokine levels, such as TNF-alpha and IL-6, have glargine, isophane, and detemir. been described in common variable immunodeficiency (CVID). We report b RESULTS: A 23 year old female with a history of CVID, T1D and AIE 3 cases of elevated serum interleukin-1beta (IL-1 ) levels in patients with presented with a 2-week history of localized skin reactions to subcutaneous CVID. insulin (both basal glargine and short-acting insulin lispro) but not to METHODS: A retrospective chart review was performed of 3 CVID b subcutaneous immunoglobulin. She was admitted in DKA and tolerated patients with elevated IL-1 . continuous insulin (IV) drip, but continued to react to subcutaneous RESULTS: Case 1 is a 56 year-old female with CVID and Hashimoto’s insulin. Skin reaction started as a fixed pruritic red macule which thyroiditis who developed muscle stiffness, arthralgias and daily fevers progressed to a purpuric, indurated lesion that ulcerated over the ensuing (Tmax 104F) which persisted despite intravenous immunoglobulin (IVIG), 24 hours with insulin injection. The severity of reactions varied by insulin antibiotics, corticosteroids, NSAIDs and rituximab. An autoinflammatory b preparation and dose. Lesional skin biopsy demonstrated leukocytoclastic disorder was suspected when she was found with elevated IL-1 22.9 pg/ vasculitis. Intradermal skin challenge with various insulin formulations mL (nL < 3.9) and responded to anakinra (IL-1 receptor antagonist) with b reproduced a purpuric vasculitic lesion with expectant changes as previ- resolution of symptoms and normalization of IL-1 levels. ously experienced. She failed to tolerate injectable insulin after high dose Case 2 is a 49 year-old male with CVID complicated by incapacitating methylprednisolone. Patient was restarted on her immunomodulatory arthritis and nodular lymphoid hyperplasia of the intestine with malab- b therapy with 6-MP which she was on maintenance dosing for AIE. sorptive diarrhea which improved with IVIG. An elevated IL-1 68.7 pg/ mL was found when he presented with recurrent low grade fevers, myalgias Patient demonstrated tolerance to short- and long acting subcutaneous SATURDAY insulin injection after 2-weeks of 6-MP and colchicine. and upper extremity muscle weakness with fasciculations. Anakinra was b CONCLUSIONS: We believe that this is the first reported case of CLV to considered, but symptoms resolved and IL-1 normalized on high-dose insulin in a patient with CVID and autoimmunity which appeared after IVIG (1.5 grams/kg). self-discontinuation of maintenance 6-MP. Case 3 is a 26 year-old female with CVID on IVIG and stiff-person’s syndrome with limited improvement on corticosteroids, benzodiazepines A Case of Concurrent Hypogammaglobulinemia, and rituximab. She was found with an elevated IL-1b 18.6 pg/mL after 57 Cancer, and Cardiomyopathy: A Beta-Catenin complaining of daily flu-like symptoms with fevers (Tmax 101F) which Connection? improved with anakinra but her muscle stiffness still persists. CONCLUSIONS: Patients with CVID and autoimmune complications Camellia Hernandez, MD, Cecilia Mikita, MD, MPH, FAAAAI; Walter may have altered levels of pro-inflammatory cytokines including IL-1b. Reed National Military Medical Center, Bethesda, MD. They may be responsive to treatment with anakinra or high-dose IVIG. RATIONALE: Hypogammaglobulinemia is a humoral immune defi- ciency characterized by impaired antibody production resulting in recurrent infections. We present a case of hypogammaglobulinemia in an individual with primary lung adenocarcinoma and nonischemic cardio- myopathy caused by a desmoplakin gene mutation. METHODS: Clinical exams, imaging, biopsy, and laboratory evaluation. RESULTS: A 55 year old male active duty service member presents with chronic infectious rhinosinusitis. Symptoms arose on deployment to Iraq, where he exhibited persistent URI symptoms. Upon returning to the US, he developed multiple sinopulmonary infections requiring antibiotic treat- ment at 1-2 months intervals. Diagnostic testing revealed lymphopenia and decreased levels of IgG and IgM. Pneumovax administration resulted in an adequate immune response, though his clinical picture was most consistent with hypogammaglobulinemia NOS. He remained asymptomatic, until, he experienced a syncopal event while running. TTE revealed a reduced ejection fraction of 25%. A cardiomyopathy panel revealed a mutation of the desmoplakin (DSP) gene. A CT scan of the chest noted a 6mm opacity of the right upper lobe and a lobectomy with resultant pathology was consistent with two invasive adenocarcinomas. CONCLUSIONS: Defects of the DSP protein are associated with dilated cardiomyopathy and lung carcinoma through inhibition of desmoplakin tumor suppressor function via the wnt/beta-catenin signaling pathway. Beta-catenin also facilitates transcription of proteins essential to B cell All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. AB20 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2016

Quality over Quantity: A New Approach to Diagnose B-cells). Patient is managed by gamma-globulin replacement therapy 59 Specific Antibody Deficiency Using a Complement (SCIG) and he is asymptomatic for almost two years. Fixation Assay CONCLUSIONS: These cases are reported because lymphoma was the initial clinical manifestation of CVID at an older age than has been Charles A. Filion, MD, FRCPC, Paul J. Maglione, MD, PhD, Lin Rad- reported and both of them are well under gamma-globulin supplementation igan, Charlotte Cunningham-Rundles, MD, PhD; Icahn School of Medi- therapy. Increase awareness for CVID diagnosis is needed. cine at Mount Sinai, New York, NY. RATIONALE: Specific antibody deficiency (SAD) is a primary immune T Cell Abnormalities in Patients with Common deficiency characterized by lack of antibody production to polysaccharide 61 Variable Immunodeficiency antigens. As previously shown, there is no correlation between infections Adrian M. Kahn, MD, FAAAAI1,2, Gabriela Luque1, Gerardo M. and response to pneumococcal vaccines. We argue that a novel method 3,4 1 1,2 1,2 measuring the ability of immune complexes to fix complement may Gatti , Brenda Ricchi , Juan J. Garcia , Eduardo Cuestas , Ana L. Basquiera1,2, Virginia E. Rivero4; 1Hospital Privado Universitario, identify more accurately symptomatic SAD patients. 2 METHODS: 96-well plates were coated with capsular polysaccharides Cordoba, Argentina, Instituto Universitario de Ciencias Biomedicas de 3 from S. pneumoniae (serotypes 4, 14, and 23F) or C3a antibody. Plates Cordoba, Cordoba, Argentina, Fundacion para el Progreso de la Medic- 4 were then washed, blocked and washed again. The polysaccharide ina, Laboratorio de Alta Complejidad, Cordoba, Argentina, Centro de In-

SATURDAY coated-plate was incubated with serum from SAD patients and controls vestigaciones en Bioquımica Clınica e Inmunologıa (CIBICI-CONICET), supplemented with human complement. Serum was then transferred to Facultad de Ciencias Quımicas, Universidad Nacional de Cordoba, the C3a-coated plate. The plate was washed and then incubated with bio- Cordoba, Argentina. tinylated C3a antibody. After washing, the plate was incubated with strep- RATIONALE: Common Variable Immunodeficiency (CVID) is charac- tavidin-HRP. The plate was washed again and then developed with TMB terized by hypogammaglobinemia and recurrent infections. T cell substrate; absorbance was measured at an OD of 450 nm. abnormalities might participate in its immunopathology. The aim of this RESULTS: In this preliminary study, our complement fixation assay study was to analyze T cell quantity and function in patients with CVID. distinguished controls (healthy control, CVID patient treated with IVIg METHODS: Peripheral blood mononuclear cells (PBMC) were isolated and IgG deficient patient with good response to pneumococcal poly- from whole blood by Ficoll Hypaque gradient from 14 patients with CVID saccharide vaccine) (n53) from SAD patients (n53). P values were <0.05 and 14 age and sex matched control individuals. T cell phenotyping was for each serotype. Discrepancy between a specific serotype titer and the performed by flow cytometry using different monoclonal antibodies. For result of complement fixation assay were noted both in controls and SAD functional studies PBMC were cultured and stimulated with polyclonal patients. mitogens (PHA, Con A and PWD) and recall antigens (candida antigens, CONCLUSIONS: Complement fixation assay is a new functional PPD and trychophyton) for 72 hr. Cell proliferation was measured by approach to diagnose SAD in adult patients. We will now apply this titrated thymidine uptake and values expressed in cpm. IFN-g, IL 10 and IL method to a larger number of patients in order to evaluate if our assay can 17 production was measured in culture supernatants by ELISA. correlate better than serotype measurement with the severity of the RESULTS: Patients with CVID showed decreased number of CD4+ T infectious phenotype. cells when compared with healthy controls (p < 0.05). PBMC from CVID patients showed decreased proliferation indexes compared to Common Variable Immunodeficiency in Two Adult healthy controls when cultured with PHA (p < 0.05), Con A ( p < 0.05), 60 Patients Diagnosed after Lymphoma As First PWD (p < 0.05) and Trychophyton (p < 0.05). There was also significant Presentation. less IL17 production in CVID cultures stimulated with PHA and PWD (p < 0.05), while no differences were detected for IL 10 and IFN g. Maria G. Kanariou1, Sofia Tantou1, Marianna Tzanoudaki1, Marina Sia- CONCLUSIONS: Patients with CVID showed reduced T cell numbers, kantari2, Angelos Pefanis3; 1‘‘Aghia Sophia’’ Children’s Hospital, Athens, less in vitro proliferation against mitogens and less production of IL 17. Greece, 2National and Kapodistrian University of Athens, Athens, Greece, These results suggest T cell abnormalities in patients with this disease. 3‘‘Sotiria’’ General and Chest Diseases Hospital, Athens, Greece. RATIONALE: Common Variable Immunodeficiency (CVID) is a Primary Immunodeficiency with broad range of clinical manifestations; lymphomas to be one of the major causes of death in adulthood. We present two adult patients whose CVID diagnosis was performed after lymphoma disease. METHODS: Flow Cytometry and ELISA were performed for diagnosis. RESULTS: Patient A was asymptomatic to the age of 35, when he was diagnosed with B-Non-Hodgkin Lymphoma (Burkitt type). He was successfully treated with combination of anti-CD20 and CHOP. During his investigation hypogammaglobulinemia was revealed which insisted. While in complete remission, he suffered severe infections and the immune investigation shown inability to produce specific antibodies and absence of memory switching B-cells (IgD-IgM-CD27+: <0.1% on B-cells). Eight years now he is in good clinical condition with gamma-globulin (SCIG) supplementation therapy. Patient B presented at the age of middle twenties, with Hodgkin Lymphoma, and he was given ABVD chemotherapy with good response. However, five years later he underwent autologous hemato- poietic stem cell transplantation (aHSCT) after high dose chemotherapy because of relapse. Afterwards, he experienced severe bacteremic pneumococcal pneumonia and his investigation revealed extremely low immunoglobulin levels, lack of specific antibodies production and almost undetectable memory switching B-cells (IgD-IgM-CD27+: <0.6% on All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. J ALLERGY CLIN IMMUNOL Abstracts AB21 VOLUME 137, NUMBER 2

Recurrent Septic Arthritis with CVID and MGUS: A remained neurologically stable since receiving rituximab, suggesting an 62 Chicken and Egg Conundrum autoimmune etiology for her neurologic manifestations.

Evan M. Atkinson, MD, Prathyusha Savjani, MD, Laurianne G. Wild, A Case of Severe Pneumococcal Pneumonia Requiring MD, FAAAAI; Tulane University, New Orleans, LA. 64 Ventilator-Support in a Hypogammaglobulinemia RATIONALE: Common variable immunodeficiency (CVID) is associ- Patient on IVIG Infusion Therapy Despite Adequate ated with septic arthritis due to atypical bacteria such as Mycoplasma, IgG Troughs Ureaplasma, and Chlamydia. Per current criteria, the diagnosis of CVID requires exclusion of secondary causes of hypogammaglobulinemia such Ammara G. Ahmed, DO, Kholoud Wishah, MD; Case Western’s Metro- as monoclonal gammopathy of undetermined significance (MGUS). Health Medical Center, Cleveland, OH. METHODS: Case report. RATIONALE: In primary immunodeficiency disease, encapsulated RESULTS: A 48-year-old man has a 20-year history of recurrent culture- organisms play a large role in infection – one of the main culprits being negative septic arthritis involving multiple joints. Passive range of motion Streptococcus pneumoniae. It is assumed that IVIG is relatively uniform in his left knee is absent. He has no artificial joints, indwelling intravenous and contains adequate titers given that it is purified human sera of thou- (IV) catheters except those often placed for antibiotics, or other implanted sands of donors, however products are neither standardized nor quantified devices. He is HIV-negative and denies prior bacterial sinopulmonary for all pathogen-specific titers. Here we present one of our hypogamma- infections. His diabetes mellitus is well controlled on insulin. CBC shows globulinemia patients who developed sputum positive pneumococcal normocytic anemia, thrombocytosis, granulocytosis, and lymphopenia. pneumonia requiring ventilator-support despite adequate IgG troughs; Other results include 510 CD4+ cells/mL, 124 CD8+ cells/mL (low), 5 however, discovered to have inadequate pneumococcal titers. CD19+cells/mL (very low), IgG 1295 mg/dL, IgA < 5 mg/dL (low), IgM METHODS: IgG troughs routinely obtained and pneumococcal titers 32 mg/dL (low), monoclonal IgG kappa band 850 mg/dL, and resultant obtained after pneumococcal infection. non-clonal IgG 445 mg/dL (low). Protective serotypes post-PPSV23 and RESULTS: This 67 year old female patient presented to the ED in subsequently PPV13 are, respectively, 0/14 and 3/11. Tetanus and diph- respiratory distress and admitted for respiratory failure secondary to theria titers are normal. Evaluations in rheumatology, infectious disease, pneumonia. CXR revealed RLL consolidation and sputum culture positive and hematology clinics have been negative. Due to his laboratory results for Streptococcus pneumoniae. IgG trough on admission was 1470 mg/dL. and significant history of recurrent infections, we initiated IgG replace- Pneumococcal IgG Antibody panel to 23 serotypes were non-protective. ment therapy and are following this patient closely. Patient was treated with IV antibiotics, eventually weaned off the venti- CONCLUSIONS: Potential co-existence of CVID and MGUS presents a lator, and sent home on Bactrim prophylaxis and continued IVIG infusions. diagnostic challenge. As our collective knowledge of CVID evolves, CONCLUSIONS: We believe it would be beneficial to routinely monitor perhaps we can better define the immunologic relationship of CVID and and quantify antibody titers against encapsulated organisms in patients on MGUS. Evaluation for monoclonal gammopathy should be considered in IVIG replacement therapy in addition to obtaining IgG trough levels, given

patients with a history concerning for humoral immunodeficiency. these organisms play a big role in infection in our PID patients and to help SATURDAY determine if patients need to be on dual therapy with antibiotic prophylaxis. Neurologic Complications of Common Variable 63 Immunodeficiency: A Case Report and Review of A Case of Inflammatory Bowel Disease and Common the Literature 65 Variable Immunodeficiency.

Jenna T. Nguyen, MD, Katherine E. Gundling, MD; UCSF, San Fran- Shahab Virani, MD, Praveen Govender, MD; Boston University Medical cisco, CA. Center. RATIONALE: Common variable immunodeficiency is associated with a RATIONALE: Common Variable Immunodeficiency (CVID) has a myriad of clinical manifestations—several phenotypes have been multitude of clinical manifestations. We present a case that had both described. Neurologic manifestations of CVID, however, are less common recalcitrant infectious complication and inflammatory bowel disease (IBD) and not well summarized in the literature. After our patient suffered related to an undefined primary immunodeficiency consistent with CVID. significant neurologic morbidity, we sought to determine the range of METHODS: esophagogastroduodenoscopy ( EGD) and colonoscopy, neurologic conditions associated with CVID. immunodeficiency evaluation. METHODS: Case report and review of the literature. RESULTS: A 38 year old woman presented 3 years ago with persistent RESULTS: A 42 year-old woman was diagnosed with CVID in 2007 after bilateral lower quadrant pain, nausea, vomiting and diarrhea. In her initial presenting with pneumonia, recurrent cough, and presumptive coccidio- workup, EGD and colonoscopy demonstrated scalloping and cobble stoning mycosis. Lung biopsy demonstrated lymphocytic interstitial pneumonia of duodenum, and multiple ulcerations with colitis throughout the duodenum with granulomatous inflammation, which stabilized on mycophenylate. and colon. Pathology of the duodenum and ileum showed partial villous Her course was complicated by lymphocytic colitis, refractory to multiple atrophy with reactive lymphoid follicles in the lamina propria. Colonic medications, bilateral choroidal lesions and optic neuritis. pathology showed intraepithelial lymphocytosis with reactive lymphoid She subsequently developed left-hand weakness and incoordination. MRI follicles. Plasma cells were absent in the small bowel and rarely seen in the demonstrated enhancing lesions of the left cerebellar hemisphere with colon. This histological feature, in conjunction with giardiasis and campylo- mass effect. A seizure soon followed along with evidence of more bacter infections raised the potential diagnosis of CVID. Serologic immuno- extensive meningeal enhancement. Two biopsies and CSF analyses with deficiency evaluation confirmed the diagnosis with low serum culture dependent and independent methods revealed no specific etiology. immunoglobulins and impaired response to polysaccharide antigens only. Significant clinical improvement was seen after three days of IV Her clinical course was dominated by recalcitrant giardiasis infection that methylprednisolone. Her medications were subsequently changed to failed to resolve despite numerous antimicrobial regimens and commence- rituximab and azathioprine with neurologic stability achieved for the ment of IVIG. However, upon initiation of oral steroids her GI symptoms past 6 months. markedly improved, the chronic infection was eradicated and IBD improved CONCLUSIONS: Though rare, neurologic complications have been with restoration of the architectural changes seen on pre-treatment biopsies. described in patients with CVID. These include infections of the brain or CONCLUSIONS: There is little literature on gastrointestinal manifesta- spinal cord, autoimmune conditions, progressive neurodegeneration and tions of CVID. We present a patient with both infectious and inflammation unusual manifestations of the immunodeficiency itself, among others. The bowel disease related to CVID and show that treatment of the IBD with patient described here had no evidence of infection or lymphoma, and has steroids was required to help eradicate the chronic giardial infection. All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. AB22 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2016

Two New Mutations in TACI Identified to be Causing capsular polysaccharides was found in CVID patients with lymphoproli- 66 Disease in Patients with Common Variable ferative complications compared than those without. Immunodeficiency CONCLUSIONS: Levels of serum IgM recognizing specific antigens can differentiate CVID patients with history of pneumonia or lymphoprolifer- Roula Daher, MD1,2, Elizabeth A. Secord, MD, FAAAAI3,4, Pavadee ative complications. This may reconcile the fact that higher IgM levels Poowuttikul, MD5,6; 1Detroit Medical Center, Detroit, MI, 2Children’s have been linked to both protection against infection and susceptibility to Hospital of Michigan, Detroit, MI, 3Children’s Hospital of Michigan lymphoproliferative disease as the specificity of these IgM responses Department of Allergy Immunology, Detroit, MI, 4Wayne State University appears to be significant. School of Medicine, Detroit, MI, 5Pediatrics- Allergy/Immunology Divi- sion, Children’s Hospital of Michigan, Detroit, MI, 6Pediatrics- Allergy/ Treatment with Azathioprine and Rituximab in a Immunology Division, Wayne State University School of Medicine, De- 68 Pediatric Patient with CVID and Granulomatous troit, MI. Liver Disease RATIONALE: Common Variable Immunodeficiency (CVID) is a com- Tammy Peng, MD1, Laura Wozniak2, Bita V. Naini3, Maria Garcia- plex primary immunodeficiency with the major feature of hypogamma- 1 1 globulinemia. Patients with CVID usually do not have a genetic diagnosis, Lloret, MD, FAAAAI ; Division of Allergy and Immunology, Depart- ment of Pediatrics, David Geffen School of Medicine at UCLA, Los An- however up to 15% of patients with CVID have been found to have 2 SATURDAY geles, CA, Division of Gastroenterology, Department of Pediatrics David mutations of the gene TNFRSF13Bencoding TACI (transmembrane acti- 3 vator and calcium-modulator and cyclophilin-ligand interacter). Six muta- Geffen School of Medicine, Department of Pathology, David Geffen tions have been recognized thus far that are linked to a diagnosis of CVID. School of Medicine at UCLA, Los Angeles. Here, we identify two additional mutations that are found in the RATIONALE: Common variable immunodeficiency (CVID) is an im- TNFRSF13B gene encoding TACI in patients with CVID. munodeficiency characterized by hypogammaglobulinemia and increased METHODS: TNFRSF13B DNA Sequencing Test was performed by susceptibility to infections. In a subset of patients, non-infectious LabCorp and Correlagen Diagnostics on family members of two families complications such as autoimmunity, granulomas and lymphoproliferative with CVID. The coding sequence of TNFRSF13Bwas amplified by PCR, disease are prominent. Granulomatous disease of the lung (GLILD) is a and each PCR product then sequenced bi-directionally using the Sanger well-recognized entity but the spleen, liver and lymph nodes can also be sequencing methodology. affected. There is no standard therapy for granulomatous disease in CVID. RESULTS: We investigated two families with CVID and identified the A recent retrospective study by Chase et al. suggests that therapy with c.81G>A TNFRSF13B homozygous mutation in two siblings of Family A azathioprine and rituximab may be effective for CVID associated GLILD and the father and two children of Family B. There was an additional in adults. We present a CVID patient with granulomatous hepatitis and c.674a>G heterozygous mutation identified in Family A. Neither of these pulmonary nodules who had resolution of the granulomas after azathio- mutations have been previously identified to be associated with CVID, they prine and rituximab. were both labeled having as unclear significance for CVID thus the test was METHODS: Serial imaging and liver biopsies pre- and post- treatment inconclusive. with azathioprine and rituximab were performed. CONCLUSIONS: We believe that in addition to the six already RESULTS: A 16-year-old female with CVID presented with a rapidly recognized mutations in TACI that are linked to CVID, the c.81G>A enlarging liver and spleen shortly after diagnosis. Evaluation for infectious TNFRSF13B homozygous mutation and the TNFRSF13B c.674a>G het- etiologies was negative. Liver biopsy showed lobular hepatitis with erozygous mutation are linked to CVID as well. granulomatous inflammation composed of abundant T cells and histio- cytes. Chest CT demonstrated multiple pulmonary nodules and a calcified Relationship of Specific IgM Responses with granuloma. Therapy with azathioprine and rituximab was initiated. After 67 Infection and Lymphoproliferative Disease in one year of treatment without adverse effects, there was resolution of lung Common Variable Immunodeficiency nodules and repeat liver biopsy showed no abnormalities. CONCLUSIONS: Granulomatous disease in CVID can result in severe Tukisa D. Smith, MD, MS, Paul J. Maglione, MD, PhD, Charlotte Cun- organ dysfunction. The etiology of these granulomas is unclear but ningham-Rundles, MD, PhD; Icahn School of Medicine at Mount Sinai, polyclonal lymphocytic infiltration is a prominent finding. New York, NY. Immunosuppressive therapies have been tried with variable results. This RATIONALE: While common variable immunodeficiency (CVID) is the first report of efficacious azathioprine and rituximab therapy in the markedly impairs IgA and IgG responses, IgM production is retained in treatment of granulomatous hepatitis in CVID. some patients. This retained IgM production is linked with protection against infection as well as susceptibility to lymphoproliferative compli- cations. To gain more insight into the role of IgM in CVID, we examined whether antigen-specific IgM levels differentiated patients with history of pneumonia or those with lymphoproliferative complications. METHODS: Serum IgM recognizing bacterial (capsular polysaccharides, cell wall polysaccharides, flagellin, lipopolysaccharide) or natural IgM (forssman antigen, phosphocholine) antigens were measured by enzyme- linked immunosorbent assay. Patients meeting consensus guidelines for CVID as well as age-matched controls were included in this study. Retrospective chart review was utilized to determine history of infections and other medical complications. This study was approved by the institutional review board of the Icahn School of Medicine at Mount Sinai. RESULTS: Compared to CVID patients without history of pneumonia, those with history of pneumonia had significantly lower levels of IgM recognizing bacterial cell wall antigens and flagellin, but interestingly had similar levels of IgM recognizing pneumococcal capsular polysaccharides. In contrast, significant reduction of serum IgM recognizing pneumococcal All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. J ALLERGY CLIN IMMUNOL Abstracts AB23 VOLUME 137, NUMBER 2

Adult-Diagnosed Chronic Granulomatous Disease A Case of Acquired C1 Esterase Inhibitor (C1-INH) 69 71 Deficiency As the Presenting Manifestation of Common Variable Immune Deficiency (CVID) Derek M. Smith, MD1, Charles N. Webb, MD1, G. William Palmer, MD, 2 1 FAAAAI ; Wilford Hall Ambulatory Surgical Center, San Antonio, TX, Andrew Parker, MD1, David Hagin, MD1, Summer E. Monforte, MD2, 2 Boise Valley Asthma and Allergy Clinic, Boise, ID. Andrew G. Ayars, MD1, Matthew C. Altman, MD1; 1University of Wash- RATIONALE: Chronic granulomatous disease (CGD) is a rare disease ington, Seattle, WA, 2St. Peter’s Medical Group, Helena, MT. characterized by the inability of phagocytes to produce sufficient oxidative RATIONALE: Acquired angioedema is a rare syndrome of recurrent burst needed to kill intracellular organisms. Most patients have X-linked episodes of angioedema without urticaria caused by an acquired deficiency CGD(phox91 deficiency); however, about 30% have an autosomal of C1-INH. CVID is a heterogeneous primary immunodeficiency that is recessive form which has a similar, yet milder phenotype. characterized by susceptibility to infections and immune dysregulation METHODS: Dihydrorhodamine oxidation assay was performed by including autoimmunity. Here we offer a rare case report of a patient with ViraCor Laboratories. angioedema due to acquired C1-INH deficiency presenting as the initial RESULTS: A 48year old woman with known systemic lupus erythematosus manifestation of CVID. and inflammatory bowel disease presented to her physician due to high fevers METHODS: Flow cytometry immunophenotyping was performed at the and cough which required admission to the hospital for intravenous antibiotics Immunology Diagnostic Laboratory in Seattle, WA. ELISA testing for and oxygen supplementation for presumed pneumonia. Computed tomogra- autoantibodies to C1q and C1-INH were performed by the Advanced phy of her chest revealed diffuse nodular densities and a left lower lobe Diagnostic Laboratories in Denver, CO. infiltrate. Nodule biopsies were positive for Aspergillus. While inpatient, she RESULTS: This female patient presented at age 58 with episodic swelling of suffered from septic emboli and blood cultures grew Nocardia. Subsequent the face without urticaria. Workup for angioedema revealed a C4 level that laboratory evaluation for primary immunodeficiencies revealed no evidence was undetectable on multiple occasions. C1-INH level was 12 mg/dL (21-39) of cellular, humoral, or complement deficiency. Flow cytometry revealed a with 4% function. There was no family history of angioedema. C1q level was deficient neutrophil oxidative burst by dihydrorhodamine assay in an auto- undetectable. Given findings consistent with acquired angioedema, the somal recessive pattern. Thereafter, she received antimicrobial prophylaxis patient underwent extensive evaluation for malignancy that was negative. with interferon-g, trimethoprim/sulfamethoxazole, and voriconazole in addi- Subsequently, immunoglobulin levels were found to be low – IgG 369 mg/dL, tion to prednisone and sulfasalazine. Unfortunately, she succumbed to compli- IgA 36, and IgM 30. Vaccine titers were also low. The patient had a remote cations from septic shock about 14months later. history of pneumonia but no other significant infectious history. B-cell CONCLUSIONS: Our case emphasizes a classic presentation of CGD, immunophenotyping and C1q/C1-INH autoantibody testing are underway. yet in an adult. Clinical trials have proven that prophylactic treatment with CONCLUSIONS: Though it is well known certain autoimmune condi- interferon-g, trimethoprim/sulfamethoxazole, and itraconazole individu- tions can be the initial manifestation of CVID, we believe this is a rare ally reduce infections in patients with CGD. Data regarding treatment of report of autoimmune C1-INH deficiency as the presenting feature of the inflammatory complications are less robust and have only proven the CVID. Consideration of CVID may be warranted in patients who present SATURDAY effectiveness of corticosteroids. If the immunosuppression is overly potent, with acquired angioedema without another cause. then fatal infections have occurred, specifically in patients treated with Allergen Exposure Increases Triggering Receptor tumor necrosis factor-a inhibitors. 72 Expressed on Myeloid Cell (TREM)-2 Expression on Abnormal Newborn SCID Screen and Lymphopenia in Lung Dendritic Cell Subsets in a Murine Model of Asthma an Infant Exposed to in Utero Folfirinox Chemotherapy 70 Sannette C. Hall1, Devendra K. Agrawal2; 1Department of Biomedical Daniel H. Petroni, MD, PhD1, Kathey Mohan, ARNP1, Andrew Sinces, Creighton University, Omaha, NE, 2Department of Biomedical Coveler, MD2, Troy R. Torgerson, MD, PhD3, Suzanne Skoda-Smith, Sciences and Center for Clinical and Translational Science, Creighton MD1; 1Seattle Children’s Hospital, Seattle, WA, 2Seattle Cancer Care University School of Medicine, Omaha, NE. Alliance, 3Seattle Children’s Hospital Research Institute, Seattle, WA. RATIONALE: Dendritic cells (DCs) are professional antigen presenting RATIONALE: Newborn screening for severe combined immune defi- cells which traffic from the lungs to the lymph nodes to present processed ciency measures T-cell receptor excision circles (TRECs) as a biomarker antigens to T-cells driving an inflammatory (Th2) response in atopic for naive T-cell production. Other non-SCID conditions have been reported individuals. The recently discovered TREM-2 surface receptor has been to cause a positive SCID newborn screens such as 22q deletion syndrome, shown to be expressed on dendritic cells; however, its role in asthma is yet CHARGE syndrome and idiopathic CD4 lymphopenia. Here we report an to be elucidated. Here, we examined the effect of allergen exposure on infant girl who presented with initial absent TRECs and mild T-cell TREM-2 expression in the airways and on lung DC subsets. lymphopenia after in utero exposure to 7 cycles of 5-fluorouracil, METHODS: Female Balb/c mice were sensitized and challenged with irinotecan, and oxaliplatin (FOLFIRINOX) during the second and third ovalbumin or PBS for a total of 20 days. Lung tissues from both groups trimester for maternal treatment of pancreatic cancer. were harvested and examined for protein and mRNA expression of METHODS: TREC screen by Washington State Department of Health TREM-2. DCs were sorted using autoMACS and FACS to determine and flow cytometry by Seattle Children’s laboratory. TREM-2 -positive lung DC subsets. RESULTS: Patient’s initial TREC screen was 14#/mL at 23 hours of life RESULTS: Sensitization and challenge with ovalbumin resulted in (critically low 0-20#/mL). Flow cytometry at 3 days of life (dol) revealed increased airway hyper-responsiveness, mucus secretion, airway eosino- T and NK cell lymphopenia with a CD3 count of 1035 but philia, and total IgE in serum and BALF. TREM-2 mRNA expression in normal CD4CD45RA+ percentage (80%). On dol 7 TRECs were still whole lung was significantly higher (p<0.05) in the allergen-sensitized and low at 8#/mL but CD3 count rose to 1303. At dol 28, TRECs increased to challenged mice which was associated with increased protein expression in 120 and the patient’s lymphopenia resolved with normal mitogen response the lungs. Analysis of CD11c+MHC-IIhi lung DCs revealed that the OVA- to PHA. We recommended the patient proceed with her normal infant sensitized and challenged group had greater density of cells that were vaccines with the exception of live viral vaccines. CD11b+CD103- and CD11b+CD103+ compared to the control. TREM-2 CONCLUSIONS: We believe this is the first reported case of an abnormal expression was significantly higher (p<0.01) on the CD11b+CD103+ cells SCID newborn screen induced by in utero exposure to FOLFIRINOX when compared to the CD11b+CD103- cells. chemotherapy. It is reassuring that both TRECs and lymphopenia normalized CONCLUSIONS: Allergen-sensitization and challenge increases the with time. The lag in TRECs recovery compared to the T-cell count may indicate expression of TREM-2 in the airways and on the surface of lung DC subsets a reversible thymic dysfunction related to the in utero chemotherapy exposure. which may contribute to increased airway inflammation in allergic asthma. All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. AB24 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2016

Cinnamon-Induced Contact Stomatitis: A Propos of for a higher throughput of raw material and allergenic extract samples 73 Two Cases using 5-10 mL of each reagent.

Ekaterini I. Syrigou, PhD1, Photis Psarros2, Maria Zande1, Nikolaos K. Molecular Reference Materials for Standardization of Syrigos1, Maria Vasiliou1, Athanasios Sinaniotis1, Konstantinos Syrigos3; 75 Allergen Measurements 1Department of Allergy, Sotiria General Hospital, Athens, Greece, € 2Department of Allergy, Athens Naval Hospital, Greece, 3Athens School Sabina Wunschmann, PhD, Kristie N. Prtorich, Cathy Minichino, Heav- of Medicine, Greece. en Cerritos, Lisa D. Vailes, Martin D. Chapman, PhD, FAAAAI; INDOOR RATIONALE: Cinnamon contact stomatitis (CCS) is a rare delayed Biotechnologies Inc., Charlottesville, VA. hypersensitivity reaction. We report two cases of contact stomatitis RATIONALE: Allergen measurements are widely used for determination induced by cinnamon powder and cinnamon-flavored chewing gums. of the potency of allergy vaccines, for environmental exposure assess- METHODS: Case 1: A 31-year old female had been diagnosed with CCS ments, and for validation of IgE molecular diagnostics. With the exception by a stomatologist due to symptomatic episodes of pain, burning and of Bet v 1 and Phl p 5a, few purified allergen standards have been redness of the tongue and the buccal mucosa at the occlusal level following developed. The aim of this study was to produce purified allergen use of cinnamon-flavored chewing gums. Case 2: A 39-year old female had standards, with defined specifications, that could serve as Molecular been initially diagnosed with herpetic gingivostomatitis, due to the Reference Materials (MRM) for use in allergy diagnostics, enzyme- or SATURDAY presence of widespread erosive lesions on the gingiva and buccal mucosa fluorescent immunoassays, and multiplex arrays. at initial intraoral examination, but this diagnosis was changed to probable METHODS: Natural and recombinant food, dust mite, pollen and animal 5 CCS after negative cultures and serologic testing for HSV as well as allergens (n 11) were purified by affinity and/or gel-filtration chroma- recurrence of lesions upon rechallenge with cinnamon. tography and analyzed by SDS-PAGE, LC-MS/MS, ELISA, and FEIA or RESULTS: Case 1: Patch tests for fragrance mix (including cinnamic chimeric IgE ELISA. Natural allergens from peanut, dust mite and animal alcohol and cinnamic aldeyde) were performed with positive results, while were lyophilized using different buffer conditions. Real time stability data patch testing for cinnamon powder was negative. The patient was advised are collected from frozen liquid allergens and lyophilized allergens. to avoid use of cinnamon-flavored chewing gums, with no recurrence of RESULTS: Allergen purity, assessed by LC-MS/MS after Trypsin digest symptoms during a follow up period of 5 months. Case 2: Patch tests for and /or silver-stained SDS-PAGE, was >95%. Real time stability tests of fragrance mix were performed with negative results, while patch testing for frozen liquid allergens (up to 24 months) and frozen lyophilized allergens, cinnamon powder was positive. The patient was advised to avoid showed comparable potency in allergen-specific ELISA and no signs of consumption of cinnamon powder and had no recurrence of stomatitis degradation on SDS-PAGE. Monoclonal antibody ELISA and IgE during a 4 month follow up period. reactivity of recombinant allergens showed excellent correlations with CONCLUSIONS: Cinnamon contact stomatitis is a rare condition natural allergens. needing proper evaluation from a stomatologist as well as an allergologist CONCLUSIONS: Optimized, ISO 9001 compliant, bioprocessing path- in order to set the correct diagnosis. ways have been established to yield pure, immune-reactive natural and recombinant allergens. These MRM are stable and will improve the A Promising Technology for Characterizing Proteins, standardization of allergy diagnostics and vaccines used for 74 Antigens and Allergens in Extracts and Source immunotherapy. Materials

Jack D. Kelly; Greer Laboratories. RATIONALE: Genetic and environmental factors can affect the compo- sitions of allergenic extracts and can lead to variabilities in proteins, antigens, and allergens from one product lot to another. Traditional characterization methods (SDS-PAGE/Western blotting) have not been conducive for high throughput screening of allergenic extracts and source materials. A new technology can facilitate the production of these profiles. The objectives herein are: 1) demonstrate the application of this technology (‘‘WES’’) for source material assessments, 2) demonstrate that both WES and traditional techniques provide qualitatively similar protein and antigenic profiles, and 3) illustrate the quantitative capabilities of WES. METHODS: Source materials and allergenic extracts were evaluated for total protein (Bradford) and protein/antigenic profiling (WES Nanotechnology Capillary Electrophoresis from ProteinSimple, Santa Clara, CA, or conventional SDS-PAGE/Western Blotting). WES kits contain sample preparation reagents, pre-filled plates with proprietary electrophoretic reagents, disposable capillary cartridges, and all post- sample preparation steps (loading, washing, immunoprobing, data anal- ysis, incubation time) are fully automated. RESULTS: Both protein and antigenic patterns were qualitatively similar between WES and the traditional techniques. WES provided several additional benefits, including small reagent volume (5-10 mL), quantita- tion, high throughput (3-4 hour run times), complete automation of reagents and assay conditions, analytical integrations, matrix-based mo- lecular weight determination, and real-time migration visualizations. CONCLUSIONS: WES assays were simple to perform and provided both similar qualitative data compared to traditional methods and useful quantitative data with full automation. This new nanotechnology allows All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. J ALLERGY CLIN IMMUNOL Abstracts AB25 VOLUME 137, NUMBER 2

A Study of Immunogenetic Associations with Peanut activation markers significantly varied between these groups, with the 76 Allergy Utilizing a Novel DNA Repository CD16+CD1c+ population expressing high levels of CD86 and PD-L2. CONCLUSIONS: We have identified three subpopulations of human Jonathan A. Hemler, MD1, Elizabeth S. Marston, MD2, Jason H. dermal DCs that preferentially migrate out of the skin in response to Karnes, PhD3, Andrew M. Glazer, PhD3, Elizabeth J. Phillips, MD4,5, primary exposure to an allergen. The CD16+CD1c+ population expressed Simon A. Mallal, MBBS4,6, Peggy L. Kendall, MD1,7; 1Vanderbilt Univer- high levels of PD-L2, which has also been shown to be elevated in a Th2 sity School of Medicine, Division of Allergy, Pulmonary, and Critical skewing dermal DC population in the mouse. Further characterization of Care Medicine, Department of Medicine, Nashville, TN, 2Vanderbilt Uni- these cells will improve our understanding of the function and role of these versity School of Medicine, Monroe Carrell, Jr. Children’s Hospital Pedi- DC subsets, and may provide an additional therapeutic target for the treat- atric Residency Program, Nashville, TN, 3Vanderbilt University School of ment of allergic diseases. Medicine, Division of Clinical Pharmacology, Department of Medicine, Nashville, TN, 4Institute for Immunology & Infectious Diseases, Murdoch Tacrolimus: A Heart Pill to Swallow University, Murdoch, Australia, 5Vanderbilt University School of Medi- 78

cine, Division of Infectious Diseases, Department of Medicine, Nashville, 1 2 3 6 Tara V. Saco, MD , Dennis K. Ledford, MD , Sweta Shah, MD , Eli- TN, Vanderbilt University School of Medicine, Center for Translational 3 3 1 Immunology and Infectious Diseases, Nashville, TN, 7Vanderbilt Univer- marys Perez-Colon, MD , Lacey Harrington, MS-IV ; Department of In- sity School of Medicine, Department of Pathology, Microbiology and ternal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, 2University of South Florida and the James A. Haley Immunology, Nashville, TN. 3 RATIONALE: A fundamental knowledge gap exists regarding genetic VA Hospital, Tampa, FL, University of South Florida College of causes of peanut allergy (PA). Large genetic databases now make it Medicine. possible to conduct detailed human genome studies to identify contributors RATIONALE: Tacrolimus-induced hypertrophic cardiomyopathy to disease. (HOCM) is a rare phenomenon. Tacrolimus-induced achalasia has not METHODS: BioVU, a unique biorepository of >200,000 DNA samples yet been documented. We present potentially the first case of tacrolimus- matched to de-identified electronic medical records (EMR), was used to induced achalasia and concomitant tacrolimus-induced HOCM. identify subjects for study of HLA alleles associated with peanut allergy METHODS: Literature review was performed to hypothesize a connec- (PA). 65 PA patients and 170 peanut tolerant controls (PC) were identified tion between tacrolimus- HOCM and calcineurin inhibitor-induced in BioVU using an algorithm ratified by expert review. Of these, 16 PA and achalasia. 43 PC self-identified White patients had genotypic data available for RESULTS: A 66 year old male with a history of renal transplant secondary analysis. HLA alleles were imputed from IlluminaÒ HumanExome to hypertension and lithium toxicity in 2010, on tacrolimus, presented with BeadChip data using SNP2HLA. HLA allele associations were tested in dysphagia and dyspnea for three months. The patient underwent esoph- a dominant model with PLINK with significance considered at ageal manometry, which revealed type II achalasia, characterized by aperistalsis due to pan-esophageal pressurization. An echocardiogram alpha50.05. SATURDAY RESULTS: No significant associations (p<0.05) were detected. (ECHO) ordered for a brief episode of atrial fibrillation revealed a septal Suggestive associations included HLA-DQB1*05*02 (p50.07, OR thickness of 18 mm, and an ejection fraction (EF) of 75-80 %, suggestive of 1.25), which correlated with increased risk of PA, and HLA A*68 HOCM. Cardiac magnetic resonance imaging results were also suggestive (p50.10, OR 0.70), which correlated with decreased risk of PA. of HCOM. The patient’s ECHO prior to transplant showed normal left CONCLUSIONS: The trend in HLA-DQ associating with PA risk ventricular thickness with an EF of 60%. Given the association of conforms with previous studies localizing risk to the HLA class II HLA- calcineurin inhibitors with HOCM and achalasia, tacrolimus was believed DR/DQ region. HLA sequencing amongst all PA and PC will be performed to be the causative agent. to increase the power to detect associations within the HLA locus. The CONCLUSIONS: Tacrolimus-induced HOCM has been documented in BioVU repository has provided: 1. A novel platform for studying genetic transplant recipients. One proposed mechanism involves decreased nitric contributions to PA with the goal of creating a model to define its specific oxide synthetase (NOS) activity via calcineurin inhibition, which increases immunopathogenesis and 2. An algorithm for a specific PA phenotype that 70-kD S6 kinase activity leading to altered protein synthesis and cardiac can now be validated across a large network of EMRs with DNA hypertrophy. While there are no reported cases of tacrolimus-induced repositories. achalasia, one case report documented manometry-proven achalasia secondary to another calcineurin inhibitor, cyclosporine A. Decreased The Role of Human Dendritic Cells in Cutaneous NOS at the gastro-esophageal junction has been documented in achalasia. 77 Allergen Recognition and Immune Activation We present potentially the first case of tacrolimus-induced achalasia and concomitant tacrolimus-induced HOCM. Anna R. Wolfson, MD, Caroline L. Sokol, MD, PhD, Andrew D. Luster, MD, PhD; Massachusetts General Hospital, Boston, MA. RATIONALE: Dendritic cells (DCs) initiate the immune response against a wide range of pathogens. There is evidence in the mouse that Th1 versus Th2 differentiation is defined by the DC subset that activates na€ıve T cells, however, the analogous DC subsets in the human have yet to be determined. We sought to identify the DC subset responsible for Th2 skewing in human skin. METHODS: Using an ex vivo human skin explant model, we analyzed the DCs that responded to and migrated out of skin specifically in response to novel allergen exposure (papain) versus exposure to the non-allergenic protein ovalbumin (OVA). DCs were phenotyped by flow cytometry. RESULTS: We identified three populations of CD45+CD11c+HLA-DR+ DCs which preferentially migrated out of the skin in response to papain im- munization: CD14-/CD16- DCs (5-fold increase compared to OVA), CD14+ DCs (2-fold increase compared to OVA), and CD16+CD1c+ (3- fold increase compared to OVA). Expression of costimulatory and All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. AB26 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2016

Averting Danger: A Case of Anaphylaxis to RabavertÒ subset of patients discontinued their daily (maintenance) use of ICS 79 therapy. CONCLUSIONS: Patients with moderate to severe allergic asthma Sarah W. Spriet, DO, Taylor A. Banks, MD, Cecilia Mikita, MD, MPH, utilizing add-on omalizumab therapy are consistently described in the FAAAAI; Walter Reed National Military Medical Center, Bethesda, MD. literature as experiencing a reduction in the use of both ICS and OCS. RATIONALE: Rabies post-exposure treatment is a medical necessity. Two rabies vaccines are available in the United States; purified chick Defining the Percentage of T Helper 17 Cells in embryo cell culture vaccine (PCECV, RabAvertÒ) and gelatin-free human 81 Patients with Eczema and Allergic Disease diploid cell vaccine (HDCV, ImovaxÒ). We report a case of PCECV-trig- gered anaphylaxis. Ranjeet Minocha, MD, John M. Routes, MD, FAAAAI, Mary METHODS: After clinical evaluation, patient and a volunteer control Hintermeyer, APNP, Trivikram Dasu, PhD, Erin Hammelev, Tucker underwent skin prick and intradermal testing to the rabies vaccines, Keuter, Aniko Szabo, PhD, James W. Verbsky, MD, PhD; Medical College vaccine components, and rabies immunoglobulin. Vaccine challenge was of Wisconsin, Milwaukee, WI. then performed. RATIONALE: Decreased percentage of Th17 is seen in RESULTS: A healthy 15 year old male presented to the Emergency Hyperimmunoglobulin E Syndrome (HIES), although reports have Department after a live bat was found in his home, captured, and found to suggested that TH17 levels are also low in atopic disease. Since eczema SATURDAY have rabies. Mucous membrane exposure could not be ruled out and human is often the first, and sometimes only presenting symptom of HIES, it is rabies immunoglobulin (Imogam Rabies – HTÒ) and PCECV were admin- important to differentiate between the two entities. The purpose of this istered. Within minutes, he developed dyspnea, stridor and generalized project was to define age dependent normal percentages of Th17 cells in hives. Symptoms resolved within one hour after treatment with antihista- healthy control, patients with eczema and allergic disease, and compare mines and IV corticosteroids and he was referred to Allergy- that to known patients with HIES. Immunology. On day 3 post-exposure, patient and control underwent METHODS: In this retrospective study, 47 patients suspected of having skin prick testing to undiluted PCECV, egg, gelatin, HDCV and Imogam. HIES from the Children’s Hospital of Wisconsin (Milwaukee, WI) were Skin prick was positive to PCECV and gelatin. Intradermal testing (IDT) analyzed using Flow Cytometry. Cells were activated with PMA/ionomy- using 0.02 mL of 1:100 dilution to HDCV and Imogam was negative. cin, stained with antibodies to CD4/CD8, and then stained for intracellular IDT using 0.02 mL of 1:10 dilution was negative to Imogam, positive to IL17a. Patients selected for the study had a pretest diagnosis of eczema, HDCV; however, considered an irritating dose given identical results in recurrent infections, or both. 6 control. Patient tolerated a 10/90 challenge to HDCV and completed RESULTS: The mean percentage of Th17 was 0.78 SE 0.11. The mean 6 post-exposure series using this vaccine. age was 13.40 SE 1.95. Th17 levels increased significantly as age CONCLUSIONS: Skin test results and successful challenge to HDCV increased (p<0.005) with no significant differences between sexes. Th17 suggest gelatin allergy. Awareness of the potential for IgE-mediated levels trended lower in patients with eczema and atopic disease, but were reactions to rabies vaccine is important. Challenge to HDCV should be not statistically significant compared to controls. Several patients with considered in select patients. HIES were included in this analysis and demonstrated very low levels of Th17 cells. Reduction in Corticosteroid Use Among Patients CONCLUSIONS: There is an age dependent increase in Th17. While 80 Receiving Omalizumab in Real World Settings: A patients with eczema and atopic disease had decreased production of Th17, Systematic Literature Review of Non-Randomized they were not significantly different from healthy controls. Very low levels Studies of Th17 tend to favor a diagnosis of HIES.

Reynold A. Panettieri, MD1, Jonathan Corren, MD2, Susan Gabriel, MSc3, Kimberly M. Ruiz, EdM4, Bethany Sawchyn, PharmD4, Jennifer A. Colby, PharmD4, Meryl Mendelson, MD3; 1University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, 2David Geffen School of Medicine at UCLA, Los Angeles, CA, 3Novartis Phar- maceuticals, East Hanover, NJ, 4Xcenda, Palm Harbor, FL. RATIONALE: The objective was to provide a summary of the real-world steroid-sparing outcomes associated with omalizumab treatment in inadequately controlled moderate to severe allergic asthma. METHODS: A systematic literature review was conducted to identify studies of omalizumab treatment in patients >_12 years with moderate to severe allergic asthma. A search of MEDLINE and EMBASE databases was conducted for relevant studies published from 2003 to 2014. Included study designs were prospective observational studies and retrospective studies. Outcomes of interest were corticosteroid-sparing effects, including reduction in use of oral corticosteroids (OCS) and inhaled corticosteroids (ICS). Study quality was assessed by the Newcastle-Ottawa Quality Assessment Scale of Cohort Studies (for nonrandomized studies). RESULTS: A total of 19 studies evaluated OCS usage and 12 studies evaluated ICS usage. The proportion of patients discontinuing mainte- nance OCS ranged from 20.5% to 74.2%. A reduction in the proportion of maintenance OCS users was reported in 6 studies. A statistically significant reduction in daily dose was reported in 3 studies, ranging from 35% to 95% (7 mg to 21 mg reduction per day). Statistically significant reductions in ICS usage were reported in 50% of studies (6/12) and the remainder of studies described a reduction with descriptive analyses only. Overall, patients treated with omalizumab reduced their daily use of ICS and a All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. J ALLERGY CLIN IMMUNOL Abstracts AB27 VOLUME 137, NUMBER 2

Prevalence of Atopic Diseases in Patients with medium for controls. Supernatants for evaluating the cytokine levels, 82 Humoral Primary Immunodeficiency: A Comparison harvested cells for mRNA cytokines and miRNA by RT-qPCR. of a Single Center and the US Immunodeficiency RESULTS: Serum IgE and IgG4 anti-Dp showed significantly higher in S- Network (USIDNET) IgE+ than S-IgE- or CT subjects. IgG3 to Dp showed significant higher levels in S-IgE+ than CT group. Dp-specific IgA and IgG1 were not Alice S. Chau, MD1, Artemio M. Jongco, III, MD, PhD, MPH2,3, Laura different among the groups. IL-5 was significantly higher in supernatants Helfner, MD4, James C. Fagin, MD5, Vincent R. Bonagura, MD, after Dp-stimulation from S-IgE+ than S-IgE- or CT groups but not for IL- FAAAAI2,6; 1Department of Medicine, Hofstra North Shore-LIJ School 4, IL-10, IL-13, IL-17 and IFN-g levels. Higher IL-5 levels in S-IgE+ of Medicine, Manhasset, NY, 2Feinstein Institute for Medical Research, compared to S-IgE- and CT groups and higher IFN-g levels were found in Manhasset, NY, 3Division of Allergy & Immunology Hofstra North S-IgE+ compared to CT; and higher TGF-b expression in S-IgE- group. Shore-LIJ School of Medicine, Great Neck, NY, 4Division of Allergy & miRNAs expression was similar among the groups. Immunology, Departments of Medicine and Pediatrics, Hofstra North CONCLUSIONS: Data suggest that the mechanism involved in S-IgE- is Shore-LIJ School of Medicine, Great Neck, NY, 5Allergy & Clinical different from S-IgE+ group, and our findings showed that antibody, Immunology, Division of ProHEALTH Care Associates, New Hyde, cytokine and miRNAs profiles analyzed in this study were not able to NY, 6Division of Allergy and Immunology at North Shore Long Island discriminate these groups. Jewish Health System, Great Neck, NY. RATIONALE: Humoral primary immunodeficiency diseases (PIDDs) Inhibition of Inflammation and Mucus Production By arise from defects in B cell differentiation, maturation, and class switch 84 Bordetella Pertussis Whole-Cell Vaccine in a recombination. Nevertheless, a subset of these patients demonstrate atopic Murine Model of Allergic Rhinitis

disease with corresponding elevated IgE. We characterized the prevalence 1 2 and kinds of atopic conditions present in two distinct populations. Marcelo Vivolo Aun, MD , Fernanda Arantes-Costa , Francine Maria 2 € 2 METHODS: We determined the prevalence of IgE-mediated atopic Almeida , Thayse Regina Bruggermann , Beatriz Mangueira Saraiva-Ro- manholo3,4, Isabella S. Genaro2,3, Milton Arruda Martins, MD, PhD2, disease and immunologic characteristics of humoral PIDD patients seen 1 1 1 at an academic medical center immunology clinic (retrospective chart Jorge Kalil, MD, PhD , Pedro Giavina-Bianchi, MD, PhD ; Clinical Immunology and Allergy Division, University of Sao Paulo, Sao Paulo, review, 2001-2011) and enrolled in the USIDNET Registry (queried 5/5/ 2 2015). The following diagnoses were included: congenital agammaglob- Brazil, Department of Internal Medicine, University of Sao Paulo School of Medicine, Sao Paulo, Brazil, 3Hospital Public Employee of Sao Paulo ulinemia (279.04), idiopathic agammaglobulinemia (279.00), selective 4 IgA deficiency (279.01), IgG subclass deficiency (279.03), specific (IAMSPE), Sao Paulo, Brazil, University City of Sao Paulo (UNICID), antibody deficiency (279.19), and hyper IgM syndromes (279.05). Sao Paulo, Brazil. RESULTS: Sixty-Five of 92 clinic patients and 616 of 4087 registry RATIONALE: Bordetella pertussis whole-cell vaccine (Pw) has shown to participants were included in the analysis. The distribution of PIDD inhibit inflammation in animal models of asthma induced by ovalbumin and aeroallergens. We evaluated the effects of diphtheria-tetanus-pertussis diagnoses was as follows (clinic;USIDNET): 279.00 (32.0%; 2.3%), SATURDAY 279.01 (22.0%; 4.5%), 279.03 (0%; 1.9%), 279.04 (20.0%; 61.7%), (DTPw) vaccine in a murine model of allergic rhinits induced by 279.05 (3.0%; 23.9%), and 279.19 (23.0%; 5.8%). The distribution of Dermatophagoides pteronyssinus(Derp). atopic diagnoses were as follows: allergic rhinitis(38.5%; 8.6%), METHODS: The protocol lasted 30 days. BALB/c mice were divided into asthma(28.6%; 43.6%), drug allergy(11.0%; 28.8%), eczema(6.6; 6 groups, which were sensitized subcutaneously (s.c.) with saline solution 16.5%), and food allergy(2.2%; 2.5%). ImmunoCAP or skin prick testing or Derp 50mcg, in three injections. Three groups were submitted to saline, and serum IgE values were available in 41 and 55 clinic patients, with or without diphtheria-tetanus (DT) and DTPw vaccines. The other respectively, while serum IgE was documented in 131 database patients. three groups received Derp with or without DT and DTPw vaccines. In both cohorts, 279.04 and 279.05 patients had the most number of Subsequently mice underwent intranasal challenge with saline or Derp for undetectable IgE. 7 days and were sacrificed 24h after the last challenge. We measured serum CONCLUSIONS: Humoral PIDD patients can develop IgE-mediated specific IgE, the density of leukocytes infiltration in nasal mucosa and we type 1 hypersensitivities, many with documented serum IgE levels. The measured the acidic nasal mucus content. distribution of PIDD and atopic diagnoses differ between the two RESULTS: Animals sensitized with Derp produced specific IgE, which populations. Both registry and single center data are informative and do was decreased by both vaccines. Derp+DTPw group developed lower not necessarily demonstrate similar trends. levels of IgE anti-Derp (p<0.05), in comparison to Derp and Derp+DT groups. Furthermore, DT and DTPw vaccines decreased density of Evaluation of Antibody, Cytokine and Mirnas in polymorphonuclear leukocytes infiltration in comparison to Derp group 83 Patients with Ige-Mediated and Non-IgE Mediated (p<0.05). We also found that both vaccinated groups had lower levels of Rhinitis in Brazilian Subjects Triggered By House acidic nasal mucus (p<0.05). Moreover, Derp+DTPw group had lower Dust Allergen Exposure quantities of acidic nasal mucus than Derp+DT group (p<0.05). CONCLUSIONS: In this murine model of allergic rhinitis, DTPw vaccine Ernesto A. Taketomi, Juliana S. Miranda, Jair Cunha-Junior, PhD, Ana decreased serum specific IgE, inflammatory infiltrate and acidic mucus in C. A. M. Pajuaba; Federal University of Uberl^andia, Uberlandia, Brazil. upper airways. Pw vaccine should be evaluated as an option to induce RATIONALE: The aims were to investigate antibody responses to immune regulation in respiratory allergy. Dermatophagoides pteronyssinus (Dp), cytokine levels, relative expression of mRNA cytokines and microRNA (miRNA) in patients with rhinitis symptoms triggered by HDM exposure and with or without systemic IgE (S-IgE-) and control (CT) subjects. METHODS: Groups divided in S-IgE+ (n 5 32), S-IgE- (n 5 19), and CT (n 5 31) by clinical symptoms, skin prick test (SPT) and specific IgE to Dp were analyzed. Serum IgG1, IgG3, IgG4, and IgA specific to crude Dp allergen were measured by ELISA. PBMCs from subjects (S-IgE+,15;S- IgE-,11;CT,10) were isolated and stimulated with Dp and mitogen or All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. AB28 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2016

Usefulness of Component-Resolved Diagnosis (CRD) Vacuolar Serine Protease Major Allergen of Fusarium 85 in Patients with Pet Allergy 87 Proliferatum

Wolfgang Hemmer, PhD, Gabriele Sesztak-Greinecker, MD, Felix Horng-Der Shen, Hsiao-Yun Tai, Chang-Ching Yeh, Keh-Gong Wu; Tai- Wantke, MD, FAAAAI, Stefan Wohrl, MD, MSc, FAAAAI; Floridsdorf pei Veterans General Hospital, Taipei, Taiwan. Allergy Center, Vienna, Austria. RATIONALE: Fusarium species are prevalent airborne fungi and recog- RATIONALE: Polysensitization to several animals is common in pet nized as causative agents of human respiratory atopic disorders. The pur- allergy. The molecular basis and clinical relevance often remains unclear. pose of this study is to identify and characterize important allergens of METHODS: We studied IgE binding patterns in 311 patients sensitized to F. proliferatum. cat, dog and/or horse (123 m/188f, mean age 32617 yrs) using Phadia METHODS: IgE-reacting F. proliferatumcomponents were identified by ImmunoCAPÒfor rFel d 1, serum albumins (nFel d 2/nCan f 3), lipocalins immunoblot. Characterization of allergens and determination of IgE cross- (rFel 4/rCan f 1/rCan f 2/rEqu c 1), and rCan f 5. reactivity were performed by cDNA cloning and immunoblot inhibition RESULTS: Skin tests were positive to more than one species in 50.8%. In studies. cat sensitization, reactivity with Fel d 1/2/4 was 87/2/7% in patients RESULTS: The 36.5 kDa IgE-binding component of F. proliferatum re- positive to cat alone (n5134), 91/11/25% in patients positive to cat+dog acted with a monoclonal antibody FUM20 against fungal vacuolar serine (n575), and 86/37/76% in those positive to cat+dog+horse (n562). In dog protease allergens. The cDNA of F. proliferatum vacuolar serine protease SATURDAY allergy, reactivity with Can f 1/2/3/5 was 32/0/5/53% in patients positive to (Fus p 9.0101) was cloned. Nine serum samples known previously IgE- dog alone (n519), 36/4/11/26% in patients positive to cat+dog (n575), binding against the vacuolar serine protease allergen of Penicillium chrys- and 53/16/37/26% in those positive to cat+dog+horse (n562). Can f 1, 2 ogenum (Pen ch 18) showed IgE immunoblot reactivity against rFus p and 5 represented dog-specific allergens particularly recognized by dog 9.0101. The purified rFus p 9.0101 can inhibit IgE and FUM20-binding owners (p<0.001). Anyhow, symptoms after dog exposure were similarly against the 36.5 kDa component of F. proliferatum. Thus, a novel and frequent in subjects either positive or negative to Can f 1/2/5 (79 vs 66%). important F. proliferatum vacuolar serine protease allergen (Fus p Equ c 1 was the major allergen (85%) in patients sensitized to horse and 9.0101) was identified. The rPen ch 18 can inhibit IgE-binding against horse+cat (n520). Equ c 1 correlated with Fel d 4 (r50.72), and ;50% of rFus p 9.0101. It indicates that IgE cross-reactivity between the patients reported adverse reactions to both animals. No correlation was Fusarium and the Penicilliumvacuolar serine protease allergens also exists. found between other lipocalins. Both rFus p 9.0101 K88A and rPen ch 18 K89A mutants did not inhibit CONCLUSIONS: Current CRD can often, but not always, explain IgE-binding against rFus p 9.0101. Lys88 was considered a critical core polysensitization. As cross-reactions appear to be often clinically relevant, amino acid in IgE-binding against Fus p 9.0101 and a residue responsible the practical benefit from discriminating between genuine sensitization and for IgE cross-reactivity between Fus p 9.0101 and Pen ch 18 allergens. cross-sensitization might be limited in clinical practice. CONCLUSIONS: Our results indicate vacuolar serine protease is an important allergen of F. proliferatum and an IgE cross-reactive major pan- B Cell Isotype Switching Is Dependent upon the fungal allergen. 86 Duration of B Cell Activation and Dose of Antigen Relationship of Der f1 and Der p1 Levels in House Tae Kwan Lee1, Se Jin An1, Ji-Mok Kim1, Jae Ho Lee, MD, PhD2; 88 Dust in the Midwestern US 1Chungnam National University Hospital, Daejeon, South Korea, 2Depart- ment of Pediatrics, Chungnam National University, Taejeon, South Korea. Charles S. Barnes, PhD1, Freddy Pacheco, MS1, Jay M. Portnoy, MD, RATIONALE: In the T and B cells interaction, the CD40 ligand FAAAAI2; 1Children’s Mercy Hospital, Kansas City, MO, 2Division of molecules of the activated helper T cells stimulate B cells by the manner Allergy & Immunology, Children’s Mercy Hospitals and Clinics, Kansas of direct physiologic contact. The activated B cells proliferate and City, MO. differentiate to secrete IgA, IgM, IgG and IgE in the presence of RATIONALE: Two species of house dusty mite (Dermatophagoides far- lymphokines. inae and D. pteronyssinus) are common in the Midwestern US. Knowledge METHODS: Female BALB/C mice were used between 8 to 16 weeks of of measured levels of house dust mite allergenic proteins in vacuumed age. Plasma membranes were prepared from CD40 mRNA transfected to house dust can be a helpful parameter when evaluating home allergen Sf-9 cells. High and low concentration of CFSE-labeled small B cells were avoidance and remediation strategies. To evaluate the relationship of Der incubated with plasma membranes with Th2 cell culture supernatants in f1 levels to Der p1 levels we conducted the following studies. the round bottomed 96 well plate for various periods and analyzed by flow METHODS: House dust was collected from homes in the Kansas City cytometry. B cell culture supernatants were assayed for IgM, IgG1, and IgE Metropolitan area that participated in 4 studies of allergens in housing and according to the concentrations of B cells and the duration of culture by schools during the past 7 years. Between 1 and 3 dust samples were using sandwich ELISA. collected per house. House dust was analyzed for levels of Der f1 and Der RESULTS: B cells were divided from second day of culture and up to p1 allergen using specific monoclonal antibodies and commercially more than eight times on fifth day. The numbers of cell division cycle were available kits (InBio). Values were reported as nanograms per gram of dust. almost same in low and high B cell concentration groups. B cells secreted RESULTS: We analyzed 1353 house dust samples over the period of 7 IgM, IgG1 and IgE serially from the third division. But it was more years. The maximum Der f1 level was 86,778 and the maximum Der p1 prominent in low B cell concentration groups than higher B cell groups. level was 13,743. The Mean Der f1 level was 378 6 2438 and the mean Der CONCLUSIONS: B cell isotype switching from IgM to IgG1 and IgE was p1 level was 248 6 602. Der f1 was above the level of detection in 95% of correlated with number of cell divisions. Finally, the dose of antigen and samples and Der p1 was above the LOD for 97% of samples. The duration of B cell stimulation play an important role in the B cell division correlation between Der f1 levels and Der p1 levels was 0.08. cycles linked with isotype switching. CONCLUSIONS: Most homes contained measurable levels of both Der f1 and Der p1 allergen proteins. The moderate but positive correlation between the two mite allergens indicates that conditions conducive to the growth of both types of mites occur in many homes. All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. J ALLERGY CLIN IMMUNOL Abstracts AB29 VOLUME 137, NUMBER 2

An Exploratory Proof of Concept Study to Quantify the Mobility of Aeroallergens in Home: Effect of Location 89 Major Cat Allergens, Fel d1 and Fel d4 from Domestic 91 of Air Sampling and Implication for Evaluation of House Cats Patient Exposure

William H. Yang, MD1, Suzanne Kelly, PhD1, Nate Stepner, D.Litt1, Julian Gordon, PhD1, Paul Detjen, MD2, Andrea Wachter1, Prasanthi Douglas Boeckh, DVM2, Jacob Karsh, MD1, Jimmy Yang, MBA1; 1Red Gandhi, MBA, MPH1; 1Inspirotec Inc, Glenview, IL, 2Kenilworth Medical Maple Trials Inc., Ottawa, ON, Canada, 2Merivale Cat Hospital, Ottawa, Allergy & Immunology, Kenilworth, IL. ON, Canada. RATIONALE: We developed a user-friendly airborne allergen sampling RATIONALE: Cat dander is ubiquitous in our environment and is one of device for patients with allergic asthma or rhinitis. This device was the most potent indoor allergens causing an IgE mediated Type 1 allergic previously evaluated for its use in the bedroom. Here we run multiple response. While patients may be sensitized to several different allergens devices at multiple locations within a house to determine whether bedroom found in the dander, the major ones are Fel d1 and Fel d4 with more than aeroallergen profile is representative of the whole house. 80% of these individuals exhibiting IgE antibodies to these two allergens. METHODS: The devices were run at the same time at 12 locations in a The purpose of this preliminary work was to measure the levels of Fel d1 home occupied by a family and a dog. The dog had access to all rooms and Fel d4 found in saliva, fur and urine of male and female domestic house except the basement. Twelve common household allergens were tested cats and to determine whether there are differences in allergen levels with MARIAä multiplex immunoassays kits from Indoor dependent on breed, gender, sterilization status and age. Biotechnologies. Biomass measurements on the same samples were METHODS: Cats volunteered by owners from a local animal hospital performed by spectrophotometry. Allergen and biomass capture increased were used for this study. Owners signed an informed consent prior to any linearly for 5 days and plateaued between 5 and 7 days. Five days was sample collection. Twenty cats were studied, five in each of four cohorts: therefore selected as the standard sampling time. neutered males, neutered females, females not in oestrus and males. The RESULTS: Allergen profiles showed similar levels of Can f 1 (dog) at all breed, age, weight and health status of each cat was recorded. testing locations except for a trace found in the basement from where the Commercially available ELISA kits were used to measure the allergen dog was excluded. Mold Asp f 1 was found in the basement but in no other levels and a standard curve created from the Fel d1 and Fel d4 standards. location. Four locations showed timothy grass at borderline detectable RESULTS: Triplicate samples were analyzed to allow for a sufficient levels. No other allergens were detected. Biomass was within a cv of +14%, sample size for analysis and comparison. showing relative consistency of air quality throughout the house. CONCLUSIONS: The information generated by this study will be used to CONCLUSIONS: Outdoor allergens may appear sporadically. Results determine the characteristics of cats to be housed in a cat allergen challenge are consistent with a dynamic equilibrium throughout the house depending room in order to obtain consistent levels of airborne allergen. on air flow and pet movements. Home aeroallergen sampling from any of several locations may accurately reflect a person’s allergen exposure. Modulatory Effects of Aspergillus Colonization and

90 Abpa on Blood and Sputum Granulocytes in CF Homes Assessed As a Result of Physician Referral SATURDAY 92 Have Higher Fungal Burden Yael Gernez1, Jeffrey Waters2, Colleen E. Dunn2, Zoe Davies2, Cassie Everson2, Rabindra Tirouvanziam3, Leonore Herzenberg4, Richard B. Jill R. Hanson, MD1, Charles S. Barnes, PhD1, Jay M. Portnoy, MD, Moss, MD5; 1Mount Sinai Hospital, 2Stanford, School of Medicine, FAAAAI2; 1Children’s Mercy Hospital, Kansas City, MO, 2Division of 3Emory University School of Medicine, Department of Pediatrics, At- Allergy & Immunology, Children’s Mercy Hospitals and Clinics, Kansas lanta, GA, 4Stanford, School of Medicine, Stanford, 5Stanford, School City, MO. of Medicine, Palo Alto, CA. RATIONALE: Exposures in the home environment can play a significant RATIONALE: Fifteen to sixty percent of CF patients are colonized with role in health, prompting physicians to obtain an environmental history. We Aspergillus fumigatus (Af) [CF-AC] and are at risk for allergic broncho- hypothesized that homes assessed following physician referral would have pulmonary aspergillosis [CF-ABPA]. Although airways inflammation in higher fungal counts. CF is typically characterized by neutrophilia, ABPA-associated inflam- METHODS: Air samples were obtained from homes assessed after mation is defined by eosinophilia. We hypothesized that blood basophil and physician referral. A control group consisted of samples obtained from blood and sputum eosinophils and/or neutrophils may be primed or homes of healthy children. Samples were obtained using a Biostage activated in CF-ABPA or CF-AC patients when compared to CF patients collector operating at 15 L/minute for 10 minutes. Mold inhibitory agar without Af colonization or ABPA [CF]. (Remel Labs; Lenexa, KS) was utilized for media. The mean number of METHODS: Using flow cytometry, we measured surface CD63 and viable fungal colonies per cubic meter of air was compared between the CD203c on basophil and Dectin 1, CD16, CD63 and CD66b on blood and groups utilizing independent sample t-tests. induced sputum neutrophils as well as surface CCR3 (eotaxin receptor) on RESULTS: The mean number of total viable fungal colonies in the referral eosinophils from CF-ABPA (N511), CF-AC (N59), and CF (N510) group was significantly higher than the control group (536.40 vs 268.11; patients. We also studied the blood granulocytes from patients with celiac p50.0001). Prominent mold species in both groups were Alternaria, disease as controls. We measured serum IL-17 by Elisa. Cladosporium and Penicillium. A higher mean number of colonies was RESULTS: No differences were observed within the three groups of CF seen in the referral group for Penicillium (132.67 vs 36.34; p50.0005). patients in any activation surface markers on blood neutrophils or on IL-17 There was no difference between the two groups in regard to Alternaria levels. Levels of surface CCR3 on blood eosinophils and CD203c on or Cladosporium. There was a significant difference in the presence of basophils were increased in CF-ABPA patients compared to CF-AC (0.04 Aspergillus, with the referral group having a higher mean number of col- and <10-3respectively). In the sputum, the levels of surface CD66b were onies (85.91 vs 6.44; p50.003). Nineteen individual species of mold higher on the neutrophils from patients with CF compared to CF-AC were identified in the referral group, as compared to 9 species in the control (P50.03). group. CONCLUSIONS: Blood neutrophil activation profiles are similar in CF, CONCLUSIONS: Patients referred by a physician for an environmental CF-AC and CF-ABPA patients, while the observed increased expression of assessment resided in homes with a higher mean number of viable fungal CCR3 on blood eosinophils from patients with CF-ABPA indicates the colonies. This is of uncertain clinical significance, with future studies systemic immunopathology of this complication, complements our previ- needed. ously described activation of blood basophils in CF-ABPA (ERJ accepted). All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. AB30 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2016

Prevalence of Sensitization to Mold Allergens in Is There a Temporal Relationship Between Outdoor 93 Patients with Respiratory Allergy 95 Alternaria alternata Spore Counts and Specific IgE Alternaria alternata Levels? Barbara Elizondo-Villarreal, Sandra N. Gonzalez-Diaz, MD, PhD, FAAAAI, Alfredo Arias-Cruz, MD, FAAAAI, Lucia Leal-Villarreal, Ma- Hani Hadi, MD1, Jay M. Portnoy, MD, FAAAAI1, Charles S. ria Del Carmen Zarate-Hernandez, MD, Dulce M. Rivero-Arias, Olga P. Barnes, PhD1, Vincent Staggs, PhD2; 1Division of Allergy & Immu- Monge Ortega, Jr, Jesus A. Ibarra-Chavez; UANL. nology, Children’s Mercy Hospitals and Clinics, Kansas City, MO, 2Chil- RATIONALE: Sensitization to fungi is recognized as a risk factor for dren’s Mercy Hospitals and Clinics, Kansas City, MO. exacerbations among patients with asthma diagnosis, however, its RATIONALE: Outdoor spore counts exhibit significant seasonal varia- contribution as a cause of allergic disease is still a subject of debate. The tion. We hypothesize a temporal relationship between outdoor Alternaria aim of this study is to know the fungal sensitization among patients spore levels and measured sIgE levels. consulted for respiratory symptoms in a tertiary center of allergy, as well to METHODS: Data on outdoor spore levels were collected for Alternaria assess the prevalence by diagnosis, type of fungi and age group. alternata between March and November, 1998 to 2012. Collections were METHODS: A retrospective study was conducted, obtaining data from made from a fifth floor rooftop in Kansas City. Spores were collected the records of skin tests of patients attended at an allergy center in with a Burkard device and slides read by NAB certified counters using Monterrey, Mexico, between January, 2010 and December, 2014. These the 12 traverse method in four hour increments. Patient Alternaria IgE SATURDAY tests included: Alternaria alternata, Helminthosporium sativum, blood levels were retrieved from a clinical laboratory database from Hormodendrum cladosporioides, Penicillium chrysogenum, Rhizopus nig- January 2000 to September 2012. IRB approval was obtained. We looked ricans, Aspergillus fumigatus. for a relationship for the time period 2000-2012. Patients with sIgE < 0.35 RESULTS: 5,325 skin test were performed. 877 (16.65%) were positive were excluded. Units of time were defined in weeks. for fungi. The most prevalent was Alternaria alternata with 5.4%. The Data was analyzed using SAS. Average weekly Alternaria counts and IgE highest prevalence was identified in the 0 – 10 years age group, with results were log-transformed. The logarithmic correlation between average 6.4%, followed by 3.5% in the 11 – 20 years age group. The most prevalent counts and sIgE were computed for the same week up to twelve weeks mold in patients with asthma was Alternatia alternata with 6.7%. prior. Twelve weeks was chosen as the cutoff, otherwise one would be in Aspergillus sensitization prevalence among patients with asthma was 3%. part of the season where measurements for three months would have CONCLUSIONS: The highest prevalence of sensitization was found in already been made. the 0 – 10 years age group. The most prevalent mold was Alternaria RESULTS: Correlation between weekly Alternaria spore levels and sIgE Alternata. levels ranged from -0.009 to +0.205 during the twelve week period. Alternaria counts 2 weeks prior exhibited a significant positive correlation Association of Aspergillus Monosensitization with (0.205) with subsequent positive sIgE levels (p <0.001). 94 Asthma and Rhinosinusitis CONCLUSIONS: There is a correlation between outdoor Alternaria counts two weeks prior and measured sIgE Alternaria levels. This 1 2 Julie T. Abraham, MD , Maria A. Barcena Blanch, MD , Roxana I. correlation may justify more rigorous studies to determine possible 3 1 2 Siles, MD ; Cleveland Clinic, Cleveland, OH, Cleveland Clinic Founda- association between Alternaria spore counts and sIgE levels. tion, Cleveland, OH, 3Cleveland Clinic. RATIONALE: Aspergillus fumigatus is a ubiquitous mold linked to Aerobiology of Yeasts: Viable Colonies and respiratory disease. Previous studies demonstrate conflicting results 96 Molecular Identification from Burkard Samples regarding asthma and rhinitis in patients sensitized to molds. We aim to identify the association of aspergillus monosensitization with severity and Josh D. McLoud, MS, Estelle Levetin, PhD, FAAAAI; University of control of asthma and rhinosinusitis. Tulsa, Tulsa, OK. METHODS: We performed a retrospective chart review of patients who RATIONALE: Various fungal spores are commonly identified microscop- underwent skin testing from 2012 to 2015. We included patients with ically on Burkard air samples; however, yeasts are not identified on these negative skin prick tests who underwent intradermal skin testing (IDST). samples. By contrast, yeast colonies commonly occur on culture-based air RESULTS: Out of 1467 randomly selected cases, 215 (154 females and 61 samples, but are seldom identified to genus or species. Since several yeasts males) met inclusion criteria and were grouped based on IDST: 1) negative are known allergens, their atmospheric concentrations should be elucidated. IDST (n593); 2) positive aspergillus only (n534); 3) other positive The current study was undertaken to develop molecular markers and inhalants (n588). Mean age was 52.0615.7 years. Overall asthma rate was methods for detecting the presence of yeast in atmospheric samples. 38.1% (29%, 56% and 41% respectively; p<0.05), with no significant METHODS: One-minute air samples for culturable fungi were collected difference in asthma severity between groups (p50.44). 79% of patients in weekly from February through July 2015 with a single-stage Andersen group 2 reported asthma control, compared to <50% in other groups sampler using malt extract agar. Cultures were identified by microscopy and (p50.06). Overall rhinosinusitis rate was 97.2% (98%, 94% and 98% colony morphology. Samples for molecular analysis were collected using a respectively; p50.46). 50% of patients in group 2 reported control of Burkard volumetric 7-day spore trap and DNA was extracted from samples rhinosinusitis, compared to 20% in other groups (p<0.05). There was no on four days. The molecular analysis included species-specific primers for statistical difference in rhinosinusitis control among patients in groups 1 Aureobasidium pullulans and Saccharomyces cerevisiae along with genus- and 3 (p50.97). specific primers for Rhodotorula. DNAwas amplified by conventional PCR. CONCLUSIONS: Monosensitization to Aspergillus was associated with RESULTS: During the 6 months of viable sampling, total yeast higher asthma rate, but not with increased asthma severity or control. concentrations varied from none on 6 February to 954 CFU/m3 on 22 Monosensitization to Aspergillus did not differ in the rate of rhinosinusitis, May, when yeasts were 47% of total colonies observed. Additionally, but was associated with better control compared to the other groups. Rhodotorula accounted for 777 CFU/m3 on May 22. Molecular markers detected the presence of Rhodotorula on the Burkard samples for all four days tested and Aureobasidium on three of the days. Saccharomyces cere- visiae was not detected on any of the tested samples. CONCLUSIONS: This molecular method using conventional PCR can determine the presence and identity of yeasts from Burkard samples. More work is needed to quantify and determine seasonal trends of these important allergens. All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. J ALLERGY CLIN IMMUNOL Abstracts AB31 VOLUME 137, NUMBER 2

Raining Mold? cadmium or folate levels at 24 months of age and risk of allergic or 97 respiratory diseases. CONCLUSIONS: Higher folate with lower cadmium levels during James J. Anderson, MLT1,2, G. Daniel Brooks, MD, FAAAAI3; 1Envi- pregnancy may contribute to increase the risk of AD in early childhood. ronmental Allergy, London, ON, Canada, 2Environmental Allergy/OSH- TECHINC, London, ON, Canada, 3The Asthma & Allergy Center, Prevalence of Respiratory Viruses in Patients with Omaha, NE. 99 Acute Respiratory Infections in Korea

RATIONALE: The spring seasons of 2013-2015 in Omaha NE were 1 2 2 2 warm and wet with frequent thunderstorms and heavy rains. The possible Jin-sung Park , Hee-Dong Jung , Hyang-Min Jung , Sung-Soon Kim , Chang-Keun Kim, MD, FAAAAI1; 1Asthma & Allergy Center, Inje Uni- effect on airborne fungal spores was studied. 2 METHODS: 24 hour Burkard spore trap samples (May-July of 2013, 2014, versity Sanggye Paik Hospital, Seoul, South Korea, Korea Centers for & 2015) were analyzed for fungal spore content. Local weather data and Disease Control and Prevention, Osong, South Korea. ‘‘weather events’’obtained from NOAA for the same time period were noted. RATIONALE: Acute Respiratory Infections (ARI) are the most common RESULTS: In mid-May of each year, mold spore levels rose quickly and infectious disease that caused significant morbidity and mortality with remained high through June and July. Very high mold counts (> than consequently an enormous economic burden. Since Dec 2005, Korea 50,000 spores/M3) were also recorded during the study period: 23 (2013, Centers for Disease Control and Prevention has been running surveillance 24 (2014), and 31 (2015). ‘‘Wet-weather’’ spora (ascospores & basidio- system KINRESS(Korea Influenza and Respiratory Virus Surveillance spores) were more abundant than air dry spora (Cladosporium & System) for the detection of major respiratory viruses. We investigated the Alternaria), but the latter were also well represented. Frequent rain events viral pathogen causing ARI in Korea, 2013. ranged from heavy rains to many hours of light rain or drizzle. METHODS: We performed multiplex PCR/RT-PCR on respiratory CONCLUSIONS: (1) Weather can have a profound effect on the amount specimen(throat oral nasal swab) to determine the prevalence of 14 viruses and type of airborne fungal spores: our NAB station recorded abundant including adenovirus(HAdV), parainfluenza virus(HPIV) 1, 2, 3, respira- amounts of wet-weather spora along with lesser but plentiful amounts of tory syncytial virus(HRSV) A and B, influenza virus(IFV) H1N1pdm09, dry air spora from May through July, 2013-2015. In contrast, we had H3N2, B, human coronavirus(HCoV) 229E, NL63 and OC43, human previously reported extraordinary amounts of Cladosporium & Alternaria rhinovirus (HRV), human bocavirus(HBoV) and human spores aerosolized over a one month period when ‘‘black corn’’ was metapneumovirus(HMPV). And the statistical analysis was performed to harvested after a severe drought. (2) Large amounts of both wet and dry air investigate the characteristics of age-distribution, seasonality, and clinical spora can be released over an extended period of time. (3) More research features of ARI patients. into ascospore and basidiospore allergy may be warranted. RESULTS: Respiratory viruses were detected by 49.4% of enrolled patients(n515,050), and 1-5 year-old age group accounted for almost. Role of Cadmium and Folate Levels in Risks of However, significant differences were not observed depending on the age group of virus detection rate. HAdV, HPIV, HRSV, HCoV, HBoV and 98 Allergic and Respiratory Diseases of Early SATURDAY Childhood: The Mothers and Children's HMPV were mainly detected from under 5 years old. IFV were mainly Environmental Health Study detected on over 6 years old. HRSV, IFV, HCoV infections were peaked in winter season. In summer, incidence of HPIV and HBoV were increased. Ja Hyeong Kim, MD1, Eun-Hee Ha, MD2, Hye sook Park, MD3, Mina When we analyzed the association of viral infection with clinical feature, Ha, MD4, Yun-Chul Hong, MD5, Jin-A. Jung, MD6, Yangho Kim, MD7; almost infections were correlated with fever, cough and runny nose. 1University of Ulsan College of Medicine, Ulsan University Hospital, Ul- CONCLUSIONS: Our data suggest that there was a meaningful relation- san, 2Department of Preventive Medicine, School of Medicine, Ewha ship between viral infection and typical manifestation of known clinical Womans University, Seoul, South Korea, 3Department of Preventive Med- feature as well as seasonality and age distribution. icine, School of Medicine, Ewha Womans University, Cheonan, South Ko- rea, 4Department of Preventive Medicine, Dankook University College of Medicine, Seoul, 5Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, South Korea, 6Dong-A University College of Medicine, Busan, South Korea, 7Department of Occupational and Environmental Medicine, University of Ulsan, Collage of Medicine, Ulsan University Hospital, Ulsan, South Korea. RATIONALE: Maternal diet affects offspring DNA methylation. However, the results for the effect of cadmium and folate status during pregnancy or childhood on development of allergic or respiratory disease are still unknown. METHODS: In total, 917 mother–child pairs from a prospective birth cohort in South Korea were studied. Data regarding the children’s allergic and respiratory outcomes were obtained from questionnaires by the mothers at postnatal months 6, 12, and 24. Serum cadmium and folate levels were measuredinthe mothers at mid-and late pregnancy, and intheir children at24 months of age. Atopic biomarkers were measured in the cord blood (CB) and at 24 months after birth. At 24 months data of 462 children were available. RESULTS: We compared the individuals of high folate with those of low folate. Individuals of high folate during had lower levels of cadmium (1.51 mg/L vs 1.44 mg/L, p<0.05 at mid pregnancy: 1.59 mg/L vs 1.56 mg/L, p<0.01 at late pregnancy). Higher folate (>_9.5 ng/mL) with lower cadmium (<1.5 mg/L) levels during mid pregnancy were associated with increased risk of AD at 24months of age (adjusted odds ratio [aOR] 0.36, 95% CI (0.14 to 0.95), p50.04. However there was no relationship between All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. AB32 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2016

Prescription of Adrenaline Injector to Outdoor Delay in Asthma Diagnosis and Risk of Common 100 Workers Who Had Experienced an Anaphylactic 102 Respiratory Infection in Young Children Reaction after a Hymenoptera Sting in Japan Mir Ali1, Elizabeth Krusemark2, Chung I. Wi, MD2, Sunghwan Masamitsu Tatewaki; Dokkyo Medical University Koshigaya Hospital, Sohn, PhD3, Hongfang Liu, PhD3, Euijung Ryu, PhD3, Young J. Juhn, Saitama, Japan. MD, MPH2; 1Sanford Children’s Hospital, Sioux Falls, SD, 2Dept of Pe- RATIONALE: Forestry and field workers who work outdoors are at high diatric and Adolescent Medicine, Mayo Clinic, Rochester, MN, 3Mayo risk of Hymenoptera stings and may develop occupation-related allergies Clinic, Rochester, MN. after being stung. We reported that approximately 40% of these workers RATIONALE: While asthma is associated with increased risk of respi- had specific IgE to Hymenoptera venom. However, clinical surveys of ratory infections, little is known about the impact of a delay in asthma Hymenoptera stings in the occupational setting and prescription of diagnosis on the risk of respiratory infections among young children. adrenaline injector to affected workers have rarely been reported. We METHODS: A random sample of a birth cohort (2011-2012) was enrolled surveyed outdoor workers in Japan who had experienced an anaphylactic for a retrospective study. Using predetermined asthma criteria, we defined reaction after a Hymenoptera sting to examine the rate of prescription of ‘‘delayed asthma diagnosis’’ if the asthma index date when the criteria was adrenaline injectors. first met regardless of physician diagnosis was 1 month or greater prior to a METHODS: Questionnaires on Hymenoptera stings were completed by physician diagnosis of asthma. History of Streptococcal pyogenes upper SATURDAY 1353 male forestry and field workers, and 365 (231 men, 134 women) respiratory infection and tympanostomy tube insertion (a proxy of office workers who acted as controls between July and November 2009. recurrent and persistent otitis media) and availability of asthma medica- Among the participants, 294 had experienced anaphylaxis after a tions were evaluated in relation to a delay in asthma diagnosis. Hymenoptera sting. RESULTS: Among 150 subjects, 53% were male, 95% Caucasian, and RESULTS: Among the subjects, 184, 25, 24, and 61 had experienced median age at the last follow-up date was 2.8 years (IQR: 2.6-3.1). Thirty- anaphylaxis of Mueller grade 1, 2, 3, and 4, respectively. Toxic systemic eight subjects (25%) met the criteria for asthma, of whom 29 (76%) had reactions due to multiple Hymenoptera stings were excluded from the delayed asthma diagnosis (median delay: 1.7 year). Children who had analysis. A prescription of an adrenaline injector was given to only 45 delayed asthma diagnosis tend to have less prescription for any asthma (24%) subjects who had experienced grade 1 anaphylaxis, 7 (28%) who medication compared to those who did not (median number of dispensing: had grade 2, 2 (8%) who had grade 3, and 16 (26%) who had grade 4. These 0.6 vs 2.0 per year, p50.10). All subjects with tympanostomy tube results indicate that a prescription of adrenaline injector was given to only insertion (n59) and/or Streptococcal infection (n54) had delayed asthma 20% of subjects who had experienced an anaphylactic reaction after a diagnosis. Hymenoptera sting in Japan. CONCLUSIONS: A significant proportion of children have delayed CONCLUSIONS: Adrenaline injectors should be prescribed to Japanese asthma diagnosis, which might limit access to preventive and therapeutic forestry and field workers who work outdoors and have experienced interventions for asthma potentially resulting in the increased risk of anaphylaxis due to a Hymenoptera sting. common respiratory infections during early childhood. Future studies with a larger sample-size needs to replicate our findings. A Two Pronged Approach to the Detection of 101 Cimex Lectularius (common bed bug) Using Novel Bed Bug Proteins

Natasha Gordon, PhD1, Luke O’Shaughnessy, PhD1, David Fitzpatrick, PhD2, Sean Doyle, PhD2, Bruce Mitchell, MD1; 1airmid healthgroup ltd, Dublin, Ireland, 2Maynooth University, Maynooth, Ireland. RATIONALE: The exponential increase of Cimex lectularius (common bed bug) infestations in households, schools and businesses has resulted in major problems for home owners and the hospitality industry. The devel- opment of immunoassays to identify the presence and extent of the infes- tation has been made possible by the production of monoclonal antibodies to two major proteins. METHODS: Proteomics of whole bed bug lysates using a transcriptome compiled database identified 2 novel proteins of interest which have not been previously characterised. Monoclonal antibodies were raised and screened for cross reactivity and specificity to bed bugs and a range of household insects. A number of antibody based detection assays have been developed. RESULTS: 225 bed bug proteins were identified via proteomic analysis, two novel bed bug proteins were selected for development into antibody based detection assays. The first, bed bug protein 1 (BBP1) is derived from the exoskeleton and is evident in all stages of the bed bug life cycle while the second is exclusively found in the egg shell (Egg shell protein). The monoclonal antibodies raised against both proteins exhibit high sensitivity and have a LOD of one bed bug and one egg. CONCLUSIONS: Novel bed bug proteins have been identified and used to develop antibody based detection assays. These assays identify different life stages allowing a broad approach to both bed bug detection and the monitoring of eradiation methodologies. All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. J ALLERGY CLIN IMMUNOL Abstracts AB33 VOLUME 137, NUMBER 2

Prevalence of Sensitization to Airborne Allergens Supplementation with the Antioxidant 103 Among Elderly Population 105 Sulforaphane Does Not Protect Airway Epithelium Against O3-Induced Injury In Vivo Adile Berna Dursun1, Filiz Mercantepe2, Vehbi Ayhan2; 1Recep Tayyip Erdogan University, School of Medicine, Rize, Turkey, 2Recep Tayyip Er- Michelle L. Hernandez, MD1, Katherine Mills, BA2, Allison J. Bur- dogan University School of Medicine, Rize, Turkey. bank3, Matthew J. Kesic, PhD4, Charity Duran, PhD3, David B. Peden, RATIONALE: Although the elderly population steadily increasing in all MD, MS, FAAAAI5; 1University of North Carolina at Chapel Hill School over the world, there is limited data on the prevalence of atopic of Medicine, Chapel Hill, NC, 2University of North Carolina Chapel Hill sensitization in this population. The aim of the study is to investigate the School of Medicine, Chapel Hill, NC, 3UNC School of Medicine, Chapel prevalence of atopic sensitization in elderly subjects. Hill, NC, 4Methodist University, Fayetteville, NC, 5Office #544, Campus METHODS: The study investigates the patients of third level adult allergy Box 7310, University of North Carolina at Chapel Hill School Medicine, outpatient clinic in one year and compares the elderly population with the NC. rest of the population. The study population consisted of 82 (F/M: 56/26) RATIONALE: Airway epithelial cell injury is the initial event in ozone _ _ subjects aged >60 years and 954 (F/M: 679/275) subjects aged <60. (O3)-induced inflammatory responses. Oral supplementation with sulfo- Sensitization was determined by using skin prick test with common raphane (SFN), an antioxidant compound derived from broccosprouts, up- airborne allergens (house dust mite-HDM; molds, animal dander, tree- regulates expression of NRF2-regulated antioxidant enzymes in airway grass-weed pollens). epithelial cells at baseline. We hypothesized that antioxidant supplementa-

RESULTS: The mean age of the elderly population is 66.560.63 (60-81) tion can decrease O3-induced inflammation by modulating epithelial cell year and the most common reasons for the admission of them are chronic antioxidant gene expression in vivo. nasal symptoms, generalized pruritus and suspicion of drug allergy. METHODS: Thirteen healthy volunteers completed a double-blinded, Prevalence rate of atopic sensitization is 61% in the elderly population placebo controlled crossover study where they consumed either SFN-rich whereas the rate is 75.3% in subjects aged <60y. There is female broccosprout homogenate (BSH) vs alfalfa sprout homogenate (placebo). predominance in older atopic subjects (661% of F vs 50% of M), but not After 3 days of daily supplementation, they underwent a 2-hour 0.4 part per

in younger ones (75.8% of F vs 76.1% of M). Polysensitization is mostly million O3 exposure. Plasma levels of SFN and its major metabolites, determined in subjects with chronic nasal symptoms in both populations. Sulforaphane-N-acetylcysteine (NAC) and Sulforaphane-Glutathione Twenty-two percent of elderly subjects are sensitized to HDM, 17.1% to (GSH) were obtained. We assessed changes in nasal epithelial cell weed pollen, 15.9% to Cladosporium, 13.3% to grass pollen and 12.2% to mRNA expression of NRF2 and the NRF2-regulated antioxidants

birch pollen. Sensitization to animal dander is higher in elderly subjects (GSTM1, GSTP1, NQO1, and HO1) four hours after the O3 exposure. than younger ones (12% vs 7.5%). The effect of BSH v. placebo was compared by paired T-test. CONCLUSIONS: Atopic sensitization should not be underestimated in RESULTS: Three days of supplementation with BSH significantly subjects aged >_60 years. increased levels of SFN (p50.001) and its major metabolites, SFN-NAC

(p50.002) and SFN-GSH (p<0.001) compared to placebo. Despite these SATURDAY Eosinophilic Bronchitis Caused By Exposure to increases in SFN and metabolite levels, we did not see a significant 104 Wheat Flour in the Workplace difference in post-O3 nasal epithelial cell mRNA expression of NRF2 or NRF2-regulated antioxidant genes between placebo v. BSH treatment. Olga Vega Matute, MD, Marta M. Ferrer, MD, PhD, FAAAAI, Carmen CONCLUSIONS: BSH supplementation successfully increased periph- M. Damelio, MD, Amalia Bernad, MD, Roselle Catherine Yu Madamba, eral blood levels of SFN and its major metabolites in healthy volunteers. Gabriel Gastaminza, MD, PhD; Department of Allergy and Clinical However, supplementation with BSH does not confer protection against O3 Immunology Clinica Universidad de Navarra, Spain. -induced changes in airway epithelial cell oxidative stress in vivo. RATIONALE: eosinophilic bronchitis (EB) is characterized by cough, eosinophilia detectable in the sputum and responsive to corticosteroids, without airway hyperresponsiveness. Here, we described the case of a patient who developed eosinophilic bronchitis caused by wheat flour in her workplace. METHODS: skin prick test (SPT) to flours, chest computed tomography (CCT), spirometry, fraction of exhaled nitric oxide (FeNO), bronchial challenge with methacoline (BCM), expiratory peak-flow (EPF) and eosinophil count in sputum (ECE) basal and after challenge test (CT) were performed. RESULTS: we present a 30 year old, female, smoker, working in the laboratory of a flour factory for 3 years. She has had itchy eyes, rhinorrhea and cough, with minimal expectoration, without wheezing for two months. Improved when she was treated with steroids, symptoms reappeared when discontinued. Asymptomatic during holidays. Evaluation was done during her 1 week of sick leave. Lung auscultation, CCT, spirometry, FeNO, BCM and ECE were normal. She had only one positive SPTwith semolina. A CT was performed by passing the semolina, from her factory, from one tray to another; tracking the EPF and serial spirometries, presenting cough, without fall in FEV1 values and normal EPF. But after 4 to 5 days, she presented variability in the EPF with continuous cough. 7 days post CT, we repeated the ECE detecting 5% eosinophils. BCM was negative at all times. ECE was repeated while she was away from her job with only 1% eosinophils seen. CONCLUSIONS: we report an unusual of EB caused by wheat flour exposure in the workplace. All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. AB34 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2016

The Relevance of Residential Environment to (p50.001 in 13–14-years-old boys and p50.02 in 16–17-years-old boys). 106 Atopy Prevalence Based on Skin Prick Test in However, there was no significant association between mean annual UVin- Rural Community Cohort in Korea dex and the prevalence of current eczema for girls in all three age-groups. CONCLUSIONS: UV index was significantly associated with the Eun-Jin Kim, PhD1, Dankyu Yoon2, Hye-Sun Lim3, Jeom-Kyu Lee4, Joo prevalence of current eczema in boys, but not in girls. This study was Shil Lee, PhD5; 1Division of Allergy and Chronic Respiratory Diseases, supported by the Health and Labour Sciences Research Grant for Research Department of Biomedical Sciences, Korea National Institute of Health, on Allergic Disease and Immunology from the Ministry of Health, Labour Osong Health Technology Administration Complex, Osong, South Korea, and Welfare, Japan. 2Korea Institute of Health, South Korea, 3Korea National Institute of Health, South Korea, 4Korea National Intitute of Health, South Korea, Occupational Contact Urticaria to Cow's Milk in 5National Institute of Health, Seoul. 108 the Absence of Cow's Milk Allergy in a RATIONALE: Atopic sensitization varies among countries but it has not Cheesemaker

known what kinds of factors are critical for it, although various things are 1 2 3 supposed to be important element such as age, obesity, lifestyle, allergen. Claire Mailhol , Anne Marie Rabain , Julie Herry , Alain Didier, MD PhD4; 1Department of Pulmonology and Allergology, Toulouse cedex 9, Especially, it is considered that residential environment, such as urban or 2 3 rural area may have an effect on sensitization. Thus we evaluated the France, Department of Pulmonology and Allergology, Department of

SATURDAY distributions of atopy prevalence in rural community cohort in Korea. Occupational Medicine, Fabienne Cantrelle-Mathat, Cabinet medical 4 ^ 4 METHODS: Skin Prick Test for 12 common allergens were performed on boulevard Pierre Benoıt, Rodez, France, Larrey Hospital, CHU, Tou- 1,730 persons aged 7 to 82 from the general population. Atopy was defined louse, France. as sensitization to at least more than 1 allergen. Allergic diseases were RATIONALE: Most cases of cow’s milk allergy (CMA) in adults have defined as a history of asthma, allergic rhinitis or atopic dermatitis persisted from childhood. In the literature, contact urticaria to cow’s milk is diagnosed at any point in the lifetime. MBPT was also examined for mostly associated with CMA. Here, we describe a case of isolated allergic asthma diagnosis by physician. Statistical analysis was conducted occupational contact urticaria to cow’s milk. by R statistics software. METHODS: Skin prick tests (SPTs) were performed with fresh cow’s RESULTS: Of 1,730 subjects, 57.6% was female (n5996). Age range was milk-derived products. Specific IgE (sIgE) assays were performed using 60.15615.06. Asthma prevalence was 3.5% and the average of atopy the ImmunoCAP system (Thermofisher Scientific, Sweeden). prevalence was 24.5%. The most common sensitizing allergen was Der f RESULTS: A 35-year-old patient with a history of atopy had worked as a (14.5%) and Der p (11.3%) in all age group. The highest atopy prevalence cheesemaker (using cow’s milk) for 3 years. He developed severe urticaria was shown at teenagers (58.5%). on the arms and neck following direct or indirect contact with dairy CONCLUSIONS: Atopy prevalence showed various range with age in the products that he handled at work. Most recently, he developed eczema on community It was supposed that household income, education level and the back of the forearms at the end of a working week. Skin disorders old age may affect atopy prevalence. Comparing with previous nationwide always resolved during vacations. SPTs with fresh cow’s milk, whey, butter study, the prevalence of asthma was relatively low. Further investigation is and cream were all positive. SIgE assays were positive for c cow’s milk needed for urban area with broad ranges of age to give clues for residential (56.70 kUA/l) and its components alphalactalbumin (1.35 kUA/l), environments effect on atopic sensitization. betalactoglobulin (36.40 kUA/l) and casein (23.40 kUA/l). The patient reported that his consumption of dairy products never triggered the Ultraviolet Index Is Associated with the symptoms of food allergy. This was confirmed by a negative oral challenge 107 Prevalence of Eczema in Boys test with 298 ml of fresh cow’s milk. CONCLUSIONS: To the best of our knowledge, this is the first ever report Koichi Yoshida, MD1, Mari Sasaki, MD1, Yuichi Adachi, MD, PhD2, Emi of occupational contact urticaria to cow’s milk in the absence of CMA and Kawaguchi, MD3, Masayuki Akashi, MD4, Yukihiro Ohya, MD, PhD5, including component-resolved exploration. The present case demonstrates Hiroshi Odajima, MD, PhD6, Akira Akasawa, MD, PhD1; 1Division of Al- that food allergy and sIgE-positive skin allergy operate through different lergy, Tokyo Metropolitan Children’s Medical Center, Tokyo, Japan, pathways. 2Department of Pediatrics, University of Toyama, Toyama, Japan, 3Clin- ical Research Support Center, Tokyo Metropolitan Children’s Medical Center, Tokyo, Japan, 4Department of Pediatrics, Saitama City Hospital, Saitama, Japan, 5Division of Allergy, National Center for Child Health and Development, Japan, 6Fukuoka National Hospital, Fukuoka, Japan. RATIONALE: Although climate conditions have been reported to be related with childhood eczema, the relationship between ultraviolet (UV) and eczema is not fully understood. Our aim was to assess the association between UV index and the prevalence of childhood eczema. METHODS: Data from the 2008 nationwide, cross-sectional, question- naire-based survey in Japan was analyzed. In this survey, children in three age groups (6–7-year-old, 13–14-year-old and 16–17-year-old) were selected from a random sample of schools from all 47 prefectures. UV index of each prefecture was acquired from the data of the Japan Meteorological Agency, and was categorized into quartiles. RESULTS: Of the179, 218 children recruited, 149,464 replied to the questionnaire. After omitting incomplete data, 138,128 were analyzed. Even after adjusted for confounders including climate factors, the prevalence of current eczema in 6–7-year-old boys in prefectures with the third- and highest-quartile mean annual UV index were significantly lower compared to that with the lowest-quartile (p50.01 and p<0.001). In adolescents, the prevalence of current eczema in the highest-quartile was significantly lower compared to those with the lowest-quartile for boys All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. J ALLERGY CLIN IMMUNOL Abstracts AB35 VOLUME 137, NUMBER 2

Hymenoptera Venom-Induced Anaphylaxis in were less severe than the first one, with a statistically significant difference 109 Acute Care Settings (p-value50.031). CONCLUSIONS: Our study confirmed importance of an early identifi- Stephanie Eng, MD1,2, Magee L. DeFelice, MD1,2; 1Thomas Jefferson cation of those workers at risk for HVA,through an detailed clinical history, University Hospital, Philadelphia, PA, 2Nemours/A.I duPont Hospital during healthcare surveillance. Competent Physician should be possibly for Children, Wilmington, DE. supported by an allergist, for appropriate diagnostic procedures and RATIONALE: Anaphylaxis is a severe, potentially life-threatening prescription of VIT. Moreover, it would be very important to improve allergic reaction. Venom-induced anaphylaxis can be especially worker’s ability to manage an acute event on workplace, by specific dangerous, and patients are typically seen in acute care settings when training courses, especially when occupational risk is recognized. systemic reactions occur. Elevated tryptase levels can be used to support the diagnosis of anaphylaxis when obtained within a few hours of symptom Value of Basophil Activation Test for Evaluating onset. For patients with venom allergy, immunotherapy significantly 111 Immediate Reactions to Proton Pump Inhibitors

decreases the risk of recurrent systemic reactions. Studies examining 1 2 physician recognition and management of anaphylaxis due to hymenoptera Maria Salas, MD, PhD , Esther Barrionuevo, MD, PhD , Inmaculada Dona,~ MD, PhD3, Oliver Munoz-Daga~ 4, Francisca Gomez, MD, PhD1, venom are underrepresented in the primary literature. 5 5 METHODS: An electronic case-based survey describing a child experi- Tahia D. Fernandez, PhD , Adriana Ariza, PhD , Maria Isabel ~ 5,6 5,7 encing venom-induced anaphylaxis was completed by physicians in acute Montanez, PhD , Cristobalina Mayorga, PhD , Miguel Blanca, MD, 8,9 2 1 care settings. PhD , Marıa Jose Torres, MD, PhD ; Allergy Unit, IBIMA-Regional 2 RESULTS: There were 45 total participants, with backgrounds in University Hospital of Malaga, Malaga, Spain, Allergy Unit, IBIMA, Regional University Hospital of Malaga, UMA, Malaga, Spain, 3IMABIS emergency medicine, urgent care, and primary care. 20% (9/45 physicians) 4 elected not to treat with epinephrine and 24.4% (11/45) did not refer the Foundation, Malaga, Spain, 1Allergy Unit, Regional University Hospital of Malaga-IBIMA, UMA, Malaga, Spain, 5Research Laboratory, IBIMA- child to an allergist. Of the 36 physicians (80%) who treated with 6 epinephrine, 13.9% (5/36) responded that the patient was either not Regional University Hospital of Malaga-UMA, Malaga, Spain, BIO- experiencing anaphylaxis or they were unsure. Less than 1% of physicians NAND-Andalusian Centre for Nanomedicine and Biotechnology, Spain, 7 (3/45) elected to obtain a tryptase level. While 75.6% (34/45) of responders Allergy Unit, IBIMA-University Hospital of Malaga, Malaga, Spain, 8 9 referred the patient to allergy, 57.8% (26/45) did not know the patient Allergy Service, Carlos Haya Hospital, Malaga, Spain, Allergy Unit, should start venom immunotherapy despite positive testing confirming IBIMA, Regional University Hospital of Malaga, UMA, Malaga, Spain. hymenoptera allergy. RATIONALE: Proton pump inhibitors (PPI) are widely used and although CONCLUSIONS: There is a need for additional education regarding allergic reactions to them are rare, the incidence has increased in recent recognition and treatment of anaphylaxis induced by hymenoptera venom, years. Most publications describe isolated cases and limited data are which can be particularly life-threatening. Moreover, increased awareness available about the value of skin tests. Therefore, the diagnostic approach is the drug provocation test (DPT), which is not risk free given that reactions of the utility of tryptase levels in the acute setting and the indications for SATURDAY venom immunotherapy is critical for the proper care of patients with can be severe. The aim of the study was to assess the value of the basophil hymenoptera-induced anaphylaxis. activation test (BAT) for the diagnosis of immediate allergic reactions to PPI. Observational Study in Patients with Hymenoptera METHODS: We evaluated 20 patients with confirmed immediate allergic 110 Allergy: Role of Occupational Exposure, Allergen reactions to PPI. Patients with anaphylaxis or shock were diagnosed by Immunotherapy, and Indications for Prevention clinical history, once other possible causes were ruled out, and those with urticaria by DPT. BAT with omeprazole, lansoprazole, and pantoprazole Alessandra Toletone1, Susanna Voltolini, MD2, Donatella Bignardi2, were performed in all patients and in 14 subjects with good tolerance to Paola Minale2, Costantino Troise, MD3, Giovanni Passalacqua, MD4, PPI. Guglielmo Dini5, Emanuela Massa1, Alessio Signori1, Paolo Durando1; RESULTS: The PPIs involved were omeprazole (N518) and lansoprazole 1Department of Health Sciences, Postgraduate School in Occupational (N52). A total of 11 cases (55%) reported anaphylaxis, 7 (35%) Medicine, Genoa, Italy, 2Allergy Unit, Genoa, Italy, 3Allergy Unit, Gen- anaphylactic shock and 2 (10%) urticaria. BAT was positive in 16 cases ova, Italy, 4Allergy and Respiratory Diseases, IRCCS San Martino Hospi- (66.66%): 13 (81.25%) to omeprazole, 6 (37.5%) to pantoprazole and 2 tal-IST-University of Genoa, Italy, 5Department of Health Sciences, (12.5%) to lansoprazole. No differences were found in the time between iostatistics Unit, Genoa, Italy. the reaction and the study comparing those patients who gave a positive RATIONALE: Sensitization to hymenoptera venom can cause important BAT results and those who were negative. BAT specificity was 78.57%. consequences on occupational activity, such as the modification of capacity CONCLUSIONS: Immediate hypersensitivity reactions to PPI do occur, to work, or abandonment of job, because of the risk or life-threatening with omeprazole being the drug most frequently involved and anaphylaxis allergic reactions which may occur. Aim of this study was to describe role the most common clinical entity. BAT is a useful method for diagnosing of occupational exposure to hymenoptera stings at work, and to assess these patients. effect of Venom Immunotherapy (VIT) in reducing severity of allergic episodes in workers exposed to repeated stings. METHODS: We conducted an observational prospective study including patients referred to our Units between 2000 and 2013, with an ascertained diagnosis of hymenoptera venom allergy, and treated with VIT. Reactions were graded according to standard system, at initial presentation and after re-stings when receiving VIT. RESULTS: 184/202 patients had a complete data set. In 17.4% of patients, allergic reaction occurred during work activities, in all cases outdoor. Patients (mean age 56616.2 years) were diagnosed as having HVA and prescribed with VIT. Out of them 31.5% previously stung by hymenoptera on work, were re-stung at workplace during VIT. The reactions at re-sting All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. AB36 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2016

Evaluated the Diagnostic Utility of Interferon- Additionally, we calculated sensitivity, specificity, positive predictive 112 Gamma Enzyme-Linked Immunospot (ELISPOT) value (PPV), negative predictive value (NPV), and likelihood ratios for Assays in 117 Patients with Non-Immediate Drug skin tests and oxaliplatin-specific IgE. Hypersensitivity Reactions RESULTS: 74 oxaliplatin-reactive patients were assessed. 41 (55%) patients underwent DPT. 59% of all DPTs were negative. Only one patient Suda Punrin1,2, Pattarawat Thantiworasit, MSc1, Pungjai Mongkolpa- suffered a severe reaction during DPT. thumrat3, Jettanong Klaewsongkram, MD4,5; 1Division of Allergy and Sensitivity for oxaliplatin-specific IgE (0.35UI/L cut-off point) was 34%, Clinical Immunology, Department of Medicine, Faculty of Medicine, Al- specificity 90.3%, PPV 85%, NPV 45.9%, negative likelihood ratio 0.7 and lergy and Clinical Immunology Research Group, Chulalongkorn Univer- positive likelihood ratio 3.5. sity, Bangkok, Thailand, 2Queen Saovabha Memorial Institute, The Thai CONCLUSIONS: DPT is of vital importance as a diagnostic tool for Red Cross Society, Bangkok, Thailand, 3King Chulalongkorn Memorial excluding oxaliplatin hypersensitivity (59% were negative) and therefore Hospital, The Thai Red Cross Society, Bangkok, Thailand, 4Chulalong- avoiding desensitization to non-hypersensitive patients. korn University, Faculty of Medicine, Department of Medicine, Division Whenever positive, skin tests and oxaliplatin-specific IgE could be useful of Allergy and Clinical Immunology, Chulalongkorn Allergy and Clinical to confirm oxaliplatin hypersensitivity. Immunology Research Group, Bangkok, Thailand, 5King Chulalongkorn Whenever negative, skin tests and oxaliplatin-specific IgE seem less useful Memorial Hospital, Thai Red Cross Society, Thailand. and need DPT to achieve a diagnosis. SATURDAY RATIONALE: To evaluate the diagnostic utility of Interferon (IFN) -gamma Enzyme-linked Immunospot (ELISPOT) assay in non-immediate Determining Non-Irritating Concentration for drug hypersensitivity reactions (DHR). 114 Intradermal Skin Test with Commonly Prescribed METHODS: Medical records of patients who were diagnosed non- Antibiotics in Korean Adults

immediate DHR and underwent ELISPOT at our hospital between 2012 1,2 1,3 1,2 and 2015 were retrospectively examined. Ha Kyeong Won , Min-Suk Yang, MD, PhD , Woo-Jung Song, MD , Yoon-Seok Chang, MD, PhD1,4, Sang Heon Cho, MD, PhD1,2, Heung- RESULTS: Total 117 individuals were included (mean age 53 years, range 1,2 1,2 1 7-97), most were in-patients. Sixty-six (56.4%) were female. Thirty Woo Park, MD, PhD , Kyung-Up Min, MD, PhD ; Department of In- ternal Medicine, Seoul National University College of Medicine, Seoul, (25.6%) were immunocompromised. One-third concurrently received 2 systemic corticosteroids. For the clinical entities, 46(39.3%) subjects South Korea, Institute of Allergy and Clinical Immunology, Seoul Na- tional University Medical Research Center, Seoul, South Korea, 3SMG- experienced severe cutaneous adverse reactions and 43(36.8%) had 4 maculopapular exanthems (MPE). In the majority of cases, ELISPOT SNU Boramae Medical Center, Seoul, South Korea, Department of Inter- was performed with multiple implicating medications simultaneously and nal Medicine, Seoul National University Bundang Hospital, Seongnam, within a month after symptom onset. Number of drug-specific IFN-gamma South Korea. secreting cells was analyzed by incubating PBMCs with culprit or RATIONALE: Although the data on validity of skin test with drugs expect alternative drugs, and more than 20 spot-forming cells/106(PBMCs) was for penicillin is still scarce, positive skin reaction at non-irritating considered positivity. Entirely, sixty-nine agents had been tested. concentrations with relevant history is generally accepted for diagnosis Majority were antibiotics, allopurinol, anticonvulsants, anti-tuberculosis, of drug allergy. In this study, we intended to exam the maximal non-irritant non-steroidal anti-inflammatory drugs (NSAIDs) and radiocontrast media. drug concentrations for intradermal skin test in Korean adults. Among those investigated, 45(38.5%) patients yielded a positive test. METHODS: Sixty one healthy volunteers were recruited. Seventeen Proportion of positive outcomes was 62.5% in acute generalized exan- parenteral antibiotics including beta-lactams and fluoroquinolones were thematous pustulosis, 50% in acute interstitial nephritis, 41.8% in MPE, evaluated. Skin tests were performed by two steps with antibiotics as 40.0% in drug rash with eosinophilia and systemic symptoms and drug- following; A) Intradermal skin test by using full strength concentration of induced hepatotoxicity, 35.2% in Stevens-Johnson syndrome, 33.3% in each drug and, if the result was positive, serially diluted concentration till delay urticaria and angioedema, 25% in fixed drug eruption, and 16.7% the result was negative; B) Confirming the concentration on step A in 20 in toxic epidermal necrolysis. Subsequently, 41(35%) persons underwent more subjects. All subjects were allowed to participate in multiple testing drug provocation test. Of which resulted in the sensitivity, specificity, pos- using different drugs. itive predictive value, negative predictive value of 50%, 95.1%, 77.8% and RESULTS: The mean age of the subjects is 35.0 and females are more than 84.8%, respectively. males (77%). Both previous drug concentrations based on literatures and CONCLUSIONS: IFN-gamma ELISPOT could be potentially applied in the results of this study are reproducible in ampicillin/sulbactam, management of DHR. aztreonam, ciprofloxacin, clindamycin, nafcillin and penicillin G. Only ceftriaxone among the cephalosporins showed the same result as the Diagnostic Tests in Hypersensitivity to Oxaliplatin previous value. In addition, the discrepancy between previous known 113 Beyond Clinical History concentrations and the values of this study is more 10-fold and over in azithromycin, levofloxacin, meropenem, piperacillin/tazobactam, SMT/ Paula Lopez-Gonzalez, MD, Ricardo Madrigal-Burgaleta, MD, Pilar TMP, and vancomycin. Inter-individual variability of the skin test results Berges-Gimeno, PhD, Emilio Solano-Solares, MD, Laura Carpio- using cefotetan, azithromycin, and vancomycin was more than 100-fold Escalona, MD, Emilio Alvarez-Cuesta, MD, PhD; Ramon y Cajal Univer- range. sity Hospital, Madrid, Spain. CONCLUSIONS: To improve the reliability of skin test, study with the RATIONALE: Drug provocation test (DPT) with oxaliplatin is consid- numerous subjects would be necessary to standardize non-irritating drug ered in some review articles but previous works do not clearly show data concentration for skin test. about DPT with this drug. Our objective is to assess the usefulness of including DPT as an important diagnostic tool in oxaliplatin hypersensitivity. METHODS: A prospective, observational, longitudinal study was carried out including patients who, during a 3-year period, had suffered a hypersensitivity reaction to oxaliplatin at the Ramon y Cajal University Hospital and had been referred to our Allergy Division’s Desensitization Program. All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. J ALLERGY CLIN IMMUNOL Abstracts AB37 VOLUME 137, NUMBER 2

The Effect of Penicillin Allergy Testing on Future Safety of Two-Step Graded Challenges to Beta- 115 Healthcare Utilization and Morbidity: A Case- 117 Lactams Using a Single-Blinded Placebo- Control Study Controlled Protocol

Eric M. Macy, MD, FAAAAI1, Yu-Hsiang Shu, MS, PhD2; 1SCPMG Melissa Iammatteo, MD1, Denisa Ferastraoaru, MD, MSc2, Santiago Department of Allergy, 2Kaiser Permanente Southern California. Alvarez Arango, MD3, Niharika Thota, MD3, Ayobami Akenroye, MD, RATIONALE: The effect outpatient penicillin allergy testing has on MPH3,ElinaJerschow,MD,MSc1; 1Albert Einstein College of Medicine/ future healthcare utilization (HU) and morbidity is unknown. Montefiore Medical Center, Bronx, NY, 2Albert Einstein/Montefiore Medical METHODS: HU and morbidity in 500 penicillin allergic cases, only 8 Center,Bronx,NY,3Albert Einstein College of Medicine, Bronx, NY. penicillin allergy test-positive, seen from 6-8-2010 to 3-29-2012, were RATIONALE: Graded challenges are performed to exclude immediate compared to non-tested controls. Five penicillin allergic controls were hypersensitivity reactions. Weaimed tovalidate the safety of two-step graded matched to each case by gender, age, weighted Charlson comorbidity index challenges (test doses) by comparing the reaction rate of two-step challenges (CCI), and outpatient office visits during a 2-year lead-in period. Hospital with placebos in patients with a negative skin test to beta-lactams. days, new drug allergies, and antibiotic exposures were determined over a METHODS: We performed a five-year retrospective chart review of all 36 to 62 month follow-up period. patients who underwent single-blinded placebo-controlled two-step chal- RESULTS: Cases had a mean (95% CI) lead-in CCI of 1.65 (1.44–1.87) lenges to beta-lactams in an outpatient setting. and 13.73 (12.76–14.7) outpatient visits per year of healthplan coverage RESULTS: Between 2010 and 2015, 154 patients underwent 162 (YHC). Controls had a mean lead-in CCI of 1.7 (1.6–1.8) and 12.08 challenges to beta-lactams. The majority of patients was female (81.2%) (11.69–12.47) outpatient visits per YHC. For cases, hospital days per YHC with a mean age of 51.4 years (SE 61.5). All challenges were preceded by increased significantly less than for control subjects, 1.62 (1.13–2.11) to negative skin testing and most (98%) were preceded by placebo. Reactions 2.16 (1.00–3.31) [133%] versus 0.73 (0.59–0.87) to 2.02 (1.43–2.61) to placebo occurred in 11.3% of challenges (n518) and to beta-lactams in [277%], (p < 0.0001). Antibiotic courses per year fell significantly more in 6.2% (n510). Patients who reacted to placebos were female (100%, cases, - 0.85 versus -0.62, (p 5 0.0212). Cases had significantly fewer p50.04) and more likely to have a history of multiple reported drug al- new drug allergies at the end of the follow-up period, +0.044 versus +0.18, lergies: 4.6 (SE 60.9) vs. 2.5 (SE 60.5) drug allergies in those who reacted (p < 0.0001). The top 5 antibiotics cases were exposed to were penicillins, to medication (SE 60.5) vs. 2.4 (SE 60.1) drug allergies in those who had 1st generation cephalosporins, quinolones, tetracyclines, and macrolides no reaction (p<0.01). The majority of all reactions was mild and subjective versus macrolides, quinolones, clindamycin, 1stgeneration cephalosporins, (n524/28, 86%) with spontaneous resolution (n5 25/28, 89%). Reactions and tetracyclines for controls. to placebos included pruritus (n512), sensation of throat tightness (n52), CONCLUSIONS: Penicillin allergy testing was associated with a smaller and hives (n51). Reactions to medications included pruritus (n54), increase in hospital days, a greater fall in antibiotic usage, fewer new drug tingling (n53), and fatigue (n53). No anaphylactic reactions occurred. allergies, and significantly less macrolide, quinolone, and clindamycin CONCLUSIONS: This study validates the safety of two-step challenges

exposure over the next 3 to 5 years. to beta-lactams. Since a greater number of reactions occurred to placebo SATURDAY rather than to beta-lactams, it is likely that some reactions are not due to The Effect of a Penicillin Allergy Algorithm on drugs. 116 Perioperative Antibiotic Choice Amoxicillin Challenges in Marine Recruits Joseph A. Grillo, MD1, Karen Ravin, MD2, Magee L. DeFelice, MD3; 118 Reporting Penicillin Allergy 1Nemours A.I. du Pont Hospital for Children, Wilmington, DE, 2Nem- ours/A.I. duPont Hospital for Children, 3Nemours/A.I duPont Hospital Jeremy D. Waldram, MD1, Mark H. Tucker, MD2; 1Scripps Clinic, San for Children, Wilmington, DE. Diego, CA, 2Naval Branch Health Clinic, Bonita, CA. RATIONALE: Cephalosporins are the preferred medications for periop- RATIONALE: Marine recruits commonly report a beta lactam allergy erative antimicrobial prophylaxis. Due to the potential risk of cross- upon arriving to boot camp. This has significant implications during and reactivity between penicillins and cephalosporins, alternatives such as after recruit training, but logistics typically prevent evaluation. clindamycin are often administered to patients who report penicillin METHODS: Over a 13 month period, 244 Marine recruits in San Diego, allergy. Clindamycin has potential to cause adverse hemodynamic effects CA were evaluated for beta lactam allergy. They reported being allergic to when used in the perioperative setting, and lacks gram negative coverage. these medications on their intake paperwork. Data regarding reaction METHODS: The Nemours/A.I. duPont Hospital for Children developed history, exposure since reaction, and additional medical history was an algorithm to evaluate penicillin allergic patients who present to the obtained prior to evaluation. Seventy-five recruits underwent penicillin operating room. The algorithm recommends use of cephalosporins in skin testing followed by oral challenge to amoxicillin 250mg if skin test select patients based on the clinical history of the penicillin reaction. The negative, while 169 recruits had oral challenge without skin testing. perioperative antibiotics administered to penicillin allergic patients who Recruits with negative oral challenges went on to receive intramuscular were screened using the protocol from May to June of 2015 were compared penicillin G per standard recruit prophylaxis protocol. to a historical cohort from May to June of 2014. RESULTS: All 75 recruits who underwent penicillin skin testing had RESULTS: Fifty-four penicillin allergic patients (male to female ratio of negative skin tests and negative oral challenges to amoxicillin. Of the 169 1:1) were screened using the algorithm. There were 46 penicillin allergic recruits that proceeded directly to oral challenge, 168 (99.4%) had a patients (male to female ratio of 2:3) in the pre-intervention group. When negative challenge. A single recruit developed neck erythema, globus, and the algorithm was employed, clindamycin use decreased from 32.6% throat itching after oral challenge. The symptoms responded rapidly to (15/46) to 9.3% (5/54) and the use of 1st or 2ndgeneration cephalosporins intramuscular epinephrine and diphenhydramine. All of the 243 recruits increased from 67.3% (31/46) to 88.8% (48/54). having had negative amoxicillin challenges successfully received their CONCLUSIONS: In the preoperative setting, a penicillin allergy routine prophylactic intramuscular penicillin G injection without reaction. algorithm increased cephalosporin and decreased clindamycin use. CONCLUSIONS: Oral beta lactam challenge without prior penicillin Preoperative penicillin skin testing for penicillin allergy has also been skin testing may be an efficient, safe, and cost-reducing method of shown to increase the use of cephalosporins, however, skin testing in this evaluating military recruits with reported beta lactam allergy. setting may not always be practical. A penicillin allergy algorithm is an The views expressed herein are those of the author and do not necessarily effective and efficient screening tool that could be expanded institution- reflect the official policy or position of the Department of the Navy, wide and implemented at other tertiary care centers. Department of Defense, nor the U.S. Government All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. AB38 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2016

Outcomes and Safety of Single-Step and Multi- SMX allergy. 1 patient failed without significant morbidity. This suggests 119 Step Antibiotic Drug Challenges that GDEs to TMP-SMX are generally safe/efficacious and 3-step GDEs may be used more often if the clinical scenario so dictates. Stephanie L. Mawhirt, DO1, Luz S. Fonacier, MD, FAAAAI1, Rose Calixte, PhD2, Mark A. Davis-Lorton, MD, FAAAAI2, Marcella R. Evaluating Risk Factors for a Positive Oral Aquino, MD, FAAAAI1; 1Winthrop University Hospital, Allergy & 121 Challenge Despite Negative Penicillin Skin Immunology, Mineola, NY, 2Winthrop University Hospital, Mineola, NY. Testing RATIONALE: Antibiotic challenge methods are varied in practice. Megan S. Motosue, MD1, Sara M. May, MD1, Jay Jin, MD, PhD1, Miguel Compared to single-step challenges, multiple steps potentially offer 2 1 2 increased safety. We aimed to investigate the outcomes of single-step A. Park, MD ; Mayo Clinic, Rochester, MN, Department of Internal and multi-step challenges to determine dose-related challenge reactions. Medicine: Division of Allergic Diseases, Mayo Clinic, Rochester, MN. METHODS: We conducted a five year retrospective study of patients with a RATIONALE: The objective of this study was to assess risk factors for a history of antibiotic allergy undergoing antibiotic challenge. Challenges positive oral challenge in pediatric patients with negative penicillin skin were classified as 1-step (full-dose) or multi-step: 2-step (1/10th-remaining tests (PST). dose) and 3-step (1/100th-1/10th-remaining dose). Gathered data included pa- METHODS: We conducted a retrospective study evaluating a total of 108 _ tient characteristics, index reaction history, and challenge outcome details. pediatric patients (age <18y) with history of penicillin allergy who after SATURDAY RESULTS: Antibiotic challenges were performed in 179 patients (mean negative PST either underwent formal oral challenges in our clinic or age 62.6 years; 55.9% female). Patients undergoing single or multi-step informal oral challenges. The latter was defined as a full dose oral challenges had comparable demographics and index reaction severity. penicillin given after negative PST as clinically indicated by their primary Seventeen (9.5%) patients experienced challenge reactions: 5/48 penicil- care doctor. PST was performed using standard methods utilizing lins, 3/76 cephalosporins, 6/48 carbapenems, and 3/7 fluoroquinolones. benzylpenicilloyl-polysine, penicillin G, benzlpenicilloate, negative con- Reactions occurred in [5/28] single-step and [12/151] multi-step chal- trol, and histamine control. This study was IRB approved and charts were lenges (17.9% vs 7.9%). A significant trend between a greater dose reviewed for demographics, formal oral challenge results, and subsequent received and a positive challenge was observed as 70.6% of patients penicillin or aminopenicillin exposures. reacted on the full or remaining dose (p<0.001), however these reactions RESULTS: Thirty patients (median age at reaction 2.25 years, range 0.33- were less severe overall (rho5-0.53; 95% CI5-0.73 to -0.33). Of 6 10) underwent formal penicillin oral challenges, and seventy-eight patients anaphylatic reactions (four 3-step, one 2-step, one full-dose), no reactions (median age at reaction 2 years; range 0.25-12) underwent informal oral occurred on the 1/100th dose and the 2-step reacted on the 1/10th dose. challenges. Patients who underwent formal oral challenges were more CONCLUSIONS: Regardless of single or multi-step method utilization, likely to have a reaction compared to those who underwent informal oral 5 the majority of patients reacted following the final dose administration and challenges (p 0.0199). Compared to the informal challenge group, these reactions tended to be less severe. Performing a 2-step challenge patients who had formal challenges were more likely to have immediate 5 would have captured all anaphylactic reactions as no patients reacted on the type reactions (onset <1 hour) (6/30 vs 1/77; p 0.0017) and had a shorter 5 first step of a 3-step challenge suggesting no conferred safety with 3-step interval from skin testing to challenge (74.9 vs 547 days; p 0.0001). challenges. CONCLUSIONS: Immediate type reactions along with a shortened time interval between reaction and oral challenge were associated with a higher Graded Escalating Doses of Trimethoprim- likelihood of having a reaction on oral challenge despite negative PST. 120 Sulfamethoxazole in Immunocompetent Patients with Previous History of Delayed Rash to Sulfa A Case of Urticaria to Lansoprazole, Confirmed By Antimicrobials 122 Challenge

1 2,3 1 1 2 1 Anita N. Wasan, MD , Anil Nanda, MD ; Allergy and Asthma Center, Vuong A. Nayima, DO , John T. Anderson, MD ; University of Ala- 2 3 bama - Birmingham, Birmingham, AL, 2University of Alabama at Bir- Lansdowne, VA, Asthma and Allergy Center, Lewisville, TX, UT- mingham, Birmingham, AL. Southwestern Medical Center, Dallas, TX. RATIONALE: Allergy to sulfonamide antibiotics often present w/ RATIONALE: Lansoprazole is a proton pump inhibitor used to treat a delayed cutaneous reactions ranging from mild exantham to severe variety of gastrointestinal conditions. We present a case of urticaria and exfoliating dermatitis. Much of the literature demonstrates safety/efficacy oral challenge to lansoprazole. of graded challenge/desensitization in immunocompromised patients. METHODS: Our patient was referred for evaluation of a possible However less is known about immunocompetent patients. We present a lansoprazole allergy. case series of oral graded dose escalations (GDE) of trimethoprim- RESULTS: A 31 year old woman with a history of heartburn and diarrhea sulfamethoxazole (TMP-SMX) in immunocompetent patients. was evaluated with an upper endoscopy. She was diagnosed with gastritis METHODS: Chart review of patients admitted at a tertiary medical center and was placed on lansoprazole. Within a few hours of lansoprazole over 2 years. Patients were selected from allergy/immunology consult service ingestion, she developed diffuse urticaria, which resolved with self- w/history of allergy to TMP-SMX with need for resistant infection. Several administered diphenhydramine. Skin prick testing with 1:1 concentration GDE protocols were used w/some modification based on clinical scenario. of 15 mg/5 mL lansoprazole suspension was negative with appropriate RESULTS: 11 patients: age 12-63yo; 9 w/cystic fibrosis (CF), 1 controls. An in office challenge was conducted to lansoprazole. She quadriplegia, 1 COPD. Delayed rash reported in 10 patients; 7 w/ pruritus, tolerated 7.5 mg after 30 minutes. She then was given 15 mg lansoprazole, 2 nausea/vomiting, 1 skin sloughing. Time of reaction to GDE is < 1 year to and within a few minutes of this dose, she developed urticaria on her legs. decades. Some patients received multiple GDEs resulting in 18/19 She was successfully treated for this allergic reaction with appropriate successful attempts. 1 unsuccessful GDE had repeat fixed drug eruption therapy. In addition, she also has a history of urticaria upon ingestion of w/skin sloughing. There were seven 3-step GDEs, dosed at 1/100 then 1/10 ranitidine, a histamine H2 antagonist. In consultation with gastroenter- then full dose. 3 patients had > 6-step GDE followed by 3-step GDEs ology, an alternative therapy, sucralfate, was initiated with benefit. thereafter on readmission. Other GDEs varied between 6-30 steps, with CONCLUSIONS: This case demonstrates a clinical allergic (urticaria) intervals of 15min-12hrs between doses. reaction to lansoprazole, despite a negative skin prick test. Even with CONCLUSIONS: CF patients are unique w/frequent need for TMP-SMX negative skin testing, an oral supervised challenge is recommended. If but are otherwise immunocompetent. We demonstrate safety/efficacy to a alternative therapies are unavailable, desensitization may be considered. variety of GDEs in these immunocompetent patients w/history of TMP- All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. J ALLERGY CLIN IMMUNOL Abstracts AB39 VOLUME 137, NUMBER 2

Reaction Doses in Aspirin Desensitization for The Investigation of Suspected Beta-Lactam 123 Aspirin-Exacerbated Respiratory Disease 125 Allergy in Children; Comparison of Contemporary Clinical Practice By International Specialists 1 2 Charles Schuler, MD , James L. Baldwin, MD, FAAAAI , Alan P. 1 1 1 3 1 Ru-Xin M. Foong , Kirsty Logan , Michael Perkin , George Du Toit, Baptist, MD, MPH, FAAAAI ; University of Michigan, Dept of Internal 2 1 2 MD, FAAAAI ; Department of Paediatric Allergy, London, United Medicine, Ann Arbor, MI, University of Michigan Allergy Immunology 2 3 Kingdom, St Thomas’ Hospital, London, United Kingdom. Specialty Clinic, Ann Arbor, MI, University of Michigan, Division of Al- RATIONALE: Beta-lactam allergy is commonly suspected in childhood lergy and Clinical Immunology, Ann Arbor, MI. with health implications for the individual and wider public. Diagnostic RATIONALE: Aspirin desensitization is a recommended procedure for modalities include skin prick tests (SPT), specific-IgE tests, intradermal patients with aspirin-exacerbated respiratory disease (AERD). Current (ID) tests and drug provocation challenges (DPC). The aim of this study protocols advise supervised aspirin administration up to doses of 325 mg was to compare contemporary practice amongst International specialists to with the 650 mg dose administered at home. It is unclear what percentage help inform standardized practice for the diagnosis of beta-lactam allergy. of patients reacts at 325 mg during desensitization. METHODS: Anonymized electronic questionnaire surveys were distrib- METHODS: A chart review of aspirin desensitization procedures for uted over 3 months through International Allergy Societies for completion AERD performed from 2011-2015 at the University of Michigan Allergy/ by Specialists who assess children. Immunology clinic was performed. Reactions and associated doses were RESULTS: 81 specialists, practicing in 16 countries completed the characterized as upper or lower reactions, with severity marked by number questionnaire. There is great variability between countries, in the selection of separate upper symptoms and FEV1 decrease. Baseline AERD history, of diagnostic tests. There is poor agreement on positive cut off values (IgE, prior aspirin challenge, medications, and spirometry were also collected. SPT and ID) and practical techniques used to measure SPT or ID wheal RESULTS: A total of 64 aspirin desensitization protocols were reviewed. diameters. DPC were considered the gold standard investigation with 62% of subjects were on a leukotriene receptor antagonist and/or zileuton at 93.8% of respondents undertaking DPC over the last 12 months; 64% of desensitization. One patient reacted to 325 mg with a very mild lower respondents considered DPC extremely useful for both exclusion and respiratory symptom that resolved spontaneously without treatment. confirmation of beta-lactam allergy. However, there is a lack of consensus Twelve patients did not react, six of whom had a previous positive in-office on when and how DPC should be performed. Overall, DPC are safe - only aspirin challenge. All other patients had a reaction to a lower dose. The most 2.6% of our respondents had patients who required intramuscular frequent initial provoking dose was 81 mg. 64% of subjects had upper adrenaline and none had patients requiring admission to intensive care. airway symptoms, 39% had lower symptoms, and 30% had both upper and CONCLUSIONS: There is a discrepancy between Allergy Specialists lower symptoms. After an initial reaction at a lower provoking dose, no throughout the world in the selection and interpretation of tests used to diagnose subject had a reaction when subsequently receiving the 325 mg dose. and manage suspected beta-lactam allergy. The standardization of tests CONCLUSIONS: During aspirin desensitization, there are extremely few remains a priority in order to safely and effectively manage beta-lactam allergy. reactions at the 325 mg dose. This suggests that the in-office portion of the

desensitization protocol can be shortened. Hypersensitivity Reactions to Rituximab: 53 SATURDAY 126 Successful Desensitizations in 7 Patients with AERD: A Composite Symptom Score to Identify Severe, Near-Fatal Reactions Positive Aspirin/NSAID Challenges 124 Yuval Tal, MD PhD1, Dina Ben Yehuda, MD2, Meir Shalit, MD, 1 2 1 Kevin A. Cook, MD1, Nathan Wineinger, PhD2, Kristen M. Dazy, MD1, FAAAAI , Eyal Lebel, MD ; Allergy and Clinical Immunology Unit, 1 Department of Medicine, Hadassah Hebrew University Medical Center, Katharine M. Woessner, MD, FAAAAI , Ronald A. Simon, MD, 2 FAAAAI1, Andrew White, MD, FAAAAI1; 1Scripps Clinic, San Diego, Jerusalem, Israel, Department of Hematology, Hadassah-Hebrew Univer- CA, 2Scripps Translational Science Institute, San Diego, CA. sity Medical Center, Jerusalem, Israel. RATIONALE: Rituximab is a chimeric mouse-human monoclonal antibody RATIONALE: The gold standard for diagnosing aspirin exacerbated with a paramount role in some hematological malignancies. Hypersensitivity respiratory disease is by aspirin/NSAID challenge with the development of reactions (HSRs) to rituximab are common; and vary from mild urticaria to symptoms, or decrease in FEV1 or NIF. There is currently no validated severe, life-threatening events. While in most patients, the Boston 12-step symptom score to assist in objectively identifying a positive challenge desensitization procedure will suffice, patients who have endured severe based on symptoms alone. reactions may warrant pre-medication prior to the desensitization protocol. We METHODS: Retrospective chart review was performed on 47 patients who describe our experience with the modified protocol in patients who underwent had undergone aspirin desensitization. Patients had recorded symptoms severe, life-threatening reactions following previous rituximab administrations. during desensitization (nasal congestion, runny nose, sneezing, itchy nose, METHODS: A total of seven hematological patients were included. All had itchy/watery eyes, itchy ears, itchy mouth/tongue, tight throat, wheezing, experienced severe anaphylactic or immunocytotoxic reactions during chest tightness) at hourly intervals using a scale of 0 to 10. Positive reactions rituximab administration. Four patients had suffered a cardiovascular collapse, had been identified by a supervising allergist utilizing reported symptoms as of which one sustained a cardiac arrest and two required prolonged intensive well as objective changes in FEV1 or NIF. A composite scoring system was care unit hospitalizations. The seven patients were treated with pharmacologic derived using the sum of weighted individual symptom scores. prophylaxis prior to a 12-step desensitization protocol. Prophylaxis included RESULTS: All symptoms were independently (all p<0.05) and jointly three doses of prednisone, high doses of H1 blockers, and an H2 blocker. (p57.74x10-16) associated with a positive challenge. Scores for sneezing Montelukast was added in two patients. We describe the patient demographics, and itchy/watery eyes were most strongly predictive of a positive challenge the severity and characteristic of the initial HSRs and the outcomes of with odds ratios of 2.38 and 2.03 respectively for a one unit increase in subsequent rituximab administration utilizing the modified protocol. score. The weighted composite symptom score demonstrated strong asso- RESULTS: Fifty-three modified desensitization protocols were success- ciation with positive challenges with an area under the curve of 0.88. A low fully completed (with a 100% success rate). Mild HSRs appeared in only composite score threshold yielded a 91% sensitivity and 64% specificity, three of the procedures. Six of the patients are currently in remission of while a high threshold yielded a 73% sensitivity and 92% specificity. their hematological disorder. CONCLUSIONS: A composite symptom score provides a 3rd objective CONCLUSIONS: A modified protocol including pharmacologic prophy- measure with which to identify positive challenges. Our scoring system laxis prior to the standard 12-step desensitization procedure is reliable and may be utilized to identify mild reactions, treat early symptoms prior to safe even among patients who had experienced near-fatal HSRs. This a severe reaction, and to provide objective measurement of symptoms in protocol should be considered in patients who mandate rituximab AERD research studies. administration despite a severe previous reaction. All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. AB40 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2016

Experience with Desensitizations to Taxanes in an subtypes and/or nasal polyps can prevent erroneous diagnosis of ‘‘sinus 127 Allergy Department in Madrid (Spain) infection’’ and overuse of antibiotics which places patients at risk for drug reactions and/or resistance. Mercedes Saenz de Santa Marıa, MD, Gabriela Zambrano, MD, Marıa L. Baeza, MD, PhD, Sonsoles Infante, MD, Alberto Alvarez-Perea, MD, Descriptive Analysis of Patients with Allergic Pilar Tornero, MD; Hospital General Universitario Gregorio Maran~on, 129 Reactions to Fluoroquinolones Allergy Department, Madrid, Spain. 1 ~ 2 RATIONALE: Desensitization to taxanes allows to continue standard Esther Barrionuevo, MD, PhD , Inmaculada Dona, MD, PhD , Fran- cisca Gomez, MD, PhD3, Oliver Munoz-Daga~ 4, Arturo Ruiz, MD5, Anto- front-line treatments in patients with infusional reactions. 6 5 7 METHODS: A descriptive-retrospective analysis was performed. Clinical nio Guzman , Maria Auxiliadora Guerrero , Maria Dolores Ruiz , Rosa 8 9 3 1 records of patients with desensitizations to taxanes, from January 2008- Garcia , Miguel Blanca, MD, PhD , Marıa Jose Torres, MD, PhD ; Al- July 2015, were reviewed. lergy Unit, IBIMA, Regional University Hospital of Malaga, UMA, 2 RESULTS: Thirty-two patients (21 paclitaxel; 11 docetaxel) with imme- Malaga, Spain, Allergy Service, IBIMA-Regional University Hospital of Malaga-UMA, Malaga, Spain, 3Allergy Unit, IBIMA-Regional Univer- diate reactions (IR) (15% mild, 42% moderate and 43% severe) and one 4 6 sity Hospital of Malaga, Malaga, Spain, 1Allergy Unit, Regional Univer- with a mild delayed reaction, were selected. Mean age 53.2 12.2, 91% 5 female. Symptoms were: 75% cutaneous, 70% respiratory, 49% abdom- sity Hospital of Malaga-IBIMA, UMA, Malaga, Spain, Allergy Unit,

SATURDAY Regional University Hospital of Malaga-IBIMA, UMA, Malaga, Spain, inal, 39% cardiovascular, 36% back pain and 21% neurological. 6 Intradermal tests (IDT) were positive in 2 patients with IR to docetaxel. Pharmacy Unit, Regional University Hospital of Malaga-IBIMA, 7 They completed 137 desensitization cycles. All patients started with a UMA, Malaga, Spain, Allergy Service, IBIMA-Regional University Hos- pital of Malaga, Malaga, Spain, 8Allergy Service- Carlos Haya hospital. standard 12-step protocol, initially adapted in most of them (91%) 9 according to the severity of the initial reaction. Modifications included: Spain, Malaga, Spain, Allergy Unit, Regional University Hospital of Ma- pretreatment (81%: 85% received AAS-montelukast and 15% montelu- laga-IBIMA, UMA, Malaga, Spain. kast), increased final flow (74%) and additional steps (9%). RATIONALE: Fluoroquinolones (FQ) are the second most frequent cause There were 12 IR in 137 cycles (8.7%) in 10 patients. The reactions were of hypersensitivity to antibiotics after betalactams. In recent years, an less severe (75% mild, 25% moderate) than their original reaction. Seven of increase in the number of patients allergic to these drugs has been detected. them required new cycles. The protocol was modified in 5 without new The aim of our study was to describe the clinical characteristics and the reactions (pretreatment before certain steps 75%, additional step 50% and methods used for diagnosing patients with allergy to FQ. increase the length of a step 25%). One of the 2 patients without a new METHODS: Patients attending our allergy unit with reactions suggestive modification developed a reaction. of allergy to FQ were evaluated in 2005-2014. Diagnosis was achieved by There was one patient who withdrew the treatment. clinical history, basophil activation test (BAT) and drug provocation test CONCLUSIONS: A initial adaptation of the desensitization protocol (DPT) when necessary. according the severity of reactions may increase its tolerance. RESULTS: A total of 365 patients with suggestive allergic reaction to FQ Most of the patients tolerated increased flow rates at the last steps, were evaluated, of which 140 were confirmed as allergic (38,35%). Just 6 narrowing the procedure. over two thirds (69,28%) were female, and the mean age was 54.75 19,36 (18-80) years. Sixty five per cent reacted less than 1h after drug Anaphylactic Shock Caused By Moxifloxacin administration and 35% more than 1h later. Moxifloxacin was the FQ 128 without Cross-Reactivity to Other Fluoroquinolones involved in 60.86% of cases, Ciprofloxacin in 20.28%, Levofloxacin in 13% Norfloxacin in 4.34% Ofloxacin in 1.44%. The most frequent clinical Rung-chi Li, DO, PhD1, Jonathan A. Bernstein, MD2; 1Department of In- entity was anaphylaxis (55.71%) followed by generalized urticaria ternal medicine, The Christ Hospital, Cincinnati, OH, 2University of Cin- (33.57%), exanthema (7.14%) and angioedema (3.57%). In patients with cinnati College of Medicine, Cincinnati, OH. immediate reactions, the diagnosis was achieved using BAT in 64.70%, by RATIONALE: Quinolones, divided into 4 structural classes, have broad clinical history in 29.41% and by DPT in 5.88%. In patients with non- activity against gram-positive and gram-negative bacteria. Because they immediate reactions, diagnosis was performed by clinical history in are prescribed more frequently due to confounding drug allergies and/or 55.55%, by DPT in 33.33% and by TAB in 11.11%. drug resistance, allergic reactions are emerging more frequently. CONCLUSIONS: Most reactions induced by FQ were immediate Controversy exists regarding the cross-reactivity risk for quinolone allergic (anaphylaxis), being Moxifloxacin the drug most frequently involved. reactions. Herein, we present a patient experiencing moxifloxacin The BAT seems to be a useful method for diagnosing these patients. anaphylaxis who could tolerate another class of quinolone. METHODS: Prick skin testing (PST) and oral graded challange. RESULTS: A 56 year old non-atopic male with nasal polyps unresponsive to oral corticosteroids, rhinitis medicamentosa, obstructive sleep apnea and recurrent sinusitis without previous drug allergies was prescribed moxi- floxacin for a refractory sinus infection after 4 weeks treatment with a first generation antibiotic. Within 20 minutes after the first dose he developed shortness of breath, nausea, flushing and vascular collapse resulting in myocardial infarction. His presenting concern was being able to take quinolone antibiotics for sinus infections. PST showed a 10mm wheal/ 25mm flare response after 15minutes to moxifloxacin (400mg/10ml); PST to levofloxacin (250mg/5ml) and ciprofloxacin (250mg/5ml) were nega- tive. Oral graded provocation to ciprofloxacin (Total dose 1 gram at 250mg/5ml) revealed no reaction. Subsequently, nasal polypectomy and proper post-operative medical management has resulted in no recurring ‘‘sinus infections’’ requiring antibiotics. CONCLUSIONS: This case illustrates the absence of cross-reactivity of quinolones confirmed by PST and oral graded challenge in the outpatient setting. Furthermore, proper diagnosis and management of rhinitis All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. J ALLERGY CLIN IMMUNOL Abstracts AB41 VOLUME 137, NUMBER 2

Effectiveness of Premedication and Rapid Diagnosis and Management of Infusion-Related 130 Desensitization in Hypersensitivity to L-Asparaginase 132 Hypersensitivity Reactions to Enzyme Replacement Therapy for Lysosomal Diseases: The Role of Jin-Tack Kim, MD, PhD1, Hwan Soo Kim, MD2, Yoon Hong Desensitization Chun, MD3, Jong-seo Yoon, MD, PhD4, Hyun Hee Kim, MD5; 1Depart- ment of Pediatrics, Uijeongbu St. Mary’s Hospital, The Catholic Univer- Carolina Sanchez Aranda1, Luis Felipe C. Ensina, MD2,In^es Camelo sity of Korea, College of Medicine, Uijeongbu, Gyeonggi-Do, South Nunes3, Marcia Mallozi, MD1, Ana Maria Martins3, Dirceu Sole, MD, Korea, 2Dept of Pediatrics, Colleg of Medicine, The Catholic University PhD, FAAAAI1; 1Federal University of S~ao Paulo, S~ao Paulo, Brazil, of Korea, 3Dept. of Pediatrics, College of Medicine, The Catholic Univer- 2Universidade Federal de S~ao Paulo, S~ao Paulo, Brazil, 3Federal Univer- sity of Korea, 4Dept. of Pediatrics The Catholic University of Korea, sity of S~ao Paulo. 5Department of Pediatrics, The Catholic University of Korea College of RATIONALE: Enzyme replacement therapy (ERT) has been used in the Medicine, Bucheon-si, South Korea. treatment of lysosomal diseases (LD). ERT with human recombinant RATIONALE: L-asparaginase is a crucial chemotherapeutic agent for the enzymes has shown to slow disease progression and improve the quality of treatment of acute lymphoblastic leukemia. However, hypersensitivity to life. Infusion-related reactions (IRR) to ERT can occur and can be severe, L-asparaginase is common which limits its usage. precluding further ERT. This study was aimed at standardizing the METHODS: We performed 44 cases premedication and 3 cases of management of IRR. desensitization in 16 patients with hypersensitivity to L-asparaginase. METHODS: Patients under ERT for Mucopolysaccharidosis (I, II and VI), RESULTS: With premedication, 33 cases completed L-asparaginase Gaucher, Fabry and Pompe diseases were followed at Federal University of injection with no hypersensitivity reaction. 11 cases showed mild hyper- S~ao Paulo, from January 2011 through December 2014. In the presence of sensitivity reaction, such as urticaria. Desensitization was performed in 3 signs consistent with adverse reaction, ERT was stopped and skin tests for cases: 2 cases were successful and in 1 case, medication was switched to specific IgE assay were performed. In patients with symptoms of acute Erwiniaasparaginase. infection after infusion and with negative skin tests, ERTwas maintained at the CONCLUSIONS: Premedication and desensitization appears to be useful same infusion rate. In patients without a history of infection and with negative in helping patients receive desired dose of L-asparaginase in pediatric tests, ERTwas maintained with increased infusion rate. For those patients with patients with acute lymphoblastic leukemia. positive ST that continued reacting after adjustments in the IR, a patient and dose specific rapid 3 bags 12-steps desensitization protocol was generated. An Adolescent Male Presenting with RESULTS: Among seventy-five LD patients receiving ERT, 12 (16%) 131 Nonpigmenting Fixed Drug Eruption to Ceftriaxone developed adverse reactions during infusion. Urticaria was the most prevalent event (40%), followed by fever (20%), chills (20%), cough (13%) 1 2 1 Adam Byrne, MSc, MD , Moshe Ben-Shoshan, MD, MSc ; McGill and anaphylaxis (13%). Five patients (42%) had positive skin tests. Of 2 University, Montreal Children’s Hospital, The Research Institute of the these, four were successfully underwent rapid desensitization in 12 steps.

McGill University Health Centre, Meakins- Chrisitie Laboratories, Divi- CONCLUSIONS: Considering the importance of these drugs in reducing SATURDAY sion of Paediatric Allergy and Clinical Immunology, Department of Pae- LD morbidity and mortality, it is critical to recognize the early signs of diatrics, Montreal Children’s Hospital, Montreal, QC, Canada. IRR, understand their mechanism and their management including RATIONALE: A fixed drug eruption (FDE) is a cutaneous reaction that desensitization. occurs repeatedly in the same area following exposure to the culprit drug. FDE typically has a benign course. We present a case of a child presenting The Role of Carbapenems and Cephalosporines in with a fixed drug eruption to ceftriaxone. 133 Patients with Confirmed Penicillin Allergy METHODS: An observed graded challenge to intravenous ceftriaxone. RESULTS: Our patient is a healthy 13 year-old boy with a known peanut Mona Sulaiman Al-Ahmad, MD1, Tito Rodriguez Bouza2; 1Department allergy who presented at the emergency department of the Montreal of Microbiology, Faculty of Medicine, Kuwait University, Kuwait, 2Drug Children’s Hospital with pre-auricular cellulitis and fever. His blood tests Allergy Unit, Department of Allergy, Al-Rashed Allergy Center, Kuwait. revealed no leukocytosis but an elevated C-reactive protein and erythrocyte RATIONALE: There is lack of studies on cross reactivity of carbapenems sedimentation rate. He was treated with 2g of ceftriaxone intravenously. and cephalosporins in patients with penicillin allergy, as well as on the Within 5 minutes, he developed a 3 cm elevated lesion superior to the left negative predictive value of penicillin allergy evaluation in the Arabian Gulf orbit that resolved within 1 hour of appearance. On subsequent visit, a countries.we sought to evaluate the use of carbapenems and cephalosporins graded challenge was performed. The patient tolerated well 10% of the in penicillin-allergic patients and clarify the negative predictive value of full total dose; however, within 30 minutes after receiving 90% of the dose, the allergy evaluation in an Arabian Gulf Country, Kuwait. patient developed the same reaction at the same location. The lesion METHODS: Allergy workup was performed on patients suspected of resolved within 1 hour. The patient was challenged to oral cephalexin the penicillin allergy from 2009 to 2014. Patients presenting with anaphylaxis following day with no reaction, and was prescribed oral cephalexin to or tested positive, were offered testing for meropenem and cephalosporin. complete the treatment. Patients tested negative were contacted by phone to check subsequent CONCLUSIONS: The patient’s history and challenge are consistent with betalactam intake. a FDE. To the best of our knowledge, this is the first case report on FDE to RESULTS: Out of 189 patients tested for betalactams, we had 76 (40.2%) ceftriaxone in children. Given increased use of ceftriaxone, clinicians with positive results. Among positive patients, we had 65 (85.5%) who should be aware of the possible development of FDE to ceftriaxone. A presented initial reaction to penicillin and 25 (38%) of them were graded drug challenge is useful in establishing the diagnosis of FDE to challenged with alternative medication with tolerance except for two ceftriaxone. patients; one to meropenem and one to cefuroxime. We had 11 (14.5%) who presented initial reaction to cephalosporin with tolerance to alterna- tive medications. Phone calls to all 113 (59.8%) patients with negative betalactam testing showed that 17 (15%) took betalactams and 23 (20.3%) did not. Only 2 patients reported reaction but rejected retesting. CONCLUSIONS: It is safe to administer carbapenems and cephalospo- rins to our patients with positive penicillin skin testing, by a graded challenge. Our calculated negative predictive value for penicillin testing is 88.2 to 100%, which is similar to other studies. All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. AB42 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2016

A Case Report of Dress with Prolonged Latency reactions. Overall, 93% of those evaluated were determined not to require 134 Period Related to Zonisamide in a Child avoidance of beta lactams after evaluation. CONCLUSIONS: Patients with documented beta lactam allergy were Fatima Khan1, Joel Mendelson, MD2; 1Newark Beth Israel Medical Cen- rarely allergic upon evaluation. This study supports more aggressive ter, NJ, 2Newark Beth Israel Medical Center. interventions to identify incorrectly documented or invalid cases of beta RATIONALE: Drug reaction with eosinophilia and systemic symptoms lactam allergy leading to erroneous avoidance. (DRESS) is a severe, possibly life- threatening adverse drug reaction that typically occurs two to eight weeks following exposure to anticonvulsants, Perioperative Use of Cefazolin in Patients with sulfonamides and antiviral medications, amongst other implicated drugs. 136 Reported Penicillin Allergy Patients typically present with fever, lymphadenopathy, rash and end-organ involvement. Key laboratory findings include atypical lymphocytosis, Allison Ramsey, MD, Mary Staicu, PharmD, Leanna Liu, PharmD; Ro- eosinophilia, and elevated liver enzymes. We report a case of DRESS with chester General Hospital. a latency period more prolonged than any previously presented in the RATIONALE: Cephalosporin antibiotics are the mainstay of surgical medical literature to the best of our knowledge. prophylaxis given their favorable safety and efficacy profile. Despite a low METHODS: The patient met all criteria for DRESS according to the risk of cross-reactivity, cephalosporins are not recommended in patients RegiSCAR criteria which is a widely used scoring system for the diagnosis with a reported IgE-mediated penicillin allergy. We assessed the incidence SATURDAY of DRESS. and characteristics of reactions in patients with a reported penicillin allergy RESULTS: An 8-year old with history of uncontrolled complex seizures prescribed cefazolin perioperatively. with control on zonisamide presented with diffuse maculopapular rash, METHODS: We performed a retrospective analysis in a cohort of lymphadenopathy, mild facial edema and fever. Her lab values showed morbidly obese patients who received cefazolin perioperatively, evaluating white blood cell count– 16.5 k/CMM, eosinophil %-15, absolute the penicillin allergy history and tolerability of perioperative cefazolin in eosinophil count–2,475, atypical lymphocytes-23%, elevated liver func- those with a reported penicillin allergy. The primary outcome was the tion tests: alanine aminotransferase-338 unit/L, aspartate aminotransferase occurrence and type of reactions documented within 72 hours of the first 144 unit/L, alkaline phosphatase-582 unit/L, ammonia-102 UMOL/L. perioperative dose. HHV-6 IgM was elevated. All other studies including antistreptolysin RESULTS: A total of 838 patient encounters were reviewed. Of these, 89 antibodies, cytomegalovirus, parvovirus, enterovirus were negative. (11%) patients reported a penicillin allergy. The documented historical Abdominal ultrasound showed mild hepatosplenomegaly. Zonisamide reactions ranged from rash (42%), hives (25%), unknown (12%), itching was discontinued. The child was started on high dose steroids and (4%), and other (4%). Non-immune mediated reactions were described in hydroxyzine. After 5 days of high dose steroids; the rash had improved eleven (12%) patients. and patient was started on a steroid wean. Post-cefazolin administration, adverse reactions included gastrointestinal CONCLUSIONS: We believe this is the first reported case of DRESS with events (12%), itching (2%), shortness of breath (1%), and acute kidney a latency period of 84 weeks and 5 days. injury (1%). There was no statistically significant difference in adverse reactions between the penicillin allergy and the non-penicillin allergy Retrospective Review of Beta Lactam Allergy groups. No life-threatening adverse reactions occurred. 135 Prevalence in a Referral Population CONCLUSIONS: Our analysis demonstrates the overall safety of peri- operative cefazolin in patients with a history of mild to moderate reported Andrew Wakeman, BSc(Hon)1, Alexander Singer, MB, BaO, BCh, penicillin adverse reactions, indicating that use of cefazolin in these CCFP2, Elissa Michele Abrams, MD, FRCPC3, Thomas V. Gerstner, patients should be considered in a monitored setting. MD, FRCPC4; 1University College Dublin, 2University of Manitoba, Department of Family Medicine, Manitoba Primary Care Research Network, Winnipeg, MB, Canada, 3University of Manitoba, Department of Paediatrics and Child Health, Section of Allergy and Immunology, Winnipeg, MB, Canada, 4University of Manitoba, Department of Paediat- rics and Child Health, Section of Allergy and Immunology. RATIONALE: It has been estimated that 8% of the general population are labelled as beta lactam allergic. Avoidance of beta lactam antibiotics in hospital correlates with higher rates of antibiotic resistant infection, patient morbidity and higher costs of treatment. METHODS: A cross-sectional retrospective chart review of all evalua- tions for beta lactam allergy by a community allergy clinic from June 2010 to July 2015. RESULTS: Our sample includes 311 referred patients with a recent history of a reaction to a beta lactam antibiotic. Mean age was 11.6 (SD 17.3); 49.5% of patients were male. Evaluation was based on reaction history, intradermal testing in those with histories that were vague or suggestive of an IgE mediated hypersensitivity, and/or oral beta lactam challenge. There were only 1/107 positive intradermal tests, and 6/297 positive oral challenges. Following the consultations, only 0.64% were considered to be at increased risk of future IgE mediated reactions. A further 2.3% were considered to be at increased risk of serious delayed- type III and IV reactions (serum sickness and Stevens-Johnson). 3.9% were advised they could avoid beta lactams to prevent future mild delayed All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. J ALLERGY CLIN IMMUNOL Abstracts AB43 VOLUME 137, NUMBER 2

Patients Taking Amoxicillin-Clavulanic Can (91.8%) with no history of penicillin allergy. There were significantly more 137 Become Simultaneously Sensitized to Both Drugs caesarean sections in women with unverified penicillin allergy, 30.4% versus 27.6% (p50.0004). Mothers with unverified penicillin allergy spent Adriana Ariza, PhD1, Tahia D. Fernandez, PhD1, Cristobalina significantly more days in the hospital in the 6 months after delivery, Mayorga, PhD1, Maria Salas, MD, PhD2, Nekane Barbero, PhD3, Maria 3.5561.51 versus 3.4662.00 (p 5 0.002). GBS-positive pregnant women Isabel Montanez,~ PhD1,3, Angela Martın-Serrano1, Ruben Fernandez1, with unverified penicillin allergy were significantly more likely to receive Luisa Galindo, RN4, Miguel Blanca, MD, PhD5, Marıa Jose Torres, clindamycin or vancomycin. Only 7 GBS-positive women had penicillin MD, PhD2; 1Research Laboratory, IBIMA-Regional University Hospital allergy testing at Kaiser Permanente Southern California during this time. of Malaga-UMA, Malaga, Spain, 2Allergy Unit, IBIMA, Regional Univer- CONCLUSIONS: Penicillin allergy testing pregnant women who are sity Hospital of Malaga, UMA, Malaga, Spain, 3BIONAND-Andalusian GBS-positive prior to delivery may result in decreased hospital utilization, Centre for Nanomedicine and Biotechnology, Department of Organic as well as less morbidity. Chemistry, IBIMA, UMA, Malaga, Spain, 4Allergy Unit, IBIMA, Regional University Hospital of Malaga, UMA, Malaga, Spain, 5Allergy Hypersensitivity to Butylscopolamine: A Case Service, IBIMA-Regional University Hospital of Malaga-UMA, Malaga, 139 Report Spain. Francisco Javier Iglesias-Souto1, Olga Arbazagoitia1, Jacob Rosquete2; RATIONALE: Betalactam antibiotics are the most frequent cause of 1 2 hypersensitivity reactions to drugs mediated by a specific immune Allergy Department, Internal Medicine Department, Hospiten Sur, Ten- mechanism. Amoxicillin (AX) is the most often elicitor, which was erife, Spain. originally prescribed alone, and is now often prescribed alongside RATIONALE: Butylscopolamine bromide— also known as hyoscine clavulanic acid (CLV). After the administration of AX-CLV, there are butylbromide — is an anticholinergic antispasmodic agent used to treat subjects who develop AX allergy whilst tolerating CLV, whilst for others pain and discomfort caused by abdominal cramps. Although it is widely the opposite occurs. To our knowledge, there are no clinical reports of used, reports of immediate hypersensitivity reactions after butylscopol- patients with IgE-mediated allergy to both AX and CLV. amine administration are unusual. METHODS: Skin testing was performed by skin prick test and if negative METHODS: We present a case of a 52 years old male patient, without followed by intradermal test. Serum specific IgE determination was history of adverse reactions to drugs, who suffered an episode of immediate performed by ImmunoCAP and basophil activation test (BAT) was generalized urticaria and facial angioedema after administration of performed by flow cytometry. Single blind placebo controlled drug intravenous butylscopolamine bromide. The patient was treated in the provocation test was performed to assess tolerance to other penicillins. emergency department, receiving intramuscular adrenaline and intrave- RESULTS: Case 1: 48 year-old woman who developed urticaria and nous corticosteroids, with good response and clinical improvement. angioedema 45 min after the oral administration of AX-CLV. Case 2: 43 Subsequently, the patient was referred to our outpatient clinic for year-old woman who developed systemic pruritus with generalised urti- evaluation of a possible butylscopolamine allergy. RESULTS: We conducted an allergy study, consisting in skin tests with caria and facial and tongue angioedema 15 min after the oral administra- SATURDAY tion of AX-CLV.The allergological work-up indicated that the two patients the drug involved (butylscopolamine bromide 20 mg/ml). Skin prick tests were allergic to both AX and CLV with good tolerance to BP and penicillin with butylscopolamine were negative. Intradermal tests with progressive V. Both patients gave positive skin test results to AX and CLV, showed concentrations of butylscopolamine were positive at 1/100 and 1/10 specific anti-AX IgE and gave positive BAT results to AX and CLV. dilutions. All tests were negative in 10 control patients. Oral provocation CONCLUSIONS: Our study provides evidence that sensitization to both with the drug was dismissed. AX and CLV can appear in the same patient. To our knowledge this is the CONCLUSIONS: We present a rare case of urticaria and angioedema due first study showing this sensitization pattern. to butylscopolamine bromide. Positive intradermal tests with this drug suggest an allergic IgE-mediated mechanism. Morbidity in Pregnant Women with Group-B 138 Streptococcus Infection and Unverified Penicillin Allergy

Shilpa Desai, MD1, Qiaoling Chen, MS2, Michael S. Kaplan, MD, FAAAAI1, Scott Rasgon, MD3, Eric M. Macy, MD, FAAAAI4; 1Kaiser Permanente Los Angeles Medical Center, Los Angeles, CA, 2Kaiser Per- manente Department of Research and Evaluation, Pasadena, CA, 3Kaiser Permanente Los Angeles Medical Center, 4Kaiser Permanente Health Care Program, Department of Research and Evaluation, Pasadena, CA. RATIONALE: The morbidity potentially associated with unverified penicillin allergy in pregnant women with group B streptococcus (GBS) colonization is unknown. Penicillin allergy testing has been shown to be safe in pregnant women, but is done infrequently. We retrospectively determined healthcare utilization and morbidity in a large cohort of pregnant women with GBS with and without an unverified history of penicillin allergy. METHODS: All pregnant women with a positive culture for GBS in a five year period, 1-1-2009 to 12-31-2014, were identified using Southern California Kaiser Permanente electronic health records. Those with a history of an active, but unverified, penicillin allergy noted prior to delivery were compared to those with no penicillin allergy history. Method of delivery, hospital utilization over the 6 months after delivery, and antibiotic exposures within 3 days of delivery was determined. RESULTS: There were 39,374 (23.1%) GBS-positive women with 42,524 pregnancies, 3,500 (8.2%) with unverified penicillin allergy and 39,024 All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. AB44 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2016

Immune-Mediated Reactions to Vancomycin: A and history of ‘‘near miss’’ (NM) was determined. Data were analyzed 140 Systematic Review using Mann-Whitney 2-sided test and Fisher’s exact test. RESULTS: About two-thirds (66/105) had knowledge of AF, which was Jasmit S. Minhas, MD1, Paige G. Wickner, MD, MPH2, Aidan A. associated with significant increase in override of alerts for duplicate Long, MD, FAAAAI3, Aleena Banerji, MD4, Kimberly G. Blumenthal, (p50.02) and discontinued (p50.02), but not drug interactions (p50.90) or MD3; 1Lahey Hospital & Medical Center, Tufts University School of drug allergy (p50.09). Knowledge of AF was not associated with Medicine, Burlington, MA, 2Division of Rheumatology, Allergy, and increased NM (p50.15) or PGY level (p50.34). Immunology, Department of Medicine, Brigham and Women’s Hospital, Of those with knowledge of AF, those who suffer (55/65), did not Harvard Medical School, Chestnut Hill, MA, 3Division of Rheumatology, significantly override any type of alert more than those who don’t suffer Allergy and Immunology, Department of Medicine, Massachusetts Gen- (p5 0.81, 0.16, 0.12, and 0.79, respectively), have more NM (p51.0), or be eral Hospital, Harvard Medical School, Boston, MA, 4Division of Rheu- affected by PGY level (p50.12). matology, Allergy and Immunology, Department of Medicine, CONCLUSIONS: Knowledge of, but not the emotional response to, AF Massachusetts General Hospital, Harvard Medical School, MA. was associated with increased overrides in orders which may decrease RATIONALE: Vancomycin is a broad-spectrum antibiotic whose use is efficiency, but not result in adverse drug effects, including allergic drug limited by adverse drug reactions (ADRs). While vancomycin toxicities reactions. are known, there are limited data on vancomycin hypersensitivity reactions SATURDAY (HSRs). We aimed to identify the most commonly reported vancomycin Fixed Drug Eruption to Arylpropionic Acids HSRs through systematic review. 142 METHODS: We performed a literature search for English-language case reports and series from 1982 through 2015 (last search July 31) on Ovid Abdonias Rodriguez Gamboa, MD, Dasha Roa Medellin, MD, Marga- MEDLINE and PubMed. Search included subject heading vancomycin rita Acevedo Matos, MD, Blanca Noguerado, MD, Patricia Rojas, MD, with subheading ‘‘adverse effects,’’ and separately text word searches for Manuel De Barrio, MD; Hospital General Universitario Gregorio ~ vancomycin with a list of specified HSRs. References of identified articles Maranon, Department of Allergy, Madrid, Spain. were reviewed to find additional articles. Each assessed case was reviewed RATIONALE: In literature there are many reports of fixed drug eruption by two investigators. Clinical data were collected and summarized. (FDE) caused by nonsteroid anti-inflammatory drugs (pirazolones, oxi- RESULTS: Of 200 identified articles, 86 were screened, 65 were fully cams and aspirin), despite of its widely used, FDE due to arylpropionic assessed, and 54 cases were included in the analysis. Vancomycin HSRs acids nonsteroidal anti-inflammatory drugs (AANSAID) has been excep- were immediate (anaphylaxis, n57) and non-immediate (n547). Non- tionally described. immediate HSRs included linear IgA bullous dermatosis (LABD, n523), METHODS: A retrospective-descriptive study was performed in our drug rash eosinophilia and systemic symptoms (DRESS) syndrome Allergy Unit from April 2008 to May 2015: we reviewed 397 medical (n515), acute interstitial nephritis (AIN, n56), and Stevens-Johnson records of patients with suspected allergy reactions to AANSAID (patients syndrome/toxic epidermal necrolysis (SJS/TEN, n53). Median days of with NSAIDs intolerance were excluded). 127 patients were diagnosed to vancomycin therapy prior to HSR onset was 7 [3.5, 10] for LABD, 21 allergy to AANSAID (94 immediate reactions, 33 delayed reactions) [18,28] for DRESS, 26 [11,28] for AIN, and 9 [9.13] for SJS/TEN. Overall We performed patch tests (PT) on residual lesion and healthy skin with case fatality was 8/54 (14.8%), with no difference between immediate and ibuprofen (5% pet), naproxen (10% in DMSO) with reading at 24 hours. non-immediate HSRs (p51). Oral blind challenge test (OCT) was performed if PT were negative. CONCLUSIONS: Vancomycin causes a variety of HSRs; cases were RESULTS: Five patients were attended with clinical symptoms of FDE 6 most commonly non-immediate with LABD most frequently reported. We due to AANSAID: 3 women and 2 men. Mean age 47.6 11.9 years. observed a high frequency of HSR mortality. Further data are needed to Two cases were due to ibuprofen (40%) diagnosed by positive PT in identify the frequency and severity of vancomycin HSRs. residual lesion in both cases; 3 cases with naproxen (60%): 2 was diagnosed by positive PT in residual lesion (one case, the patient accepts Peer Survey of Alert Fatigue in Physicians in a performed OCT with ibuprofen, ketoprofen and nabumetone with negative 141 Large Inner City Training Hospital: Does It Affect results) and 1 case by anamnesis (OCT was not performed because of the Drug Allergy Surveillance? localization in genital zone). CONCLUSIONS: PT was useful in the diagnosis of FDE due to Adam El Sehamy, MD1,2, Naureen Kabani, MD1, Amanda AANSAID. Most frequent culprit drug was naproxen, followed by Nussdorf, BS.3, YiFeng Chen, MD4,5, Rauno Joks, MD2,6; 1Department ibuprofen. of Medicine, 2Center for Allergy and Asthma Research, 3College of Med- In our serie, 5 cases of 127 patients with allergy to AANSAID were icine, SUNY Downstate Medical Center, Brooklyn, NY, 4Department of diagnosed of FDE. Medicine at SUNY Downstate Medical Center, Brooklyn, NY, 5Center FDE is an uncommon manifestation of allergy to AANSAID. for Allergy and Asthma Research, Brooklyn, NY, 6Department of Medi- cine, SUNY Downstate Medical Center, Brooklyn, NY. RATIONALE: Electronic decision support (e.g. CPOE Alerts) is designed to help prevent errors and promote efficiency and safety with EMR. However, physicians may overlook frequent notifications with resultant adverse effects, including drug allergic reactions. Prevalence of this alert fatigue (AF) in physicians-in–training is understudied. We determined knowledge and manifestations of AF in resident and attending physicians at a large inner city hospital. METHODS: De-identified written surveys were completed by 105 physicians, resident (n588)(PGY-1 to PGY-5) and attending (n517), who were queried about 1) knowledge of, and 2), if knowledgeable, whether they ‘‘suffered’’ from AF. Percent of override of 1) drug interactions, 2) drug allergy, 3) duplicate order, and 4) discontinued orders All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. J ALLERGY CLIN IMMUNOL Abstracts AB45 VOLUME 137, NUMBER 2

Etiologies and Clinical Characteristics of 97 Patients Harvard Medical School, Boston, MA, 3Partners HealthCare System, Bos- 143 Diagnosed with Severe Cutaneous Adverse Reactions ton, MA, 4Harvard Medical School, Boston, MA. from Six Tertiary Medical Centers in Thailand RATIONALE: Angiotensin-converting enzyme inhibitors (ACEI) are the leading cause of drug-induced angioedema in the United States. Most Jettanong Klaewsongkram, MD1,2, Pawinee Rerknimitr, MD2,3, Ticha epidemiologic ACEI angioedema data are from large multi-center clinical Rerkpattanapipat, MD4, Kumutnart Chanprapaph, MD5, Papapit trials. Our objective was to identify the incidence and risk factors of ACEI Tuchinda, MD6, Leena Chularojanamontri, MD7, Napatra angioedema using a large integrated electronic health record (EHR). Tovanabutra, MD8, Wareeporn Disphanurat, MD9, Panlop METHODS: We conducted a retrospective cohort study of all ACEI Chakkavittumrong, MD9, Chutika Srisuttiyakorn, MD10, Pattarawat prescriptions over nine years at a large academic center. We determined Thantiworasit, MSc1,2, Chonlaphat Sukasem, B. Pharm, PhD11, Yuttana frequency, timing, and risk factors for ACEI angioedema considering five Srinoulprasert, MD, PhD12; 1Division of Allergy and Clinical Immu- years after prescription. All data were derived from EHR sources, with nology, Department of Medicine, Faculty of Medicine, Allergy and Clin- angioedema defined by EHR reactions of angioedema, swelling, edema, or ical Immunology Research Group, Chulalongkorn University, Bangkok, lip, face, tongue, throat or mouth swelling. Thailand, 2King Chulalongkorn Memorial Hospital, Thai Red Cross Soci- RESULTS: There were 134,945 patients prescribed ACEI between ety, Bangkok, Thailand, 3Division of Dermatology, Department of Medi- January 1, 2000 to September 30, 2008; 0.66% (n5888) developed cine, Faculty of Medicine, Chulalongkorn University, 4Allergy angioedema during the subsequent five years. Age and gender were similar Immunology and Rheumatology Division, Faculty of Medicine, Ramathi- but patients with hypertension (0.75% vs. 0.42%, p<0.0001) and NSAID bodi Hospital, Mahidol University, 5Division of Dermatology, Department allergy (1.10% vs. 0.64%, p<0.0001) were more likely to develop ACEI of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol Uni- angioedema than those without. We identified a 0.07% incidence of ACEI versity, 6Department of Dermatology, Faculty of Medicine Siriraj hospital, angioedema within one month and 0.23% incidence during the first 12 Mahidol University, 7Department of Dermatology, Faculty of Medicine, months. Incidence of angioedema was relatively constant over the subse- Siriraj Hospital, Mahidol University, 8Department of Internal Medicine, quent four years (0.10%-0.12%). Lisinopril (87.1%), enalapril (4.3%), and Chiang Mai University, 9Dermatology Unit, Department of Medicine, benazepril (3.0%) were the most common causative ACEI. Faculty of Medicine, Thammasat University, 10Division of Dermatology, CONCLUSIONS: The incidence of ACEI angioedema within a large EHR Department of Medicine, Phramongkutklao Hospital, 11Division of Phar- is consistent with large clinical trial data. While angioedema risk is twice as macogenomics and Personalized Medicine, 12Department of Immu- high in the first year, we observed a persistent and relatively constant risk nology, Faculty of Medicine Siriraj Hospital, Mahidol University. yearly for the next four years. Risk factors need to be studied further. RATIONALE: To analyze demographic data, clinical manifestations, and etiologies of drug-induced severe cutaneous adverse reactions (SCARs) in The Low Expression of Tim-3 in Patients with Thailand. 145 Maculopapular Exanthema (EMP) Induced By METHODS: Patients newly diagnosed with acute generalized exanthem- Drugs Can Impaired Disease Control. SATURDAY atous pustulosis (AGEP), drug reaction with eosinophila and systemic 1 1 symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic Tahia D. Fernandez, PhD , Francisca Palomares, PhD , Maria Salas, MD, PhD2, Inmaculada Dona,~ MD, PhD2, Esther epidermal necrolysis (TEN) between December 2013 and August 2015 2 1 1 and fulfilled criteria of probable or definite SCARs based on RegiSCAR Barrionuevo, MD, PhD , Adriana Ariza, PhD , Raquel Jurado , Miguel 3 1,4 validation criteria were prospectively recruited in our registry. Blanca, MD, PhD , Cristobalina Mayorga, PhD , Marıa Jose Torres, MD, PhD2; 1Research Laboratory, IBIMA-Regional University Hospital RESULTS: One-hundred and three SCAR patients were initially reported 2 from 6 tertiary medical centers. Six patients eventually diagnosed with of Malaga-UMA, Malaga, Spain, Allergy Unit, IBIMA, Regional Univer- 3 pustular psoriasis, exfoliative dermatitis, acrodermatitis enteropathica, or sity Hospital of Malaga, UMA, Malaga, Spain, Allergy Unit, Regional 4 generalized bullous fixed drug eruption were later excluded. The average University Hospital of Malaga-IBIMA, UMA, Malaga, Spain, Allergy age of 97 SCAR patients was 52.7 years (range 17-97). Sixty-five (67.0%) of Unit, IBIMA-University Hospital of Malaga, Malaga, Spain. them were female. DRESS, SJS/TEN, and AGEP were diagnosed in 39, 41, RATIONALE: In cutaneous non-immediate reactions to drugs, like EMP, and 17 patients, respectively. Allopurinol (21), aromatic anticonvulsants several lymphocyte subtypes are involved, mainly with a Th1-phenotype. (19), beta-lactam antibiotics (15), and sulfonamides (9) contributed to about However the involvement of other lymphocyte subtypes like Th17-cells two-third of all reported SCAR cases. Overall mortality rate was 8.2% (8/ has not been studied yet. Moreover, numbers of both lymphocyte subsets 97). Most common culprit drugs were phenytoin (10) in DRESS, allopurinol can be controlled by the interaction of the receptor Tim3 with Gal9 (12) in SJS/TEN, and beta-lactams (13) in AGEP. Lymphocyte trans- inducing their apoptosis. The aim of the study was to analyse the formation test and/or interferon-gamma enzyme-linked Immunospot assay expression of Tim3 in patients with drug induced EMP. have been performed in 34 cases and positive invitro drug allergy diagnostic METHODS: Peripheral blood cells (PBMC) and skin biopsies were tests were demonstrated in 25 tested patients (73.5% positive rate). obtained from 18 allergic patients and 10 tolerant subjects. Immunohistochemical staining and flow cytometry were carried out to CONCLUSIONS: Allopurinol and anticonvulsants were the most com- + + + mon causes of drug-induced severe cutaneous adverse reactions in determine the presence of Th1 (CXCR3 ) and Th17 (RORgt IL17 ) CD4- Thailand. In vitro tests for drug allergy diagnosis can be helpful to identify cells and the expression of Tim3. the culprit drugs. RESULTS: The involvement of Th1-CD4-cells in EMP were confirmed, with higher levels compared to controls in both, skin (p<0.0001) and PBMC Epidemiology and Incidence of ACE Inhibitor (p50.032 during the acute phase and p50.039 after resolution). However, 144 Angioedema Utilizing a Large Electronic Health we could not find any difference in the frequencies of Th17-cells between Record patients and controls. The expression of Tim3, was strongly decreased in patients (p<0.0001 in skin), mainly in Th1-CD4-cells during the acute phase Aleena Banerji, MD1, Kimberly G. Blumenthal, MD2, Kenneth H. (p<0.0001), but also after resolution (p50.039). Interestingly, the expres- Lai, MA3, Li Zhou, MD, PhD4; 1Division of Rheumatology, Allergy sion of Tim3 in Th17-cells was similar in patients and controls. and Immunology, Department of Medicine, Massachusetts General Hospi- CONCLUSIONS: The low expression of Tim3 in the effector cells during tal, Harvard Medical School, MA, 2Allergy and Immunology, Division of the acute phase could be the responsible of the impaired regulation of these Rheumatology, Allergy, and Immunology, Medical Practice Evaluation cells in EMP. Their low expression after resolution could serve as a Center, Department of Medicine, Massachusetts General Hospital, biomarker for these reactions. This axis could be a target to develop strategies to control and diagnose these reactions. All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. AB46 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2016

Allergy to Benznidazole: Cross-Reactivity with Intravenous provocation with heparin was not performed because of the 146 Other Nitroimidazoles severity of the episodes developed by the patient (4 anaphylaxis). CONCLUSIONS: - In this study the frequency of heparin allergy is low Blanca Noguerado, MD1, Patricia Rojas, MD2, Maria Calderon, MD3, but increasing, being the most common type of reaction delayed-type Cristina Morales, MD4, Pilar Tornero, MD5; 1Allergy Department. Hospi- hypersensitivity (DTH). tal General Universitario Gregorio Maranon,~ madrid, Spain, 2Hospital - We observed a high cross-reactivity among LMWHs and Heparin. General Universitario Gregorio Maranon,~ Department of Allergy, madrid, - Challenge is considered the gold standard for the diagnose, being the clin- Spain, 3Internal Medicine Department. Hospital General Universitario ical findings similar to previous reported. Gregorio Maranon,~ 4Department of Allergy, Gregorio Maran~on University Hospital, Madrid, Spain, 5Allergy Department. Hospital General Univer- Allergy Patterns in a Tertiary Care Referral Center sitario Gregorio Maranon.~ 148

RATIONALE: Benznidazole (Bzn) is a nitroimidazole drug used as first- 1 2 line treatment for Chagas disease, a potentially life-threatening illness Maria A. Barcena Blanch, MD , Julie T. Abraham, MD , David M. Lang, MD, FAAAAI3; 1Cleveland Clinic Foundation, Cleveland, OH, caused by Trypanosoma cruzi. Many adverse effects had been reported 2 3 with it, including allergy reactions such as exanthemas, dermatitis and Cleveland Clinic, Cleveland, OH, 9500 Euclid Avenue - A90, Cleveland AGEP. Alternative therapeutic nitroimidazole drugs for this group of pa- Clinic, Cleveland, OH. SATURDAY tients are important for treatment of other parasitic infections. We aim to RATIONALE: We have analyzed contents of the ALLERGY field in our study hypersensitivity reactions to Bzn and cross-reactivity with metroni- electronic medical record (EMR), to identify rates and characteristics of dazole (Mtn), another nitroimidazole drug. self-reported ‘‘allergy’’ in a large tertiary care referral center population. METHODS: Five patients with non-immediate skin reactions due to Bzn, METHODS: Demographic and allergy data were extracted from our EMR all presented with maculo-papular exanthema, were referred to our Allergy for outpatients and inpatients with point-of-care assessment of ‘‘allergy’’at Department. Patch tests (PT) with Bzn 10% and Mtn 10% in DMSO, were Cleveland Clinic (CC) sites in the USA, from August 1988 to August 2015. made with readings at day 2 (D2) and D4. Single blind oral challenge test RESULTS: A total of 7,814,799 (51% males, 47% females) patients were (SBOCT) was performed in patients with allergy confirmed to Bzn and evaluated at CC; 1,491,102 self-reported ‘‘allergies’’ were recorded. The negative PT with Mtn. top 10 were penicillin, sulfa, codeine, amoxicillin, morphine, seasonal RESULTS: PT with Bzn were positive in 5/5 patients (100%) at D2 and allergies, aspirin, latex, contrast, and iodine, which comprised 87.5% of all D4. PT with Mtn were negative in 4/5. Only one patient had both positive reported items. Beta-lactams accounted for 47% of the total, sulfa 24%, PT. SBOCT with Mtn was negative in all of them (4/4). codeine 13%, morphine 6%, aspirin 6%, latex 5.4% and ACE-inhibitors CONCLUSIONS: PTwith Bzn was diagnostic in 100% of patients so was 2.8%. Drug allergy to these items was more frequent in males (72%) very useful for the diagnosis, suggesting type IV-hypersensitivity mech- compared to females (28%) and patients over age 35: 35-65 years (45%) anism. Cross-reactivity between Bzn and Mtn was low, only found in 1 and 65 and older (39%). Penicillin allergy was reported in 4.6% of the total patient that was sensitizated to both nitroimidazoles. 100% of patients with population, with the highest prevalence in ages 35-65. Patients age 0-17 negative PT to Mtn had negative SBOCT (negative predictive value of were more likely to report amoxicillin than penicillin allergy (47% vs. 32%). There was a statistically significant difference for penicillin allergy 100%). We think that is important to test both drugs in these patients in 2 order to give them alternative therapeutic treatment for other parasitosis in males compared to females (p<0.05, X ). Frequency of ACE-inhibitor disease. reported allergy was higher in males and African-Americans. CONCLUSIONS: The overwhelming majority of self reported ‘‘allergy’’ Allergy to Heparins involves antibiotic or analgesic medications. These data highlight the 147 substantial morbidity related to medications, particularly beta-lactams, withheld due to self-reported ‘‘allergy’’ in a large tertiary care center Francisco Javier Ruano Perez, MD1, Diana Perez Alzate, MD2, Natalia population. Blanca-Lopez, MD PhD2, Maria Luisa Somoza, MD2, Maria Vazquez De La Torre, MD3, Maria Isabel Garcimartin, MD2, Elisa Haroun, MD1, Ga- briela Canto, MD, PhD2; 1Infanta Leonor - Universitary Hospital, Madrid, Spain, 2Allergy Unit. Infanta Leonor University Hospital, Madrid, Spain, 3Infanta Leonor, University Hospital, Madrid, Spain. RATIONALE: The Incidence of reactions to heparins may be higher than previously thought. Extensive cross-reactivity among unfractionated hep- arin and low molecular weight heparins (LMWH) has been described. Aim: To characterize the patients with hypersensitivity to Heparins and the cross-reactivity among heparins in our clinical practice. METHODS: Retrospective study was performed in our Allergy Unit from 2013-2015. Clinical data were registered from all patients who developed heparins hypersensitivity. Skin/challenge test were performed with the heparin involved and with others LMWH. RESULTS: From a total of 20 patients, 10 were finally diagnosed of allergy to at least one heparin. Mean age: 61,25y.o. From these, 37.5% had other drug allergies (NSAID, Contrast agents) and 37.55% were atopic. Nine out of 10 cases developed cutaneous symptoms and one anaphylaxis. Patch test with the suspected drug was positive in one case to Bemiparin and Enoxaparin. Prick/ID were performed in all patients, with one positive result in delayed reading. Positive Subcutaneous challenge were: Enoxaparin in 40%, Bemiparin in 10%, Enoxaparin and Bemiparin i30%, Enoxaparin, Bemiparin, Nadroparin, Tinzaparin and Heparin in 10% and Heparin in10%. All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. J ALLERGY CLIN IMMUNOL Abstracts AB47 VOLUME 137, NUMBER 2

Allergic Reactions to Dipyrone: Immediate and performed. Cross-reactivity to histamine H2receptor antagonists was also 149 Non-Immediate Responses distinguished. RESULTS: Over 7 years, 584 patients suffered adverse reactions to Inmaculada Dona,~ MD, PhD1, Francisca Gomez, MD, PhD2, Tahia D. ranitidine. The most common manifestation was cutaneous symptoms. Fernandez, PhD3, Adriana Ariza, PhD3, Arturo Ruiz, MD4, Maria Isabel Among them, 99 patients (17.0%) experienced anaphylaxis. In a single- Sanchez Rivas5, Cristina De Leyva5, Maria Isabel Montanez~ 6, Antonio center study, skin prick tests were positive in 91.7% of ranitidine-induced Guzman7, Miguel Blanca, MD, PhD1, Maria J. Torres, MD, PhD8; 1Al- anaphylaxis patients. Cimetidine and proton pump inhibitors showed no lergy Service, IBIMA-Regional University Hospital of Malaga-UMA, cross-reactivity with ranitidine based on the skin prick test, oral Malaga, Spain, 2Allergy Unit, IBIMA-Regional University Hospital of provocation test, or clinical determination. Surprisingly, 19 patients Malaga, Malaga, Spain, 3Research Laboratory, IBIMA-Regional Univer- (82.6%) re-introduced ranitidine and re-experienced the same adverse sity Hospital of Malaga-UMA, Malaga, Spain, 4Allergy Unit, Regional reactions because ranitidine was not considered the culprit drug. University Hospital of Malaga-IBIMA, UMA, Malaga, Spain, 5Allergy CONCLUSIONS: Although ranitidine is known as a safe drug, it can also Unit, Regional University Hospital of Malaga-IBIMA, UMA, Malaga, cause diverse adverse reactions, including anaphylaxis. This study Spain, 6Research Laboratory, IBIMA, Regional University Hospital of demonstrates the need to pay attention to adverse reactions to ranitidine Malaga, UMA, Malaga, Spain, 7Pharmacy Unit, Regional University Hos- and consider ranitidine as a cause of anaphylaxis. pital of Malaga-IBIMA, UMA, Malaga, Spain, 8Allergy Unit, Regional University Hospital of Malaga, IBIMA, UMA, Malaga, Spain. Broken Heart Syndrome (Takotsubo Cardiomyopathy) RATIONALE: Pyrazolones are the most common cause NSAIDs hyper- 151 Induced By Epinephrine

sensitivity. We studied a large group of patients with immediate and non- 1 1 immediate selective responses (SR) to dipyrone. Muhammad A. Imran, MD , Haroon Khalid, MBBS , Saima Karim, DO2, Selina A. Gierer, DO3; 1University of Kansas Medical Cen- METHODS: Patients with suspiction of hypersensitivity to dipyrone were 2 3 evaluated. We verified acetilsalicilic acid-tolerance and classified patients ter, Yale School of Medicine, CT, University of Kansas Medical Center, as immediate or non-immediate responders if they showed symptoms less Kansas City, KS. or more than 1hour after dipyrone administration. Skin tests were RATIONALE: Takotsubo cardiomyopathy is characterized by transient performed and if negative, basophil activation test (BAT) for immediate acute systolic cardiac failure that mimics myocardial infarction in the responders. If negative results, we performed drug provocation test (DPT) absence of underlying coronary artery disease. with dipyrone. METHODS: A 21-year-old Caucasian female presented with acute RESULTS: A total of 137 patients were included: 114 reacted within one oropharyngeal angioedema without urticaria. On physical examination hour (single NSAID-induced urticaria/angioedema/anaphylaxis; she had angioedema of the lips, tongue and normal vital signs. She was SNIUAA); 23 after one hour (single-NSAID-induced delayed hypersen- incorrectly administered epinephrine 0.3 mg (1:1000) intravenously rather sitivity reactions; SNIDHR). More specifically, 73.72% reacted within 30 than intramuscularly. Over the following hours, she developed hypoten- sion, tachycardia and tachypnea which required intubation and vasopres- minutes; 9.48% 30-60 minutes; 6.56% 1-2 hours; 3.64% 2-8 hours and SATURDAY 6.56% after over 24 hours. Most SNIUAA patients developed anaphylaxis sors. A chest X-ray revealed bilateral diffuse alveolar opacities consistent (66.66%, p50.0001); for SNIDHR urticaria was more frequent (52.17%, with pulmonary edema. An electrocardiogram showed sinus tachycardia p50.014). Skin testing was positive for 62.04% of all cases and BAT for and a transthoracic echocardiogram revealed a left ventricular ejection 35.89% of SNIUAA patients with negative skin tests. In 5.1% cases DPT fraction of 10% with global hypokinesis. Over the next 48 hours, her blood with dipyrone was needed. In 22.62% of cases DPT was not indicated, pressure normalized, hypoxia resolved and she was successfully extubated. being diagnosed by repeated allergic episodes in spite of negative skin and Repeat echocardiogram on days 3 and 5 demonstrated significant BAT. improvement in ejection fraction, 30% and 50%, respectively. Cardiac CONCLUSIONS: SNIUAA to dipyrone is the most frequent group with catheterization did not reveal evidence of coronary artery disease. anaphylaxis being the most common clinical entity. It may occur with RESULTS: The pathophysiology of Takotsubo cardiomyopathy has been interval longer than 1hour. The SNIDHR occur in a very low percentage. attributed to catecholamine- induced myocardial toxicity and coronary The low sensitivity of diagnostic tests may be due to incomplete vasospasm. The combination of high dose and fast infusion rate of characterization of the chemical structures of dipyrone and its metabolites. epinephrine may have provoked our patient’s cardiomyopathy. Despite the grave presentation of Takotsubo cardiomyopathy, it is usually rapidly Adverse Drug Reactions of Ranitidine: A reversible with a good prognosis. 150 Pharmacovigilance Study in Korea CONCLUSIONS: Prompt intramuscular administration of epinephrine 0.3 mg (1:1000) is the cornerstone of treating anaphylaxis. Epinephrine at a Kyung Hee Park1, Da Woon Sim1, Hye Jung Park1, Kyoung-Yong concentration of 1:1000 intravenously should generally be avoided for the Jeong2, Jae-Hyun Lee1, Jung-Won Park1; 1Division of Allergy and Immu- treatment of anaphylaxis due to risk of iatrogenic Takotsubo cardiomyop- nology, Department of Internal Medicine, Yonsei University College of athy. If intravenous epinephrine is needed, 0.1 mg (1:10,000) should be Medicine, 2Institute of Allergy, Yonsei University College of Medicine, administered with caution (at a slow rate). Seoul, South Korea. RATIONALE: Ranitidine is widely prescribed medication and are known to be safe. However, there were 99 ranitidine-induced anaphylaxis patients in pharmacovigilance study of ranitidine in Korea. The purpose of this study was to determine the incidence, clinical features, and diagnostic methods for ranitidine-induced anaphylaxis. METHODS: Ranitidine-related pharmacovigilance data from 2007 to 2014 were reviewed. Adverse drug reactions with causal relationships were selected and clinical characteristics analyzed including anaphylaxis. Clinical manifestations, outcomes, and administration-related information were assessed. For further investigation, 8 years of pharmacovigilance data were collected at a single center. Twenty-three ranitidine-induced anaphy- laxis patients participated in in vivo and in vitro studies. Skin prick tests, intradermal tests, oral provocation tests, and laboratory tests were All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. AB48 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2016

Systemic Reactions to Aeroallergen Analysis of Venom Hypersensitivity Reactions and 152 Immunotherapy: A Retrospective Review of Our 154 Subsequent Preventative Management in VA Practice Patient Population

Matthew T. Tallar, MD1, Leslie M. Gimenez, MD, FAAAAI2, Heidi T. V. Priya J. Patel, MD1, Alan H. Wolff, MD2; 1Rutgers - New Jersey Medical Zafra, MD, FAAAAI3, Asriani M. Chiu, MD, FAAAAI3; 1Medical Col- School, Newark, NJ, 2Rutgers New Jersey Medical Center, Newark, NJ. lege of Wisconsin, 2Medical College of Wisconin, Milwaukee, WI, 3Med- RATIONALE: According to the latest practice parameter, referral to an ical College of Wisconsin, Milwaukee, WI. allergist is appropriate for any patient who has had an allergic reaction to RATIONALE: Aeroallergen Immunotherapy (AIT) is a proven and hymenoptera and is a potential candidate for immunotherapy. As a quality effective treatment for patients with allergic disease. Unfortunately, it is control measure, we determined whether physicians at our hospital not without risks. The rate of systemic reactions (SR) has been estimated to followed this recommendation. We also looked to see if patients with be approximately 0.1% of injection visits in 2-5% of patients. We have systemic reactions had been prescribed epinephrine for self- noticed an increased frequency of SR in our clinic over the past several administration. years and hypothesize that our rate of reactions is higher than current METHODS: We searched our electronic medical records for all patients estimates. with a documented history of insect allergy. The type of reaction was METHODS: Eighteen patients fit inclusion criteria of having a systemic determined to be systemic, local or unclear. We also determined if SATURDAY reaction to AIT between 11/1/12 and 10/31/14. Controls (n548) were epinephrine was prescribed, if there was a referral to an Allergist and gathered from two immunotherapy appointment slots directly before and whether venom immunotherapy was offered if indicated. after patients with a systemic reaction. RESULTS: Of the 620 veterans with a documented insect allergy, about RESULTS: The number of systemic reactions per visit at our institution 61% had a systemic reaction, 6% had a local reaction and the rest of the over the study period was 0.002%. Sixty six percent of patients had a grade descriptions were unclear. Only 53% of those with a systemic reaction were 2 systemic reaction. Patients with systemic reactions were more likely to prescribed epinephrine, although in 67% the prescription was expired. have had a previous systemic reaction (p 5 0.0012, OR 8.6, CI 2.32-31.81) Allergy and Immunology consultation was obtained in 12% of those or large local reaction (p 5 0.02, OR 5.5, CI 1.33-22.69) compared to the identified as having a systemic reaction. control population. CONCLUSIONS: A surprisingly low percent of patients with systemic CONCLUSIONS: In our program, the major risks for a systemic reaction reactions to venom stings saw an Allergist and were prescribed self- to immunotherapy were a prior systemic or large local reaction. Systemic injectable epinephrine. Also very few of these patients had active reactions occurred less frequently in our program than what is reported in prescriptions for their epinephrine. It is important to educate physicians the literature. As part of a quality improvement initiative we demonstrated to prescribe self-injectable epinephrine and refer to an Allergist when a the overall safety of our immunotherapy program. systemic reaction to venom allergy is identified.

Safety and Efficacy of Hymenoptera and Fire Ant Platelet Activating Factor Acetylhydrolase Levels 153 Rush Immunotherapy in Children 155 at Baseline and during Allergic Reactions

Wiparat Manuyakorn, MD, PhD, Suwat Benjaponpitak, MD, Wasu Jacob D. Kattan, MD1, Thomas Kraus, PhD1, Thomas Moran, PhD1, Kamchaisatian, MD, Cherapat Sasisakulporn, BSc, Wanlapa Teawsom- Hugh A. Sampson, MD, FAAAAI2; 1Icahn School of Medicine at Mount boonkit, RN; Division of Pediatric Allergy and Immunology, Department Sinai, New York, NY, 2Department of Pediatrics, Icahn School of Medi- of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol Uni- cine at Mount Sinai, New York, New York, USA. versity, Bangkok, Thailand. RATIONALE: Platelet Activating Factor Acetylhydrolase (PAF-AH) RATIONALE: This study was to evaluate the safety and efficacy of rush activity has been inversely correlated with allergic reaction severity. We immunotherapy (RIT) with hymenoptera and fire ant and identify risk sought to develop a rapid assay to quantify PAF-AH, to determine its utility factors for systemic reactions (SRs) in children. in the diagnosis of anaphylaxis, and to examine its use as a baseline marker METHODS: A 10 year retrospective review was conducted in children of potential anaphylaxis severity. receiving hymenoptera and/or fire ant RIT. The 3-days RIT protocol METHODS: Monoclonal antibodies to PAF-AH were produced in a consisted of hourly subcutaneous injections to achieve the maintenance murine model and used to develop a Luminex assay for quantifying PAF- dose 100mg of hymenoptera venom or 0.5 ml of 1: 100 wt/vol fire ant. AH. Blood samples were obtained from healthy controls and subjects Safety of RIT was assessed using Subcutaneous Immunotherapy Systemic presenting to the emergency department with allergic reactions. Subjects Reaction Grading System. Efficacy was assessed by the reaction after from the emergency department were followed-up as outpatients and a exposure. baseline blood sample was obtained. RESULTS: Fifty children were reviewed: 22 with fire ant, 17 with honey RESULTS: The PAF-AH assay was tested in 24 healthy adults at 2 time bee, 20 with mixed vespid, 2 with paper wasp RIT. Eleven children points 1 month apart. Median PAF-AH levels were 33.20 ng/mL for received 2 different allergens RIT. The mean age was 10.06+ 2.78 years. healthy controls at visit 1; 33.35 ng/mL at visit 2. 59 subjects presenting 92% of studied children were male. 32 systemic reactions (3.93%) were with an allergic reaction have been enrolled; 18 subjects have followed-up occurred in 814 RIT shots: 10 (1.2%) grade I SRs, 18(2.2%) grade II SRs for baseline visits. The median PAF-AH level (42.73 ng/mL) was higher at and 4(0.49%) grade III SRs. There was no association of SRs with age, baseline in the allergic subjects (P50.05) and significantly higher at the gender, atopic history, the level of IgE sensitization and type of insect. time of the allergic reaction (47.70 ng/mL, P<0.001) compared to the Among 23 patients experienced accidental exposure, 6 patients had no healthy controls. In subjects who returned for baseline visits, the PAH-AH reaction, 1 patient developed grade II reaction and 3 children with fire ant levels were higher in 15 (83.3%) subjects at the time of the allergic reaction RIT experienced grade III systemic reaction. However, these gr III (median increase 21.8% compared to baseline). reactions were resolved after increased the maintenance dose to 0.5 ml CONCLUSIONS: PAF-AH levels were similar when measured one of 1:50 wt/vol fire ant. month apart in healthy controls. The majority of subjects had higher CONCLUSIONS: Rush immunotherapy with hymenoptera and fire ant in PAF-AH levels at the time of the allergic reaction compared to baseline, children is safe and has low severe systemic reaction. It is an alternative likely reflecting increased levels of Platelet Activating Factor. treatment for patients requiring rapid protection. All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. J ALLERGY CLIN IMMUNOL Abstracts AB49 VOLUME 137, NUMBER 2

Baseline CD63 Expression in Patients with a novel strategy for treating these patients when they must continue to 156 Exercise Induced Anaphylaxis (EIA) exercise.

Liat Nachshon, MD1, Moshe Appel, PhD1, Michael R. Goldberg, MD, Wheat-Dependent, Exercise-Induced Anaphylaxis PhD1, Arnon Elizur, MD1,2, Yitzhak Katz, MD, FAAAAI1,2; 1Assaf Har- 158 Can be Elicited without Exercise (And With ofeh Medical Center, Zerifin, Israel, 2Department of Pediatrics, Sackler Other Co-factors)

School of Medicine, Tel Aviv, Israel. 1,2 1,2 RATIONALE: Exercise-induced anaphylaxis is a rare, potentially fatal Morten J. Christensen, MD , Esben Eller, MSc, PhD , Charlotte G. Mortz, MD, PhD1,2, Knut Brockow, MD3,4, Carsten Bindslev-Jensen, syndrome diagnosed by an exercise challenge. No cellular correlates are 1,2 1 definitively associated with this syndrome. The relevance of the Basophil MD, PhD, DMSci, FAAAAI ; Department of Dermatology and Allergy Center, Odense University Hospital, Odense, Denmark, 2Odense Research Activation Test (BAT) as an EIA marker was investigated. 3 METHODS: Patients with medically documented EIA (n54, two without Center for Anaphylaxis (ORCA), Odense, Denmark, Department for 5 Dermatology and Allergy Biederstein, Klinikum rechts der Isar, TU Mu- atopic background), and controls (n 4), were evaluated by standardized 4 pulse-controlled ergometry followed by maximal effort treadmill running. nich, Munich, Germany, Technical University Munich, Munich, The exam was stopped with the first objective signs of an allergic reaction Germany. or upon physical fatigue. Whole blood before and after exercise, was RATIONALE: Wheat-Dependent, Exercise-Induced Anaphylaxis incubated with RPMI and IL3 or with addition of anti-IgE. Bloods from six (WDEIA) is a distinct clinical entity of wheat allergy characteristically atopic patients without EIA, were also tested. The ratios of the geometric elicited during exercise. We investigated if a clinical reaction could be mean fluorescent intensities of APC-anti CD63 or PE-anti CD203c over elicited by intake of high amounts of gluten without exercise or by intake of those of their respective isotype controls (termed CD63-Ratio and CD203- gluten together with aspirin. Ratio, respectively), were calculated on HLA-DR-, CD123+ gated METHODS: We prospectively investigated 30 patients (age 20.2 – 71.0 basophils. years) with a case-history of WDEIA. Diagnostic workup included RESULTS: The CD63-Ratio in IL3-treated basophils was significantly specific-IgE (s-IgE), (ThermoFischer, Uppsala, Sweden): 26 positive to higher in EIA patients than in controls, in samples taken before exercise omega-5 gliadin (mean 12.0 kU/L [1.14-46.7]) and Skin Prick Test (SPT) (ranges: 5.2-8.7 versus 2.8-3.7, respectively, p50.03 Student’s two-tailed with wheat flour (28 positive, mean 6.3mm [3.0-10.0]) and gluten (28 t test) and after exercise (ranges: 3.9-7.9 versus 2.2-2.9, p50.04). No positive, mean 5.7mm [3.0-11.5]). Titrated oral challenge was performed 5 differences in CD203-Ratio were observed between the EIA and control with refined gluten (80g) at rest (n 30) and combined with exercise on a 5 5 groups. Interestingly, the CD63-Ratio for the atopic, non-EIA patients treadmill (n 30) or with aspirin 1000mg (n 14) on separate days. (range: 3.8-8.0) was also elevated in relation to the controls (p50.004). No RESULTS: WDEIA was confirmed by challenge either at rest without 5 5 differences in the CD63-Ratio or the CD203-Ratio between the EIA and cofactors (n 16) or with exercise as a co-factor (n 30). Threshold for the control groups were observed in anti-IgE treated basophils, before or after clinical reaction was lowered (mean 65 %) when oral challenge was combined with exercise (n530) or with aspirin in (n513). Nine of the 13 exercise. SATURDAY CONCLUSIONS: The elevated baseline CD63 expression in EIA patients aspirin positive patients experienced lower threshold with aspirin than may reflect a reactive basophil population, which may emerge indepen- during exercise. Concomitant with a lower threshold, severity score dently of atopy. (Sampson 2003) was higher in the majority of the patients with addition of exercise (n 5 18) or aspirin (n58). Exercise-Induced Anaphylaxis Successfully Treated CONCLUSIONS: Open oral gluten challenge at rest and/or in combina- 157 with Hydroxychloroquine tion with exercise or aspirin is a sensitive test for diagnosing WDEIA. The reaction can be elicited at rest, rendering exercise and other cofactors such Aaron K. Kobernick, MD, MPH1, Maya R. Jerath, MD PhD2; 1Univer- as aspirin facilitators lowering threshold and increasing severity of the sity of North Carolina, Chapel Hill, NC, 2University of North Carolina at reaction. Chapel Hill, Chapel Hill, NC. RATIONALE: Exercise-induced anaphylaxis is a diagnosis that presents unique challenges for patients whose livelihood is dependent on their ability to physically exert themselves. For patients refractory to suppres- sive antihistamine therapy and unable to practice avoidance, alternative treatment modalities are not well described. We report a case of recurrent, exercise-induced anaphylaxis in a young man in the military, successfully treated with hydroxychloroquine. METHODS: After treatment failure with histamine blockade, a trial of hydroxychloroquine was performed. RESULTS: The patient is a 32 year-old man in the military who experienced several episodes of anaphylaxis associated with exercise. The typical episodes would occur during very strenuous anaerobic episodes, such as weight lifting, and involve cutaneous, gastrointestinal, and cardiovascular symptoms. The usual causes of anaphylaxis, such as food allergy, medication reaction, mastocytosis, cholinergic urticaria, and food-exercise associated anaphylaxis were considered and systematically ruled out. The patient did not improve with suppressive antihistamine therapy. Two months after the addition of hydroxychloroquine 200 milligrams twice daily, the patient experienced no further anaphylactic reactions and was able to resume high-intensity exercise. He will remain on hydroxychloroquine indefinitely. CONCLUSIONS: To our knowledge, we report the first case of exercise- induced anaphylaxis successfully treated with hydroxychloroquine. Immunomodulatory therapy for exercise-induced anaphylaxis represents All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. AB50 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2016

Pretreatment with Ibrutinib, a Bruton's Tyrosine respectively, p50.02) and lower thigh circumference (22.75 vs 25.54, 159 Kinase Inhibitor, Reduces Passive Systemic respectively, p<0.001). There was a significant positive correlation of thigh Anaphylaxis in a Murine Model circumference and STBD (R5 0.7, P<0.001).Thigh circumference of 25 cm provides the sensitivity of 79.3% and specificity 50% in predicting Jennifer A. Regan, MD, PhD1, Rebecca Krier-Burris, MS2, Jeremy STBD at least 1 inch. O’Sullivan, PhD3, Paul Bryce, PhD4, Bruce S. Bochner, MD, FAAAAI5; CONCLUSIONS: A large proportion of infants may be a risk of having 1Department of Medicine, Division of Allergy-Immunology, North- adrenaline prefilled syringe to intraosseous route when using 1 inch needle. western University Feinberg School of Medicine, IL, 2Northwestern Uni- versity, 3Department of Medicine, Division of Allergy-Immunology, Effects of Intramuscular Epinephrine on Northwestern University Feinberg School of Medicine, 4Division of Al- 161 Cardiovascular Parameters during IgE-Mediated lergy-Immunology, Department of Medicine, Northwestern University Allergic Reactions to Peanut 5 Feinberg School of Medicine, Chicago, IL, Department of Medicine, Di- 1 2 vision of Allergy-Immunology, Northwestern University Feinberg School Monica Ruiz-Garcia, MD , Carl Hayward, MD, PhD , Alistair Tang, BSc1, Andrew Clark, MRCPCH, MD3, Isabel J. Skypala, PhD, of Medicine, Chicago, IL. 1,4 2 RATIONALE: There is an unmet need for therapeutics able to prevent RD , Stephen R. Durham, MA, MD, FRCP , Alexander R. Lyon, PhD, FRCP2,4, Robert J. Boyle, MBChB, PhD5, Paul J. Turner, FRACP, serious allergic reactions including food allergy and anaphylaxis. Bruton’s 1,6 1 2 SATURDAY PhD ; Imperial College London, United Kingdom, National Heart tyrosine kinase (Btk) has been shown to be critical for allergen reactivity in 3 mast cells and basophils by transducing high affinity IgE receptor and Lung Institute, Imperial College London, United Kingdom, Depart- ment of Medicine, University of Cambridge, Cambridge, United crosslinking signals into cellular activation and mediator release. We 4 sought to determine the effect of ibrutinib, an FDA-approved, irreversible Kingdom, Royal Brompton and Harefield NHS Foundation Trust, Lon- don, United Kingdom, 5Section of Paediatrics, Imperial College London, Btk inhibitor for B cell malignancies, on systemic anaphylaxis using a 6 murine model. United Kingdom, University of Sydney, Australia. METHODS: Anaphylaxis was induced in BALB/c mice using an RATIONALE: Intramuscular (IM) epinephrine (adrenaline) is the established model for passive systemic anaphylaxis. In brief, mice were treatment of choice for anaphylaxis but little data exists on the sensitized by intravenous injection of 50 mg of ovalbumin (OVA)-specific cardiovascular effects of IM epinephrine during anaphylaxis, as such IgE, then 24 hours later challenged by systemic administration of 50 mg episodes typically occur outside a medical facility. OVA. To test the effect of ibrutinib, mice were pretreated with 12.5 mg/kg METHODS: Seven peanut-allergic adults who experienced anaphylaxis ibrutinib or vehicle control via gastric gavage either as a single treatment (3 (and received IM epinephrine) during double-blind, placebo-controlled hours) or two treatments (23 and 3 hours) prior to OVA challenge. food challenges to peanut (as part of the TRACE Peanut Study) were RESULTS: Pretreatment with ibrutinib compared to vehicle control evaluated using continuous 12-lead ECG and non-invasive haemodynamic inhibited passive systemic anaphylaxis as determined by a reduction of monitoring. Heart rate (HR), stroke volume (SV), systolic and diastolic drop in body temperature and an improvement in clinical scores. Inhibition blood pressure (sBP, dBP), cardiac output (CO), total peripheral resistance was observed with both the single and dual ibrutinib pretreatment (TPR), PR, QRS and QTc intervals were measured. Skin blood flow was regimens. measured using laser Doppler. CONCLUSIONS: These findings suggest that ibrutinib inhibits systemic RESULTS: Administration of 0.5mg epinephrine IM resulted in a anaphylaxis in a murine model. Blockade of the Btk pathway may significant improvement in symptoms, but did not result in consistent represent an achievable and clinically relevant therapeutic approach for and clinically relevant effects on measures of cardiovascular physiology or prevention of anaphylaxis. ECG between individuals. There was a small increase in HR (median 4.4 bpm, P50.03) and QTc interval (14.8ms, 4-22.9ms, P50.02) but the Optimal Needle Length of Epinephrine Prefilled clinical relevance is unclear. No significant changes were found for the 160 Syringe in Thai Infants other parameters studied. No participant required a second dose of epinephrine. Buntita Bamrungchaowkasem, MD1, Wiparat Manuyakorn, MD, PhD1, CONCLUSIONS: These preliminary data suggest a limited and incon- Nichanun Ruangwattanapaisarn, MD2, Suwat Benjaponpitak, MD1, Wasu sistent effect of a single dose of IM epinephrine on cardiovascular Kamchaisatian, MD1; 1Division of Pediatric Allergy and Immunology, measurements during food-triggered anaphylaxis. The data are limited Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Ma- by the small sample size and nature of the reactions experienced, with no hidol University, Bangkok, Thailand, 2Department of Radiology, Faculty participant having refractory anaphylaxis. Further work is needed to of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, identify determinants of a prompt physiological response to epinephrine Thailand. during allergic reactions. RATIONALE: Intramuscular epinephrine is the first line drug in the treatment of anaphylaxis. Epinephrine prefilled syringe is an alternative prescription instead of epinephrine auto-injector, especially in developing countries. CDC has recommended 1 inch (2.54 cm) needle for intramus- cular injection in infants. The current study was to find the optimal needle length for epinephrine prefilled syringed in infants METHODS: Infants between the age of 1 month to 2 years with normal weight and height were enrolled. Skin to muscle depth(STMD) and skin to bone depth(STBD) measurement using ultrasound at the mid-anterolateral thigh were performed by radiologist. RESULTS: Seventy-five infants were enrolled. STMD were ranged from 0.46 to 2.08 cm. STBD were ranged from1.31 to 3.56 cm. Twenty-nine infants (38.6%) had STBD less than 1 inch. Comparison between infants who had STBD less than 1 inch and those with STBD at least 1 inch, 69% of infants who had STBD less than 1 inch were male while 19% of infants who had STBD at least 1 inch were male (P50.02). Infants who had STBD less than 1 inch had a significant lower body mass index (15.77 vs 16.88, All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. J ALLERGY CLIN IMMUNOL Abstracts AB51 VOLUME 137, NUMBER 2

Correct Use of Epinephrine Autoinjectors in Prescription of Epinephrine Autoinjectors to 162 Relation to Health Literacy in Patients with Food 164 Children with Food Allergies in a General Allergies Pediatric Clinic

Maureen Egan, MD, Julie Wang, MD, FAAAAI; Icahn School of Med- Tamar Weinberger1, Ari Zelig, MD2, Allison Gault, MD1, Julie Wang, icine at Mount Sinai, New York, NY. MD, FAAAAI1; 1Icahn School of Medicine at Mount Sinai, New York, RATIONALE: Anaphylaxis occurs in an estimated 1.6% of the United NY, 2Albert Einstein College of Medicine, Bronx, NY. States population with food allergies being the trigger in 31% of cases. RATIONALE: Current guidelines recommend the prescription of Epinephrine Autoinjectors (EA) are essential in management of anaphy- epinephrine autoinjectors to all children with food allergies. We assessed laxis. A national assessment of health literacy noted that 44% of adults whether specific factors are associated with general practitioners’ pre- have below or basic health literacy, which is associated with adverse health scription of epinephrine autoinjectors to children with food allergies. outcomes. However, no study to date has examined the correct use of EA in METHODS: A retrospective chart review was performed of children with relation to health literacy. a diagnosis of food allergy over a one-year period from a general pediatrics METHODS: Parents of children with known food allergies who had practice. Charts were reviewed for prescription of epinephrine, type of food previously been prescribed an EpiPen were included. Participants were allergy, age, sex, prior systemic reaction or anaphylaxis, coexisting asthma, administered the Newest Vital Sign (NVS), a validated instrument to assess atopic dermatitis, environmental allergies, and emergency department health literacy. Additionally, subjects demonstrated use of an EpiPen that visits for allergic reactions or asthma exacerbations. was evaluated based on a previously established 6 step checklist. RESULTS: Of the 317 charts analyzed, 139 had documented peanut and/ RESULTS: 38 subjects were approached, 2 declined to participate. Of the or tree nut allergy. 76.3% of those with peanut and/or tree nut allergy 36 parents included, 8.3% had a score of 0-1 on NVS assessment indicating received epinephrine prescriptions compared to 53.9% among those a high likelihood of limited literacy, 16.7% had a score of 2-3 indicating without (p<0.001). Patient’s with a history of anaphylaxis were also possible limited literacy while 75% patients had a score of 4-6 indicating more likely to receive a prescription (78.6% versus 58.4%, p50.001) as likely adequate health literacy. Amongst patients with a NVS score of <4, were asthmatic patients (68.8% versus 56.3%, p50.023). After adjusting 44% (4/9) demonstrated correct use of an EpiPen (correct use defined as for confounding variables, children with peanut and/or tree nut allergy proper demonstration of all 6 steps). Among patients with a NVS of >_4, were 2.2 times more likely to receive prescriptions for epinephrine 48% (13/27) demonstrated correct use. The difference between the groups (OR52.20 (95% CI 1.29-3.75, p50.004)) and children with prior was not statistically significant (p50.85). anaphylaxis were twice as likely to receive prescriptions (p50.014). CONCLUSIONS: Correct use of EpiPen was demonstrated in less than CONCLUSIONS: Peanut and/or tree nut allergy and a history of 50% of parents of children with known food allergies. The ability to anaphylaxis are associated with a significantly higher likelihood of correctly demonstrate use of EpiPen was not correlated with health literacy receiving epinephrine autoinjector prescriptions from pediatricians. Since adequacy. pediatricians play a vital role in managing children with food allergies,

further education must be provided to ensure that all children with food SATURDAY 163 When Is Epinephrine Used in Anaphylaxis? allergy are adequately preparedto treat any allergic reactions that may occur. Epinephrine Use in the New York City Public Alberto Alvarez-Perea, MD, Margarita Tomas-Perez, MD, Beatriz 165 School District Ameiro, MD, Patricia Martinez-Lezcano, MD, Gabriela Zambrano, MD, Marıa L. Baeza, MD, PhD; Hospital General Universitario Gregorio Elizabeth Feuille, MD1, Cheryl Lawrence2, Caroline Volel3, Scott H. Maran~on, Allergy Department, Madrid, Spain. Sicherer, MD, FAAAAI1,4, Julie Wang, MD, FAAAAI1; 1Icahn School RATIONALE: Epinephrine is the drug of choice for anaphylaxis, of Medicine at Mount Sinai, New York, NY, 2Office of School Health, however it is widely underused. New York City Department of Health and Mental Hygiene, New York, METHODS: An observational study of all anaphylaxis at the general and NY, 3Mailman School of Public Health, Columbia University, 4Depart- pediatric Emergency Department (ED) was led in a third-level hospital in ment of Pediatrics, Icahn School of Medicine at Mount Sinai, New Madrid. Adults were included May 2009-2010 and children March 2012- York, NY. 2014. Multivariate analysis was used to find factors that induced the use of RATIONALE: There remains a paucity of data regarding use of student- epinephrine. specific and stock epinephrine in schools. There is significant potential for this RESULTS: At the EDs, 259 patients were attended. Adults (n5116): information to influence policy regarding management of allergic reactions 49.1% female, mean age 44.4617.4 years, 19.8% atopic (25% severe and to provide insight into risks to allergic children in the school environment. anaphylaxis). Only 44% were diagnosed with anaphylaxis at the ED. METHODS: In order to determine the nature and frequency of 39.7% received epinephrine. Children (up to 15 y/o, n5133): 56,69% epinephrine use in schools, nursing records were reviewed from July female, mean age 5.564.3 years, 69.2% atopic (14.3% severe anaphy- 2008 through July 2013 for the New York City public school district, which laxis). 52.6% diagnosed of anaphylaxis at the ED. Epinephrine was serves approximately 1.2 million children in over 1,800 schools. administered to 43.6%. Epinephrine use was not related to severity of RESULTS: Within the New York City public school district, nursing anaphylaxis, age, gender or atopy. It was only related to having been records report 38 administrations of epinephrine in the school year starting diagnosed with anaphylaxis at the EDs (OR 33.1; 95%CI 15.5-71). At the in 2008, 35 in 2009, 65 in 2010, 86 in 2011, and 114 in 2012. Just 20.7% of Allergy Department, 176 patients were subsequently attended (51.7% epinephrine uses were for students with a medication administration form adults, 88.7% children). Adults 41.7% drugs, 25% food; children 89.8% (MAF) for epinephrine on file. After the incident, 29.0% sought medical food. Epinephrine autoinjector (EAI) was prescribed to 28.3% adults, evaluation and subsequently provided a MAF to the school. However, 55.1% children (p50.001). Prescription of EAI increased in food allergy 50.3% remained without a MAF for epinephrine. (OR 15.2; 95%CI 2.5-91.1). It was unrelated to severity of anaphylaxis, CONCLUSIONS: In conclusion, epinephrine use in schools appears to be management at the EDs, age, gender or atopy. rising steadily, with a majority of uses in students without MAF for CONCLUSIONS: A correct diagnosis of anaphylaxis at the EDs is epinephrine. This rise may represent an increase in appropriate uses of this determinant for the epinephrine use. The use of epinephrine is not related to life saving medication for anaphylaxis, or a true rise in frequency of severe the severity of the anaphylaxis at the EDs. EAI is more prescribed to allergic reactions. Lack of MAF for a majority of epinephrine uses suggests a children, probably due to the more common food allergies. significant unmet need for allergy evaluation for at risk children and confirms the importance of stocking non-student specific epinephrine in schools. All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. AB52 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2016

Epinephrine Use in Schools for Food-Induced triggers were most frequent (60.1%, 622/1035); however, triggers were 166 Anaphylaxis unknown in 21.6% of events (224/1035). CONCLUSIONS: The unpredictability of anaphylaxis is highlighted by Angela Tsuang, MD, MSc1, Haidi Demain2, Kathleen Patrick, RN3, the frequency of events with unknown triggers (21.6%) and of events Michael Pistiner, MD, MMSc4, Julie Wang, MD, FAAAAI1; 1The Icahn occurring in individuals with no known allergies (25.0%). Results under- School of Medicine at Mount Sinai, New York, NY, 2Founder and Medical score the necessity for comprehensive preparedness training in US schools. Director of Allergy Safe Kids, Inc., Denver, CO, 3Assistant Director of Ò Health & Wellness, Colorado Department of Education, Denver, CO, EPIPEN4SCHOOLS Survey Combined Analysis: 4Harvard Vanguard Medical Associates, Boston, MA. 168 Staff Training and Use of Epinephrine Auto- RATIONALE: This study aims to assess epinephrine use in schools to Injectors

treat food-induced anaphylaxis. 1 1 METHODS: An anonymous questionnaire was distributed to all attendees Susan L. Hogue, PharmD, MPH , Suyapa Silvia, PhD , Kelly Hollis, MBA1, Margaret J. Wooddell, PhD, MBA2, Diana Goss, BS1, at the Colorado school nurse training sessions in spring of 2015. Chi- 1 1 3 squared test was used to compare proportions (STATA11). Dawn Odom, MS , Darryl Cooney, MS , Martha V. White, MD, CPI ; 1RTI International, Research Triangle Park, NC, 2Mylan Specialty, Can- RESULTS: 201 of 261 surveys were completed (77% response). Most of 3 the nurses had 1-5 years of experience (26%) or 6-10 years (26%). 40% of onsburg, PA, Institute for Asthma & Allergy, Wheaton, MD.

SATURDAY RATIONALE: A pilot survey of US schools participating in the nurses covered 5 or more school buildings, and 9% reported epinephrine Ò being given at least once by unlicensed staff. EPIPEN4SCHOOLS program (Mylan Specialty L.P., Canonsburg, PA) In the 2014-2015 school year, 5% reported epinephrine was given by described anaphylactic events reported during the 2013-2014 school _ unlicensed staff at least once in schools with one nurse covering <5 year. Because large school districts (>50 schools per district) were under- buildings. In contrast, significantly more unlicensed staff members represented in the findings, the survey was readministered to these large administered epinephrine at least once (14%) in schools with one nurse districts. Here, an updated analysis combining all school responses is covering 5 or more buildings (p50.027). The proportion of nurses covering presented. 5 or more school buildings was similar among the rural, suburban and METHODS: This cross-sectional, web-based pilot survey assessed urban settings. There was no significant difference in the proportion of anaphylactic events in US schools participating in the EpiPen4Schools schools where epinephrine was given by unlicensed staff at least once program. among the 3 settings (p50.084). RESULTS: Among 6574 responding schools, 1140 anaphylactic events The majority of nurses reported that school staff received anaphylaxis were reported. Of the 1059 events with data on epinephrine auto-injector training (81%); however 63% reported that the staff received training for (EAI) use, 76.5% (810/1059) were treated with EAIs on school property. only < 30 minutes. Nurses felt that in-person training (79%) and hands-on Stock EAIs from the EpiPen4Schools program were used to treat 38.0% of demonstration (56%) are the most effective. events (385/1012). Of the 6088 schools reporting on staff training for CONCLUSIONS: Schools with a high building to nurse ratio had anaphylaxis recognition, 37.3% (2268/6088) provided training for the significantly more unlicensed staff members administering epinephrine. school nurse and select staff; 28.2% (1717/6088) and 30.4% (1851/6088) Training should be extended to non-nursing staff in the form of hands-on provided training for most and all staff, respectively. More than half of training in order to increase student safety. schools (55.0%, 3332/6053) permitted the school nurse and select staff to administer epinephrine to treat anaphylaxis; 15.6% (942/6053) and 21.5% EPIPEN4SCHOOLSÒ Survey Combined Analysis: (1300/6053) permitted most and all staff, respectively, to administer 167 Prevalence and Triggers of Anaphylactic Events epinephrine. CONCLUSIONS: Thirty-eight percent of anaphylactic events were Martha V. White, MD, CPI1, Suyapa Silvia, PhD2, Kelly Hollis, MBA2, treated with EAIs provided by the EpiPen4Schools program, highlighting Margaret J. Wooddell, PhD, MBA3, Diana Goss, BS2, Dawn Odom, MS2, the importance of stocking EAIs. Because a majority of schools permitted Jennifer Bartsch, MStat2, Susan L. Hogue, PharmD, MPH2; 1Institute for only the school nurse and select staff to treat anaphylactic reactions, Asthma & Allergy, Wheaton, MD, 2RTI International, Research Triangle students may frequently be in settings without personnel trained to treat Park, NC, 3Mylan Specialty, Canonsburg, PA. anaphylaxis. Results emphasize the need to provide training to manage RATIONALE: The EPIPEN4SCHOOLSÒ program (Mylan Specialty anaphylaxis and improve access to EAIs in schools. L.P., Canonsburg, PA) provides EpiPenÒ (epinephrine injection) Auto- Injectors to qualifying public and private US schools. Results of a pilot sur- vey described characteristics of anaphylactic events occurring in an initial set of participating schools during the 2013-2014 school year. This survey was subsequently readministered to large US school districts (>_50 schools per district), which were underrepresented in initial survey findings. Here, data from schools in large districts were added to initial findings in a comprehensive combined analysis. METHODS: A cross-sectional, web-based pilot survey was distributed to US schools participating in the EpiPen4Schools program. RESULTS: A total of 1140 anaphylactic events were reported among 6574 participating US schools. Status of the affected individual was reported for 1063 events; of these, 89.5% (951/1063) occurred in students, 9.2% (98/1063) occurred in staff members, and 0.8% (8/1063) occurred in visitors. Of the events occurring in students with data on grade level (n5891), 44.9% (400/891) occurred in students in high school, 18.9% (168/891) occurred in students in middle school, and 32.5% (290/891) occurred in students in elementary school. Twenty-five percent of all reported events (262/1049) occurred in individuals with no known allergies. Triggers were reported for 1035 events. Among these, food All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. J ALLERGY CLIN IMMUNOL Abstracts AB53 VOLUME 137, NUMBER 2

Likelihood of Having Self-Injectable Epinephrine An Interdisciplinary Approach to Perioperative 169 in Adult and Pediatric Patients Presenting for 171 Anaphylaxis: A Tertiary Pediatric Center Evaluation of Food Allergy Experience

Carolyn H. Baloh, MD1, Daniel Winger, MS2, Tara Shankar, MD3, Atoosa Kourosh, MD, MPH, Karen Thursday S. Tuano, MD, Dipika Merritt L. Fajt, MD3, Todd David Green, MD, FAAAAI1; 1Children’s Patel, MD, Nicholas Rider, DO, Sara Anvari, MD, Lenora M. Hospital of Pittsburgh of UPMC, Pittsburgh, PA, 2UPMC, 3University Noroski, MD, MPH, Kristin H. Dillard, MD, Filiz O. Seeborg, MD, of Pittsburgh Medical Center, Division of Pulmonary, Allergy and Critical MPH; Baylor College of Medicine and Texas Children’s Hospital, Depart- Care Medicine, Pittsburgh, PA. ment of Pediatrics, Section of Immunology, Allergy and Rheumatology, RATIONALE: Food allergy is a leading cause of anaphylaxis, and Houston, TX. underprescription of epinephrine is well documented; we were interested RATIONALE: The estimated incidence of peri-operative anaphylaxis in comparing trends related to this in pediatric and adult populations at one (PA) is 1:3,500-1:20,000. Although rare, PA causes morbidity and poses academic medical center. significant risk of mortality (3-9%). The most common causal agents are METHODS: Retrospective chart review of 100 pediatric and 222 adult neuromuscular blocking agents, antibiotics and latex. In the operative patients seen at Children’s Hospital of Pittsburgh of UPMC or UPMC for a setting, patients are exposed to multiple intravenous, inhaled and topical diagnosis of food allergy June 15, 2004 through June 15, 2014. 53 adult and agents in rapid succession. Unless the cause of PA is quickly identified 26 pediatric patients were excluded. Final adult n: 169. Final pediatric n: necessary procedures will be delayed. 74. This review was IRB exempt approved. METHODS: Retrospective chart review for one year at Texas Children’s RESULTS: 64% of adults and 58% of children seen by a physician for Hospital included 8 patients with confirmed PA (5 cardiac, 1 dental, 1 food allergy had self-injectable epinephrine prior to their first allergy visit. radiology, 1 tonsillectomy). Skin prick and intradermal testing (ST) were Adults referred by a PCP were significantly less likely to have epinephrine performed with exposed agents and additional medications in collabora- (p50.036) than those seen by another physician, with a similar trend in tion with surgery teams for upcoming surgeries. children (p50.070). 62% of adults and 86% of children previously treated RESULTS: Most common presenting symptoms were bronchospasm, with epinephrine for anaphylaxis had self-injectable epinephrine. Children hypotension and urticaria. Positive ST were found to Vecuronium, (p50.002) and adults (p50.034) with tree nut allergy were more likely to Cefazolin, Vancomycin, Midazolam, Ketamine, Methylprednisolone, have epinephrine than those with a different food allergy, including peanut. Triamcinolone, Chlorhexidine, Fentanyl and Morphine. Vancomycin and Peanut-allergic adults were more likely to have epinephrine (p50.007). Triamcinolone were not exposures but tested prior to upcoming procedures Milk-allergic children were less likely to have epinephrine (p50.03), as based on collaborative plans. Of 3 patients ST positive to opioids, 2 were adults with fruit allergy (p50.008). 42% of children avoiding 3 or subsequently tolerated Morphine challenge. Vecuronium, Cefazolin, more foods had epinephrine while 66% avoiding less than 3 foods had Midazolam, Ketamine, Chlorhexidine and Methylprednisolone were epinephrine (p50.047), a trend not seen with adults. identified as true causal agents and avoided.

CONCLUSIONS: Adult and pediatric patients presenting to an allergist CONCLUSIONS: In addition to common causal agents in PA, more SATURDAY for food allergy have a lower than optimal rate of having self-injectable unusual agents like steroids and topical agents besides latex should also be epinephrine. investigated. Since drugs such as Vancomycin and opioids can produce false positive ST, graded challenge may be required to validate ST when Recurrent Idiopathic Anaphylaxis in a Woman alternatives are unavailable. An interdisciplinary team approach with close 170 after Suspected Food Poisoning collaboration between allergy, anesthesia and surgical teams is key to planning the diagnostic work-up and advancing to surgery safely and Carl B. Lauter, MD, FAAAAI; Beaumont Health System, Royal Oak, expeditiously. MI. RATIONALE: Recurrent idiopathic anaphylaxis represents a vexing clinical problem associated with stress for patients and allergists. The cause is often not identified despite exhaustive testing. METHODS: The history of a 54-year-old woman with repeated bouts of unexplained anaphylaxis is reviewed. The relationship between preceding or active infection (emphasis on GI infections) and chronic idiopathic urticaria (CIU) and anaphylaxis was explored by electronic media search (PubMed, Google) and review of reference lists of published articles. The literature on the relationship of Campylobacter jejuni, infection and urti- caria is reviewed. Gastrointestinal infections (Giardia, Anisakis) have been better documented in such patients. RESULTS: The patient had persistent flatulence, looser and more frequent bowel movements for months after recovery from a bout of food poisoning. A diagnosis of ‘‘post infectious irritable bowel syndrome’’ was made by a gastroenterologist. These symptoms were not related to her simultaneous diagnosis of CIU and idiopathic anaphylaxis. After treatment with azithromycin (positive stool culture for Campylobacter jejuni) she had a systemic allergic reaction. Subsequently, the diarrhea and urticaria/ anaphylaxis cleared. Campylobacter jejuni has been reported to cause chronic urticaria, but predominantly in children. A related organism, Helicobacter pylori, has been associated with CIU. Anaphylaxis has not been related to Campylobacter, infection in the past. CONCLUSIONS: Chronic urticaria and recurrent bouts of mild unex- plained anaphylaxis were triggered by Campylobacter jejuni infection. The allergic and GI symptoms resolved after treatment. Gastrointestinal infec- tions should be looked for in patients with urticaria or anaphylaxis. All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. AB54 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2016

Increasing Trends in the Nationwide Incidence of Accuracy of ICD-10 Coding for Anaphylaxis 172 Anaphylaxis Visiting Emergency Room in Korea 174 from 2007 to 2013 Monthida Uthairat, MD, Teeranai Sakulchit, MD, Pasuree Sangsupawa- Young Min Ahn, MD1, Eun-Hee Chung2, Youn Kyung Won3, Yoo Mi nich, MD, PhD; Prince of Songkla University, Hat-yai, Thailand. Chung4; 1Department of Pediatrics, Eulji University School of Medicine, RATIONALE: ICD-10 is the classification system used most often by South Korea, 2Department of Pediatrics, National Medical Center, Seoul, allergists worldwide. It has been used as a proxy for anaphylaxis cases in South Korea, 3National Medical Center, South Korea, 4National medical retrospective studies. However, it is not considered appropriate for clinical center, South Korea. practice. The objective of this study was to determine the accuracy of ICD- RATIONALE: Anaphylaxis is a severe, life threatening allergic reaction, 10 coding for anaphylaxis in an emergency department (ED). usually presenting at ER. We aimed to study about nationwide prevalence METHODS: We performed a 5-year retrospective chart review from 2010 and compare the regional difference in the ER visiting incidence of to 2014 of patients under the age of 18 years who were diagnosed at the ED anaphylaxis in Korea. with ICD-10 codes T78.0-T78.4. All charts were reviewed to identify METHODS: We retrospective analyzed the National Emergency anaphylaxis by using the World Allergy Organization (WAO) anaphylaxis Department Information System records of 117 emergency room in clinical diagnostic criteria as the gold standard. A positive predictive value Korea with diagnosis code of anaphylaxis based on ICD-10 codes, was calculated for ICD-10 codes T78.0-T78.2 which are the codes to SATURDAY T78.0, T78.2, T80.5, T88.6, T63.4 from 2007 to 2013. diagnose anaphylaxis. A negative predictive value was calculated for ICD- RESULTS: The nationwide ER prevalence of anaphylaxis is 10.1 cases per 10 codes T78.3-T78.4 which are the codes to diagnose angioedema and 100,000 in Korea during 2007-2013. Male and female were total 17,454 to allergy (unspecified). 17,423. An Increasing trend of annual incidence rates is observed from 2007 RESULTS: A total of 379 ED patients with ICD-10 codes T78.0-T78.4 to 2013, such as 2007: 7.3, 2008: 10.9, 2009: 12.8, 2010: 14.7, 2011: 7.0, were reviewed. We found 82 patients who met the anaphylaxis diagnostic 2012: 8.2, 2013: 9.6 per 100,000 PY respectively. Among the 16 region, criteria by WAO. Sixty-nine medical records with ICD-10 codes T78.0- Kangwon province has the most highest incidence (15.8/100.000 PY) T78.2 had a positive predictive value of 88.4% (95% CI 78.7 to 94.0). The followed by Seoul(15.7), Jeju special autonomous province(15.3) Gyeonggi negative predictive value of 310 medical records with ICD-10 codes T78.3- (11.8). Busan has the lowest incidence(3.3). Age specific incidence rates T78.4 was 93.2% (95% CI 89.8 to 95.5). showed a gradual increasing peaking between 19 to 49 years. There is some CONCLUSIONS: ICD-10 coding for anaphylaxis had high positive and monthly variance, highest in August and September and lowest in January negative predictive values. and February. The final diagnosis code that related food reaction was 3.1%, adverse effect of drug 7.8%, venomous 2.1%, serum 0.45% and unspecified The Incidence of Anaphylaxis in a Large Health anaphylactic shock 86.6%. The outcomes of ER patients were hospitaliza- 175 Maintenance Organization: A Review of tion(16.9%), admission to ICU(0.7%) and death(0.1%). International Classification of Diseases Coding CONCLUSIONS: The incidence of anaphylaxis presenting at nationwide and Epinephrine Auto-Injector Prescribing ERs in Korea is found to be increasing from 2007 to 2013. The reasons of 1 1 regional difference and seasonal variation will be studied further. Deena Pourang, MD , Javed Sheikh, MD, FAAAAI , Shefali A. Samant, MD1, Michael Batech2, Michael S. Kaplan, MD, FAAAAI1; Analysis of Anaphylaxis Trigger Factors and 1Kaiser Permanente Los Angeles Medical Center, 2Kaiser Permanente 173 Treatment during a Five Year Period in a Vilnius Department of Research and Evaluation. University Hospital RATIONALE: Accurate estimates of the incidence of anaphylaxis are limited. Current ICD-9 codes make it difficult to accurately diagnose Audra Blaziene1, Neringa Buterleviciute2, Viktorija Paltarackiene2,Law- anaphylaxis and to assess appropriate epinephrine prescribing. The purpose rence M. DuBuske, MD, FAAAAI3,4; 1Vilnius University Medical School, of this study is to quantify the incidence and demographic character of Lithuania, 2Vilnius University Faculty of Medicine, Vilnius, Lithuania, patients with anaphylaxis-related ICD-9 codes in a large health maintenance 3George Washington University School of Medicine, Washington, DC, organization, and analyze epinephrine prescribing and dispensing rates. 4Immunology Research Institute of New England, Gardner, MA. METHODS: All patients included had at least 12 months of continuous RATIONALE: Anaphylaxis is increasing worldwide in prevalence. The membership over a 4-year period from January 1st, 2008 to December 31st, World Allergy Organization criteria emphasize the rapid onset and multiple 2012 and were selected based on anaphylaxis-related ICD-9 codes signs and symptoms of anaphylaxis. The aim of our study was to analyse (n5159,172). This algorithm was extrapolated from a previous study anaphylaxis, based on WAO criteria, and to evaluate trigger factors, clinical that used expanded ICD-9 codes to identify more cases of anaphylaxis. patterns and treatment of anaphylaxis in a Vilnius, Lithuania hospital. Individual chart reviews found that many expanded ICD-9 codes METHODS: Patients with anaphylaxis hospitalized in Vilnius University represented unconfirmed cases of anaphylaxis, and therefore were Hospital Santariskiu Klinikos over five year period (2009–2014) were excluded, resulting in analysis of 52,405 patients. assessed. 103 patients (57: 55.34% women/46: 44.66% men) were noted to RESULTS: Incidence of anaphylaxis over 4 years was 2.07%, with female have anaphylaxis. The mean age of patients was 45.77 (range 20–83) years. predominance (56.5%) over males (43.5%). Epinephrine was prescribed in RESULTS: The most frequent suspected triggers were drugs (39 cases: 16.2% of total cases. Highest rates of epinephrine prescription were for 37.86%), mainly NSAIDS (17 cases); insect stings (31cases: 30.09%); and traditional ICD-9 codes 995.0 (other anaphylactic shock) and 995.60- food (5 cases: 4.85%). Anaphylaxis ocurred most commonly in summer 995.69 (anaphylactic shock caused by food) at 49.3% and 58.6%, (38 cases: 35.7%). The cardiovascular system (94 cases: 91.26%) and skin respectively. Of the cases where an epinephrine auto-injector was pre- (90 cases: 88.26%) were impacted most frequently, followed by respiratory scribed, it was dispensed 95.9% of the time, independent of copayment (56 cases: 54.34%) and gastrointestinal (23 cases: 22.33%) systems. amount. Epinephrine as an initial treatment was administered for 61 (59.22%) CONCLUSIONS: Low epinephrine auto-injector prescribing rates in patients. 37 (35.92%) patients were treated in the intensive care unit. cases of anaphylaxis suggests the continued difficulty in the diagnosis of CONCLUSIONS: Drugs were the main suspected triggers of anaphylaxis. anaphylaxis and may result in suboptimal treatment of potential future Cardiovascular symptoms were the most frequent, followed by the skin and episodes. Additionally, these data suggest that the expanded algorithm of respiratory symptoms. One third of patients were treated in the intensive anaphylaxis-related ICD-9 codes, as reported previously, may overesti- care unit. Use of epinephrine as initial therapy remains less than expected mate true cases of anaphylaxis. considering the recent guidelines advising its use as intial treatment. All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. J ALLERGY CLIN IMMUNOL Abstracts AB55 VOLUME 137, NUMBER 2

Alpha-Gal Hypersensitivity: A Case Series from or biochemical abnormalities (except for monoclonal components) are de- 176 Good Ol' Rocky Top Tennessee tected between attacks. CONCLUSIONS: ISCLS-related shock is diagnosed by severe shock, Mike Tankersley, MD, FAAAAI1, Alan DeJarnatt, MD2, Ross DeJar- hemocencentration and hypoproteinemia. Detection of IgG monoclonal natt2; 1University of Tennessee Health Sciences Center, 2Allergy and band serves for further confirmation. Compared to other hypovolemic Asthma Care. shocks, fluid replacement and VA should be minimized, with judicious use RATIONALE: Galactose-alpha-1,3-galactose hypersensitivity (alpha- of colloids to maintain adequate perfusion. gal) is a recently reported condition associated with the production of specific IgE to this oligosaccharide found in mammalian meat. A registry Comparison of Pediatric Anaphylaxis at Montreal was maintained of alpha-gal patients to more fully understand this 178 Children's Hospital and British Columbia condition in our patient population. Children's Hospital: Rate, Clinical Characteristics, METHODS: A retrospective chart review of a single-site Allergy practice Triggers and Management

in Tennessee was conducted of the clinic’s alpha-gal registry of patients 1 2 3 seen from 2010-2015. Alison YM. Lee, MD , Paul Enarson, MD, PhD , Ann Clarke, MD, MSc , Sebastian La Vieille, MD4, Harley Eisman, MD5, Edmond S. Chan, MD, RESULTS: There were 38 patients diagnosed with alpha-gal hypersen- 6 7 8 sitivity over a five-year period (2010-2015). Patient characteristics FAAAAI , Christopher Mill, BSc, MPH , Lawrence Joseph, PhD , Moshe Ben-Shoshan9; 1Pediatric Residency Program, Department of Pediatrics, included: mean age at diagnosis 50.7 years (range 14-74 years), 44.7% 2 were male (17/38), mean alpha-gal IgE 29.7 kU/L (range 1.1-97.3; two University of British Columbia, Vancouver, BC, Canada, Division of Emergency Medicine, Department of Pediatrics, University of British patients excluded from mean with levels >100). Four patients had follow- 3 up alpha-gal levels which had all decreased: patient 1 (6.2 to 1.9 kU/L after Columbia, Vancouver, BC, Canada, Division of Rheumatology, Depart- ment of Medicine, University of Calgary, Calgary, AB, Canada, 4Health 42 months), patient 2 (23.2 to 8.7 kU/L after 42 months), patient 3 (82.3 to 5 58.7 kU/L after 34 months) and patient 4 (95.2 to 1.3 kU/L after 48 Canada, Food Directorate, Ottawa, ON, Canada, Emergency Department, Department of Pediatrics, Montreal Children’s Hospital, Montreal, QC, months). Signs and symptoms included cutaneous pruritus, urticaria, 6 angioedema, hoarseness, dyspnea, nausea, vomiting, diarrhea, lighthead- Canada, Division of Allergy & Immunology, Department of Pediatrics, Faculty of Medicine, University of British Columbia, BC Children’s Hos- edness, hypotension, and syncope. Culprit foods included beef, pork, 7 venison, cow’s milk, and lamb. Time between onset of signs and symptoms pital, Vancouver, BC, Canada, University of British Columbia, Vancou- ver, BC, Canada, 8Division of Clinical Epidemiology, Department of to diagnosis was 1 month-15 years. Time between ingestion and signs/ 9 symptoms was 1-6 hours. Medicine, McGill University Health Center, Montreal, QC, Canada, Di- CONCLUSIONS: Alpha-gal hypersensitivity is not an uncommon food vision of Allergy and Clinical Immunology, Department of Pediatrics, hypersensitivity as demonstrated by the 38 patients diagnosed in this Montreal Children’s Hospital, Montreal, QC, Canada. single-site clinic in Tennessee over a 5-year period. All medical care RATIONALE: To compare the rate, triggers and management of anaphylaxis between two Canadian pediatric emergency departments providers should maintain a high index of suspicion of this condition in SATURDAY patients presenting with anaphylaxis in the absence of an immediate (PEDs). allergen association. METHODS: As part of the Cross-Canada Anaphylaxis REgistry (C- CARE), children presenting to Montreal Children’s Hospital (MCH) and A Case of Idiopathic Systemic Capillary Leak BC Children’s Hospital (BCCH) PED with anaphylaxis were recruited. 177 Syndrome: Masquerader of Anaphylaxis – an Characteristics, triggers and management of anaphylaxis were docu- Emblematic Case from a Cohort of 21 Patients mented using a standardized data entry form. The differences in de- mographics, triggers, pre-hospital and in-hospital management were Maddalena A. Wu1, Marta Mansi, MD1, Andrea Zanichelli1, Avner determined. Reshef, MD2, Marco Cicardi1; 1Department of Biomedical and Clinical RESULTS: Between June 2014–2015, 148 of 46,321 cases to the BCCH Sciences ‘‘Luigi Sacco’’, University of Milan, Luigi Sacco Hospital, Mi- PED were of anaphylaxis, a rate of 0.32%(95%CI,0.27%,0.38%), similar lan, Italy, 2Allergy, Clinical Immunology & Angioedema Unit, Chaim to MCH’s rate of 0.38%(0.34%,0.42%) from 321 of 83,684 cases. There Sheba Medical Center, Tel Hashomer, Israel. were no substantial differences in demographics (age, sex) nor preexisting RATIONALE: Idiopathic systemic capillary leak syndrome (ISCLS) asthma. However, known eczema and food allergy were more commonly presents with recurrent episodes of hemoconcentration and life-threatening reported at BCCH than MCH (9.5%[5.5%,15.7%] vs 2.5%[1.2%,5.0%], hypovolemic shock. Failure to differentiate it from anaphylaxis and other and 63.5%[55.2%,71.2%] vs 49.5%[43.9%, 55.1%] respectively). In both types of distributive shock may lead to dire iatrogenic consequences. centers the majority of cases were triggered by food (BCCH 87.8% METHODS: We describe a patient newly diagnosed with acute ISCLS [81.2%,92.4%], MCH 83.5%[78.9,87.3]), of which peanuts were the most and review a cohort of 21 patients. common culprit (23.8%[17%,32.3%] and 20.1%[15.6%,25.6%] respec- RESULTS: A 49-year-old-man presented to the emergency department tively). Distribution of anaphylaxis severity was comparable between complaining of abdominal pain and pre-syncopal episodes. His medical centers. Pre-hospital treatment was similar in epinephrine administration history was noncontributing. Physical examination showed abdominal (BCCH 28.4%[21.4%,36.5%], MCH 35.2%[30.0%,40.7%]); however, tenderness, hypotension, tachycardia. Blood tests revealed Hct 61.7%, more antihistamine was given in BC (59.5%[51.1%,67.4%]) than WBC 24,740/mm3, plasma creatinine 1.26 mg/dl, albumin 9 g/L. Chest- Montreal (45.2%[39.7%,50.8%]). In-hospital management differed in abdominal CTwas unremarkable. Response to fluid replacement and vaso- terms of increased epinephrine, antihistamine, and steroid use at BCCH active amines (VA) was poor: progressive edema developed in the muscles (56.4%[47.7%,64.1%], 60.1%[51.7%,68%] and 70.9% [62.8%,78.0%] of the limbs and in the myocardial wall. ISCLS-related distributive shock respectively) compared to MCH (41.4% [36.0%,47.0%], 38.6% was diagnosed at 5 hours from admission and the patient transferred to [33.3%,44.2%] and 10.6%[7.5%,14.6%] respectively). ICU. Fluid replacement was drastically reduced (250 mL/4 hours), VA CONCLUSIONS: There are substantial differences in co-morbid condi- tapered. Myocardial pseudohypertrophy reverted in 2 hours, shock and he- tions and management practices in pediatric anaphylaxis across Canadian moconcentration in 48 hours. The post-acute phase was characterized by Centers. It is crucial to develop training programs that aim to increase severe rhabdomyolysis, renal failure, bilateral peroneal nerve palsy. epinephrine use in anaphylaxis cases. Review of 21 patients files shows almost identical clinical presentation, suggesting that fluid and VA administration should be restricted during acute ISCLS to prevent iatrogenic consequences. No relevant symptoms All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. AB56 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2016

A Law Is Not Enough: Geographical Disparities in CI 19.1, 32.0). The presence of serious reaction was the only factor 179 Stock Epinephrine Access in Kansas associated with epinephrine administration [OR51.26; 1.1, 1.5]. CONCLUSIONS: Our results draw from the first prospectively docu- Marissa A. Love, MD, Madison Breeden, BS, Kyle Dack, BA, Alyssa mented data of anaphylaxis cases presenting to out-of-hospital EMS. The Milner, BA, Andrew C. Rorie, MD, Selina A. Gierer, DO; University of results reflect previously identified risk factors for anaphylaxis, with food, Kansas Medical Center, Kansas City, KS. drugs and insect stings as the most common culprits. The suboptimal RATIONALE: We sought to identify geographic disparities and existing proportion of cases treated with epinephrine highlights an ongoing need for barriers to receiving life-saving epinephrine in Kansas schools. patient and health-care provider education. METHODS: A survey of school nurses was conducted at the 2015 Kansas School Nurse Association conference. Excel was used to analyze the Prehospital Administration of Epinephrine in descriptive data, which was compared to demographics published by the 181 Pediatric Anaphylaxis – a Statewide Perspective U.S. federal government. Leslie M. Cristiano, MD1, Brian C. Hiestand, MD1, William A. RESULTS: In 2009, the Kansas legislature authorized accredited schools 1 1 to stock emergency epinephrine, pre-dating federal legislation in 2013. Gower, MD , Katherine C. Gilbert, MD , Jason W. Caldwell, DO, FAAAAI1, Antonio R. Fernandez, PhD2, James E. Winslow, MD1; Unfortunately, stock epinephrine remains limited to only a few Kansas 1 2 communities. Our survey revealed significant disparities in implementing Wake Forest School of Medicine, Winston-Salem, NC, EMS Perfor- SATURDAY stock epinephrine, with 59 of 105 counties reporting. Only 20 counties mance Improvement Center, University of North Carolina, Chapel Hill, stocked epinephrine in at least 1 school. When stratifying by household NC. income, 60% of schools that stocked epinephrine were in the top 10% of RATIONALE: Timely administration of epinephrine is critical in the wealthy counties, whereas 41% that did not were in the bottom 50%. Of treatment of anaphylaxis. Very little information is available on the rates of schools stocking epinephrine, 35% were in the wealthiest county. Further, administration of epinephrine by EMS providers caring for pediatric 70% of schools with stock epinephrine were associated with the largest patients in the prehospital setting. urban cores in Kansas. Nurses cited cost, legal liability, having a METHODS: We examined data from the NC EMS database (PreMIS) prescribing physician, lack of staff knowledge or training, and lack of from 2010-2013 to determine rates of epinephrine administration in administrator support as reasons why injectable epinephrine was not pediatric patients with anaphylaxis. We studied patients <18 years of stocked in their schools. age with an EMS provider impression of ‘‘allergic reaction.’’ Anaphylaxis CONCLUSIONS: Our study reveals unequal access to life-saving was present if there was hypotension (defined as SBP <90 or DBP <45 for epinephrine across Kansas, despite state and federal legislation. Further patients age 11 and older, and SBP <70 + (2 x age) for patients ages 0-10), investigation is necessary to resolve this inequality, which disproportion- or impaired respirations (defined as description of labored or absent ately affects Kansas communities. respirations, or RR <12 or >30). We determined the overall rate of epinephrine administration. A multivariate logistic regression was then Anaphylaxis Cases Treated By out-of-Hospital constructed to examine the impact of the following variables on 180 EMS in Western Quebec appropriate epinephrine administration: age <7, non-white race, rural county of case origin, duration of transportation from scene, and presence Magdalena J. Grzyb, MD1, Ann Clarke, MD, MSc2, Nofar Kimchi3, of a paramedic. Colette Lachaine4, Sebastian La Vieille, MD5, Lawrence Joseph, PhD6, RESULTS: 504 patients met inclusion criteria, of which 471 demonstrated Christopher Mill, BSc, MPH7, Moshe Ben-Shoshan, MD, MSc8; 1Division anaphylaxis as defined above. 157 patients received epinephrine (33.3%, of Pediatric Allergy & Clinical Immunology, McGill University, Mon- 95% CI 29-38%). Age <7 was associated with increased odds of not treal, QC, Canada, 2Division of Rheumatology, Department of Medicine, receiving epinephrine appropriately (OR 3.36, 95% CI 2.14-5.27, p University of Calgary, Calgary, AB, Canada, 3Technion American Medi- <0.001). Other variables did not have statistically significant impact on cal Students Program, Israel, 4Direction adjointe de services epinephrine administration. prehospitaliers d’urgence, MSSS, Quebec, Canada, 5Food Directorate, CONCLUSIONS: There are missed opportunities for prehospital admin- Ottawa, ON, Canada, 6McGill University, Montreal, QC, Canada, 7School istration of epinephrine in pediatric patients with anaphylaxis. Very young of Population and Public Health, University of British Columbia, Vancou- children (age <7) had increased odds of not receiving epinephrine. ver, BC, 8The Research Institute of the McGill University Health Centre, Meakins- Chrisitie Laboratories, Division of Paediatric Allergy and Clin- ical Immunology, Department of Paediatrics, Montreal Children’s Hospi- tal, Montreal, QC, Canada. RATIONALE: To describe the rate and characteristics of anaphylaxis cases presenting to out-of-hospital emergency medical services (EMS). METHODS: Over a 2-year period from May 2013, paramedics respond- ing to ambulance calls in the Outaouais region of Quebec collected data on patients with anaphylaxis, as part of the Cross-Canada Anaphylaxis Registry. Demographics, reaction characteristics and treatments were recorded at the time of patient evaluation. RESULTS: The incidence of anaphylaxis among the 67,220 ambulance calls received during the study period remained stable in years 1 and 2, at 0.31% [n5104; 95% CI 0.25%, 0.37%] and 0.36% [n5119; 95% CI 0.30%, 0.43%], respectively. The median age was 43.3 years [interquartile range: 20.9, 60.3], with female predominance (60.1%; 95% CI 53.3%, 66.5%). Food (37.2%; 31.0%, 44.0%), drugs (19.7%; 14.8%, 25.7%) and venom (17.9%; 13.3%, 23.7%) were the top triggers. Severe reactions (defined by the presence of cyanosis, SpO2<92%, respiratory arrest, hypotension, dysrhythmia, confusion or loss of consciousness) were more likely in males [OR 2.1; 1.1, 4.4] and during exercise [OR 5.2; 1.2, 22.4). Epinephrine was not administered for moderate-severe anaphylaxis in 25.0% of cases (95% All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. J ALLERGY CLIN IMMUNOL Abstracts AB57 VOLUME 137, NUMBER 2

Increase in Intensive Care Unit Admissions for admission rates. Our data contrast with recent UK and USA-based studies 182 Anaphylaxis in the United Kingdom 2008-2012 describing lower overall FA rates (0.047-0.069/100,000) and rising hos- pital anaphylaxis admission rates without a rise in fatalities. Deepan Vyas, MRCPCH1, Despo Ierodiakonou, MD, PhD1, David A. Harrison, MA, PhD2, Tim Russell2, Paul J. Turner, FRACP, PhD1,3, Robert The Economic Burden of Food Allergic Patients J. Boyle, MBChB, PhD4; 1Imperial College London, United Kingdom, 184 Managing at a Tertiary Care Center 2ICNARC, London, United Kingdom, 3University of Sydney, Australia, 4Section of Paediatrics, Imperial College London., United Kingdom. Narissara Suratannon, MD, Panida Swangsak, Jarungchit RATIONALE: We have previously reported increased anaphylaxis Ngamphaiboon, MD, Pantipa Chatchatee, MD; Division of Allergy and hospitalizations but stable fatal anaphylaxis rates over a 21-year period Immunology, Department of Pediatrics, Faculty of Medicine, Chulalong- in England and Wales. To explore whether this is related to a true increase korn University, Bangkok, Thailand. in disease, we evaluated time trends in intensive care unit (ICU) RATIONALE: Food allergy is a substantial burden for patients and anaphylaxis admissions. families by negatively affecting finances, social relationships, and quality METHODS: We assessed trends in hospital admission to intensive care of life. We aimed to estimate the economic burden of food allergy in units requiring mechanical ventilation between 2008 and 2012 using patients managed in a tertiary care center. nationally-held datasets. Incident rate ratios (IRR) were calculated for METHODS: Retrospective chart reviews and questionnaires were done in Level 3 admissions with the following ICD-10 diagnostic codes: T780 food food-allergic children at King Chulalongkorn Memorial Hospital, anaphylaxis, T782 unspecified cause, T886 iatrogenic, X23 insect sting. Bangkok, Thailand. RESULTS: There were 833 admissions due to anaphylaxis over a 5-year RESULTS: Fifty food allergic children were enrolled. Seventy-eight period: 160 due to food, 8 insect stings, 273 medication/iatrogenic and 392 percent were male. Mean age was 5.3 +/- 3.2 years. Thirty-two percent had cause unspecified. ICU admissions increased significantly over the study multiple food allergies. Overall cost was 1,953 US dollar per person per period for all anaphylaxis, with an IRR of 1.14 (95% CI 1.08-1.20, year. Direct medical cost was 1,112 US dollar per person per year and P<0.001); for iatrogenic anaphylaxis 1.20 (95% CI 1.10-1.31, P<0.001); direct non-medical cost was 841 US dollar per person per year. Direct food anaphylaxis 1.16 (95% CI 1.04-1.29, P50.01); anaphylaxis of medical cost can be divided into in-patient visit 62%, unscheduled out- unspecified cause 1.10 (95% CI 1.03-1.19, P50.005). We found no patient visit 9.4%, office visit 17.4% and emergency room visit 9.4%. The evidence for an increase in anaphylaxis due to insect venom IRR 0.66 (95% high cost for unscheduled out-patient visit and emergency room visit CI 0.36-1.10 p50.14). The age distribution of anaphylaxis admissions by reflected the accidental exposure and acute food reaction in the studied cause was similar to that previously described for fatal anaphylaxis. population. CONCLUSIONS: Rates of critical care admissions for anaphylaxis have CONCLUSIONS: Food allergy is a burden on healthcare resources as increased, in contrast to fatal anaphylaxis rates. This suggests that recent shown by this study. The high cost of unscheduled out-patient visit and trends for food and drug-induced anaphylaxis may be explained by a true emergency room visit can be reduced by patient education and proper allergen avoidance. increase in anaphylaxis with a concomitant improvement in emergency SATURDAY care. 183 Anaphylaxis Fatalities in Australia 1997 to 2013

Raymond James Mullins, FRACP FRCPA PhD FAAAAI1, Woei Kang Liew, MD2, Brynn Wainstein, FRACP, PhD3, Elizabeth H. Barnes, BAppSc, MStat4, Dianne E. Campbell, MD, FRACP, PhD5; 1ANU Medical School, Deakin, Australia, 2SBCC Baby & Child Clinic, Singapore, 3Department of Allergy and Immunology, Sydney Children’s Hospital, Sydney, Australia, 4NHMRC Clinical Trials Centre, Sydney, Australia, 5Department of Allergy and Immunology, The Children’s Hos- pital at Westmead, Westmead, Australia. RATIONALE: The objective of this study was to determine whether Australian fatal anaphylaxis (FA) rates have increased in line with increases in hospital anaphylaxis admission rates. METHODS: Australian FA and hospital anaphylaxis admission rates were examined, using data derived from the Australian Institute of Health and Welfare and the Australian Bureau of Statistics over the period 1997-2013. Time trends were analyzed using Poisson regression with year (1997 to 2013) as a continuous predictor and total population as exposure variable. RESULTS: 323 cases of FA were reported in Australia between 1997 and 2013. Fatalities were attributed to; medication (52 cases), insect stings/tick bites (21 cases), food (23 cases), serum (3 cases) or unspecified cause (224 cases). Overall FA rates increased 1.8 fold from 0.05 (1997) to 0.09/ 100,000 (2013). FA increased 6.2% per year (95% CI: 3.8 to 8.6%, P<0.0001) and food-related FA increased 9.7% per year (95% CI: 0.25 to 20%, P50.044). Total hospital anaphylaxis admissions (HAA) increased 3.9 fold, from 5.0 to 19.2/ 100,000 and food anaphylaxis admissions increased from 2.1 to 8.9 (4.2-fold) over the same period. HAA increased by 8.0% per year (95% CI: 7.8 to 8.3%, P<0.0001) and by 10.0% per year for food anaphylaxis admissions (95% CI: 9.9 to 10.6%, P<0.0001). CONCLUSIONS: We report preliminary evidence of a rise in Australian FA (and food-related FA) rates comparable with increases in hospital All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. AB58 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2016

The Effect of Vitamin D Levels on Pediatric Clinical and Epidemiological Differences in 185 Allergic Diseases: A Nationwide Population- 186 Patients with Acute Urticaria and Chronic Urticaria Based Study Mehtap Haktanir Abul, MD1, Fazil Orhan2, Zekiye Ilke Kilic Topcu2, Taner Karakas2, Ali Baki3; 1Karadeniz Technical University Faculty of Hea-Kyoung Yang1,2, Jaehee Choi3,4, Woo Kyung Kim5, So-Yeon Medicine Department of Pediatric Immunology and Allergy, Trabzon, Lee, MD6,7, Yong Mean Park8, Man-Yong Han, MD9, Myung-Il Turkey, 2Karadeniz Technical University Faculty of Medicine Department Hahm10, Yoomi Chae11, Hye-young Kim12, Kang Mo Ahn, MD2,13, Ho- of Pediatric Immunology and Allergy, 3Karadeniz Technical University Jang Kwon, MD, PhD14,15, Jihyun Kim, MD16,17; 1Department of Pediat- Faculty of Medicine Department of Pediatric Pulmonology. rics, Samsung Medical Center, Sungkyunkwan University School of Med- RATIONALE: Urticaria is commonly seen and it is difficult to determine icine, 2Environmental Health Center for Atopic Diseases, Samsung the etiologic factors in children. The aim of the study is to define different Medical Center, Seoul, Korea, 3Environmental Health Center for Atopic clinical patterns of urticaria in childhood. Diseases, 4Department of Pediatrics, Samyook Medical Center, Seoul, METHODS: This is a prospective study included the children who were South Korea, 5Department of Pediatrics, Inje University College of Med- referred to our clinic for evaluation of urticaria. Laboratory tests including icine, Seoul, Korea, 6Department of Pediatrics, Hallym University Sacred serologic, autoimmune, and allergic analyses were conducted. Heart Hospital, Hallym University College of Medicine, 7Department of RESULTS: One hundred and eighty two children (90 females and 92 Pediatrics, Hallym University Secred Heart Hospital, Anyang, South Ko-

SATURDAY males) were evaluated. The age range was 4 month- 17 years old. Of the rea, 8Kunkuk University Hospital, South Korea, 9CHA University Bun- cases, 58.2 % (n5106) were diagnosed with acute urticaria and 41.8 % dang Medical Center, Seongnam, South Korea, 10Department of Health (n576) were diagnosed with chronic urticaria. There wasn’t any signif- Administration and Management, College of Medical Science, Soonchun- icant difference in gender between acute and chronic urticaria group. The hyang University, Asan, Korea, 11Department of Occupational and Envi- median age was 5 years (range: 4 month- 16 years old) and 6.5 years (range: ronmental Medicine, College of Medicine, Dankook University, 7 month- 17 years old) for acute and chronic urticaria groups respectively. 12Department of Pediatrics, Pusan National University School of Medi- CRP, IgE, eosinophil, C3 and C4 levels are higher in acute urticaria than cine, Busan, Korea, 13Department of Pediatrics, Samsung Medical Center, chronic urticaria patients that were not statistically significant. Physical Sungkyunkwan University School of Medicine, Seoul, Korea, South Ko- urticaria was commonly seen in children with chronic urticaria (48.7%). rea, 14Preventive Medicine, Dankook University College of Medicine, Spontaneous resolution is more frequently seen in acute urticaria patients Cheonan, South Korea, 15Dankook University, Cheonan, 16Environmental than the chronic urticaria patients (p50.016). Health Center for Atopic Diseases, Seoul, South Korea, 17Department of CONCLUSIONS: There are clinical and epidemiological differences in Pediatrics, Samsung Medical Center, Sungkyunkwan University School of patients with acute urticaria and patients with chronic urticaria. Medicine, Seoul, South Korea. Recurrence, spontaneous resolution seems to be the factors associated RATIONALE: We aimed to investigate the association between concen- with the differences in both group of patients. Physical urticaria is tration of serum vitamin D levels and recent symptoms of allergic diseases commonly seen and should be questioned in children with chronic urticaria. in elementary schoolchildren. METHODS: A nationwide cross-sectional survey was conducted in the Gender- and Genetic-Dependent Sunlight Exposure first grade students from randomly selected 45 elementary schools. Recent 187 Effects on the Cumulative Incidence of Atopic symptoms of atopic dermatitis (AD) or asthma were defined as those who Dermatitis during Infancy were medically treated for AD or asthma. Recent symptoms of allergic 1,2 3 4 rhinitis (AR) were considered to be present if a child had the experience of Miwa Shinohara, MD, PhD , Eiichi Ishii , Kenji Matsumoto, MD, PhD ; 1 treatment for AR during the last 12 months and showed a positive skin Department of Pediatrics, Ehime University Hospital, Ehime, Toon, Japan, 2 prick test responses to common 18 inhalant allergens. All the children were Department of Pediatrics, Kochi University, Kochi, Namgoku, Japan, 3 examined by a pediatrician to determine the presence of eczema in their Department of Pediatrics, Ehime University Graduated School of Medicine, 4 neck and flexural areas of both arms. Serum 25-hydroxyvitamin D [25(OH) Toon, Japan, Department of Allergy and Clinical Immunology, National D] was measured by chemiluminescent microparticle immunoassay. Research Institute for Child Health and Development, Tokyo, Japan. RESULTS: The overall prevalence rates of vitamin D insufficiency (20 to RATIONALE: Sunlight, both Ultraviolet (UV) B and UVA, suppresses 29 ng/mL) and deficiency (<20 ng/mL) were 64.1% and 18.4%. The the adaptive immunity, but induces the innate immunity in the skin, and adjusted odds ratio (aOR) for the presence of AR was 0.980 (95% CI: then reduces microorganisms. However, it is unclear whether sunlight 0.962–0.998) for each increase of 1 ng/mL in 25(OH)D, while no affects the development of atopic dermatitis (AD) during infancy. association was found between 25(OH)D levels and the prevalence of Therefore, we investigate associations between sunlight exposure timings AD or asthma. The aOR per increase of 1 ng/mL in 25(OH)D was 0.974 and the cumulative incidence of AD in infants. (95% CI 0.955-0.994) for the presence of eczema on the day of survey. METHODS: Of 1,436 parent-infant pairs, 981 (68.3%) infants over the first CONCLUSIONS: A high prevalence of vitamin D deficiency and 6 months of life without vitamin supplement intake were enrolled in this cross- insufficiency was found in Korean elementary schoolchildren, and vitamin sectional study in 2009. We assessed postnatal infantile sunlight exposure, a D level was associated with recent symptoms of AD and AR. parental family history of allergic diseases (FH) and physician-diagnosed AD by self-writing questionnaires. Sunlight exposure was separated into 3 timings; until the first 6 months of life, over the first 6 months of life and now. We performed statistical analyses by using STATA software. RESULTS: The recovery rate was 97.2% (1,436/1,476). The cumulative incidence of AD was significantly higher in the infants without sunlight exposure over the first 6 months of life compared with the unexposed infants (25.0% vs 5.68%; P 5 .030), also in the infants with FH (30.0% vs 5.95%; P 5 .021). The cumulative incidence of AD was significantly higher in males without sunlight exposure during each timing compared with unexposed males (28.6% vs 6.5%; P 5 .013: 60.0% vs 6.6%; P 5 .003: 40.0% vs 6.3%; P 5 .039), but not in females. CONCLUSIONS: Gender- and genetic-dependently, sunlight exposure might affect the susceptibility to infections mediated by innate immunity in the skin, and then modulate the risk of AD in infants. All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. J ALLERGY CLIN IMMUNOL Abstracts AB59 VOLUME 137, NUMBER 2

Creating a System to Track Allergic Reactions in Determination of the Accurate Food Allergy 188 Schools 190 Prevalence and Correction of Unnecessary Food Elimination Ruchi Gupta, MD, MPH1,2, Marjorie Yarbrough, MPH3, Bridget Smith, Yuki Okada, MD1,2, Takumi Yamashita3, Yoshihiko Morikawa4,AkiraAka- PhD1,4; 1Northwestern University Feinberg School of Medicine, Chicago, sawa, MD, PhD5; 1Niijima Clinic, Tokyo, Japan, 2Department of General Pe- IL, 2Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL, diatrics, Tokyo Metropolitan Childrens Medical Center, Tokyo, Japan, 3Feinberg School of Medicine, Northwestern University, 4Edward J. Hines 3Shikinejima Clinic, Tokyo Metropolitan Bokutoh Hospital, Hideki Kuma- Jr. VA Hospital, Chicago, IL. gai, Department of Pediatrics, Jichi Medical University, Tochigi, Japan, RATIONALE: An estimated 8% of children in the United States have a 4Clinical Research Support Center, Tokyo Metropolitan Childrens Medical food allergy, and nearly 40% of children of these children have a history of Center, 5Division of Allergy, Tokyo Metropolitan Childrens Medical Center. severe reactions. To gain a better perspective of how many allergic RATIONALE: Because the true prevalence of food allergy (FA), as based reactions occur during school hours, we are developing and piloting an on the results of an oral food challenge test (OFC), is unknown, it is likely Allergic Reaction Registry for schools. that children with suspected FA unnecessarily eliminate potentially METHODS: We conducted two separate focus groups and one key causative foods. This study aimed to identify the prevalence of FA and 5 informant interview with school nurses from three K-12 schools (n 6). determine the proportion of children who unnecessarily eliminate food. Questions focused on how nurses managed allergic reactions and their data METHODS: To identify children with FA, a primary survey was needs. Based on their input, we collaborated with the nurses and conducted via questionnaire with all children aged 0–18 years old in informatics experts to further develop a reporting tool that can be accessed Niijima village (remote islands of Japan). In the secondary survey, a in REDCap or as part of an electronic charting system. detailed medical interview was conducted by doctors with children who RESULTS: Major themes identified included the importance of sharing currently did not eat some foods. The third survey involved serum food- information with other healthcare providers and creating a narrative specific IgE tests and an OFC for children with suspected FA. account in the registry. Registry data includes: demographics, type of RESULTS: Of 376 enrolled children, 374 (99.5%) completed the allergen, how the allergen came into contact with the individual, time of questionnaires. Some foods were eliminated by 18.6% and 13.0% of all exposure, where the reaction took place (location), symptoms, medications children and children >_6 years old, respectively. The target population for given, the timing of treatment and whether the individual went to the the secondary survey included 69 children who all completed the medical Emergency Room. A narrative section was also included for the nurses to interview. The target population for the third survey consisted of 35 be able to describe in more detail the reaction and care that followed if they children, of whom 26 (74.3%) underwent the blood test. An OFC was choose to do so. performed 35 times with 20 children. As a result, the prevalence of FAwas CONCLUSIONS: In order to understand the context and frequency 4.9% in children of all ages and 4.7% in children >_6 years old. Moreover, allergic reactions in schools, the successful development of a form that can 48.6% children could cease eliminating food intake. be used in different school systems is critical. This form can be shared CONCLUSIONS: It is possible that a considerable number of children across the country to achieve this goal. unnecessarily eliminate food because of suspected FA. SATURDAY

Impact of Maternal Oral Contraceptive Pills on Relationship of Influenza Virus Infection and 189 Wheeze and Allergic Outcomes in 5-Year-Olds: A 191 Complications from Viral/Bacterial Infections in Prospective Birth Cohort Study in Japan a Community Based Setting

1 2 Kiwako Yamamoto-Hanada, MD1, Limin Yang2, Tetsuo Shoda, MD, Yitzchok M. Norowitz, BS , Tamar A. Smith-Norowitz, PhD , Stephan 1 1 PhD1, Osamu Natsume, MD1, Masami Narita, MD, PhD1, Yukihiro Kohlhoff, MD ; Department of Pediatrics, State University of New 2 Ohya, MD, PhD2; 1Division of Allergy, National Center for Child Health York Downstate Medical Center, Brooklyn, NY, Department of Pediat- and Development, Tokyo, Japan, 2Division of Allergy, National Center for rics, SUNY Downstate Medical Center, Brooklyn, NY. RATIONALE: Child Health and Development, Japan. Influenza virus is a major health care burden and is associated with significant morbidity and mortality. Data on morbidity and RATIONALE: To examine the association of maternal oral contraceptive pills (OCP) use before pregnancy with wheeze and allergic outcomes in complications (pneumonia, otitis media, conjunctivitis, tonsillitis, enter- five-year-old children in Japan. itis) due to influenza virus infection in primary care settings are limited with reports mainly obtained from hospital settings. We assessed the METHODS: The Tokyo-Children’s Health, Illness and Development prevalence of complications from viral/bacterial infections in influenza- Study (T-CHILD) is a prospective, single center, birth cohort study. A questionnaire was conducted on the mothers regarding their history and positive compared with influenza- negative children presenting with duration of OCP use. To identify wheeze and allergic outcomes in the influenza-like illness (ILI) in a primary care setting. METHODS: This retrospective, practice-based chart review studied children, the questionnaire of the International Study of Asthma and complications from viral/bacterial infections in 255 children and adoles- Allergies in Childhood (ISAAC) was used. Logistic regression models cents (females/males, 1-21 years) who presented with ILI. We also were applied to estimate the association of maternal OCP use with wheeze compared the prevalence of complications by influenza vaccination status and allergic outcomes in children. Adjustments were made for maternal between influenza positive and influenza negative cases (2013-2015). history of allergy, maternal education level, maternal age at pregnancy, Comparisons for categorical variables were made using chi-squared tests. maternal BMI, maternal smoking during pregnancy, mode of delivery, RESULTS: The prevalence of complications (pneumonia, otitis media, gestational age at delivery, birth weight, parity, and gender of child. conjunctivitis, enteritis) was similar in influenza positive and influenza RESULTS: OCP use was associated with ever wheeze (adjusted odds ratio negative patients (P5NS), with the exception of tonsillitis, which was more [aOR], 1.64; 95% confidence interval [CI], 1.12-2.41), current wheeze common in patients who tested positive for Influenza B (P50.015). Patients (aOR, 1.61; 95% CI, 1.03-2.51), ever asthma (aOR, 1.64; 95% CI, 1.03- who were vaccinated were less likely to test positive for influenza compared 2.61), and ever allergic rhinitis (aOR, 1.86; 95% CI, 1.27-2.71). Compared with patients who were not vaccinated (P50.064). However, prevalence of with no prior OCP use, using OCP for more than six months statistically infections was similar in both groups based on vaccination status. increased the odds of ever wheeze (P 5 0.005), current wheeze (P 5 0.015) CONCLUSIONS: In a primary care setting, complications from viral/ 5 and ever asthma (P 0.04). bacterial infections did not differ in influenza positive compared with influenza CONCLUSIONS: Our findings suggest that maternal OCP use has a role negative patients. Vaccination with influenza vaccine may result in decreased in the development of wheeze and allergic outcomes in children. Extended duration or severity of symptoms and remains an important public health use of OCP is likely to increase the risk of wheeze and allergic outcomes. intervention. All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. AB60 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2016

The Association Between Maternal Depression No Association Between Atopic Outcomes and 192 and Child Allergic Disease 194 Pertussis Vaccine Given in Children Born on the Isle of Wight 2001-2 Ju-Suk Lee, MD, PhD1, Cheol Hong Kim, MD2, Jin-A. Jung, MD3; 1Samsung Changwon hispital, Sungkyunkwan university, Changwon, Carina Venter, PhD, RD1,2, Julia Stowe, BA (Hons)3, Nick South Korea, 2International St. Marry Hospital, 3Dong-A University Col- Andrews, PhD3, Elizabeth Miller, FRCPath3, Paul J. Turner, FRACP, lege of Medicine, Busan, South Korea. PhD4,5; 1Division of Allergy and Immunology, Department of Pediatrics, RATIONALE: Asthma and atopic dermatitis are common chronic Cincinnati Children’s Hospital Medical Center, University of Cincinnati, diseases and depression is an important comorbidity in allergic diseases. Cincinnati, Ohio, USA, Cincinnati, OH, 2University of Portsmouth, However, it is little known about the association between maternal United Kingdom, 3Public Health England, United Kingdom, 4Section of depression and child allergic diseases. This study was performed to find Paediatrics, Imperial College London, United Kingdom, 5Imperial Col- the association between maternal depression and child allergic diseases. lege London, United Kingdom. METHODS: Data were acquired from 2737 families who participated in RATIONALE: Public health bodies in the USA, Australia and Europe the Fifth Korea National Health and Nutrition Examination Surveys have noted that there has been an increase in food allergy which coincides (KNHANES), which was conducted from 2010 to 2012. with the switch from whole cell (WCP) to acellular pertussis (AcP) RESULTS: The prevalence of childhood asthma was 5.3 % and childhood vaccination in the US, Australia and Europe. AcP drives a Th2-like SATURDAY atopic dermatitis was 14.1%. The prevalence of maternal depression was immune response, in contrast to the WCP vaccine. 1.6 %. In univariate analysis, maternal depressions was associated with METHODS: The transition from WCP to AcP vaccine in the UK coincided maternal smoking, lower education level, lower economic state, lower with the establishment of a large birth cohort study on the Isle of Wight in number of household members, maternal asthma,children’s 2001/2002 to assess atopic/allergic outcomes through to age 10 years. We asthma(p<0.05) but marital status, maternal employment status, maternal analysed outcome data and linked this with the type of pertussis vaccine given atopic dermatitis, children’s sex, children’s age, children’s atopic derma- to compare rates according to the number of doses of AcP received. Outcomes titis, residence area were not associated with the presence of maternal assessed included: IgE-mediated food allergy, asthma at 3 and 10 years, depression. After adjustment, maternal depression was associated with eczema at 6 months/1 year/3 years, allergic rhinitis and atopy (positive SPT). lower house income, maternal asthma, children’s asthma.(p<0.05) RESULTS: A total of 701 children were included in the primary analysis CONCLUSIONS: The present study showed that maternal depression is which was all those who received a first infant dose before 18 weeks of age, associated with children’s asthma and not children’s atopic dermatitis. and doses 2 and 3 (if given) under 12 months of age. No significant These results warrant future studies to explore the mechanisms responsible association between any outcome measure and type of pertussis vaccine for the association between maternal depression and children’s asthma. were identified. Of those who had had at least one AcP dose 10/340 (2.9%) had IgE-mediated food allergy compared to 8/356 (2.2%) of those with no The Passive Smoking Is an Important Risk Factor AcP doses (P50.64). 193 of Allergic Diseases in Korean Adolescents CONCLUSIONS: We did not identify any link between type of pertussis vaccine received in infancy and allergic/atopic outcomes. Kyung Suk Lee, MD, PhD1, Man-Yong Han, MD2, Jun-Hyuk Song, MD3, Sun Hee Choi, MD, PhD4, Yeong-Ho Rha, MD, PhD5; Epit Prevents from the Induction of Anaphylaxis to 1Department of Pediatrics, CHA University Bundang Medical Center, 195 Further Allergens: Role of Naive Tregs Seongnam, South Korea, 2CHA University Bundang Medical Center, Seongnam, South Korea, 3Department of Pediatrics, Myongji Hospital, Lucie Mondoulet, PhD1, Vincent Dioszeghy, PhD1, Emilie Puteaux1, Goyang-si, South Korea, 4Kyung Hee University Hospital at Gangdong, Melanie Ligouis1,Veronique Dhelft1, Camille Plaquet1, Christophe Seoul, South Korea, 5Kyung Hee University Hospital, Seoul, South Korea. Dupont, MD, PhD2, Pierre-Henri Benhamou, MD1; 1DBV Technologies, RATIONALE: Smoking and drinking are hazard behaviors threaten Bagneux, France, 2Hopital Necker Enfants Malades, Paris, France. health in adolescents and influence to develop allergic diseases, but little is RATIONALE: In milk-sensitized mice, epicutaneous immunotherapy known in Korean adolescents. We sought to evaluate the association (EPIT) prevents from the induction of anaphylaxis to further allergens via a between smoking, drinking and allergic diseases. regulatory T cells (Tregs) mechanism. This study is an in-depth METHODS: We used the data of the 2014 Korea Youth Risk Behavior investigation of the Tregs subpopulations involved in this protection. Web-Based Survey that 72,060 Korean middle and high school students METHODS: After milk sensitization, mice were treated by EPITor Sham. participated in. Dependent variables were asthma, allergic rhinitis (AR) CD4+CD25+T cells were isolated from spleen and transferred into not and atopic dermatitis (AD) diagnosed within 1 year, and its treatment sensitized mice (recipient) following injection of an IL2 blocking antibody. within last 1 year. Independent variables were current cigarette smoking, Recipient mice were submitted to a peanut-sensitization procedure and passive smoking, current drinking and dangerous level of drinking. intravenously challenged with peanut. Multivariate analysis was done to investigate the relationship between In a second experiment, Tregs were isolated upon the CD62L+ surface smoking, drinking and allergic diseases. marker defining a naive Tregs population. Naive and effector Tregs were RESULTS: The prevalence of current smoking was 14.0% in male, 4.0% adoptively transferred into recipient mice, which were then submitted to in female and 9.2% in total. Passive smoking was 32.8% in male, 34.9% in peanut- sensitization and IV challenge. Outcome tools were drop in rectal female and 33.8% in total. Current drinking and dangerous level of temperature, hypersensitivity reactions and blood mouse mast cell prote- drinking were 16.7%, 7.9% in total, respectively. Current smoking was a ase-1 (mMCP1). risk factor of asthma (OR51.420, P50.000). Passive smoking was a risk RESULTS: The adoptive transfer of milk EPIT-induced Tregs to recipient factor in asthma (OR51.256, P50.000), asthma treatment (OR51.248, mice protected them from sensitization to peanut and from the induction of P50.000), AR (OR51.051, P50.014), AD and its treatment (OR51.127, anaphylaxis (p<0.01). The injection of anti-IL2 before Tregs transfer P50.000; OR51.128, P50.000). Current drinking was related to AD abrogated the protection from anaphylaxis. Noticeably, the induction by (OR51.182 P50.003) and dangerous level of drinking wasn’t a risk factor. EPITof naive Tregs also decreased in the presence of anti-IL2. The transfer CONCLUSIONS: Smoking was a significant risk factor of allergic of naive Tregs seemed to prevent from the drop in temperature after IV diseases than drinking. The rate of passive smoking was higher than challenge (p<0.001) whereas effector Tregs did not confer this protection. current smoking and was revealed a risk factor of allergic diseases’ CONCLUSIONS: The protection against sensitization to further aller- development. Prevention strategy primarily for passive smoking should be gens observed after EPIT appears to be conferred by the naive Treg implemented to prevent allergic diseases in Korean adolescents. fraction. All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. J ALLERGY CLIN IMMUNOL Abstracts AB61 VOLUME 137, NUMBER 2

Altered Serum IgE and IgG4 Response to >5). No bronchial symptoms were detected. A significant negative 196 Dermatophagoides Pteronyssinus Allergens during correlation between serum Phleum-sIgE levels and grass pollen threshold Specific Immunotherapy CPT concentration was detected (Rho -0.918, p>0.001). CONCLUSIONS: The results demonstrated that OPS system is a very Baoqing Sun, MHA1, Zheng Peiyan2; 1The First Affiliated Hospital of useful parameter to assess the response to CPT in patients with moderate- Guangzhou, Guangzhou, China, 2State Key Laboratory of Respiratory severe allergic rhinoconjunctivitis in daily practise. Disease, National Clinical Center for Respiratory Diseases, Guangzhou Does Having Prior Turbinate Surgery Influence Slit Institute of Respiratory Diseases, First Affiliated Hospital, Guangzhou Compliance Medical University, Guangzhou, China. 198 RATIONALE: We investigated the changes in serum-specific IgE (sIgE) Jessica Tattersall, MBBS(Hons); Rhinology and Skull Base research and IgG4 (sIgG4) against house dust mite (HDM) and its components Der p group, Darlinghurst, Australia. 1 and Der p 2 during specific immunotherapy (SIT), and evaluated the RATIONALE: Allergic Rhinitis affects approximately 20% of individ- clinical efficacy thereof. uals in Australia and the U.S. and can significantly impact quality of life. A METHODS: We retrospectively analyzed 51 HDM-sensitized children aged congested nose is often one of the main presenting complaints. Specific 5 to 16 years diagnosed with allergic rhinitis and/or asthma, following 36 immunotherapy has been shown to be beneficial in switching off the months of SIT. We also collected data from a contemporary control cohort of 50 allergic drive and improving patient’s symptoms. However, compliance patients administered routine medications for HDM allergy. . In the test cases, rates are variable and immunotherapy is often ceased prematurely. we recorded the sIgE and sIgG4 levels against the whole allergen of HDM (Der METHODS: A case-control study of sublingual immunotherapy (SLIT) p), Der p 1 and Der p 2 at baseline and at 6, 12, 24 and 36 months of SIT. patients at a tertiary Rhinologic clinic was performed. Patients were selected RESULTS: The serum sIgE response increased up to 6 months of SIT, but for SLIT using epicutaneous testing to confirm a clinically relevant antigen. subsequently declined. At 36 months, the anti-Der p 1 and anti-Der p 2 Patients were considered to have had turbinate surgery if performed during sIgEs plummeted below the baseline. During SIT, the increased serum the 3 years prior to commencing SLIT. Any turbinate procedure (turbino- sIgG4 response was the greatest against Der p, followed by Der p 1 and Der plasty, resection or diathermy) was included. Non-compliance with SLIT p 2. The decline in sIgE/sIgG4 ratio for Der 1 was higher than for the other was defined as active cessation of therapy or failure to reorder within the last allergensmaximum decline. Compared with older children, children aged 5 12 months. Groups were compared using Chi-squared analysis. to 8 manifested a clearer sIgG4 response, especially against Der p 1 and RESULTS: One hundred and nine patients (42.2% female, 27.87613.74yrs) Der p 2 versus Der p. were assessed. 41.3% of patients did not complete a minimum of 36mths. Prior CONCLUSIONS: SIT for HDM stimulated an early sIgE and sIgG4 turbinate surgery was noted in 35% of SLIT patients. SLIT patients who had response against HDM allergens. with a progressive decline in the ratio of undergone turbinate surgery were more likely to be males (71.4% v 48.1%, sIgE/sIgG4, especially against Der p 1. Younger children may manifest a p50.045) but were of similar age (29.59611.05yrs v 27.73614.45, p50.56). more rapid response to SIT than older ones. The difference in dropouts favoured prior turbinate surgery (50% v 28.8%,

p50.07) but was not statistically significant. SATURDAY Conjunctival Provocation Test in Daily Practice: CONCLUSIONS: In a population of patients undergoing SLIT, men were 197 Four Ocular Symptoms Vs Ocular Pruritus Score more likely to have had prior turbinate surgery. The influence of turbinate System surgery on SLIT compliance should be further investigated.

Carmen Rondon, MD, PhD1,PalomaCampo,MDPhD1, Esther House Dust Mite-Associated Allergic Rhinitis: Barrionuevo, MD, PhD2, Ana Prieto del Prado, MD3, Gador Bogas, MD1, 199 Efficacy of STG320 Sublingual Tablets of House Arturo Ruiz, MD1, Maria Auxiliadora Guerrero1, Leticia Herrero1,Pedro Dust Mite Allergen Extracts 4 5 6 1 A. Galindo , Diana Perez-Alzate, MD , Miguel Blanca, MD, PhD ; Al- Michel Roux, MD,Helene Nguyen, PharmD, Agnes Viatte, Robert K. lergy Unit, Regional University Hospital of Malaga-IBIMA, UMA, Malaga, Zeldin, MD; Stallergenes SAS, Antony, France. 2 Spain, Allergy Unit, IBIMA, Regional University Hospital of Malaga, RATIONALE: Efficacy of STG320 house dust mite (HDM) sublingual 3 UMA, Malaga, Spain, Pediatric Area. Health Center Don JoseMolina tablets has been demonstrated. Here we report the efficacy on rhinitis 4 Dıaz. Alhaurın de la Torre., Malaga, Spain, Allergy Service, General Uni- symptoms in two DBPC studies. 5 versity Hosptial of Ciudad Real, Ciudad Real, Spain, Allergy Service, Uni- METHODS: Adults with HDM-associated allergic rhinitis were enrolled in 6 versity Hospital Infanta Leonor, Madrid, Spain, Allergy Unit, Regional a natural field study (NatField) and an environmental exposure chamber study University Hospital of Malaga-IBIMA, UMA, Malaga, Spain. (EEC). In the former, subjects received STG320 500IR or 300IR, or placebo RATIONALE: Conjunctival provocation test (CPT), the confirming diag- once daily for 1 year. In the latter, subjects received 500IR, 300IR or 100IR of nostic test of ocular allergy, is underused by clinicians. We compared the STG320 or placebo, daily during 6 months. In NatField, the Average Rhinitis diagnostic accuracy of CPT in daily practice using two different symptoms Total Symptom Score (ARTSS) and individual rhinitis symptom scores score systems recommended by the EAACI Interest Group on Ocular Allergy: (sneezing, rhinorrhea, nasal pruritus, nasal congestion) were assessed over the ocular pruritus score (OPS) and 4 total ocular symptoms score (4TOSS). last 3 months of treatment. In EEC, the changes from baseline to end-of-6- METHODS: Mixed grass pollen extract (LETI SL, Madrid, Spain) was month-treatment in ARTSS (ChBLARTSS) and individual symptoms were as- used for CPT in 11 asymptomatic patients with persistent moderate-severe sessed over the 4 hours and the last 2 hours of the HDM challenges. rhinoconjunctivitis due to grass pollen and 8 controls (4 healthy subjects, RESULTS: In NatField (N5509), ARTSS Least-Square means were and 4 patients with D. pteronyssinus allergic rhinitis). The positive CPT significantly reduced (p<0.05) with relative differences from placebo of _ _ criterion was 4TOSS > 5, or OPS > 2. Response to CPT evaluated by -17.4% (500IR) and -18.5% (300IR). In the active groups, the scores for all 4TOSS (pruritus, hyperemia, tearing, and chemosis) and OPS were symptoms were lower than placebo, with significance at both doses for compared with SPT results, the gold standard (SPT). The appearance of sneezing and nasal pruritus, and at 300IR for nasal congestion. In EEC nasal and/or bronchial symptoms was also evaluated. (N5355), relative differences from placebo increased from 17.5% (100IR) to RESULTS: OPS had 100% sensitivity, specificity, positive predictive 25.8% (300IR) and 31.1% (500IR) for ChBLARTSS0-4h, and 31.3% (100IR) to value (PPV), negative predictive value (NPV), and concordance with SPT 42.3% (300IR) and 44.7% (500IR) for ChBLARTSS2-4h. The changes from (kappa index 1, p<0.001). 4TOSS had a high sensitivity (90.9%), baseline to the end-of-6-month-treatment in individual scores also improved specificity (100%), PPV (100%), NPV (88.9%) and concordance with with the increase in dose. SPT (kappa index 0.894, p<0.001). Thirty six per cent of cases with a CONCLUSIONS: The 300IR dose of STG320 was effective for the positive CPT had a positive nasal response (4 total nasal symptoms score treatment of symptoms of HDM allergic rhinitis subjects. All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. AB62 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2016

A Complication of Eosinophilic Esophagitis from Evaluation of SQ-House Dust Mite Sublingual 200 Sublingual Immunotherapy 202 Immunotherapy Tablet One-Year after Completion of a 24-Week Treatment Period Charmi Patel1, Prem K. Menon, MD, FAAAAI2; 1Baton Rouge General/ Tulane University School of Medicine, Baton Rouge, LA, 2Tulane Univer- Petra U. Zieglmayer, MD1, Hendrik Nolte, MD, PhD2, Harold S. sity School of Medicine, Asthma, Allergy and Immunology Center, Baton Nelson, MD, FAAAAI3, David I. Bernstein, MD, FAAAAI4, Amarjot Rouge, LA. Kaur, PhD2, Ziliang Li, PhD2, Rene Zieglmayer1, Rene Schmutz, MD1, RATIONALE: Sublingual Immunotherapy (SLIT) is an emerging Patrick Lemell, PhD1, Friedrich Horak, MD1; 1Vienna Challenge Cham- treatment for sensitization to aeroallergens due to convenience and lesser ber, Vienna, Austria, 2Merck & Co., Inc., Kenilworth, NJ, 3National Jew- risk of anaphylaxis. Eosinophilic Esophagitis (EoE) is described with food ish Health, Denver, CO, 4Bernstein Allergy Group, Cincinnati, OH. desensitization protocols in milk, egg and peanut, but only one case report RATIONALE: Long-term treatment effects in patients with allergic rhinitis associates EoE triggered by SLIT for pollen. have been demonstrated for Timothy grass sublingual immunotherapy tablet METHODS: Esophagogastroduodenoscopy was performed with (SLIT-tablet); however, data on long-term effects are lacking for house dust biopsies. mite (HDM) SLIT-tablets. This study assessed the treatment effect of 12 SQ- RESULTS: 11-year-old male with history of allergic rhinitis due to HDM SLIT-tablet 1 year after completion of a 24-week treatment period. sensitization to grass, trees and cats treated with grass SLIT for one-year METHODS: Subjects underwent 6-hour environmental exposure chamber SATURDAY presented with three-month history of burning epigastric pain. He has (EEC) challengesat baselineand week 24 (end oftreatment)ina randomized, associated odynophagia and dysphagia without food triggers. He tried one placebo-controlled, double-blind trial (NCT01644617) during which sub- month of esmoprazole twice daily and antacids without relief. An jects received daily 12 SQ-HDM SLIT-tablet or placebo for 24 weeks. An esophagogastroduodenoscopy revealing furrowing of the esophagus. EEC challenge was conducted approximately 1 year after trial completion as Biopsies showed up to 35 eosinophils per high-powered field and super- part of the Vienna Challenge Chamber’s annual diagnosis update of allergic ficial layering of eosinophils consistent with EoE. He was taken off SLIT subjects. The total nasal symptom score (TNSS) and nasal airflow by active with subsequent resolution of symptoms. anterior rhinomanometry were assessed from hours 2–6 of EEC challenges. CONCLUSIONS: In the literature, oral immunotherapy for milk, peanut TNSS was the sum of 4 nasal symptom scores (maximum512). and egg desensitization is described to trigger EoE. There is only one case RESULTS: Thirty six subjects who received 12 SQ-HDM SLIT-tablet and report of EoE with SLIT drops when using birch, hazelnut and alder extract 34 who received placebo were assessed at week 24; 16 subjects from each and no cases are reported as a complication of purely grass SLIT tablets. group were assessed at follow-up. Compared with baseline values, TNSS at We hypothesize that consistent exposure of an allergen that is partly week 24 improved 47% and 211% with HDM SLIT-tablet and placebo, tolerated may trigger EoE, but the mechanism is unknown. As patients respectively, and at one-year follow-up improved 34% and 10%. Nasal elect oral options over invasive subcutaneous immunotherapy, EoE should airflow decreased 33% at baseline, 21% at week 24, and 22% at follow-up be considered as an adverse effect and be studied further in these in HDM SLIT-tablet subjects, and 39% at baseline, 30% at week 24, and circumstances. Treatment is removing the offending agent and consider 30% at follow-up in placebo subjects. swallowed steroid during the initial symptoms. CONCLUSIONS: Improvement of allergic rhinitis symptoms were observed up to 1 year after completing 24-weeks of treatment with the Intralymphatic Pollen-Specific Immunotherapy for 12 SQ-HDM SLIT-tablet. 201 Nasal Allergy: Clinical Efficacy and Effects on the Induction of Pollen- Specific Antibody

Tetsuya Terada, Syuji Omura, Yusuke Kikuoka, Megumi Yoshida, Man- abu Suzuki, Shinpei Ichihara, Takahiro Ichihara, Takaki Inui, Ryo Ka- wata; Osaka Medical College. RATIONALE: Pollen immunotherapy is an effective treatment for seasonal allergic rhinitis. The most common administration route is subcutaneous, which may necessitate more than 50 allergen injections during 3 to 5 years. The newer sublingual immunotherapy is more patient friendly, but treatment duration could not be shortened. Recent evidence suggests that direct intralymphatic injections could yield faster beneficial results with considerably lower allergen doses and markedly reduced numbers of injections. In this study, we sought to improve immunotherapy by using intralymphatic allergen administration. METHODS: In an open pilot investigation followed by a double-blind, placebo-controlled study, patients with allergic rhinitis were treated with 3 intralymphatic inguinal injections of Cry j1 or placebo. At visit 2 to 4, the study subjects received three 0.1 ml injections with either placebo or 20 JAU of a standardized Japanese pollen extracts. Using ultrasound guidance and a 25-gauge needle, a superficial inguinal lymph node in right groin was aseptically injected for 30 seconds. Clinical pre and post treatment outcomes and the activation pattern of peripheral antibodies were assessed. RESULTS: Intralymphatic immunotherapy (ILIT) with Cry j1 did not elicit any severe adverse events. Patients receiving active treatment displayed an initial increase in allergen-specific IgE and IgG level. A clinical improvement was seen in active treatment group, but not in the placebo group. CONCLUSIONS: ILITwith Japanese pollen extracts indicate the clinical improvement without causing severe adverse events. All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. J ALLERGY CLIN IMMUNOL Abstracts AB63 VOLUME 137, NUMBER 2

Efficacy of Sublingual Immunotherapy to Dust throughout. To our knowledge, this is the first pediatric case, raising 203 Mites: Real-Life Study Comparing Adults and concern for the safety of pediatric aeroallergen SLIT. Children Efficacy of 300IR 5-Grass Pollen Sublingual Tablet Carla Irani, MD, FAAAAI1,2, Albert Semaan2; 1University of Alberta, 205 in the Treatment of Rhinitis Symptoms in Edmonton, AB, Canada, 2Hotel Dieu de France hospital, St Joseph Uni- Polysensitized Subjects with Grass Pollen- versity, Beirut, Lebanon. Induced Allergic Rhinoconjunctivitis RATIONALE: Sublingual immunotherapy (SLIT) is a practical form of allergen immunotherapy. Studies using SLIT to dust mites are still needed Robert K. Zeldin, MD, Yann Amistani, MSc, Josiane Cognet- to show the beneficial effect in adulthood and childhood asthma. Sice, PharmD, Kathy Abiteboul, PharmD; Stallergenes SAS, Antony, METHODS: A cohort real-life study of 97 patients comparing the efficacy France. of SLIT between children 33% and adults 67% suffering from allergic RATIONALE: The efficacy of 300IR 5-grass pollen sublingual tablet rhinitis(AR) with its effect on asthma.The study is conducted at an (Oralair) when administered to subjects with grass pollen-induced allergic outpatient clinic at Hotel Dieu de France Hospital (HDF), Beirut. Patients rhinoconjunctivitis (ARC) according to a 4-month pre-seasonal and co- with AR monosensitized (74.3%) to dust mites, and suffering from mild to seasonal regimen has been consistently demonstrated across the develop- moderate asthma (50.5%), are evaluated. Evaluation is done at inclusion ment program. Here we present the efficacy results for individual rhinitis and at 36 months after SLIT. Patients received a standardized dust mites symptoms in polysensitized subjects. extract: StaloralR 300IR (Stallergenes) 4 pressions daily. Asthma symptom METHODS: Subjects with medically confirmed grass pollen-induced score (ASS), rhinitis symptom score (RTSS), asthma medication consump- ARC for at least 2 years were enrolled in one of 4 natural field studies. All tion score (AMCS) and Rhinitis medication consumption score (RMCS) participants underwent prick skin testing to 5-grass mix or timothy and a are compared, prior to SLIT and 3 years after. panel of geographically relevant aeroallergens. Those who had a positive RESULTS: Using a t test, the average scores at inclusion and 36 months test to 5-grass/timothy and at least one other allergen were considered respectively were :In children RTSS: 17.75;5.75 (p<0.005), RMCS:5.923; polysensitized. Each day, subjects self-scored each of their rhinitis 0.923 (p<0.005), ASS:4.53;0.846 (p<0.005), AMCS:1.923;0.538 (p<0.005). symptoms (sneezing, rhinorrhea, nasal pruritus, nasal congestion) on a In adults RTSS: 15.41;4.59 (p<0.005), RMCS: 6.73;1.86 (p<0.005), ASS: scale from 0 (none) to 3 (severe). The individual symptom scores and the 5.636;0.773 (p<0.005), AMCS: 2.91;0.545 (p<0.005). The results of our Rhinitis Total Symptom Score (the sum of the four individual symptom study showed efficacy of SLIT for dust mites in both groups. scores) were analyzed descriptively. CONCLUSIONS: SLIT to dust mites is effective in both adults and RESULTS: Data from 891 polysensitized subjects, corresponding to 65% children suffering from allergic rhinitis. It is also applicable in mild to of the studied population, were analyzed. The means of each of the 5 moderate asthma. Most recent studies show that using high dose SLIT (8 individual symptom scores in the 300IR group (n 427) were significantly 5 pressions per day) may be more effective than the common regimen used lower than in the placebo group (n 464) with relative differences from

above, further studies are required. placebo of -15% (sneezing), -19% (rhinorrhea), -22% (nasal pruritus) and SATURDAY -24% (nasal congestion). The Rhinitis Total Symptom Score relative mean Eosinophilic Esophagitis Induced By Aeroallergen difference from placebo was -20%. 204 Sublingual Immunotherapy in an Enteral Feeding CONCLUSIONS: Oralair effectively reduced all rhinitis symptoms in Tube Dependent Pediatric Patient polysensitized subjects with grass pollen-induced rhinoconjunctivitis.

Cindy S. Bauer, MD1, Michaela M. Tvrdik2, Shauna Schroeder, MD1; 1Phoenix Children’s Hospital, Phoenix, AZ, 2Creighton University School of Medicine, Omaha, NE. RATIONALE: Eosinophilic esophagitis (EoE) is an increasingly recog- nized eosinophilic gastrointestinal disorder triggered by food antigens. Data suggests that aeroallergens may also play a pathogenic role. Here we present a 9-year-old male who developed EoE after initiating aeroallergen sublingual immunotherapy (SLIT). METHODS: Esophageal biopsies were performed at Phoenix Children’s Hospital. RESULTS: A 9-year-old male with history of severe feeding disturbance, G-tube dependency, autism, reflux, asthma, and allergic rhinoconjunctivi- tis was referred for esophageal eosinophilia. Initial endoscopic biopsy performed during G-tube placement for oral aversion was normal on proton pump inhibitor (PPI) therapy. Because of continued feeding refusal, repeat evaluation on elemental formula and PPI was performed and showed marked esophagitis (57 eosinophils/40X HPF in the distal esophagus; June 2013). In June 2014 on elemental diet, PPI, and non-adherence of swallowed corticosteroids, his eosinophilia persisted (32, 46, and 47 eosinophils/40X HPF in the distal, mid, and proximal esophagus, respectively). Further history revealed the patient started aeroallergen SLIT in May 2013 (grass, tree, and dust mite). Both topical corticosteroids and SLIT were discontinued and in June 2015 on elemental diet and PPI, his repeat endoscopy showed resolution of his eosinophilia. CONCLUSIONS: The resolution of esophageal eosinophilia after cessation of aeroallergen SLIT in a patient continued on elemental diet and PPI throughout, strongly implicates aeroallergen SLIT as the trigger. Two previous reports have described EoE in adults receiving aeroallergen SLIT; however, neither had baseline endoscopic biopsy nor elemental diet All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. AB64 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2016

Evaluation of Pediatric and Adult Systemic reductions in eosinophil recruitment and inflammatory cytokine (IL-4, -5 206 Reactions to Subcutaneous Immunotherapy (SCIT): and -17) production by T-cells. Interim Analysis of a Retrospective Chart Review CONCLUSIONS: These results indicate that protection established with Fel d 1 peptide immunotherapy can be extended to other co-administered Chen Lim, MD1, Cristina Sison, PhD2,PunitaPonda,MD3; 1Department of allergens, thereby potentially extending clinical efficacy. Pediatrics, Cohen Children’s Medical Center, North Shore-LIJ Health Sys- Endometrial Anaphylaxis Due to Subcutaneous tem, New Hyde Park, NY, 2Feinstein Institute for Medical Research, Biosta- Immunotherapy (SCIT): A Case Series tistics Unit, North Shore-LIJ Health System, Manhasset, NY, 3Allergy and 208 Immunology, Department of Pediatrics, Division of Allergy & Immunology, Manideep Nandigam, Frank J. Eidelman, MD, FAAAAI, Ves Dimov, Hofstra-North Shore-LIJ School of Medicine, Great Neck, NY. MD; Cleveland Clinic Florida, Weston, FL. RATIONALE: Current SCIT regimens have wide variability in practice RATIONALE: Subcutaneous immunotherapy (SCIT) aims to achieve styles and dosing strategies. Most medications require pediatric clinical clinical tolerance for allergens. Systemic reactions to SCIT are classified studies to determine appropriate doses for children. No similar guidelines into 4 grades. Uterine cramps fall under grade 2, and are rare. Literature review exist for SCIT. The objective of this study was to describe factors revealed only 3 case reports since 1997, 2 of them related to venom SCIT. influencing systemic reactions in our study population and to provide METHODS: Four cases of endometrial anaphylaxis due to SCIT with preliminary descriptive statistics.

SATURDAY environmental allergens were identified via retrospective case review of METHODS: We conducted a retrospective chart review to record the electronic medical record at allergy clinic of a tertiary referral medical number of systemic reactions (SR) to SCIT. We used a generalized linear center between 2010 to 2014. mixed model to examine variables of interest. Crude incidence rate was RESULTS: Endometrial anaphylaxis was observed during buildup phase estimated as number of SRs relative to total injections administered. of SCIT in two patients and during maintenance therapy the other two. RESULTS: Of 120 pediatric and 150 adult subjects, there was a Symptoms occurred 30-45 minutes after SCIT injections. In all cases, significantly higher proportion of males (63% vs 40%; p<0.0001) and immediate hypersensitivity reactions without uterine cramps had been subjects with asthma (62.5% vs 46%; p<0.0072) in the pediatric group reported with previous SCIT injections. Two patients had recurrent than the adult group. There was no difference in asthma classification episodes of uterine cramps even after adjusting schedule and dose of between age groups (intermittent: 29.33% vs 39.13%; p<0.2241; persistent: SCIT. Premedication with antihistamine and montelukast did not affect the 70.67% vs 60.87%; p<0.2241). Of 132 reactions, 75 SRs occurred in the reactions. Uterine cramps lasted for approximately one hour after the pediatric group; 57 SRs occurred in the adult group. The majority of administration of epinephrine and diphenhydramine. Severe uterine reactions were grades 1 or 2 (83.3%) and more likely to occur in the pediatric cramp-like pain was the sole manifestation in one patient, whereas the group. Reactions occurred more in spring and autumn (35 each) than others had associated urticaria, angioedema or diffuse erythema/flushing. summer and winter (31 each). Incidence rate (crude) for any SR was 0.2%. None of the patients had a history of dysmenorrhea prior to SCIT. No CONCLUSIONS: Our results suggest that current allergen SCIT practices vaginal bleeding was reported during uterine cramps. are associated with a higher rate of SRs in children. These results provide a CONCLUSIONS: Endometrial anaphylaxis is one of the rare adverse foundation for future studies to evaluate factors that may influence practice reactions to SCIT which may be underrecognized and underreported. This guidelines for the safe administration of SCIT in children. is the largest reported case series at this time. Increased awareness should Fel d 1 Peptide Immunotherapy Ameliorates Both facilitate more research in this rare but significant adverse reaction to SCIT. 207 Cat and Ovalbumin Responses, in a Dual Allergen Surgical Therapy Reduces Blood Eosinophil Murine Model of Allergic Airways Disease 209 Counts in Eosinophilic Chronic Rhinosinusitis

1,2 1,2 Daniel M. Moldaver , Mantej S. Bharhani , Christopher D. Dai Takagi1, Yuji Nakamaru2, Satoshi Fukuda3; 1Hokkaido University, 3 1,2 1,2 Rudulier, PhD , Jennifer Wattie , Mark D. Inman, MD, PhD , Mark Sapporo, Japan, 2Otolaryngology Hokkaido University, Sapporo, Japan, 1,2 1 Larche, PhD ; Firestone Institute for Respiratory Health, Hamilton, 3Hokkaido University. 2 3 ON, Canada, McMaster University, Hamilton, ON, Canada, University RATIONALE: It has been reported that eosinophilic chronic rhinosinusitis of Saskatchewan, Saskatoon, SK, Canada. (ECRS) coexists at high levels with asthma, and frequently recurs after RATIONALE: Peptide Immunotherapy targeting Fel d 1, the primary cat surgery. An elevated peripheral eosinophil count is an important factor in allergen, is clinically efficacious and has been shown to facilitate the spread predicting the recurrence of ECRS. In this study, we investigated postoperative of tolerance between T-cell epitopes within Fel d 1 through the generation changes in blood eosinophil count and other biomarkers in ECRS patients. of a tolerogenic environment. We sought to further explore the potential of METHODS: Twenty-two patients with ECRS who were treated with the tolerogenic environment. Specifically, we hypothesized that Fel d 1 endoscopic sinus surgery (ESS) were examined for blood eosinophil count, peptide immunotherapy could ameliorate responses to an unrelated, but co- total serum IgE and serum IL-5 before and after surgery. Data were administered, allergen. compared with those for non-ECRS patients and patients with chronic 5 METHODS: Female BALB/c mice (Charles River;6-8wks, n 4/group, rhinosinusitis without polyps. We also analyzed the differences between two independent experiments) received two intraperitoneal injections of good-controlled ECRS patients and patients who experienced recurrence. m m Fel d 1 (1 g) and ovalbumin (OVA; 10 g) in alum (D0 & 14). Peptides Fel RESULTS: The blood eosinophil count was significantly decreased after d123-38 (EQVAQYKALPVVLENA) and Fel d 129-45 (KALPVVLEN surgery in the ECRS group, but not in the non-ECRS group. Serum IL-5 ARILKNCVDAK) were administered intradermally on D28, 35 and 42. also tended to be reduced after surgery in ECRS patients. An analysis of the Mice were then concurrently exposed to OVA and Fel d 1, subcutaneously ratio of serum IL-5 (pre-ESS/post-ESS) in patients showed that it was (D49, 56 & 63). Parallel groups of mice were challenged intranasally with significantly higher in the ECRS group than in the CRSsNP group. Among either cat dander extract (CDE) or OVA, to assess the immune response to ECRS patients, the preoperative blood eosinophil count was significantly each allergen. 24-hour post challenge, mice were sacrificed and bronchoal- higher in RG patients. Furthermore, in the RG group, the blood eosinophil veolar lavage (BAL), lungs and draining lymph nodes were collected for count was significantly decreased after endoscopic sinus surgery compared assessment by cytology, histology and flow cytometry. with the good-controlled group. RESULTS: CDE and OVA challenge of sham treated mice induced robust CONCLUSIONS: The blood eosinophil count was reduced after ESS in airway eosinophilia. Peptide therapy prevented CDE-induced eosino- the ECRS patients. Postoperative changes in eosinophil count might be philia, while expanding T- and B-regulatory populations. Fel d 1 peptide used to predict the prognosis for ECRS patients. The blood eosinophil immunotherapy also protected mice from challenge with OVA,observed as count in ECRS may reflect local and systemic factors in its pathogenesis. All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. J ALLERGY CLIN IMMUNOL Abstracts AB65 VOLUME 137, NUMBER 2

Clinical Characteristics of Aspirin Exacerbated between 2002-2012 were randomly identified via ICD-9 codes. 210 Respiratory Disease in a Tertiary Care Patient Characteristics analyzed included demographics, atopy, radiologic sinus Cohort severity, and comorbid diseases. RESULTS: 319/507(63%) were female in the CRSsNP group compared to Whitney W. Stevens, MD, PhD1, Anju T. Peters, MD1, Leslie C. 393/847(45%) in the CRSwNP group. Severity of sinus disease was similar Grammer, MD1, Kathryn E. Hulse, PhD2, Atsushi Kato, PhD1, Bruce between men and women with CRSsNP. Prevalence of atopy was 52% in Tan, MD3, Stephanie S. Smith, MD3, David B. Conley, MD3, Robert C. CRSsNP versus 76% in CRSwNP (p<0.0001). In CRSsNP, atopic patients Kern, MD3, Pedro C. Avila, MD1, Robert P. Schleimer, PhD1,3; had more severe disease radiographically compared to non-atopic patients 1Department of Medicine, Division of Allergy-Immunology, North- (p<0.005). Prevalence of asthma was 36% in CRSsNP versus 56% in western University Feinberg School of Medicine, Chicago, IL, 2Division CRSwNP (p<0.0001). Comorbid asthma was not associated with sinus of Allergy-Immunology, Department of Medicine, Northwestern disease severity in CRSsNP but was significantly associated with disease University Feinberg School of Medicine, Chicago, IL, 3Department of severity in CRSwNP (p<0.0001). Comorbid conditions observed in Otolaryngology, Northwestern University Feinberg School of Medicine, CRSsNP included humoral immunodeficiency (5.7%) and autoimmune Chicago, IL. diseases (13.3%). RATIONALE: Aspirin exacerbated respiratory disease (AERD) com- CONCLUSIONS: This is the largest clinical characterization of patients prises the triad of chronic rhinosinusitis with nasal polyps (CRSwNP), with CRSsNP to date. CRSsNP patients were predominantly female asthma, and intolerance to cyclooxygenase-1 enzyme inhibitors such as whereas CRSwNP patients were predominantly male. The prevalence of aspirin. The prevalence of AERD remains unclear and few studies have asthma was higher in our cohort of CRSsNP patients than previously compared the clinical characteristics of patients with AERD to those with described. Atopy was associated with more severe disease in CRSsNP CRSwNP or asthmatics without CRS. while asthma and gender were not associated with severity. The prevalence METHODS: ICD-9 codes were used to search electronic medical records of comorbid autoimmune diseases in CRSsNP was higher than expected in (EMR) from a tertiary care center to identify 3 distinct patient groups: 1) the general population (;7.6-9.4%). CRSwNP alone; 2) CRSwNP+Asthma; and 3) AERD. For comparison, 300 patients diagnosed with asthma without CRS were randomly selected Management of Adenoid Hypertrophy in Allergic from the EMR. We evaluated clinical characteristics including lung 212 Children, How Effective Is Surgery? function, sinus surgeries, and oral corticosteroid use. Omursen Yildirim, MD1, Yusuf O. Ucal2, Andreea I. Popescu3, Mehmet RESULTS: We identified 459 patients with CRSwNP alone, 412 with 4 4 1 CRSwNP+Asthma, and 173 with AERD. The prevalence of AERD among F. Sonmez , Serhat A. Erdogan ; Istanbul Bilim University Florence all CRSwNP patients was 16%. AERD patients underwent two-fold more Nightingale Hospital Otolaryngology Department, Istanbul, Turkey, 2Istanbul Aydin University, Istanbul, Turkey, 3Sanador Medical Center, sinus surgeries (p<0.001) and were significantly younger at the time of 4 their first surgery (40 6 13 years) than CRSwNP patients (43 6 14 years, Bucharest, Romania, IGDIR State Hospital, Igdir, Turkey. RATIONALE: The aim of our study was to explore the role of allergy in p<0.05). Atopy was significantly more prevalent in patients with AERD SATURDAY (83%) or asthma (85%) than in CRSwNP (66%, p<0.05). FEV1% was the recurrence of adenoid hypertrophy after the surgical removal. significantly lower in AERD patients compared to asthmatics (80 6 18 METHODS: 285 children aged between 6 and 15 who underwent vs 86 6 17, p<0.01). Finally, more patients with AERD (13%) had corti- adenoidectomy for adenoid hypertrophy from two different centers were costeroid-dependent disease than CRSwNP+Asthma (4%, p<0.01)or enrolled. All the children were assessed before and after surgery by nasal asthma (1%, p<0.001). symptom scores and nasal fiberoptic endoscopy. Skin prick tests were CONCLUSIONS: This is one of the largest studies comparing surgical performed with common aeroallergens including house dust mites (HDM), and non-surgical AERD patients with CRSwNP patients and asthmatics. cockroach, Alternaria, animal dander, tree, grass, ragweed and mugwort AERD is common among CRSwNP and is associated with more severe pollens. sinus disease and reduced lung function compared to CRSwNP patients In order to eliminate the inadequate surgery factor, a month after surgery and asthmatics respectively. patients were reassessed and children with visible residual adenoid tissues on nasal endoscopy were excluded. Children with allergic rhinitis received Clinical Characteristics of Patients with Chronic guideline directed treatment. Twelve months postoperatively, all the 211 Rhinosinusitis without Nasal Polyps in a Tertiary children were re-examined and the adenoid regrowth rates of allergic Care Setting and non allergic children were compared RESULTS: Thirteen children were excluded due to the presence of Mariel G. Rosati, MD1, Whitney W. Stevens, MD, PhD2, Newton residual adenoid tissue and 57 due to the lack of cooperation with Li, MD2, Sumit Bose, MD2, Leslie C. Grammer, MD2, Kathryn E. endoscopic examination. Of the remaining 215 children, 65 had at least one Hulse, PhD3, Atsushi Kato, PhD2, Robert C. Kern, MD4, Bruce K. positive skin prick test. Visible recurrence was observed in 16 children in Tan, MD4, Stephanie S. Smith, MD4, David B. Conley, MD4, Pedro C. the allergic group (24.6%) and 17 in the non-allergic group (11.33%). The Avila, MD2, Robert P. Schleimer, PhD2, Anju T. Peters, MD2; prevalence of recurrence was higher in the allergic group and this finding 1Department of Medicine, Division of Internal Medicine, Northwestern was found to be statistically significant (p<0.005). HDM and Alternaria University Feinberg School of Medicine, Chicago, IL, 2Department of were the predominant allergens in the allergic group with recurrence. Medicine, Division of Allergy-Immunology, Northwestern University CONCLUSIONS: Our findings suggest that allergic rhinitis is associated Feinberg School of Medicine, Chicago, IL, 3Division of Allergy- with a high probability of recurrence after adenoidectomy, possibly caused Immunology, Department of Medicine, Northwestern University Feinberg by immunological events in nasopharynx associated with allergic School of Medicine, Chicago, IL, 4Department of Otolaryngology, North- sensitization. western University Feinberg School of Medicine, Chicago, IL. RATIONALE: Patients with chronic rhinosinusitis without nasal polyps (CRSsNP) have not been well characterized phenotypically. We performed a retrospective chart review at Northwestern University of subjects with CRSsNP using patients with CRS with nasal polyps (wNP) as a comparator. METHODS: Patients with a history of CRS with positive sinus CT (>18 y.o.) evaluated in the Allergy/Immunology or Otolaryngology clinics All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. AB66 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2016

Expression of ADAM17 and ADAM10 in Nasal New Model of Murine Allergic Rhinosinusitis 213 Polyps 215 Induced Cockroach Allergens

Woo Yong Bae, MD1, Seong Kook Park, MD2, Dae Young Hur, MD3,Tae Bethany L. Lussier, MD, Daniel G. Remick, MD; Boston University Kyung Koh, MD4, Ji Won Seo, MD4; 1Department of Otorhinolaryn- School of Medicine. gology, College of Medicine, Dong-A University, Busan, South Korea, RATIONALE: Allergic rhinosinusitis is a common comorbidity in 2Department of Otorhinolaryngology-Head and Neck Surgery, Inje Uni- patients with allergic asthma. There is believed to be a pathophysiologic versity, College of Medicine, Busan Paik Hospital, Busan, South Korea, overlap between asthma and allergic rhinitis similar histopathologic 3Department of Anatomy and Research Center for Tumor Immunology, inflammation and remodeling. Up to this point previous models required Inje University, College of Medicine, Busan Paik Hospital, Busan, South chronic daily exposure to clinically irrelevant allergens to induce histo- Korea, 4Department of Otorhinolaryngology-Head and Neck Surgery, pathologic change. This study examined murine nasal epithelial changes Dong-A University College of Medicine, Busan, South Korea. following allergic rhinitis induction with a clinically relevant allergen. RATIONALE: The ‘‘a disintegrin and metalloproteases’’ (ADAMs) are a METHODS: Six week old female ICR mice were sensitized according to multi-functional gene family that contributes to the homeostasis of the our asthma protocol via intratracheal instillation of (2)25 mL aliquots of extracellular matrix, transduction of specific intracellular signals, organ- 1:10 dilution cockroach allergen (CRA) Blag1 and Blag2 versus vehicle on ogenesis, inflammation, tissue remodeling, adhesion, and cell migration. day 0 and 14, with third allergen challenge on day 21. At the indicated SATURDAY ADAM17 is the best characterized of the sheddases, and its putative timepoints after final challenge, plasma, nasal lavage, and sinus histology substrates are widespread, including various inflammatory modulators. were collected for analysis. ADAM10 is the most similar to ADAM17 in terms of protein sequence and RESULTS: Morphometric analysis of nasal cavity measurement showed no the structural properties of their catalytic domains. significant difference in airway patency. Nasal lavage of CRA-exposed mice Objectives: To assess the roles of ADAM17 and ADAM10 in nasal polyps showed a significant increase in eosinophils and neutrophils relative to vehicle (NPs) by measuring their expression. mice (3.83x106cells/mL versus 4.20x104cells/mL p50.0344). There was a sig- METHODS: The expression of ADAM10 and 17 was investigated in NPs nificant increase in lamina propria thickness underlying olfactory epithelium at at endonasal sinus surgery (n515) and compared with that in inferior the superior nasal vault (51.2 6 2.4mm versus 65.61 6 2.2mmp<0.0001), with turbinate mucosa samples obtained from non-allergic hypertrophic rhinitis relative Bowman gland hypertrophy compared to control mice. Respiratory patients (n515). Tissue samples were analyzed by real time polymerase epithelium and submucosal glands had a 2-fold increase in mucin compared chain reaction (PCR), Western blotting, and immunohistochemical to controls (MGV 4.67 6 0.7 versus 1.62 6 0.15, p50.0112). staining. CONCLUSIONS: This is a clinically relevant model in which allergic RESULTS: The ADAM17 mRNA and protein levels were significantly rhinitis was induced in mice without direct interference with nasal higher in the inferior turbinate than in NP (P < 0.05). The ADAM10 mRNA passages. The model shows significant pathologic changes (increased and protein levels did not differ significantly between NP and the inferior eosinophils, neutrophils, lamina propria thickening) that reproduce turbinate (P > 0.05). ADAM10 and 17 were expressed mainly in findings observed in patients. inflammatory cells, submucosal glandular cells, and lining epithelial cells. CONCLUSIONS: We suggest that decreased ADAM17 expression Wnt Signaling in Nasal Polyp contributes to the development of NPs and abnormal structural tissue 216 remodeling in NPs. Ji-Hun Mo1, Young-Jun Chung2, Yun-Hee Rhee3; 1Dankook University Down-Regulated the Expression of Wdpcp Could College of Medicine, Cheonan, South Korea, 2Department of Otorhinolar- 214 Interrupt the Ciliogenesis in CRS yngology, Dankook University College of Medicine, Cheonan, South Ko- rea, 3Beckman Laser Institute Korea, Dankook University, Cheonan, Yinyan Lai, Yun Ma, Jianbo Shi; Otorhinolaryngology hospital in the South Korea. First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. RATIONALE: Wnt signaling is important in carcinogenesis, however it RATIONALE: Cilia loss is one of the significant morphologic changes in was rarely studied in the field of immunology. Recently it was identified that sinonasal mucosa from patients with chronic rhinosinusitis (CRS). wnt signaling impairs regulatory T cell function. This study was aimed to However, the mechanism for poor ciliation is still unclear.We sought to evaluate wnt signaling and its association of regulatory T cell in nasal polyp. find out the role of WDPCP, a key factor for ciliogenesis in recent METHODS: Twently two patients with chronic rhinosinusitis with nasal researches, in human sinonasal epithelia cells cilia loss from patients with polyposis (CRSwNP) were enrolled and divided into eosinophilic nasal CRS. polyps (EPs) and non-eosinophilic nasal polyps (NEPs) according to the METHODS: We investigated the expression of WDPCP in human proportion of eosinophils. Ten subjects with chronic hypertrophic rhinitis sinonasal epithelium from patients with CRS, as well as comparing them who underwent turbinoplasty were enrolled as control subjects. Expressions with control subjects. Meanwhile, we used primary human sinonasal of CD25, FOXP3, IL-17, STAT3, Wnt3a and beta -catenin were measured epithelial cells in air-liquid interface (ALI) in vitro model to observe quantitatively after immunofluorecent staining with confocal microscope. WDPCP’s expression during ciliogenesis. And PCR array targeting wnt-related genes was also performed. RESULTS: Decreased expression of WDPCP with cilia loss was detected RESULTS: Expressions CD25 and FOXP3 were significantly lower in in sinonasal mucosa from patients with chronic rhinosinusitis. In vitro EPs than NEPs or control. IL-17 expression levels were also increased in experiments, we found that WDPCP level upregulated at first, and then Eps than NEPs or control, showing inverse correlation between FOXP3 and declined. Knocking down WDPCP expression at the beginning of differ- IL-17. STAT3 did not show any significant difference between groups. entiation would reduce the quantity and length of cilia. Also, the Wnt3a did not show significant difference between groups, however, beta- stimulation of Th1 inflammatory cytokines could downregulate the catenin which is a target molecule of wnt signaling was increased in bothe expression of WDPCP. EP and NEPs compared with control mucosa. RT2 PCR array also showed CONCLUSIONS: WDPCP plays an important role in ciliogenesis of that Wnt2B, Wnt3A, Wnt5B, Wnt7B, Wnt8A, Fzd, and TCF were human airway, and it may also contribute the pathogenesis of CRS. increased in EP and that Wnt2B, Wnt5B, Wnt7B, Wnt8A and TCF were increased in NEP, suggesting the role of Wnt signaling in nasal polyps. CONCLUSIONS: Wnt signaling, which might explain decreased FOXP3 expression, was increased in nasal polyps and may play a key role in the pathogenesis of nasal polyps. All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. J ALLERGY CLIN IMMUNOL Abstracts AB67 VOLUME 137, NUMBER 2

Prolonged Allergen Exposure Causes TSLP- chronic rhinosinusitis with nasal polyp compared to the subjects with 217 Mediated Th2-Skewing in Mouse Models of chronic rhinosinusitis without nasal polyp and control subjects. Chronic Rhinosinusitis CONCLUSIONS: Our findings suggested that the imbalance of chronic, local immune responses may play important roles in the pathogenesis of Dong-Kyu Kim, MD1, Kyung Mi Eun2, Hong Ryul Jin, MD2, Seong Ho chronic rhinosinusitis with nasal polyp. Cho, MD, FAAAAI3, Dae Woo Kim, MD2; 1Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, South Korea, 2Seoul Fidarestat Decrease Allergic Sinus Congestion National University Hospital and Boramae Medical Center, South Korea, 219 3University of South Florida, College of Medicine, Tampa, FL. RATIONALE: Chronic rhinosinusitis (CRS) is characterized by a Walter C. Spear, MSc, KarryAnne K. Belanger, BSc, Spotswood dysfunctional host-environment interaction at the nasal mucosa. Miller, BSc, Igor Patrikeev, PhD, Massoud Motamedi, PhD, Kota V. Contributions of host susceptibility factors such as atopy and aspirin Ramana, PhD, Satish Srivastava, PhD, Bill T. Ameredes, PhD; University sensitivity to CRS pathophysiology are well established. However, clinical of Texas Medical Branch, Galveston, TX. studies on the effects of environmental factors are limited. This study RATIONALE: Sinus congestion and increased difficulty breathing are investigates the histological and immunological effects of allergen symptoms of allergic upper airway inflammation, requiring drug treatment exposure duration in animal models. to mitigate their effects. While steroids are effective, development of non- METHODS: A murine model for CRS with nasal polypoid lesions was steroidal alternatives are desirable to offer additional options for therapy. induced by instilling ovalbumin/Staphylococcal enterotoxin B (SEB) into An aldose reductase inhibitor, Fidarestat (FID), has been shown to have murine nasal cavities for 12 (short-term) or 24 weeks (long-term). anti-inflammatory properties, and therefore was evaluated in a guinea pig Histopathological changes were observed. Interleukin (IL)-4, IL- 17A, (GP) model, which has relevant allergic similarities to humans. IL-10, and interferon (INF)-g levels from nasal lavage fluid were measured Fluticasone, a commonly-used anti-inflammatory steroid, was utilized as using enzyme-linked immunosorbent assay. Gene expressions of IL-25, a comparator. m thymic stromal lymphopoietin (TSLP), IL-5, INF-g, CCL11, CCL24, METHODS: GPs were administered ragweed pollen (RWP; 20 g ICAM-1, VCAM-1, MMP7, and TIMP3 were analyzed from the nasal intranasally; i.n.) once per day, for 5 days, to induce allergic airway mucosa. inflammation, against which the effects of i.n. FID (0-1.0%) and RESULTS: Long-term CRS models exhibited increased polypoid lesions, Fluticasone (50-100 mcg) were compared by measurements of sinus fill edematous mucosal thickness, and eosinophil infiltration compared with volume (SFV), as an index of sinus congestion. Statistical comparisons of short-term models and showed a higher IL-4/IFN-g ratio and IL-10 level SFV were assessed by t-tests. € but lower IFN-g and IL-17A protein levels. Moreover, CCL24 and MMP7 RESULTS: As compared to naıve GPs, RWP significantly increased gene expressions increased whereas TIMP3 expression decreased in allergic sinus congestion (as decreased SFV) by over 80% (P<0.05), which longterm models compared to controls and short-term models. was subsequently reversed by Fluticasone to levels not statistically different from the na€ıve group. FID also increased SFV (and therefore Epithelium-derived IL-25 and TSLP mRNA expressions were up-regu- SATURDAY € lated in short-term and long-term CRS models, respectively. Furthermore, reduced sinus congestion) toward the naıve level, in a concentration- TSLP mRNA expression was positively associated with IL-5 (r 5 0.8754) dependent fashion, with SFVat the highest concentrations of FID being not € and inversely correlated to IFN-g (r 5 –0.7212) in CRS models. different from the naıve or Fluticasone groups. CONCLUSIONS: Prolonged allergen exposure in ovalbumin/ CONCLUSIONS: These results indicate that FID can effectively reduce SEB-induced CRS models maintains Th2 inflammation and reduces Th1 allergic sinus congestion by magnitudes similar to an anti-inflammatory inflammation, which was associated with up-regulation of TSLP. steroid, in a human-relevant guinea pig model of allergic rhinitis. Therefore, we conclude that intranasal FID may be a desirable candidate Effect of IL-10 Expression on Pathogenesis of for therapeutic development in the treatment of allergic sinus inflammation 218 Nasal Polypogenesis in the Patients with and congestion. Chronic Rhinosinusitis with Nasal Polyp Withdrawn Yong Min Kim; Chungnam National University School of Medicine, 220 Daejeon, South Korea. RATIONALE: Effect of IL-10 expression on pathogenesis of nasal polypogenesis in the patients with chronic rhinosinusitis with nasal polyp. METHODS: A total of 42 subjects were enrolled in this study (10 control subjects, 32 chronic rhinosinusitis subjects. Nasal polyp tissue and uncinated tissue were collected during surgical procedure. Real-time PCR, immunohistochemistry and phagocytosis assay were performed on the sampled tissue. RESULTS: The expression levels of the inflammatory cytokines including IL-10, IL-25, IL-17A and IFN-g were significantly higher in the tissues from subjects with chronic rhinosinusitis with nasal polyp compared to the subjects with chronic rhinosinusitis without nasal polyp and control subjects. And there were strongly positive correlation between IL-10 and other inflammatory cytokines. However, the ratios of the expression level of IL-10 to the expression levels of other inflammatory cytokines except IL-25 were significantly lower in the tissues from subjects with chronic rhinosinusitis with nasal polyp compared to the subjects with chronic rhinosinusitis without nasal polyp and control subjects. We also found that the phagocytosis ability was weaker in the tissues from subjects with All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. AB68 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2016

ATP8B1 Deficiency Enhances Hyperoxia-Induced hyperreactivity. GLA-AF (2 mg aqueous formulation) was instilled by 221 Lipid Oxidation and Apoptotic Response in Lung intranasal administration on day 14 either alone or in combination with Epithelial Cells OVA. RESULTS: Sensitization and repeated challenge with OVA resulted in an Andrew J. Cooke, MD1, Jutaro Fukumoto, MD, PhD2, Lee C. Tan3, increase in airway resistance and dynamic lung compliance that were Richard F. Lockey, MD4, Narasaiah Kolliputi, PhD5; 1Division of Allergy significantly inhibited by GLA-AF instillation. This inhibitory effect was and Immunology, Department of Internal Medicine, Morsani College of more pronounced when GLA-AF was administered with ovalbumin. OVA- Medicine, University of South Florida, Tampa, FL, 2Morsani College of induced airway hyperreactivity was also associated with a significant Medicine, University of South Florida, Tampa, FL, 3University of South increase in the release of IL-4 in bronchoalveolar lavage fluid. This Florida, 4Division of Allergy and Immunology, Department of Internal increase was significantly inhibited when GLA-AF was co-administered Medicine, University of South Florida, Morsani College of Medicine, with ovalbumin. OVA-sensitization and challenge were also associated Tampa, FL, 5Internal Medicine, Division of Allergy and Immunology, with increased serum antigen-specific IgE levels compared to saline- Department of Internal Medicine, Morsani College of Medicine, Univer- challenged animals. GLA-AF treatment reduced OVA-specific IgE serum sity of South Florida, Tampa, FL. levels, and this effect was enhanced when GLA-AF was co-administered RATIONALE: Idiopathic pulmonary fibrosis (IPF) is a progressive, with ovalbumin. fibrotic lung disease with a need for novel models to study its pathogenesis. CONCLUSIONS: Therapeutic administration of GLA-AF was effica- SATURDAY Preliminary studies indicate that mice with loss-of-function mutation at the cious in a mouse OVA induced airway hyperreactivity model, and this was ATP8B1 gene develop pulmonary fibrosis under hyperoxic conditions. further potentiated when GLA was co-administered with the eliciting This study determined if hyperoxia (which causes oxidative stress) causes antigen. ATP8B1 knock-down (KD) LA4 cells to dedifferentiate into a profibrotic phenotype. In Vitro and In Vivo Transglutaminase 2 Expression METHODS: ATP8B1-KD LA4 cells and empty plasmid-treated controls 223 in Asthma and COPD were exposed to normal versus hyperoxia for 48 hours. The protein extracts from whole cell lysate were evaluated by western blot to assess the Gyu-Young Hur, Jee Youn Oh, Jae-Kyeom Sim, Kyung Hoon Min, Sung- expression of proteins, including those related to apoptosis (BAD and Yong Lee, Jae-Jeong Shim, Kyung-Ho Kang; Korea University College of Bcl-xL), epithelial cell characteristics (pro-SPC), oxidative stress (Nrf2 Medicine, South Korea. and 4-HNE), and mesenchymal expression (vimentin). RATIONALE: Tissue transglutaminase 2 (TG2) is over-expressed in a RESULTS: ATP8B1-KD LA4 cells showed an increased expression of the variety of inflammatory diseases including allergic asthma. Both bronchial pro-apoptotic protein, BAD, and decreased expression of the anti-apoptotic asthma and chronic obstructive pulmonary disease (COPD) are character- protein, Bcl-xL, when compared to controls at 48 hrs of hyperoxia versus ized by chronic persistent inflammatory process, but the nature of the normoxia. Similarly, these cells compared to control cells exhibited inflammation is different markedly. However, in real practice, both may decreased epithelial properties with lower expression of pro-SPC. occur concurrently in some patients, and such conditions have been defined Likewise, expression of Nrf2, a marker for response to oxidative stress as asthma-COPD overlap syndrome (ACOS). Therefore, we purposed to was decreased, and 4-HNE, a marker for peroxidized lipid, was increased. evaluate the expression of TG2 in asthma, and COPD in vitro, and in vivo Finally, the expression of vimentin was increased when compared to studies. controls. METHODS: Cigarette smoke extracts (CSE) were withdrawn into a CONCLUSIONS: These results suggest that under oxidative conditions, polypropylene syringe (50mL) at a rate of one puff/min (5 times) and then ATP8B1 deficiency compromises the oxidative stress resistance mecha- bubbled slowly. For in vitro study, we used NCI-H292 cell lines, stimulated a nisms of these lung epithelial cells causing them to dedifferentiate into a by IL-13 (10ng/mL), TNF- (20ng/mL) and cigarette smoking extracts profibrotic phenotype. (CSE). TG2 expression was measured by immunoassay. To induce allergic asthma, ovalbumin sensitization and challenge was done in senescence Modulation of Lung Inflammation and Airway accelerated mouse (SAM). For smoking group, mice were exposed to five 222 Hypereactivity By the Toll-like Receptor 4 (TLR4) cigarettes a day for 5 days/week for 8weeks. Agonist Glucopyranosyl Lipid a (GLA) in a Mouse RESULTS: Co-treatment of IL-13 and TNF-a increased TG2 expression Model of Airway Allergy in NCI-H292 cells (P<0.05). CSE treatment also increased TG2 expression in cells (P<0.05). Treatment with IL-13, TNF-a and CSE showed George Qian1, Samreen Arshad1, Dongling Chen2, Xiaying Wu1, Keith decreased TG2 expression than single treatment. In vivo study, TG2 Graver3, Mayra Fernandez1, Joanne Schiding4, Timothy J. Soos5, expression was significantly increased in OVA and smoking group, Christopher Arendt2, El-Bdaoui Haddad2; 1Sanofi, MA, 2Bio-Innovation, however, it was decreased in co-treated group (OVA and smoking, Global BioTherapeutics, Sanofi, Cambridge, MA, 3Bio-Innovation P<0.05). Global BioTherapeutics Sanofi, Cambridge, MA, 4Bio-Innovation, Global CONCLUSIONS: TG2 expression was increased in both asthma and Biotherapeutics, Sanofi, Cambridge, MA, 5Bio-Innovation, Global COPD model. In ACOS model, TG2 expression was decreased compared Biotherapeutics, SANOFI, Cambridge, MA. to single asthma and COPD. RATIONALE: The pathogenic mechanisms underlying a range of allergies involve aberrant Th2 immune responses to normally innocuous antigens. The synthetic TLR4 agonist Glucopyranosyl Lipid A (GLA) is an immunomodulator that has the potential to reprogram pathogenic Th2 responses in an antigen-specific manner. The aim of this study was to assess the therapeutic efficacy of intranasal instillation of GLA alone and in combination with ovalbumin (OVA) on allergic lung inflammation and airway hyperreactivity in OVA-sensitized and -challenged BALB/c mice. METHODS: Male BALB/c mice were systemically immunized and challenged with OVA to induce lung inflammation and airway All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. J ALLERGY CLIN IMMUNOL Abstracts AB69 VOLUME 137, NUMBER 2

Anti-Interleukin (IL)-9 Antibody Increases Autolysosomal Formation Is Required for 224 Induction of Oral Tolerance in Murine Allergic 226 Autophagy-Dependent IL-18 Release from Airway Rhinitis Epithelial Cells

Soo Whan Kim; The Catholic University Of Korea and Jihyun SHIN, The Hiroki Murai, MD, PhD1, Shintaro Okazaki, MD1, Hisako Hayashi, MD, Catholic University Of Korea, Seoul, Korea. PhD1, Akiko Kawakita, MD1, Motoko Yasutomi, MD, PhD1, Sanjiv RATIONALE: The purpose of this study is to investigate the effects of Sur, MD2, Yusei Ohshima, MD, PhD1; 1University of Fukui, Fukui, Japan, anti-IL-9 antibody on oral tolerance in a mouse model of allergic rhinitis. 2University of Texas Medical Branch, Galveston, TX. METHODS: BALB/c mice were divided into 4 groups: control, allergic RATIONALE: We have previously reported that IL-18 release from rhinitis (AR), oral tolerance (OT) , and OT with anti-IL-9 antibody (OT + airway epithelial cells in response to Alternaria extract (ALT-E) is depend IL9AB) group. All mice except control group were sensitized with on autophagy activation but not on caspase 1 activation. LPS has been ovalbumin (OVA) three times for two weeks consecutively. After two shown to activate caspase 1 and autophagy and to induce oxidative stress in weeks, mice in OT and OT + IL9AB group underwent immunotherapy by macrophages through TLR4. Here, we compared LPS- and ALT-E-stimuli, feeding of OVA. During the immunotherapy, mice in OT + IL9AB group and analyzed the precise roles of activating processes of autophagy in IL- were injected with purified anti-mouse IL-9 antibody. All sensitized mice 18 release from airway epithelial cells. were challenged intranasally with OVA. Allergic symptoms, eosinophil METHODS: After A549 or NHBE cells were stimulated with ALT-E or counts in nasal mucosa and serum OVA-specific IgE were measured. LPS, IL-18 release was measured by ELISA. Autophagosome and Interferone-g, IL-4, IL-17, IL-10, TGF-ß, T-bet, GATA-3, ROR- g t, PU.1 autolysosome formations were measured by western blotting analysis and Foxp3 mRNA expression in nasal mucosa determined by real-time using LC3 and p62 antibodies, respectively. To assess the involvement of polymerase chain reaction. Flow cytometry of CD4+CD25+Foxp3+ T cells oxidative stress in the IL-18 release, the cells were pre-treated with in spleen was analyzed. antioxidants, N-acetyl cysteine (NAC) and MG132 for 1 h prior to RESULTS: In OT and OT + IL9AB group, symptom score, serum OVA- stimulation with ALT-E. specific IgE, eosinophils, IL-4, PU.1 and GATA-3 mRNA were decreased RESULTS: Stimulation with ALT-E but not with LPS induced IL-18 (p<0.05), and IL-10, Foxp3 mRNA, and CD4+CD25+Foxp3+ T cells were release from AECs. NAC and MG132 ameliorated the ALT-E-induced IL- increased compared with those in AR group (p<0.05). In OT + IL9AB 18 release. Both ALT-E and LPS provoked the formation of LC3-II, which group, symptom score and serum OVA-specific IgE were lower than those occurred in early phase of autophagy activation. ALT-E stimulation in OT group (p<0.05). Foxp3 mRNA and CD4+CD25+Foxp3+ T cells were facilitated the degradation of p62, which arose in the late phase of higher than those in OT group (p<0.05). autophagy activation, whereas LPS did not affects p62 degradation. CONCLUSIONS: Administration of anti-IL-9 antibody increased the CONCLUSIONS: Stimulation with ALT-E induced oxidative stress, induction of tolerance in a mouse model of allergic rhinitis. These results which was involved in IL-18 release as well as autophagy activation. indicate that anti-IL-9 antibody have immunomodulatory effect on The autolysosomal formation during autophagy activation seems essential

immune tolerance in allergic rhinitis model. for the IL-18 release from airway epithelial cells. SATURDAY

Reduced Nasal Brain Derived Neurotrophic Factor MD2 Facilitates Pollen and Cat Dander-Induced 225 in Aspirin Exacerbated Respiratory Disease 227 Innate and Allergic Airway Inflammation

Michele Pham, MD1, Rachel Baum, BS1, David Broide, MB, ChB, Koa Hosoki, MD, PhD, Toshiko Itazawa, MD, PhD, Istvan FAAAAI1, Andrew White, MD, FAAAAI2, Taylor Doherty, MD, Boldogh, PhD, Sanjiv Sur, MD; University of Texas Medical Branch, Gal- FAAAAI1; 1University of California San Diego, La Jolla, CA, 2Scripps veston, TX. Clinic, Division of Allergy, Asthma and Immunology, San Diego, CA. RATIONALE: The NHANES study identified several pollens and cat RATIONALE: Aspirin-exacerbated respiratory disease (AERD) is a dander as the most common allergens that induce allergic sensitization and complex syndrome of eosinophilic sinus inflammation and asthma allergic diseases. We recently reported that ragweed pollen extract characterized by hypersensitivity reactions to COX-1 inhibition. (RWPE) requires TLR4 to stimulate CXCL-mediated innate neutrophilic Neurotrophins may contribute to inflammatory responses as previous inflammation that facilitates allergic sensitization and airway inflamma- studies have revealed an elevation in brain derived neutrotrophic factor tion. Myeloid differentiation protein-2 (MD2) is a TLR4 coreceptor, but its (BDNF) levels in allergic airway disease. Further, TSLP and IL-33 have role in pollen and cat dander-induced innate and allergic inflammation has known roles in promoting eosinophilic tissue inflammation. However, not been critically evaluated. To elucidate the role of MD2 in inducing levels of IL-33, TSLP, and BDNF in AERD have not been reported. pollen and cat dander-induced innate and allergic airway inflammation. METHODS: Nasal lavage (17 patients), blood (32 patients), and urine (45 METHODS: TCMNull (TLR4Null, CD14Null, MD2Null), TLR4Hi, patients) samples were obtained from AERD patients. Samples from TCMHicells and human bronchial epithelial cells with siRNA-induced normal controls (11 patients) were also obtained. For AERD patients, downregulation of MD2 were stimulated with RWPE, other pollen allergic samples were collected at the initial visit, after aspirin desensitization, and extracts, or cat dander extract (CDE), and activation of NF-kB and/or greater than 30 days after aspirin desensitization. ELISAs were performed secretion of the NF-kB-dependent CXCL8 were quantified. Wild type with urine, serum, and nasal lavage for BDNF, IL33, and TSLP. (WT) mice or mice with siRNA knockdown of lung MD2 were challenged RESULTS: Only BDNF levels in nasal lavage samples were different and intranasally with RWPE or CDE, and innate and allergic inflammation showed reduced levels (p50.0005) in AERD patients compared with were quantified. normal controls. There were no differences in BDNF, IL33, or TSLP levels RESULTS: RWPE stimulated MD2-dependent NF-kB activation and pre and post aspirin desensitization. CXCL secretion. Likewise, Bermuda, rye, timothy, pigweed, Russian CONCLUSIONS: Recent data suggests upregulation of BDNF in severe thistle, cottonwood, walnut and CDE stimulated MD2-dependent CXCL asthma and previous studies have demonstrated elevated BDNF in chronic secretion. RWPE and CDE challenge induced MD2-dependent, CD14- sinusitis. In AERD, our data demonstrates lower BDNF levels in nasal independent innate neutrophil recruitment. RWPE induced MD2-depen- secretions. There are a variety of factors that may affect BDNF which dent allergic sensitization and airway inflammation. include concomitant medications and the unique inflammatory nature of CONCLUSIONS: MD2 plays an important role in induction of allergic AERD. It is also possible that the reduction in BDNF is a result of counter- sensitization to cat dander and common pollens relevant to human allergic regulatory factors in the disease process or related to anosmia found in diseases. these patients. All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. AB70 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2016

The Role of Autophagy in Allergic Inflammation: A Cockroach Protease Induces Allergic Airway 228 New Target for Severe Asthma 230 Inflammation Via IL-33 and TSLP Secretion By Epithelial Cells Yoo Shin, MD, PhD1, Jing-Nan Liu2, Youngwoo Choi2, Hae-Sim Park2; 1Ajou University School of Medicine, Suwon, South Korea, 2Department Naveen Arora, PhD1, Sagar Laxman Kale1, Komal Agrawal1, Shailendra of Allergy and Clinical Immunology, Ajou University School of Medi- N. Gaur, MD, FAAAAI2; 1CSIR-Institute of Genomics and Integrative cine, Suwon, South Korea. Biology, Delhi, India, 2University Of Delhi, Delhi, India. RATIONALE: Autophagy has been investigated to be involved in RATIONALE: Periplaneta americana protease activates epithelial cells inflammatory diseases, but its implications in asthma have rarely been and initiates allergic airway inflammation at mucosal surfaces. The present studied. This study aimed to explore the possible role of autophagy and its study aimed to investigate the role of protease activity in airway therapeutic potentials in severe allergic asthma. inflammation. METHODS: BALB/c mice were sensitized by ovalbumin (OVA) on days METHODS: To check the effect of its activity, BEAS-2B cells were 0 and 14, followed by primary OVA challenges on day 28-30. Mice received a exposed to proteolytically active or inactive Per a 10 and secretion of secondary 1% or 2% OVA challenges on days 44-46. After the final OVA proinflammatory cytokines was assessed in the supernatant. Per a 10 challenge, mice were assessed for airway responsiveness (AHR), cell (active and inactive) was administered i.n. to mice for three times a week composition and cytokine levels in bronchoalveolar lavage fluid (BALF). for two weeks and were sacrificed to analyse Immunoglobulin levels in SATURDAY LC3 expression in lung tissue was measured by Western blot and immuno- sera, cytokines and uric acid in BALF. The levels of cytokines and uric fluorescence staining. Autophagosomes were detected by electron micro- acid were assessed in the cockroach hypersensitive patient’s sera. scopy. 3-methyladenine (3-MA), Atg5 knockdown and anti-IL5 antibody were RESULTS: Per a 10 induces secretion of TSLP and IL-33 from BEAS-2B applied to investigate the potential role of autophagy in allergic asthma mice. cells in an activity dependent manner. They also demonstrated time RESULTS: The AHR, inflammation in BALF and LC3 expression in lung dependent increase in ATP on exposure to Per a 10. Intranasal adminis- tissue were significantly increased in 2% OVA challenged mice compared tration of active Per a 10 resulted in elevated cellular infiltration and Th2 to those of 1% OVA challenged mice (P<0.05). Additionally, eosinophils cytokines in BALF and serum IgE as compared to inactive and PBS showed prominently formation of autophagosomes and increase LC3 immunised mice. Levels of TSLP and IL-33 in the BALF of active Per a 10 expression compared with other inflammatory cells in BALF and lung tis- administered mice were elevated as compared to inactive Per a 10 and PBS sue. After inhibiting autophagy by 3-MA and Atg5 shRNA, the AHR, administered mice. Mice administered with active Per a 10 showed higher eosinophilia, IL-5 level in BALF, and inflammatory findings in histology uric acid levels. Analysis of cockroach hypersensitive patient’s sera were significantly improved. Finally, treatment of anti-IL-5 antibody revealed higher levels of IL-33 and uric acid as compared to healthy considerably reduced LC3 II expression in lung homogenate. subjects. CONCLUSIONS: Our findings suggest that autophagy is closely CONCLUSIONS: Proteolytic activity of Per a 10 causes airway correlated with the severity of asthma through eosinophilic inflammation, inflammation by elevation of TSLP, IL33 and uric acid levels. and its modulation may provide novel therapeutic approaches for severe allergic asthma. Anti-type2-Antibodies Specifically Inhibit Murine 231 Asthma Features Induced By Intranasal Cat Dander Extract Requires Myd88 to Induce Application of IL-5 and IL-13 229 Innate Neutrophil Recruitment, and Allergic Sensitization and Allergic Airway Inflammation. Hendrik Beckert1, Helen Meyer-Martin1, Stephanie Korn2, Sebastian Reuter1, Roland Buhl2; 1Pulmonary Department, University Hospital, Jo- Toshiko Itazawa, MD, PhD, Koa Hosoki, MD, PhD, Istvan hannes Gutenberg-University Mainz, Mainz, Germany, 2Pulmonary Boldogh, PhD, Sanjiv Sur, MD; University of Texas Medical Branch, Gal- Department, University Hospital, Johannes Gutenberg-University, Mainz, veston, TX. Germany. RATIONALE: We have reported that intranasal challenge with ragweed RATIONALE: The type2 cytokines IL-5 and IL-13 are central to asthma pollen extract (RWPE) induces TLR4-dependent recruitment of neutrophils pathogenesis, and innovative therapeutic approaches focus on strategic to the airways, and this neutrophil recruitment is critical for facilitating inhibition of these mediators. allergic sensitization and allergic airway inflammation. Cat dander is a METHODS: To investigate the individual effects of specific anti-type2- major indoor antigen that induces an early wave of neutrophil recruitment in antibodies on murine asthma features induced by intranasal type2 cytokine asthmatic subjects. In this study, we examined the molecular mechanisms of application Bl/6 mice received IL-5 and IL-13 (76.3 pmol each) cat dander-induced neutrophil recruitment and allergic inflammation. intranasally. Blocking antibodies specific for IL-5 or IL-13 (100 mg/ METHODS: In the innate model, WT, Tlr4KO, Tlr2KO and Myd88KO animal/timepoint) were administered twice. Cellular and functional mice were intranasally challenged once with cat dander extract (CDE). asthma features were analyzed 72 hours after cytokine application. BALF levels of neutrophils were quantified 16 h later. In the allergic model, RESULTS: IL-13 or IL-5+IL-13 treated animals developed an airway WT and Myd88KO mice were sensitized with 5 intranasal doses of CDE hyperreactivity (airway resistance at methacholine 100 mg/ml: 90.6655.7 and challenged with CDE to elucidate allergic airway inflammation. in PBS mice, 201.5671.5% in IL-13 treated mice (n54)) and goblet cell RESULTS: In the innate model, CDE challenge in WT mice increased metaplasia. IL-5 alone and in combination with IL-13 increased bone recruitment of neutrophils to the airways. This recruitment was reduced by marrow eosinophils (6.1661.27% eosinophils in PBS mice (n520), 50% in both Tlr4 and Tlr2KO mice, and abrogated in Myd88KO mice. In 10.561.9% in IL-5 mice (n511), 12.461.4% in IL-5+IL-13 mice the allergic model, repeated-challenge with CDE in WT mice induced (n511)). Similarly, synergistic application of IL-5+IL-13 enhanced BAL allergic sensitization and allergic airway inflammation characterized by eosinophil numbers (0.166027% in PBS mice, 9.2765.65% in IL-5+IL- increase of total cells and eosinophils in BALF, elevation of the levels of 13 mice). AHR and goblet cell metaplasia were suppressed by additional IL-5, IL-13, IL-33, and TSLP in BALF, stimulation of mucin in airway injection of anti-IL-13 blocking antibodies (airway resistance: 90.38 epithelial cells, and increase of total IgE and CDE specific IgE in serum. 635.36%) whereas anti-IL-5 antibodies strongly inhibited eosinophil However, all parameters were abolished in Myd88KO mice. influx into the bronchoalveolar space (4.2663.1%). CONCLUSIONS: These results indicate that Myd88 is essential for CONCLUSIONS: Blocking key type2 cytokines is an effective strategy to mediating CDE-induced innate neutrophil recruitment, and stimulating treat cytokine-induced asthma. Antibodies against type2 cytokines IL-5 allergic sensitization and allergic airway inflammation. and IL-13 differ in their individual effect on murine asthma features. All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. J ALLERGY CLIN IMMUNOL Abstracts AB71 VOLUME 137, NUMBER 2

Peanut Agglutinin Is a Novel Receptor for The IL-25 mRNA levels correlated with RV39 induced AHR in asthma 232 Dendritic Cell-Specific Intercellular Adhesion donors(R5 0.64 for each; p<0.05). Molecule-3-Grabbing Non-Integrin (DC-SIGN). CONCLUSIONS: RV39 induces mRNA expression of IL-25 in PCLS. Further, both RV39 and IL-25 causes AHR in PCLS from asthma donors Madhan Masilamani, PhD, Mohanapriya Kamalakannan, MSc, Lisa but not from controls. This finding suggests that IL-25 is not the source of Chang, BS, Galina Grishina, MSc, Hugh A. Sampson, MD, FAAAAI; the AHR, but rather it may be necessary to trigger other cells (i.e., mast Department of Pediatrics, Icahn School of Medicine at Mount Sinai, cells, ILC2 cells, T cells, or smooth muscle), leading to AHR. New York, NY. RATIONALE: The initial binding of allergens to DC-SIGN is thought to Cytokine Profiles in Breast Milk in Relation with be crucial for development of allergic sensitization. However, the precise 234 Atopic Manifestations of Mothers and Infants: role of DC-SIGN in food allergy pathogenesis is unknown. We sought to Study in Asian Population.

characterize DC-SIGN-binding glycoproteins in peanut, soybean and a 1 1 panel of allergenic and non-allergenic foods. Sirapassorn Sornphiphatphong, MD , Pantipa Chatchatee, MD , Jar- ungchit Ngamphaiboon, MD1, Sirinuch Chomtho2, Nattiya Hirankarn3, METHODS: DC-SIGN-binding and -blocking assays were performed on 1 1 human monocyte derived dendritic cells (DCs) using fluorescent-labeled Narissara Suratannon, MD ; Division of Allergy and Immunology, extracts and anti-DC-SIGN antibody respectively. Using a recombinant Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand, 2Division of nutrition, Department of Pediatrics, Fac- DC-SIGN-Fc chimera, food protein extracts were tested for DC-SIGN- 3 binding by ELISA and autoradiography. IgE immunoblotting was ulty of Medicine, Chulalongkorn University, Division of Immunology, performed using pooled sera from food allergic subjects. Department of Microbiology, Faculty of Medicine, Chulalongkorn Uni- RESULTS: Peanut agglutinin (PNA) was identified in DC-SIGN-autora- versity, Thailand, Bangkok, Thailand. diographs by mass spectrometry. PNA specifically bound to DC-SIGN on RATIONALE: Breast feeding is an early life event that may influence DCs in a calcium dependent manner and induced the expression of atopic manifestations in infants. The components of human milk may activation markers CD80, CD83, CD86 and HLA-DR in vitro. A number of differ depend on ethnicity, maternal diet and maternal underlying allergic DC-SIGN-binding proteins in allergenic foods such as peanut, soy, tree diseases. We aimed to study cytokine profiles of breast milk in Asian nuts, egg and milk were discovered. Foods that generally do not induce population in relation to allergic manifestations of mothers and infants. allergic responses in humans such as pine nuts, chickpea and corn showed METHODS: Breast milk (BM) from mothers of 22 healthy infants and 16 no binding to DC-SIGN. Several DC-SIGN-binding proteins show reac- infants with allergic symptoms were collected. Cytokines were measured tivity in serum IgE immunoblots. We have also identified novel non-IgE- by magnetic beads immunoassays. binding proteins that interact with DC-SIGN. RESULTS: There were 7 infants with atopic dermatitis(AD) and 9 infants CONCLUSIONS: We present a comprehensive report on characterization with food-induced urticaria(Ur). All AD patients expressed symptoms of DC-SIGN-binding proteins in common allergenic foods. We demon- during breastfed while urticarial patients developed symptoms only with infant allergen ingestion. IL-4 and IL-5 were not detected in BM of Ur but strate that PNA, a minor peanut allergen, is a novel ligand for DC-SIGN. SATURDAY Further functional characterization of DC-SIGN-interacting molecules in presented in 28% and 57.1% of AD group, respectively.Concentrations of food allergens may provide new openings in our understanding of the IL-4, IL-5 and IL-13 were higher in mothers of AD infants than in Ur group 5 pathology of food allergy and even novel therapeutic targets. with significant difference in IL-5 (p 0.012). IL-2 was not detected in BM of mothers of allergic infants but presented in 21% of control group IL-25 Causes Airway Hyper-Responsiveness of (p50.049). When maternal atopic history was considered, IL-13 and IL- 233 Human Precision Cut Lung Slices from Donors 17 were significantly higher in BM of mothers with asthma compared to with Asthma. non-asthmatic ones (p50.019, p50.027 respectively). Level of TGF-b and IL-10 in BM were neither associated with maternal atopic history Jordan Heath, MD1, Richard Kurten, PhD2,3, Suzanne E. House2,3, nor infant allergic manifestations. James D. Sikes4, Megan Kurten2,3, Stacie M. Jones, MD5,6, Josh L. Ken- CONCLUSIONS: Cytokines profiles in breast milk vary among maternal nedy, MD2,7; 1University of Arkansas for Medical Sciences, 2University of atopic history and infants with allergic manifestations. Maternal asthma is Arkansas for Medical Sciences, Little Rock, AR, 3Arkansas Children’s the strongest factor affecting cytokine profiles. While regulatory cytokines Hospital Research Institute, Little Rock, AR, 4UAMS/AR Children’s Hos- were not different among groups, TH2 cytokines tend to be higher in BM of pital, Little Rock, AR, 5Arkansas Children’s Hospital, Little Rock, AR, AD infants. 6Slot 512-13, University of Arkansas for Medical Sciences, Little Rock, AR, 7Arkansas Children’s Research Institute. RATIONALE: RV infection is associated with asthma exacerbations. We sought to evaluate the role of IL-25 during RVinfection, and whether IL-25 by itself was sufficient to cause AHR to carbachol in PCLS from donors with and without a history of asthma. METHODS: PCLS from donors with and without history of asthma were prepared from cadaver transplant-grade lungs and cultured ex vivo. Comparisons were made for innate immune responses between cohorts. For contractility experiments, airway cross-sectional areas were measured before and after treatment with carbachol (0.1uM and 1uM). PCLS were treated with 10 uL/mL of IL-25, while others remained untreated for 24 hours. Post-exposure responses to IL-25 were measured, as above, before and after stimulation with carbachol, and comparisons were made between cohorts. RESULTS: IL-25 mRNA was enhanced secondary to viral infection. RV39 and IL-25 caused AHR of PCLS, but only from donors with asthma (asthma: mean change from baseline (MCB) with: RVC 9%; IL-25 9%, no asthma: RVC 214%; IL-25 22.4%, untreated: MCB 22.4%; p<0.05). All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. AB72 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2016

Individual and Synergistic Effects of IL-5 and IL-13 MyD88-Mediated Innate Immune Response in a 235 on Trans-Compartmental Activation and Migration 237 Single Cat Dander Extract Challenge of Eosinophils and Murine Asthma Features John P. Kelley, MD, Koa Hosoki, MD, PhD, Sanjiv Sur, MD; University Sebastian Reuter1, Helen Meyer-Martin1, Hendrik Beckert1, Stephanie of Texas Medical Branch, Galveston, TX. Korn2, Roland Buhl2; 1Pulmonary Department, University Hospital, Jo- RATIONALE: Increasing evidence is showing that innate immune hannes Gutenberg-University Mainz, Mainz, Germany, 2Pulmonary responses, such as TLR2 and TLR4 signaling, contribute to the initiation Department, University Hospital, Johannes Gutenberg-University, Mainz, of airway allergic disorders. The shared adaptor for TLR2 and TLR4 is Germany. MyD88, but its role in initiation of allergic inflammation has not been RATIONALE: The type 2 cytokines IL-5 and IL-13 are central to asthma reported. The objective of this study was to elucidate the contribution of pathogenesis, and innovative therapeutic approaches focus on strategic MyD88 to cat dander induced innate mRNA expression in the lungs. inhibition of these mediators. METHODS: Cat Dander Extract (CDE) was administered intranasally to METHODS: To analyze the individual and synergistic effects of these both wild type (WT) and MyD88 knock out (KO) mice in single dose cytokines Bl/6 mice were treated intranasally with IL-5 (76.3 pmol, n511) challenges. After exposure to CDE, the lung mRNA expression of 192 and IL-13 (76.3 pmol, n511) alone and in combination (n511). After 72 h innate and allergic inflammation associated genes were quantified by pulmonary function as well as cytokine-induced inflammatory changes in qPCR arrays. SATURDAY bone marrow (BM), blood, lung tissue and bronchoalveolar lavage (BAL) RESULTS: A single CDE challenge in WT mice significantly increased were investigated. lung mRNA expression of Ifnar1, C5ar1, Ccr8, Nfkb1, Cd4, Ifnb1, Cd80, RESULTS: Single application of IL-5 particularly led to a distinct Il17a, Il1b, Tlr2, Nlrp3, Icam1, Nfkbia, Il10, Ccl12, Nod2, Il1a, Il6, Csf2, increase of eosinophils and their precursors in the BM (6.16 6 1.27% Cxcl10, Tnf, and Il23a. Deletion of MyD88 significantly inhibited CDE- eosinophils in PBS mice versus 10.52 6 1.93% in IL-5 mice), whereas induced upregulation of the lung mRNA expression of Ccr8, Cd80, Csf2, application of IL-13 promoted airway hyperreactivity (airway resistance at Cxcl10, Icam1, Il17a, Il1b, Il23a, Il6, Nfkb1, Nfkb1a, Nlrp3, Nod2, Tlr2, methacholine 100 mg/ml: 90.56 6 55.65% change from baseline in PBS and Tnf. mice versus 201.5 6 71.48% in IL-13 treated mice) with a slight increase CONCLUSIONS: Panther analysis of CDE-induced genes suggest of lung eosinophils and the development of goblet cell metaplasia. In activation of the following signaling pathways: angiogenesis, apoptosis, contrast to single cytokine application combinations of IL-5 + IL-13 B cell activation, CCKR, EGFR, chemokines, cytokines, Ras, T cell further enhanced eosinophil numbers in all compartments (BM: 12.4 6 activation, TLR, VEGF, and Wnt. MyD88-mediates CDE-induced innate 1.43%, blood: 7.22 6 1.74%, lung: 6.93 6 1.65%, BAL: 8.89 6 6.20%). immune response consisting of 15 genes. The contribution of these genes CONCLUSIONS: These results illustrate for the first time the effects of and signaling pathways to CDE-induced allergic sensitization and single and synergistic intranasal application of type 2 cytokines IL-5 and inflammation needs to be elucidated in future studies. IL-13 on cellular and functional murine asthma features in a comparative manner and illustrate the individual contribution of each cytokine on type 2 Dust Mite-Induced Allergic Pulmonary cytokine induced murine asthma. 238 Inflammation Is Differentially Regulated By Il33-/- and Il1rl1-/- Dendritic Cells Cardiolipin Provides a Platform for Caspase-1 236 Activation and NLRP3 Inflammasome Assembly Min Jung Lee, MD, Eri Yoshimoto, Li Li, Yoshihide Kanaoka, MD, PhD, Nora A. Barrett, MD, FAAAAI; Brigham and Women’s Hospital, Division Suzanne L. Cassel, MD, FAAAAI, Eric Elliott, Shankar S. Iyer, PhD, of Rheumatology, Immunology and Allergy, Boston, MA. Fayyaz Sutterwala, MD, PhD; University of Iowa. RATIONALE: Many studies have reported genetic associations between RATIONALE: The NLRP3 inflammasome promotes innate immunity IL-33, its receptor IL1RL1 (ST2), and asthma. However, the cellular through Caspase-1 activation and IL-1b and IL-18 maturation. Two-step sources of IL-33 and the mechanisms by which it promotes Th2 pulmonary NLRP3 activation requires an initial NFkB-activating priming stimulus inflammation are poorly understood. We and others have shown that IL-33 and secondary agonist which induces cation flux and mitochondrial stress. is elicited by house dust mite (HDM) activation of the C-type lectin However, the dynamics of inflammasome assembly and extent of receptor Dectin-2 in dendritic cells (DCs). Therefore, we sought to mitochondrial disruption required for NLRP3 activation remain uncertain. determine the contribution of IL-33 and IL1RL1 to DC-mediated allergic NLRP3 interacts with mitochondrial cardiolipin, and we hypothesized pulmonary inflammation. cardiolipin could activate NLRP3 in vitro. METHODS: C57BL/6 WT, Il33/ and Il1rl1/ bone marrow-derived DCs METHODS: Utilizing a novel in vitro broken cell system we analyzed the (BMDCs) were stimulated with PBS or HDM extract. Culture supernatants interaction of cardiolipin with the components of the NLRP3 were analyzed for cytokines by ELISA. 104 PBS- or HDM-pulsed BMDCs inflammasome. were administered intranasally to sensitize WT recipients (day 0). RESULTS: Cardiolipin specifically induced caspase-1 autocatalysis, and Recipients were challenged with 3 mg HDM on days 11 and 13, and NLRP3 and Caspase-1 formed high molecular weight complexes in the BAL fluid cellular infiltrate was evaluated on day 15. presence of cardiolipin. However, NLRP3 and ASC were dispensable for RESULTS: WT mice sensitized with HDM-pulsed Il1rl1/ BMDCs had a the molecular weight shift of Caspase-1. Finding that Caspase-1 directly marked reduction in BAL inflammation, including neutrophilia, as binds cardiolipin, we examined whether Caspase-1 associates with compared to mice sensitized with HDM-pulsed WT BMDCs. In contrast, mitochondria endogenously. NLRP3 and Caspase-1 localize to mitochon- mice sensitized with HDM-pulsed Il33/ BMDCs had a significant enhance- dria upon priming, and mitochondrial association of Caspase-1 is NLRP3- ment in BAL inflammation, especially neutrophils. Analysis of the culture and ASC- independent. In contrast, ASC associates upon secondary supernatants from HDM-pulsed Il33/ BMDCs revealed enhanced genera- stimulus in a NLRP3-dependent manner. Furthermore, mitochondrial tion of NF-kB-dependent cytokines, such as IL-23 and TNF-a,as membrane remodeling mediated by fission-inducing DRP1 appears to compared to HDM-pulsed WT or Il1rl1/ BMDCs. positively regulate NLRP3 inflammasome activation. CONCLUSIONS: IL-33 elicited in HDM-pulsed DCs reduces allergic CONCLUSIONS: Our findings suggest that Caspase-1 binds cardiolipin pulmonary inflammation. These findings suggest that, in addition to its role on stressed mitochondria, support the hypothesized pattern-recognition as a pro-inflammatory cytokine extracellularly, IL-33 can inhibit NF-kB- activity of inflammatory caspases, and solidify mitochondria as critical dependent gene expression intracellularly and negatively regulate innate regulators of immunity by serving as supramolecular organizing centers. immune cell function. All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. J ALLERGY CLIN IMMUNOL Abstracts AB73 VOLUME 137, NUMBER 2

Human Hemopoietic Progenitor Cell Toll-like and dLN. These defects in CD301b+ DC migration and localization were 239 Thymic Stromal Lymphopoietin Receptor Expression accompanied by defects in Th2 differentiation. andFunctioninAllergicAsthmaticSubjects CONCLUSIONS: We provide evidence that CCR8 mediated signaling promotes the specific migration and localization of Th2-inducing Damian Tworek, MD, PhD1, Delia Heroux, BSC2, Seamus N. CD301b+ DCs, thereby controlling the induction of Th2 differentiation. O’Byrne, MAAP3, Paul M. O’Byrne, MB, FRCPC, FRSC4, Judah A. Den- These data reveal the CCR8 pathway as a target for preventing allergic im- burg, MD, FRCPC, FAAAAI5; 1Department of Medicine, McMaster Uni- mune initiation. Additionally, it may indicate a broader role for alternative versity, Hamilton, ON, Canada, 2Division of Clinical Immunology & chemokine networks in the selective migration of DC subsets. Allergy, McMaster University, Hamilton, ON, Canada, 3Department of Medicine, McMaster University, 4Department of Medicine, Cardio-Respi- The Effect of Vitamin D Supplementation on ratory Research Group, McMaster University, Hamilton, ON, Canada, 241 Mucosal IL-5, MMP9 and Cathelicidin after 5Division of Clinical Immunology and Allergy, Department of Medicine, Nasal Allergen Challenge with Grass Pollen

McMaster University, Hamilton, ON, Canada. 1 RATIONALE: We demonstrated that cord blood human progenitor cells Natasha C. Gunawardana, MBBS, MA (Cantab), MRCP , Gaynor Campbell, PhD1, Sarah Lindsley2, Elizabeth E. Mann3, Peter J. M. (HPC) from high allergic risk newborns expressed Toll-like receptors 4 1 (TLR) less abundantly than low allergic risk infants. We also have recently Openshaw, MBBS, PhD, FRCP , Sebastian L. Johnston, MD, PhD , Catherine M. Hawrylowicz5, Trevor Thomas Hansel, MD, PhD6; 1Impe- found a key role for thymic stromal lymphopoietin (TSLP) in human 2 eosinophil and basophil differentiation from HPC in allergic subjects. rial College London, London, United Kingdom, Imperial College NHS Trust, 3King’s College London, 4Imperial Col Sch Med, St. Mary’s Hos- However, TLR or TLR-induced TSLP receptor (TSLPR) expression by 5 HPC has never been studied in allergic asthmatic subjects. pital, London, United Kingdom, MRC and Asthma UK Centre for Allergic Mechanisms of Asthma, King’s College London, London, United METHODS: The study group comprised 10 healthy and 11 allergic 6 asthmatic subjects. Asthmatics underwent diluent-controlled bronchial Kingdom, St. Mary’s Hospital, London, United Kingdom. allergen challenge. Peripheral blood (PB) was collected from both healthy RATIONALE: Vitamin D may affect the innate and adaptive immune and asthmatic subjects (before and 24 hours after diluent/allergen system in allergic disease and there is the need to study effects on the challenge). The PB HPC-enriched cell population was stimulated ex human respiratory mucosa in vivo. vivo with TLR-2 (lipoteichoic acid, LTA), TLR-4 (lipopolysaccharide, METHODS: We carried out a double-blind randomised control study of LPS) or TLR-9 (ODN2006) ligands. HPC TLR and TSLPR expression vitamin D supplementation, using grass pollen nasal allergen challenges after TLR ligation were examined pre- and post-bronchial allergen (NACs) to assess the effect on mucosal inflammatory mediators. Subjects challenge by flow cytometry. with a clinical history of hay fever and serum vitamin D (25(OH)D) levels RESULTS: Asthmatic HPC expressed significantly less TLR-2 and TLR- <75nmol/l were recruited; 12 subjects received vitamin D supplementation 9, compared to non-asthmatic HPC (p<0.05), with a similar trend for TLR- (4000U orally daily for 28-35 days) and 4 placebo. NACs were performed before and after supplementation, and nasosorption used to sample 4(p50.057). TLR-4 stimulation of asthmatic HPC yielded significantly SATURDAY higher expression of TSLPR, compared with HPC from healthy controls mucosal lining fluid (MLF) at hourly intervals to 8h. MLF was eluted by (22.51 6 4.24% vs 11.6 6 1.34%, respectively; p<0.05), with a similar spin filtration, and mediators including IL-5, MMP 9 and cathelicidin trend for asthmatic HPC after TLR-9 stimulation (p50.054). Allergen levels were measured by sensitive multiplex immunoassay. challenge led to a further increase in TSLPR expression by LPS-stimulated RESULTS: Vitamin D supplementation increased serum vitamin D levels HPC, compared to diluent (32.37 6 4.14% vs 18.25 6 4.94%, respectively; (P<0.01). Elevated levels of cathelicidin and MMP9 in nasal MLF were p<0.05). seen between 2-8h after NAC, with IL-5 increasing later at 4-8h. Within CONCLUSIONS: These findings support the involvement of HPC in the the treatment groups there was no significant difference before and after initiation and persistence of airways inflammation during infection-driven supplementation in induction of IL-5, MMP9 or cathelicidin after NAC asthma exacerbations. (AUC at 0-8h). CONCLUSIONS: Despite normalisation of vitamin D levels, there were CCR8 Mediated Cell Migration Controls Th2 no changes in NAC-induced generation of mucosal late phase mediators. In 240 Differentiation particular, levels of cathelicidin were not significantly altered, even though this is a vitamin D responsive anti-microbial peptide. Cathelicidin and Caroline L. Sokol, MD, PhD1, Ryan Camire1, Michael Jones2, Andrew MMP9 responses were closely related (r50.74, P<0.0001) and detected D. Luster, MD, PhD1; 1Massachusetts General Hospital, Boston, MA, earlier than IL-5, possibly reflecting different cell origins. 2University of Massachusetts Medical School. RATIONALE: In mouse models, allergen exposure leads to the selective migration of Th2-inducing CD301b+ dendritic cells (DCs) from the skin to the draining lymph node (dLN). The chemokine receptor CCR7 is neces- sary for DC migration to the dLN, but whether other chemokine networks control the migration of specific DC subsets is unknown. We hypothesized that allergen exposure induces novel chemokine pathways that specifically promote the migration of CD301b+ DCs. METHODS: We utilized the papain model of allergic inflammation in the mouse. Quantitative PCR was performed to examine chemokine ligand expression. Flow cytometry, confocal microscopy, and in vitro restimula- tion assays were utilized to study DC migration and subsequent immune activation in response to papain exposure. RESULTS: Exposure to the protease allergen papain induced the production of CCL8, a known ligand of CCR8. CD301b+ DCs from CCR8 deficient mice exhibited decreased migration from the skin to the dLN after papain immunization. Furthermore, CCR8 deficient CD301b+ DCs that were found in the dLN exhibited altered localization within the All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. AB74 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2016

Group 2 Innate Lymphoid Cells: New Players in downregulated CD38 and the Fcg receptor CD32. Aggregation of 242 Peanut Allergy basophils and platelets was observed upon activation with peanut, measured by co-expression of CD61. In addition to basophils, we Elisavet Ntavli1,2, Paul J. Turner, FRACP, PhD2,3, Robert J. confirmed that other cells types showed evidence of activation after Boyle, MBChB, PhD2,3, Andrew Clark, MRCPCH, MD4, Abigail O. exposure to peanut in allergic but not healthy control subjects. cDCs, pDCs Robb, BSc1,2, Stephen R. Durham, MA, MD, FRCP1,2, Mohamed H. and monocytes increased phosphorylation of S6 upon peanut exposure. We Shamji, BSc, MSc, PhD, FAAAAI1,2; 1Immunomodulation and Tolerance did not detect activation in neutrophils, eosinophils, T cells or B cells. Group, Immune Tolerance Network (ITN) Distributed Centre of Excel- CONCLUSIONS: We have established methods for profiling antigen- lence for Allergy & Asthma, Allergy & Clinical Immunology Inflamma- responsive cells in whole blood using mass cytometry. This provides tion, Repair and Development National Heart & Lung Institute, Imperial insight into novel cell types activated by allergen, and elucidation of College London, United Kingdom, 2MRC & Asthma UK Centre in signaling pathways activated in allergic effector cells. Allergic Mechanisms of Asthma, London, United Kingdom, 3Section of Paediatrics, Imperial College London, United Kingdom, 4Department of A Case of Neuropathic Pain in Monoclonal Mast Medicine, University of Cambridge, Cambridge, United Kingdom. 244 Cell Activation Syndrome RATIONALE: Group 2 innate lymphoid cells (ILC2s) are morphologi- cally similar to lymphocytes, lack lineage markers, express the prosta- Jeannie L. Bay, DO, Kaye E. Sedarsky, MD, Maureen M. Petersen, MD; SATURDAY glandin D2 receptor (CD294 or CRTH2), IL-7Ra, CD127 and secrete Walter Reed National Military Medical Center, Bethesda, MD. predominantly IL-5 and IL-13. They have been associated to asthma or RATIONALE: Neuropathic pain is an uncommon symptom in allergic rhinitis, however, their role is yet to be defined in peanut allergy. Monoclonal Mast Cell Activation Syndrome (MMAS), but one that can We hypothesized that ILC2s are involved in the pathophysiology of peanut have a significant impact on quality of life and has not yet been well allergy and that their frequency is increased following peanut allergen described in the literature. Mast cells are known to be gatekeepers of challenge. nociception and disruption of these cells’ normal homeostasis plays an METHODS: Peripheral blood mononuclear cells were collected from important role in the development of neuropathic pain in the central and peanut allergic (PA, n516), peanut sensitised (PS, n54) and non-atopic peripheral nervous system. Currently, there are no well-defined guidelines adult controls (NA, n516). PA and PS underwent double-blind placebo- for the management and treatment of neuropathic pain in mast cell controlled food challenges (DBPCFC) to peanut, as part of the TRACE activation disorders. We present a patient with neuropathic pain associated Peanut study. ILC2s, IL-5+, IL-13+ and IL-5+IL-13+ ILC2s were immuno- with MMAS and a review of the agents used in his treatment. phenotyped as lineage negative CD127+CD294+ cells, using flow METHODS: Clinical exams, skin biopsy, and immunologic laboratory cytometry. evaluation. RESULTS: The proportion of ILC2s in peripheral blood was higher in PA RESULTS: 49 year-old male with a history of MMAS (baseline serum compared to NA (3fold, p50.0006). IL-5+ ILC2s and IL-5+IL-13+ ILC2s tryptase 14.4 ng/mL, bone marrow positive for c-Kit D816V, clonal mast were raised in PA compared to NA individuals (4fold, p50.0026; cell population), autonomic dysregulation, and neuropathic pain of his 29fold, p50.0002). ILC2s were increased following a positive food chal- bilateral hands, wrists, and feet. Skin biopsies were negative for small fiber lenge in PA (1.2fold, p50.0137), however, no changes were observed after neuropathy. Various medications were employed in the management of his a non-reactive challenge. IL-5+, IL-13+ and IL-5+IL-13+ ILC2s showed no pain including gabapentin, tricyclic antidepressants, opioids, celexocib, significance difference in the non-active challenges, whereas in response to and minocycline. Although an antibiotic, minocycline’s anti-inflammatory peanut there was a substantial change in the IL-13+ ILC2s (2fold, and anti-nociceptive properties have garnered increasing attention through p50.0029). several recent studies. CONCLUSIONS: For the first time, we show that the frequency of ILC2s CONCLUSIONS: Providers should be aware that neuropathic pain is a is higher in peanut allergic patients and may contribute to the pathophys- rare but serious symptom in patients with MMAS, one that has not been iology of peanut allergy. well studied in the literature. Managing neuropathic pain associated with MMAS can be difficult and requires a multidisciplinary approach to rule Profiling the Immune Response to Peanut Using out other potential etiologies of pain and refine medication treatment 243 Mass Cytometry approaches in these medically-complex patients.

Leticia Tordesillas, PhD1, Adeeb H. Rahman, PhD2,3, Hugh A. Sampson, MD, FAAAAI1, M. Cecilia Berin, PhD1; 1Department of Pedi- atrics, Icahn School of Medicine at Mount Sinai, New York, NY, 2Human Immune Monitoring Core, 3Department of Genetics and Genomics, Icahn School of Medicine at Mount Sinai, New York, NY. RATIONALE: CyTOF (mass cytometry) improves multidimensional single cell analysis, with greater multiplexing capability, lower back- ground, and higher sensitivity for detection of phosphorylation compared to flow cytometry. We developed a CyTOF panel to study acute responses to food allergens in whole blood. METHODS: Fresh blood samples from 6 peanut-allergic and 3 healthy subjects were activated with peanut extract, anti-IgE, or media for 15 and 30 minutes, all in presence of IL3. Samples were combinatorially barcoded with palladium isotopes to reduce sample-specific batch effects and data collection variation. Pooled samples were stained with a panel of 29 metal- conjugated antibodies including markers for cell identification and activation. Cells were acquired on a CyTOF2, and SPADE analysis performed using Cytobank. RESULTS: Basophils from patients but not healthy controls upregulated known activation markers (CD63) after peanut stimulation. When activated, basophils increased phospho-ERK, -p38, and -S6, and All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. J ALLERGY CLIN IMMUNOL Abstracts AB75 VOLUME 137, NUMBER 2

Acidic Conditions Regulate Mast Cell Migration IL-4 protein production was enhanced in the presence of splitomysin and 245 and Fc Epsilon RI–Mediated Cytokine Production suppressed in the presence of resveratrol. SIRT1 knock down up regulates IL-4 mRNA expression. Yosuke Kamide, MD, PhD1, Tamotsu Ishizuka, MD, PhD2, Hiroaki CONCLUSIONS: SIRT1 may play some role in developing allergic Hayashi, MD1, Chihiro Mitsui, MD1, Akio Mori, MD, PhD1, Takeshi diseases via control IL-4 gene expression. Hisada, MD, PhD3, Kunio Dobashi, MD, PhD3, Fumikazu Okajima4, Masanobu Yamada, MD, PhD3, Masami Taniguchi, MD, PhD1; 1Clinical Hereditary Angioedema Is Associated with Research Center for Allergy and Rheumatology, Sagamihara National 247 Neuropathic Pain, Systemic Lupus Erythematosis Hospital, Sagamihara, Japan, 2Third Department of Internal Medicine, and Systemic Mastocytosis in an Analysis of a Faculty of Medical Sciences, University of Fukui, Fukui, Japan, 3Depart- Health Analytics Claims Database ment of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Japan, 4Labolatory of Signal Transduc- Chris Stevens, Joseph C. Biedenkapp, Robert Mensah, Yung H. Chyung, tion, Institute for Molecular and Cellular Regulation, Gunma University, Burt Adelman; Dyax Corp., Burlington, MA. Maebashi, Japan. RATIONALE: The plasma kallikrein kinin system (KKS) has been RATIONALE: The proton concentration or pH of blood is maintained at associated with a variety of diseases in addition to being a key mediator of 7.4 6 0.05, and inflammatory loci are associated with an acidic hereditary angioedema (HAE). We asked whether HAE patients were environment. The pH of exhaled breath condensate in patients with asthma predisposed to develop such KKS associated diseases: abdominal aortic is lower than that in healthy individuals, indicating that extracellular aneurysm, anaphylaxis, cardiac vasoplegia syndrome, Crohn’s disease, acidification contributes to the pathogenesis of allergosis. Therefore, we diabetic macular edema, idiopathic anaphylaxis, neuropathic pain, psori- hypothesized that mast cells, which play a central role in allergosis, are asis, psoriatic arthritis, retinopathy, rheumatoid arthritis, systemic lupus regulated by acidic conditions. erythematosus (SLE), system mastocytosis, systemic vasculitis, throm- METHODS: Mast cell migration was examined using the Boyden botic cerebrovascular accident, and ulcerative colitis. chamber technique. The MC/9 mouse mast cell clone sensitized with METHODS: We utilized the Truven MarketScan Database containing anti-dinitrophenyl (DNP) IgE was placed in the upper wells, and DNP- individual-level claims data from medical payers and Medicare supple- conjugated human serum albumin (DNP-HAS) was added to the lower mental plans for 80 million lives in the U.S. from 1/2010 through 7/2014. 5 wells. Mast cells in the lower wells were counted using a Fuchus Rosenthal Within this dataset, an HAE population (n 1063) and 2 control 5 calculator. DNP-IgE-sensitized MC/9 cells or bone-marrow derived mast populations: an angioedema population (n 138,851) and the general 5 cells (BMMCs) were incubated with DNP in pH-changed medium, and population (n 79,971,098) exclusive of HAE patients were defined using tumor necrosis factor (TNF)-a, interleukin (IL)-6, and IL-13 levels in the a combination of ICD-9 and prescription drug codes. Claims for comorbid supernatant were measured using enzyme-linked immunosorbent assays. diseases were identified and compared across the populations with The data were compared by using the Student’s t-test with the Bonferroni calculated odds ratios and 95% confidence intervals (CI). RESULTS: In the HAE population, SLE was observed 2.3 times more correction for multiple comparisons. SATURDAY RESULTS: Acidic pH significantly inhibited migration of MC/9 cells often (OR 2.30, 95%CI: 1.47-3.59) than the angioedema control toward DNP-HAS. In addition, extracellular acidification clearly induced population. Neuropathic pain was observed 1.45 times (OR 1.45, 95% IL-6 and IL-13 production. The viability of MC/9 cells was not affected by CI: 1.01-2.09) and systemic mastocytosis 4.79 times (OR 4.79, 95%CI: alterations in pH. 1.51-15.18) more often than the angioedema control population. CONCLUSIONS: Acidic pH inhibits MC/9 cell migration. Furthermore, CONCLUSIONS: In an analysis of a large longitudinal claims database, extracellular acidification enhances DNP-IgE–induced IL-6 and IL-13 comorbid diseases of SLE, neuropathic pain and systemic mastocytosis production in MC/9 cells and BMMCs. had a greater representation in HAE patients than other angioedema patients, suggesting that activity of the KKS may be contributing to the Regulation of IL-4 Gene Expression By SIRT1 in manifestations of these diseases. 246 Human Mast Cell

Yuji Nakamaru1, Dai Takagi2, Satoshi Fukuda3; 1Department of Otolar- yngology–Head and Neck Surgery, Hokkaido, Sapporo, Japan, 2hokkaido university, sapporo, Japan, 3hokkaido university. RATIONALE: Histone protein modification control gene transcription via chromatin remodeling. Because a differentiation from na€ıve T cell to Th2 cell was induced by the chromatin remodeling, it may regulate allergic diseases. SIRT1 is an NAD-dependent deacetylase that regulate stress response and modulates inflammation and cell survival. This study was to investigate whether SIRT1 control IL-4 production in human mast cells. METHODS: The HMC-1 (human mast cell line) was cultured with or without SIRT1 activator and inhibitor and stimulated with calcium ionophore and PMA. Four hours after the stimulation, mRNA was extracted from these cells for IL-4 real time PCR. Quantitative measure- ment of IL-4 in cell supernatant was performed using the human IL-4 ELISA kit. To clarify the direct function of SIRT1, we used small interference RNA against SIRT1. Two kinds of SIRT1 siRNA and negative control siRNA were transfected into HMC-1 cells by electroporation. RESULTS: HMC-1 cells were expressing IL-4 mRNA in unstimulated state. Stimulation with A23187 and PMA increased the expression of IL-4 mRNA at basal level. Expressions of IL-4 mRNA were enhanced in the presence of splitomysin with dose dependent manner. On the other hand, the resveratrol suppressed IL-4 mRNA expression in dose dependent manner. Quantitative measurement of IL-4 in cell supernatant revealed that All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. AB76 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2016

Anti-Apoptosis and Cell Survival Gene Expression and that substances reducing TG2 over-expressed in thalamus of EAE may 248 Profile in LAD2 Cells contribute to protection against demyelination of EAE.

Arnold S. Kirshenbaum, MD, FAAAAI1, Maarten Leerkes, PhD2, Inhibition of IgE-Mediated Allergic Reaction By Avanti Desai, MS1, Dean D. Metcalfe, MD1; 1Laboratory of Allergic Dis- 250 Pharmacologically Targeting the Circadian Clock 2 eases, NIAID, NIH, Bethesda, MD, Bioinformatics and Computational 1 2 3 1 Biosciences Branch, NIAID, NIH, Bethesda, MD. Yuki Nakamura, PhD , Atsuhito Nakao , Shigenobu Shibata ; Depart- RATIONALE: For over 10 years, LAD2 cells have been used for human ment of Immunology, Faculty of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan, 2Department of Immunology, Faculty of Medi- mast cell research. Unlike HMC1 cells which are presumed immortalized 3 by D816V KIT mutations, LAD2 cells have no mutations in KIT to explain cine, University of Yamanashi, Yamanashi, Japan, Department of Physi- their survival. We therefore examined anti-apoptosis and cell survival gene ology and Pharmacology, School of Advanced Science and Engineering, expression as a first step to understand LAD2 cell persistence in culture. Waseda University. METHODS: RNAwas prepared from both LAD2 cells and CD34-derived RATIONALE: Recently, we reported that the circadian clock temporally human mast cells (HuMCs) from normal subjects (98-I-0027). Analysis of gates signaling via the high-affinity IgE receptor (FcepsilonRI) in mast cells, genes participating in anti-apoptotic and cell survival functions was thereby generating a marked day–night variation in allergic reactions (JACI, performed using cDNA and Affymetrix GeneChip RNA Array following 2014). We therefore hypothesized that pharmacologically resetting the SATURDAY normalization. Hierarchically clustered displays of differentially expressed molecular clock in mast cells to times when FcepsilonRI signaling is reduced genes were compared for HuMCs and LAD2 cells. (i.e., when core circadian protein PERIOD2 [PER2] is up-regulated) might RESULTS: In LAD2 cells, two subunits of the anti-apoptotic gene NF- inhibit IgE-mediated allergic reactions. In this study, we determined whether kappaB, NFKB1 and NFKB2, were highly upregulated concurrent with pharmacologically resetting the molecular clock in mast cells or basophils to downregulation of the pro-apoptotic genes p53 and CDKN2A. CASP3 was times when FcepsilonRI signaling was reduced (i.e. when PER2 is up- downregulated while its substrate CDKN1A was upregulated, contributing to regulated) resulted in suppression of IgE-mediated allergic reactions. anti-apoptosis. Telomere lengthening remained a stable process. Hierarchical METHODS: We examined the effects of PF670462, a selective inhibitor clustering showed strong grouping and significant enrichment in LAD2 cells of of the key clock component casein kinase (CK)1delta/epsilon which up- differentially expressed genes participating in anti-apoptosis and cell survival. regulated PER2 in mast cells, on IgE-mediated allergic reactions both in CONCLUSIONS: The overall gene expression profile in LAD2 cells vitro and in vivo. showed enrichment for anti-apoptosis. The observation that LAD2 cells RESULTS: PF670462 suppressed IgE-mediated allergic reactions in survive without rhSCF but require rhSCF for growth, suggests that NF-kappaB mouse bone marrow-derived mast cells or basophils, and the passive activation, reduced cell cycle inhibition, decreased p53-induced apoptosis and cutaneous anaphylactic (PCA) reaction in mice, in association with stable telomere lengthening may contribute to LAD2 cell immortalization. increased PER2 levels in mast cells or basophils. PF670462 ameliorated Additional research to identify controls on the expression of these genes may allergic symptoms in a mouse model of allergic rhinitis and down-regulated help us further understand aberrant mast cell development in mastocytosis. allergen-specific basophil reactivity in patients with allergic rhinitis. CONCLUSIONS: Pharmacologically resetting the molecular clock in Transglutaminase 2 over-Expressed By Interaction mast cells or basophils to times when FcepsilonRI signaling is reduced can 249 of Mast Cells and Oligodendrocytes Induces inhibit IgE-mediated allergic reactions. The results suggest a new strategy Demyelination in the Experimental Autoimmune for controlling IgE-mediated allergic diseases. Encephalomyelitis IL-33 Induces Functional CCR7 Expression in Gwan Ui Hong1, Young Min Ahn, MD2,3, Jai Youl Ro, PhD1,4; 1Sung- 251 Human Mast Cells kyunkwan University School of Medicine, 2Eulji University School of Medicine, South Korea, 3Department of Pediatrics, South Korea, 4Sung- Maiko Emi-Sugie, PhD; Department of Allergy and Immunology, Na- kyunkwan University School of Medicine, Suwon, South Korea. tional Research Institute for Child Health and Development, Tokyo, RATIONALE: Mast cells and oligodendrocytes play important roles in Japan. autoimmune diseases like multiple sclerosis. TG2 over-expressed in various RATIONALE: Mast cells play key roles in both adaptive and innate immune inflammatory diseases has influence on the damaged axons. This study aimed responses leading to type-2 inflammation. IL-33, an epithelium-derived to investigate whether TG2 expressed in mast cells and oligodendrocytes cytokine, is released mainly from damaged tissue as an ‘‘alarmin’’ after virus induces demyelination in experimental autoimmune encephalomyelitis (EAE). infection or protease antigen exposure. IL-33 release leads to activation of -/- various cell types. IL-33 had been known to activate mast cells directly to METHODS: Wild type (WT) and TG2 (KO) mice received MOG33-55 and PT by i.p. injection to induce EAE. Bone marrow-derived mast cells (BMMCs) produce IL-5 and IL-13. However, our recent studies using a protease-induced were adaptively transferred to KO mice by i.v. injection before PT injection. asthma model found that IL-33 also induces regulatory T-cell production by BMMCs and mouse cerebral cortices-derived mature OLs (mOLs) were co- activating mast cells. We have now comprehensively examined gene- cultured. Demyelinated area was determined by luxol fast blue staining, expression profiles to elucidate how IL-33 alters mast cell function. expression of surface markers and death signaling molecules by western METHODS: Human mast cells were generated by 12-week culture of blot, co-localization of mast cells and mOLs by immunofluorescence. peripheral blood hematopoietic stem cells in the presence of SCF and IL-6. RESULTS: KO mice reduced EAE scores, demyelinated area, mast cell Mast cells were stimulated with IL-33 or with anti-IgE mAb after IgE- numbers, expression of surface markers (CD40/CD40L) in mast cells and sensitization. mRNA expression was determined by microarray and qPCR. death signaling molecules in mOLs, co-localization of mast cells and Chemotaxis assay was performed using Boyden chambers, and ERK mOLs in thalamus of EAE, whereas WT mice increased all of them in phosphorylation was determined by western blotting. thalamus. BMMCs-transferred KO mice restored all responses versus KO RESULTS: IL-33 stimulation, but not anti-IgE mAb stimulation, induced 2+ CCR7 mRNA expression in mast cells. Upon exposure to CCL19 and mice. KO-BMMCs co-cultured with mOLs decreased [Ca ]i level and the release of histamine, LTs and cytokines versus WT-BMMCs with mOLs. CCL21 (CCR7 ligands), IL-33-stimulated mast cells showed significant The mOLs co-cultured with KO-BMMCs reduced expression of various chemotaxis and ERK phosphorylation in dose- and time-dependent € death signaling molecules versus mOLs with WT-BMMCs. manners, but naıve mast cells did not. CONCLUSIONS: The data suggest that mast cells- or mOLs-expressed CONCLUSIONS: IL-33 induces not only IL-5 and IL-13 production by TG2 may induce mediators9 release and apoptosis, respectively, through human mast cells but also expression of functional CCR7 that may up-regulating expression of various stimulatory/death signaling molecules, facilitate mast cell–T cell interaction following CCL19/CCL21 exposure. All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. J ALLERGY CLIN IMMUNOL Abstracts AB77 VOLUME 137, NUMBER 2

Effect of ONO-4053 on Fc Epsilon RI Stimulated- The Role of the Mast Cell in the Anti-Viral Immune 252 Mast Cell Activation 254 Response

Shinsuke Yamaguchi, Yutaka Okada, Yoko Matsunaga, Fumio Nambu; Ruben Raychaudhuri, Brian T. Kelly, MD, MA, Jennifer L. Santoro, BS, Ono Pharmaceutical Co., Ltd. Mitchell H. Grayson, MD, FAAAAI; Medical College of Wisconsin, Mil-

RATIONALE: As prostaglandin D2 (PGD2), a chemical mediator waukee, WI. released in large amounts from mast cells, is known to be involved in a RATIONALE: Severe respiratory viral infections early in childhood are

number of allergic responses, blockage of PGD2 action might be beneficial associated with a markedly increased risk of asthma. Using the Sendai for the treatment of allergic disease. ONO-4053 is an orally active DP1 (a virus (SeV) mouse model, we defined a mechanistic pathway translating

PGD2 receptor) antagonist in phase 2 clinical trial for the treatment of viral infection into asthma. Critical to the development of post-viral asthma allergic rhinitis. The purpose of this study was to investigate the effect of is the formation of anti-viral IgE. Since IgE binds mast cells and basophils, ONO-4053 on mast cell activation after Fc epsilonRI stimulation. it would seem that they may play a role in the anti-viral immune response, METHODS: Human mast cells were differentiated from CD34-positive but this had not been previously tested. We hypothesized that via IgE mast bone marrow cells in the presence of stem cell factor (SCF), IL-6 and IL-3. cells would be required for the development of asthma after a severe After overnight sensitization with human myeloma IgE, the cells were respiratory viral infection. incubated with and without ONO-4053 at 37 8C for 60 min. Goat anti- METHODS: Wild-type (WT) and KitW-sh (mast cell deficient) mice human IgE antibody was then added to initiate the reaction, and the (n53-4) were inoculated with SeV. On day 21 post-inoculation SeV,

amounts of histamine and PGD2 after 30 min reaction, and cytokines after 6 airway hyper-responsiveness (AHR) was measured with non-invasive hours reaction were determined. two-chamber plethysmography. Lungs were homogenized and levels of RESULTS: ONO-4053 concentration-dependently inhibited Fc mucous (Muc5ac) as well as Il13 message were measured using quantita-

epsilonRI-stimulated histamine release and PGD2 production in human tive, reverse-transcript PCR and compared to Gapdh levels. Student’s t-test mast cells, but did not affect cytokines production in these cells. Other was used in data analysis. W-sh DP1 antagonists had no effect on histamine release, PGD2 production, or RESULTS: WT and Kit mice survived the viral infection, and devel- cytokines production in the stimulated mast cells. oped airway hyperreactivity and mucous cell metaplasia. Interestingly, CONCLUSIONS: The findings of this study indicate that ONO-4053 airway hyperreactivity was significantly greater in the mast cell deficient would be clinically useful for a variety of allergic diseases, including mice (p50.05 versus WT), while Muc5ac and Il13 were not different be- allergic rhinitis, by the action of both DP1 antagonism and suppression of tween the two groups. mast cell activation. CONCLUSIONS: Our data suggest that mast cells are not required for survival from a respiratory viral infection, and may even attenuate Desensitization of Different Subsets of Mast Cells development of post-viral airway hyper-reactivity. Confirmation of the 253 Associated with Different Manifestations of Food role of mast cells awaits mast cell reconstitution studies in mast cell

Allergy deficient mice, something that we are currently undertaking. SATURDAY

Sara Benede, PhD1, M. Cecilia Berin, PhD2; 1Department of Pediatrics. Airway Basophils Are Activated and Associated Icahn School of Medicine at Mount Sinai, New York, NY, 2Department of 255 with Eosinophilic Inflammation in Asthmatic Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY. Patients RATIONALE: Mast cells are key effector cells of allergic reactions, and are classified into mucosal (MMC) and connective tissue (CTMC) mast Yoshihiro Suzuki, MD, Keiko Wakahara, MD, PhD, Tomoko cells. We hypothesized that MMC and CTMC could contribute to different Nishio, MD, Satoru Ito, MD, PhD, Yoshinori Hasegawa, MD, PhD; Na- clinical manifestations of food allergy, and underlie route-dependent goya University Graduate School of Medicine, Nagoya, Japan. desensitization to foods. RATIONALE: Basophils are considered as allergy-related cells. METHODS: We evaluated mast cell activation by protease release using However, the impact of those cells in local sites is unexplored. We here two different mouse models of food allergy with gastrointestinal or examined frequencies and activation status of basophils in induced sputum anaphylaxis symptoms in response to oral challenge. Bone marrow-derived from adult asthmatic patients. MMC and CTMC were used to study desensitization in vitro. METHODS: We enrolled 51 adult stable asthmatic patients who had been RESULTS: Using sensitized mice and evaluating those with and without treated with ICS for more than 3 months. Analysis of induced sputum, clinical symptoms, we observed that anaphylaxis was significantly blood test, pulmonary function test, FeNO measurement, and Asthma associated with CTMC, but not MMC, activation. In contrast, diarrhea Control Test (ACT) were carried out. The percentages of basophils and was associated with MMC and CTMC activation. Desensitization of CD203c expression on basophils in sputum and blood were examined by a anaphylactic mice with oral immunotherapy led to suppression of both flow cytometer. MMC and CTMC activation. In vitro sensitization and activation of MMC RESULTS: Forty-four sputum samples were analyzed. Basophils were and CTMC resulted in signaling (phospho-Syk), degranulation (LAMP-1) detected as CD45+ FceRIhi SIRP-alo CD123hi c-kit- cells or CD45+ and cytokine release (IL-6, IL-13 and TNF-a). All activation parameters CD203c+ SIRP-alo CD123hi HLA-DR- cells in sputum of stable asthmatic could be desensitized in both MMC and CTMC. Extent of desensitization patients. The percentages of sputum basophils were correlated with those was correlated with extent of initial activation when an antigen-specific of eosinophils and mast cells (r50.765, P<0.001 and r50.581, P<0.001 system was used (monoclonal DNP-IgE or serum from sensitized mice), respectively). CD203c expression was significantly increased on sputum and no evidence of bystander desensitization was found. Desensitization basophils as compared with that on peripheral blood basophils of mast cells at a dose below that required for activation was only observed (92.9644.6 vs 40.5631.1, P<0.01). using anti-IgE, and not antigen. CONCLUSIONS: Basophils were activated and increased in airways of CONCLUSIONS: Different manifestations of food allergy are mediated eosinophilic asthmatic patients. Those findings suggest sputum basophils by subsets of mast cells with differing protease profiles. MMC and CTMC could be a biomarker as well as a therapeutic target of eosinophilic asthma. show similar potential to become desensitized in vitro, as well as in vivo by an oral route. All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. AB78 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2016

Generation of Mast Cells in Co-Culture with Peanut-Containing Products in Children's 256 Multiple Cell Types within an Advanced Allergy 258 Hospitals: Putting Pediatric Patients at Risk Tissue Model Laura A. Fletcher1, Tammy Pham1, Maguire Herriman1, Bridget Kiely1, Tahereh Derakhshan, Rudra Bhowmick, James H. Meinkoth, Heather Ruth Milanaik1, Gregory A. Rosner, MD2; 1North Shore-LIJ Cohen Chil- Gappa-Fahlenkamp; Oklahoma State University, Stillwater, OK. dren’s Medical Center of NY, Lake Success, NY, 2Hofstra North Shore-LIJ RATIONALE: An in vitro tissue model can be used to identify factors that School of Medicine, New York, NY. regulate inflammation, leading to better diagnostic and therapeutic strate- RATIONALE: Peanut allergy affects approximately 2% of all children in gies. Since mast cells (MCs) play a major role in allergy development, their the US. In the presumed safety of a pediatric hospital setting, the presence incorporation into the tissue model is critical. Due to difficulties in of peanut-containing products (PP) in vending machines (VM) and isolating MCs ex vivo, our objective was to generate functional MCs within nutritional closets (NC) poses an unnecessary risk to children’s health. a tissue model that mimics human physiology. Our study examines the prevalence of PP found in close proximity to METHODS: MC progenitors, isolated from leucocyte preparation of pediatric units and emergency departments (ED) of hospitals in the US. human donors, along with primary human fibroblasts were cultured in a METHODS: Residents from 52 pediatric hospitals completed an online collagen matrix to mimic connective tissue. Culture media was selected survey about their hospital. The survey asked if there were PP in the NC on based on the support of the overall growth and function of the cell types. pediatric floors and, if so, what they were. Residents were also asked to SATURDAY Samples were incubated for seven weeks to allow for MC generation and send in a picture of the VM closest to the Pediatric ED. Research personnel maturation. After six weeks, the matrix was coated with type IV collagen calculated the frequency of hospitals that carried at least one PP in their ED and fibronectin layer and primary human endothelial cells to represent a VM. Comparisons across categorical variables were performed using Chi- blood capillary. Formation of cytoplasmic granules was observed by square analysis. metachromatic staining, indicative of MCs. Expression of MC phenotypic RESULTS: Of the 42 hospitals that submitted a photo, 41 (97.6%) had at markers was determined by flow cytometry. MC function was examined least one PP in the VM nearest the Pediatric ED. Of all surveyed hospitals, after challenge with IgE and anti-IgE antibodies by quantifying the 59.6% had PP in the NC on the patient floors themselves. histamine release. CONCLUSIONS: Despite the prevalence of peanut allergy, the over- RESULTS: After seven weeks, progenitor cells appeared as mono- whelming majority of children’s hospitals surveyed unnecessarily exposed nucleated (70%) and with surface projections, representing characteristics their patients to peanut products. While many schools and early care and of MCs. The cells were positive for metachromatic granules and expressed education centers have banned all peanut-containing products, most MC phenotypic markers, 8362% c-kit and 2064% FcεRI. After activation hospitals have yet to do so. The AAP and the American Medical with anti-IgE, generated MCs released 10-fold higher histamine content Association should address this simple precautionary step that could than unactivated cells (p<0.005). have lasting implications for child safety. CONCLUSIONS: Generated cells within the tissue model exhibited in vivo MC morphology, immunophenotype, and underwent degranulation Hyperimmunoglobulin E Syndrome like Presentation in response to antigen receptor trigger. 259 in a Patient after Hemodialysis

Enhanced Development of Functional Murine Mast Tanveer Singh, Resident Physician1, Brigani Amante1,2, David Regel- 257 Cells in Human Stem Cell Factor Transgenic mann, Attending Physician1, Noorpreet Dhawan1; 1St. Vincent’s Medical Immune-Deficient Mice Center, Bridgeport, CT, 2University of Colorado Hospital, Aurora, CO. RATIONALE: Hyperimmunoglobulin E syndrome (HIES) is a rare Kshitij Gupta, PhD, Hariharan Subramanian, PhD, Hydar Ali, PhD; syndrome causing recurrent cold abscesses, sinopulmonary infections, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA. eczema and elevated IgE level. HIES can be sporadically triggered by de RATIONALE: Previous studies have shown that engraftment of human novomutations of the signal transducer and activator of transcription 3 CD34+ hematopoietic stem cells (hHSC) into immune-deficient NGS (STAT3). To date only 1case report published by Yokota K et al showing (NOD, SCID, IL2 receptor g-null) mice transgenic for membrane-bound HIES-like symptoms in a patient post Hemodialysis (HD). human stem cell factor (hSCF-NSG, ‘‘humanized mice’’) results in the METHODS: Forty years old female presented with complains of right hip robust development of human mast cells. Here, we sought to determine and thigh pain radiating to her back. Further, she had been having multiple if na€ıve NSG mice without hHSC engraftment develop endogenous mast episodes of infections in the last 10 years, with multiple hospital cells and if this response is modulated in hSCF-NSG mice. admissions for recurrent episodes of subcutaneous abscesses and 1 episode METHODS: Peritoneal lavage and skin slices of NSG and hSCF-NSG of pneumonia complicated by empyema. Her symptoms began following mice were stained with toluidine blue. Peritoneal mast cells were primed HD 10 years ago and she had an uneventful childhood period. Her CT scan with IgE and the effects of antigen and antimicrobial peptide LL-37 on showed a large abscess in the right retroperitoneal area extending to the degranulation was determined. Passive cutaneous anaphylaxis (PCA) was right groin and thigh and she was admitted with sepsis. Strikingly, the skin performed with antigen in IgE-sensitized mice and increased vascular overlying her abscess was cold to touch. She was treated with antibiotics permeability was determined. and incision and drainage. HIV ELISA was negative. Her IgE levels RESULTS: Peritoneal lavage of NSG mice contained mast cells and this exceeded 50000 kU/L. was enhanced by >4-fold in hSCF-NSG mice. Skin slices of NSG mice RESULTS: Our patient’s symptoms of HIES like recurrent sinopulmo- showed the presence of 18 6 4 mast cells per high power field (200X) but nary infections and cold abscesses with elevated IgE levels followed her this was increased to 36 6 6 in hSCF-NSG mice. NSG mice developed HD. As she had an uneventful childhood period, presence of a sporadic PCA in response to antigen but this response was increased by 3.2-fold in mutation of STAT 3 gene remains unclear, but the temporal relationship hSCF-NSG mice. between her symptom onset and her HD are consistent with post- HD CONCLUSIONS: Results presented herein suggest that previously HIES. developed humanized mice likely contain both human and murine mast CONCLUSIONS: Our patient had HIES like symptoms post HD. cells, thus compromising their usefulness to study human mast cell Indication of antibiotic prophylaxis in this patient population needs further function in vivo. However, the enhanced development of murine mast cells research. in na€ıve hSCF-NSG mice without hHSC engraftment provides a new model to study the role of mast cells on allergic responses in vivo. All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. J ALLERGY CLIN IMMUNOL Abstracts AB79 VOLUME 137, NUMBER 2

Incidence of Delayed Systemic Reactions to above average levels of PM2.5 (OR 3.2, p50.10), and exposed to tobacco 260 Subcutaneous Immunotherapy smoke (OR 2.2, p50.56). CONCLUSIONS: Results indicate a high estimated prevalence of risk of Carolyn M. Ford, RN1, Elizabeth A. Leyvas, LVN1, Jill Waalen, MD, asthma among participants. Obesity, outdoor air pollution and tobacco MPH2, Andrew A. White, MD, FAAAAI3,4; 1Scripps Clinic, San Diego, smoke exposure were identified as contributors. Future studies need to CA, 2Scripps Translational Science Institute, La Jolla, CA, 3Scripps expand upon this sample size, and ultimately improve asthma outcomes in Clinic, Division of Allergy, Asthma and Immunology, San Diego, CA, at-risk populations. 4Scripps Clinic Medical Group, San Diego, CA. RATIONALE: The guidelines for safe subcutaneous immunotherapy Characterization of Environmental Risk Factors administration put forth by AAAAI recommend a 30 minute in-office wait 262 Among Inner-City Schoolchildren with Physician after injection, stating that the majority of serious systemic reactions occur Diagnosed Asthma from the Pittsburgh Region

within 30 minutes of receiving an injection. However, less is known about 1 2 delayed systemic reactions occurring outside of a clinic setting. We wanted Paige E. Dewhirst, MPH , Jennifer Paden Elliott, PharmD , Albert Presto, PhD3, Tricia Morphew, MSc4, Erica Butler, BS, CCRC5, Nicole to determine what percent of reactions occurred after 30 minutes within in 5 6,7 6 our practice. Pleskovic, BS , David P. Skoner, MD , Deborah A. Gentile, MD ; 1American Lung Association, 2Duquesne University, Pittsburgh, 3Carne- METHODS: We retrospectively evaluated all systemic reactions from 4 5 November 1, 2004 to November 1, 2014 to determine time from injection gie Mellon Univesity, Morphew Consulting, LLC, CA, Allegheny Singer Research Institute, Pittsburgh, PA, 6Allegheny Health Network, to onset of symptoms. 7 RESULTS: Of the 57,102 injections that were given over 10 years, there Pittsburgh, PA, Department of Medicine, Allegheny General Hospital, were 72 systemic reactions among 50 patients. Of the total number of Pittsburgh, PA. reactions, 52.8% (38 instances) occurred after 30 minutes. Seven patients RATIONALE: Pediatric asthma remains a public health concern among experienced symptom onset as late as 90 or more minutes post injection. inner-city schoolchildren from Pittsburgh. The purpose of this study was to The percentage of patients who required epinephrine did not differ based determine the prevalence of physician diagnosed asthma and the relation- on reaction time (p50.65). This dataset was unable to determine any ship between certain environmental risk factors and diagnosis among this factors predicting the likelihood of a delayed reaction such as age, sex, population. allergen content or duration of successful immunotherapy. METHODS: This study was approved by the Allegheny Singer Research CONCLUSIONS: Our data suggest that even with a 30 minute in-office Institute-Allegheny Health Network Institutional Review Board. Informed wait time, approximately half of systemic reactions occurred outside the consent/assent was obtained from all subjects prior to participation. Fifth clinic. Although in our series of patients there were few emergency grade students were recruited from twelve Pittsburgh schools. Physician treatments and no fatalities, the risk of severe reactions to allergy shots diagnosed asthma was ascertained using a standardized, validated survey. outside the clinic remains. The results underscore the importance of Relationships between physician diagnosed asthma and environmental risk factors, including obesity (BMI), poverty (public health insurance), educating patients about the symptoms of systemic reactions, proper SATURDAY epinephrine self-administration, and the possibility of delayed onset of outdoor air pollution (NOx), psychological stress (salivary cortisol), and to- symptoms. bacco smoke exposure (salivary cotinine) were analyzed using logistic regression. Pilot Study Identifies Obesity, Outdoor Air RESULTS: 267 subjects were enrolled (37.5 % African American, 47.6% 261 Pollution, and Tobacco Smoke Exposure As female). The prevalence of physician diagnosed asthma was 28.7%. Contributors to High Estimated Prevalence of Factors influencing odds of physician diagnosed asthma included elevated Risk of Asthma in Inner-City Schoolchildren from BMI (p50.032) public vs private health insurance (p50.002), NOx expo- Pittsburgh Region sure (p50.023), and salivary cortisol (p50.34). A strong interaction was identified between poverty and psychological stress (p50.004) such that Tricia Morphew, MSc1, Jennifer Paden Elliott, PharmD2, Paige E. the odds of physician diagnosed asthma was 6.88 times greater Dewhirst, MPH3,4, Nicole Pleskovic, BS3, Erica Butler, BS, CCRC3, Da- (p50.002) in subjects with public health insurance and elevated salivary vid P. Skoner, MD5, Deborah A. Gentile, MD3,5; 1Morphew Consulting, cortisol levels (>1 SD above mean). LLC, Manhattan Beach, CA, 2Duquesne University, Pittsburgh, 3Alle- CONCLUSIONS: Results indicate a high estimated prevalence of gheny Singer Research Institute, Pittsburgh, PA, 4American Lung Associ- physician diagnosed asthma among participants. Obesity, poverty, outdoor ation, 5Allegheny Health Network, Pittsburgh, PA. air pollution, and psychological stress were identified risk factors. Future RATIONALE: Pediatric asthma is a public health concern in the inner- efforts need to focus on improving asthma outcomes in this at-risk city of Pittsburgh. The purpose of this pilot study was to develop efficient population. and accurate methods to assess the prevalence of asthma among school- children in Pittsburgh. METHODS: This study was approved by the Allegheny Singer Research Institute-Allegheny Health Network Institutional Review Board. Informed consent/assent was obtained from all subjects prior to participation. Fifth grade students were recruited from twelve Pittsburgh schools. Estimated prevalence was calculated for those subjects at risk for asthma and those previously diagnosed with asthma. Relationships between contributors, including poverty (public health insurance), outdoor air pollution (PM2.5), tobacco smoke exposure (salivary cotinine), psychological stress (salivary cortisol), and obesity (BMI) were explored using logistic regression analyses. RESULTS: 267 subjects were enrolled (37.5% African American (AA), 41.6% female, 44.2% public insurance). Results demonstrate that 40.4% of subjects were at risk of asthma, 28.7% had a previous diagnosis and 11.7% were newly identified. Subjects at highest risk of asthma were those overweight (OR5 2.0; p50.39) or obese (OR5 2.8; p 50.002), exposed to All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. AB80 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2016

Rate of Food Introduction after a Negative Oral Slit Adhesion in Brazilian People 263 Food Challenge in the Pediatric Population 265

Jessica Gau, NP, CRC1, Sally A. Noone, RN, MSN2, Zara Atal3, Jaime Fernando M. Aarestrup, MD, PhD1, Beatriz Aarestrup2, Tamara A. de Ross, RN, MSN4, Jennifer Fishman, RN, BSN5, Beth D. Strong, RN, Freitas3, Glaciele M. M. Rezende3, Nathalie J. Guimar~aes e Silva3, Raissa CCRC6, Carly Ehritz, RN, MSN3, Julie Wang, MD, FAAAAI2; 1Mt. Sinai M. Cabrera3; 1Universidade Federal de Juiz de Fora - MG- Brazil, Juiz de School Medicine, New York, NY, 2Icahn School of Medicine at Mount Si- Fora, Brazil, 2Universidade Federal de juiz de Fora- MG - Brazil, Brazil, nai, New York, NY, 3Icahn School of Medicine at Mt. Sinai, 4The Icahn 3SUPREMA. School of Medicine at Mount Sinai, New York, NY, 5Ichan School of RATIONALE: Although the sublingual allergen-specific immunotherapy Medicine at Mount Sinai, New York, NY, 6Icahn School of medicine at (SLIT) is a routine treatment in many Latin America countries there are Mount Sinia, New York, NY. few studies related to the adherence of sublingual immunotherapy (SLIT) RATIONALE: Oral food challenges (OFCs) are performed to diagnose with no reports in the Brazilian population. food allergy persistence or outgrowth. This study evaluated the rate of food METHODS: A retrospective cross-sectional study with 218 patients from introduction following a negative OFC and reasons for failure to introduce an Allergy and Immunology Service in Juiz de Fora, MG, Brazil were challenged foods at home. performed in patients with diagnosis of rhinitis and/or asthma that received METHODS: An anonymous survey was distributed to parents of children SLIT for dust mites based on the results of the Prick Test The participants SATURDAY with food allergy during follow-up visits. Thirty-three respondents were divided by sex and into three age groups: A) 2 to 12 years; B) >_ 12 reported having had 75 OFCs. Data collected included challenged food, years to 18 years ; C) >_ 18. We evaluated adherence after 4 months (the end result of the OFC, the frequency of food introduction, and reasons for of the induction phase) and 12 months of treatment. failure to incorporate the challenged food into the diet on a regular basis. RESULTS: The general adherence of SLIT in four months was 66.1% RESULTS: Of the 75 OFCs, 52 were negative OFCs. After completion of (70.2% in male group and 61.5% in female group). The analysis of 52 negative OFCs, 4 foods (8%) were not added to the diet, 10 foods (19%) adherence by age, group A showed 70.6% of adherence, B 63.3% and C are included in the diet a few times a year, 9 foods (17%) are included 61.6% in the fourth month. After 12 months of treatment, the total of monthly, 17 foods (32%) are included weekly, and 9 foods (17%) are adherence was 46.3% (51.8% in male and 40.4% in female) and the included daily. 27% of the foods were never introduced or seldom included adherence of the groups A, B and C were, respectively: 52%, 40% and in the diet after a negative OFC. Reasons included dislike (5), fear (3), and 41.9%. the food not being part of the diet (3). Three did not provide reasons. The CONCLUSIONS: The SLIT, although it’s safety and easier to manage, foods most avoided were tree nuts, peanut, and chickpea. has limitations in the adherence on the Brazilian population , especially CONCLUSIONS: After a negative OFC, about a quarter of the foods were after the induction phase. The results indicate that educational proceedings still being avoided for various reasons. Post-challenge counseling and must be perform to improve the SLIT adhesion. dietary guidance to address potential barriers may be beneficial to increase rates of food introduction following negative OFCs. Idiopathic Angioedema: Difficult Cases and 266 Uncommon Findings

Withdrawn Laura E. Noonan, MSN, FNP-C1, Oral Alpan, MD1,2, Denise 264 Loizou, RN3, Ozlem Goker-Alpan, MD3; 1O&O Alpan, LLC, Fairfax, VA, 2Amerimmune, LLC, VA, 3O&O Alpan, Fairfax, VA. RATIONALE: Idiopathic angioedema is a poorly defined disorder. We present two cases of steroid and antihistamine non-responsive angioedema whose workup showed genetic variations outside the immune and com- plement pathways that may be potential triggers for their symptoms. METHODS: Whole exome sequencing (WES) performed by Gene Dx. RESULTS: The first case is a 17 year old female who presented with recurrent swelling of her face, hands, and feet, headaches, and severe abdominal pain. She has normal C1 esterase inhibitor level and function. Symptoms are not relieved by antihistamines or steroids. The patient has moderate relief with use of C1 esterase inhibitor. WES identified compound heterozygosity for p.E172K and p.G216R variants of the TIE- 1 gene. This has been found in a murine model to cause vascular leakage. The second case is a 20 year old female with a history of recurrent swelling of her lips and tongue with normal C1 esterase inhibitor level and function. She gets no relief with allergy or HAE treatments. WES showed she is heterozygous for a variant of unknown significance of the PDE11A gene. In vitro studies demonstrate that PDE11A is involved with cyclic AMP (cAMP) and cyclic GMP (cGMP) metabolism, and mutations lead to increased cGMP and cAMP levels in cell models. We hypothesize that increased cAMP and cGMP levels may contribute to sustained vasodilation and enhancement of triggers leading to the severity of her symptoms. CONCLUSIONS: Genetic evaluation, such as WES, may provide insight for patients whose angioedema does not respond to conventional allergy or HAE treatments. All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. J ALLERGY CLIN IMMUNOL Abstracts AB81 VOLUME 137, NUMBER 2

Specific Anti_A/B Immunoaffinity Chromatography that PAL is required by law. Previous severe allergic reaction decreased the 267 Step Reduces Isoagglutinin Levels in an odds of purchasing foods using PAL. Intravenous Immunoglobulin Product CONCLUSIONS: Ten to forty percent of respondents stated that they bought products with PAL. Purchasing behaviors also varied by country Alphonse P. Hubsch, Annette Gaida, Ibrahim El Menyawi, Sandra Wy- and previous reaction severity. Improved awareness and guidelines are mann, A. Adriano Marques, Nicole Spiegl, Thomas Roten, Eleonora needed to assist consumers in their purchasing decisions. Widmer; CSL Behring AG, Berne, Switzerland. RATIONALE: Titers of anti-A and anti-B antibodies (isoagglutinins) in High Rate of Uncontrolled Asthma Among intravenous immunoglobulin (IVIG) products correlate with the risk of 269 Inner-City Schoolchildren from Pittsburgh Region hemolysis. Therefore, it is hypothesized that reduction of anti-A/B may Erica Butler, BS, CCRC1, Nicole Pleskovic, BS1, Jennifer Paden reduce this risk. 2 1,3 4 METHODS: We tested the effect of a specific immunoaffinity chroma- Elliott, PharmD , Paige E. Dewhirst, MPH , Tricia Morphew, MSc , David P. Skoner, MD5,6, Deborah A. Gentile, MD1,5; 1Allegheny Singer tography (IAC) step, using a blood group A and B trisaccharides-coupled 2 resin, added to the manufacturing process of an IVIG (PrivigenÒ, CSL Research Institute, Pittsburgh, PA, Duquesne University, Pittsburgh, 3American Lung Association, 4Morphew Consulting, LLC, Manhattan Behring). Anti-A/B in the final product was measured by the direct agglu- 5 6 tination test (DAT). Historical PrivigenÒ lots produced without the IAC Beach, CA, Allegheny Health Network, Pittsburgh, PA, Department of step or other measures of isoagglutinin reduction (donor screening) were Medicine, Allegheny General Hospital, Pittsburgh, PA. used as comparators. A fluorescence-activated cell sorting (FACS)-based RATIONALE: Pediatric asthma is a public health concern in the inner- anti-A/B binding assay was used to compare intermediate products before city of Pittsburgh. Uncontrolled disease impacts upon school attendance/ and after the IAC step. performance, physical activity and socialization. The purpose of this study RESULTS: The most frequent titer in 44 IAC lots was 1:8 (range 1:8 to was to determine the rate of disease control among school children with 1:16) for anti-A, and 1:4 (1:4 to 1:8) for anti-B. In 294 historical lots, the documented asthma. most frequent titer was 1:32 (1:8 to 1:64) for anti-A, and 1:16 (1:4 to 1:32) METHODS: This study was approved by the Allegheny Singer Research for anti-B. FACS analyses showed a reduction of 87% (81% to 91%) for Institute-Allegheny Health Network Institutional Review Board. Informed anti-A, and 87% (82% to 93%) for anti-B as a result of the IAC step. consent/assent was obtained from all subjects prior to participation. Fifth CONCLUSIONS: We have shown that, with the introduction of an IAC grade students with asthma were enrolled from twelve Pittsburgh schools. step in a production-scale IVIG (PrivigenÒ) manufacturing process, a Parents were surveyed using an abbreviated, validated survey to assess reduction of anti-A/B by 2 to 3 titer steps (equivalent to 75.0% to asthma control. Relationships between potential contributing factors, 87.5%) is feasible. The impact of this isoagglutinin reduction on the risk including poverty (public health insurance), outdoor air pollution (black of hemolysis is currently under investigation. carbon), tobacco smoke exposure (salivary cotinine), psychological stress (salivary cortisol), and obesity (BMI) were explored using logistic regression analyses. Food Allergen Labeling and Purchasing Habits in SATURDAY 268 the US and Canada RESULTS: 108 subjects were enrolled (41.7% African American, 49.1% female, 50.5% public insurance). Results demonstrated that 45.4% had Mary Jane Marchisotto1, Laurie Harada, BA2, Opal Kamdar, MD3, uncontrolled asthma . Black carbon exposure was the only unadjusted Bridget Smith, PhD4,5, Kemrani Khan6, Scott H. Sicherer, MD, FAAAAI7, factor that influenced odds of uncontrolled disease (OR54.9 first vs third Stephen L. Taylor, PhD8, Veronica LaFemina1, Maria Antonella quartile; p<0.05). Adjusted analysis showed that risk of uncontrolled Muraro, MD, PhD9, Susan Waserman, MD, FAAAAI10, Ruchi Gupta, asthma was higher in those with public vs private insurance and no tobacco MD, MPH5,11; 1FARE, 2Anaphylaxis Canada, Toronto, ON, Canada, smoke exposure (OR55.9; p<0.050), and overweight females vs males 3Department of Pediatrics, Ann & Robert H. Lurie Children’s Hospital (OR5 21.1; p< 0.05). of Chicago, 4Edward J. Hines Jr. VA Hospital, Chicago, IL, 5Northwestern CONCLUSIONS: Results indicate a high rate of uncontrolled asthma University Feinberg School of Medicine, Chicago, IL, 6Food Allergy Can- among school children from the inner-city of Pittsburgh. Identified ada, 7Icahn School of Medicine at Mount Sinai, New York, NY, 8Univer- contributors to uncontrolled disease include outdoor air pollution, public sity of Nebraska, Lincoln, NE, 9University Hospital of Padua, Padua, Italy, health insurance in those not exposed to tobacco smoke and overweight/ 10Department of Medicine, McMaster University, Hamilton, ON, Canada, obesity in females. Future studies need to focus on improving asthma 11Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL. outcomes in at-risk populations. RATIONALE: Food allergies are increasing with the primary treatment being allergen avoidance. Mandatory allergen labeling has improved the safety of food for consumers. However, the presence of precautionary allergen labeling (PAL) has resulted in confusion amongst many con- sumers as to its significance. METHODS: Food Allergy Research and Education (FARE) and Food Allergy Canada launched a survey on consumer food purchasing behavior in response to different food allergen labels in the US and Canada. Participants included those with food allergies and their caregivers who purchased their food. Data for 6,684 participants were analyzed. Associations between respondents’ country of origin, severity of previous reactions, and purchasing behaviors were analyzed using multiple logistic regression models. RESULTS: The top 6 allergens in the US and Canada in order were peanut, tree nuts, egg, milk, shellfish and soy. Buying practices varied based on phrasing that was used on advisory labels. Overall, 11% of respondents purchased foods stating ‘‘may contain allergen’’ and 40% purchased foods stating ‘‘manufactured in a facility that also processes allergen’’. While 29% of respondents were unaware that the law requires labeling of major allergens, 46% were either unsure or incorrectly believed All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. AB82 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2016

Characterizing Pediatricians' Management of Food mepolizumab was ranked first for treatment effect were (1) 91.6% and (2) 270 Allergy to Improve Care Coordination 99.6%; the corresponding probabilities for omalizumab were (1) 8.4% and (2) 0.4%. Alana Otto, MD1, Ashley Dyer, MPH2,3, Bridget Smith, PhD3,4, Ruchi CONCLUSIONS: An indirect comparison versus omalizumab Gupta, MD, MPH3,5; 1Ann & Robert H. Lurie Children’s Hospital of found trends in favor of mepolizumab in reducing the rate of clinically Chicago, 2Ann and Robert H. Lurie Children’s Hospital, Chicago, 3North- significant exacerbation among treatment-eligible severe asthma patients. western University Feinberg School of Medicine, Chicago, IL, 4Edward J. Funding: GSK (HO-13-9058). Hines Jr. VA Hospital, Chicago, IL, 5Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL. Multiple Selective Responders Should Not be RATIONALE: Pediatricians are often first-line providers for children 272 Confounded with Cross-Intolerance to Nsaids with food allergy. The role of the pediatrician in the diagnosis and 1 2 management of food allergy has not been well defined. We therefore sought Natalia Blanca-Lopez, MD, PhD , Diana Perez-Alzate, MD , ~ 3 4 to characterize pediatricians’ adherence to published best practice Inmaculada Dona, MD, PhD , Maria Luisa Somoza, MD , Cristobalina Mayorga, PhD5, Marıa Jose Torres, MD, PhD6, Jose A. Cornejo- guidelines for the diagnosis and management of childhood food allergy. 7 8 4 METHODS: Medical records of children ages 0-18 years were obtained Garcia, PhD , Miguel Blanca, MD, PhD , Gabriela Canto, MD, PhD ; 1Allergy Service, Infanta Leonor Hospital, Madrid, Spain, 2Allergy Ser- from three urban primary care pediatric practices. Patients were included if 3 SATURDAY they had an encounter between January 2012 and January 2015 containing vice, University Hospital Infanta Leonor, Madrid, Spain, Allergy Unit, IBIMA, Regional University Hospital of Malaga, UMA, Malaga, Spain, an ICD-9-CM code for an initial food allergy diagnosis. Records were 4 analyzed to describe provider adherence to NIAID guidelines, including Allergy Unit. Infanta Leonor University Hospital, Madrid, Spain, 5Research Laboratory, IBIMA-Regional University Hospital of Malaga- documentation of clinical reaction history; diagnostic testing; prescription 6 of injectable epinephrine; caregiver counseling and/or education; and UMA, Malaga, Spain, Allergy Unit, IBIMA-Regional University Hospi- tal of Malaga, Malaga, Spain, 7Research Laboratory, IBIMA, Regional referral to an allergist. 8 RESULTS: Patients (n 5 123) had a mean age of 4 years and were most University Hospital of Malaga, UMA, Malaga, Spain, Allergy Unit, commonly allergic to egg (22%) and tree nut (17%). Clinical reaction his- IBIMA, Regional University Hospital of Malaga, UMA, Malaga, Spain. tory was documented in 99% of encounters. Allergen-specific IgE was or- RATIONALE: Hypersensitivity reactions to NSAIDs can be classified as dered for 24% of patients. Epinephrine prescription was documented for cross-intolerance where vasoactive mediators are released by nonspecific 67% of patients. Emergency action plans were documented in 24% of en- immunological mechanisms, and selective responders mediated by IgE counters, caregiver counseling in 70%, and referral to an allergist in 68%. antibodies or T cells. Those responding to several no chemically-related CONCLUSIONS: Adherence to best practice guidelines varied between NSAIDs are considered cross-intolerants. The existence of responders to specific recommendations. Improving partnerships and role delineation several NSAIDs with good tolerance to ASA was studied. between allergists and pediatricians is critical to improve coordination of METHODS: We searched in the dabase of the National Spanish Network care. for the Study of Adverse Reactions to Drugs and Allergens the possible existence of cases with immediate reactions to different NSAIDs and good Comparative Effectiveness of Mepolizumab and tolerance to ASA confirmed by drug provocation tests (DPT). In these the 271 Omalizumab in Severe Asthma: An Indirect selective response to the culprit NSAIDs was confirmed. Comparison RESULTS: We found 20 cases that acomplished these criteria. The higher number of episodes occurred with a pyrazolone derivative (dipyrone) Gillian Stynes1, Sarah Cockle1, Necdet Gunsoy, PhD2, Daniel C. Park3, followed by ibuprofen and other arylpropionic acid derivatives (ketoprofen Jaro Wex4, Jenny Wilson1, Eric Bradford, MD5, Frank C. Albers, MD, and naproxen), diclofenac, paracetamol and COX-2 inhibitors. A total of PhD6, Rafael Alfonso-Cristancho, MD, PhD, MSc3; 1GlaxoSmith Kline, 60 episodes were reported, being 3 NSAIDs involved in 15 cases, and more Value Evidence and Outcomes, Stockley Park, United Kingdom, 2Glaxo- than 3 drugs in 5 patients. Smith Kline, Clinical Statistics, Stockley Park, United Kingdom, 3Glax- CONCLUSIONS: Subjects with reactions to different NSAIDs but good oSmithKline, Value Evidence Analytics, Philadelphia, PA, tolerance to ASA exist. In patients with multiple responses to NSAIDs if 4Pharmarchitecture, London, United Kingdom, 5GlaxoSmithKline, Respi- tolerance to ASA is not known it should be assessed before being ratory R&D, Research Triangle Park, NC, 6GlaxoSmithKline, Respiratory considered as cross-intolerants. This study adds a new phenotype to Medical Franchise, Research Triangle Park, NC. hypersensitivity reactions to NSAIDs. Further studies are in progress to RATIONALE: Mepolizumab, a novel anti-IL5 monoclonal Antibody determine how many cases with NSAIDs hypersensitivity belong to these (mAb), and omalizumab, an anti-IgE mAb, target different phenotypes of category. severe asthma. Some patients will be eligible for both treatments. No head- to-head comparison exists. This study assessed the comparative effective- ness of mepolizumab (100mg fixed-dose subcutaneous injection) and omalizumab (licensed dose range per IgE level/weight), in addition to standard of care, in severe asthma via an indirect comparison. METHODS: A systematic literature review and Bayesian network meta- analysis were performed (GSK ID 200227/H0-13-9058). Included studies were double-blind randomized controlled clinical trials (RCTs) >_12 weeks’ in duration among severe asthma patients >_12 years old, with a documented exacerbation history and receiving high-dose inhaled corti- costeroids plus >_1 additional controller. Two populations were examined: subjects potentially eligible for (1) both mAbs (2) either mAb. RESULTS: (1) 561 and (2) 1,652 subjects were included. Both treatments reduced the rate of clinically significant exacerbations versus placebo. Further, mepolizumab was associated with a reduction in clinically significant exacerbations versus omalizumab, in both populations: (1) Rate ratio [RR]: 0.66; 95% Credible Interval [CrI]: 0.37, 1.19; (2) RR: 0.63; 95% CrI: 0.45, 0.89. The probabilities in each population that All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. J ALLERGY CLIN IMMUNOL Abstracts AB83 VOLUME 137, NUMBER 2

Epidemiology of Clinical Oral Food Challenges 55% (n544) underwent skin prick or serum specific IgE testing for the fruit 273 (OFC) at Baylor College of Medicine/Texas and/or nut with positive results in 66% (n529) of these patients. Children's Hospital (TCH) Food Allergy Program: CONCLUSIONS: This data suggests that in patients with seasonal A Retrospective Chart Review allergies, fruit and nut allergy is more common than in those without seasonal allergies. In those with oral symptoms who underwent testing, the Kwei Akuete, MD, MPH1, Danielle Guffey, MS2, Charles G. majority (66%) had evidence of an IgE mediated sensitivity. It remains to Minard, PhD2, Maria G. Buheis, MD1, Kristin H. Dillard, MD3, be determined if these patients have isolated OAS or are at risk for I. Celine Hanson, MD, FAAAAI1, Lenora M. Noroski, MD, MPH3, Filiz anaphylaxis. O. Seeborg, MD, MPH3, Carla M. Davis, MD1; 1Baylor College of Med- icine and Texas Children’s Hospital, Department of Pediatrics Section of The Use of an Interdisciplinary Team to Treat Immunology, Allergy and Rheumatology, Houston, TX, 2Dan L. Duncan 275 Eosinophilic Esophagitis (EoE) in a Pediatric Institute for Clinical and Translational Research, Baylor College of Med- Patient 3 icine, Houston, TX, Baylor College of Medicine and Texas Children’s 1 1 2 Hospital, Department of Pediatrics, Section of Immunology, Allergy Katie Kemp, RN , Emily Weis, MD , Brianne Schmidt, RD , Kimberly Brown, PhD2; 1Allergy Asthma Immunology of Rochester, Rochester, and Rheumatology, Houston, TX. 2 RATIONALE: Currently, little is known regarding the use of OFCs in NY, University of Rochester. clinical practice settings. Data from the TCH-Allergy/Immunology clinic RATIONALE: Eosinophilic Esophagitis (EoE) is an allergic inflamma- over 6 years is reported to understand the use of OFCs in clinical practice. tory condition of the esophagus, recently becoming more widely known. METHODS: OFC data was collected from 2008 through 2013 using the An interdisciplinary approach to treatment can improve outcomes for these electronic medical record system. Descriptive statistics were used to assess patients. Here we present a case where this approach was used to treat a patient demographics and clinical characteristics. The food challenged, pediatric patient with EoE who was found to have multiple food allergies, specific IgE(sIgE), total IgE, and outcome comparisons between years gastrointestinal (GI) disease, failure to thrive, feeding disorder and anxiety. were tested using Chi-square test, Fisher’s exact test, or Kruskal-Wallis METHODS: An interdisciplinary approach to treatment of EoE in a test. pediatric patient. RESULTS: A total of 258 OFCs were performed in a clinical, non- RESULTS: 10 year old female presented with frequent abdominal pain, research setting from 2008 through 2013. The number of challenges varied poor weight gain, and reported history of multiple food allergies. A by year, with 69% performed in 2011-2013(p50.002). Specifically, the pathological diagnosis of EoE was made and treatment with swallowed percentage of baked food challenges increased over time from 3%(2008) to glucocorticoids was initiated. Initial improvement was seen on follow up 25%(2013)(p50.006). FPIES varied by year with the highest percentage of histology. However, symptomatically she worsened and experienced a challenges noted in 2010(N59/34;p50.002). Patient total IgE and sIgE decline in growth and nutritional status. Allergy work up revealed multiple values significantly varied over time (p50.011 and p50.001, respectively) food allergies that may have been contributing to the worsening EoE and GI symptoms. Achieving dietary compliance was difficult due to the with the highest median values occurring in 2011. The OFC passage rate SATURDAY did not vary significantly over time (p50.43). Overall, 84%(N5213/258) number of foods being eliminated (allergy and empirical elimination), passed the food challenge. presence of pediatric feeding disorder, anxiety, and other psychosocial CONCLUSIONS: Our data shows that the number of patients undergoing stressors. Extensive patient and family education, personalized nutritional OFCs has increased in this center with 84% of patients passing. The counseling and frequent follow up with all disciplines was needed as increase in the proportion of baked food challenges highlights a trend of treatment was implemented. physicians to introduce baked milk and egg into the diet of milk/egg CONCLUSIONS: Close collaboration of the interdisciplinary team was allergic patients. This observation coupled with the high pass rate of OFCs instrumental in providing support to the patient and family that ultimately indicates it is safe to perform OFCs in a clinical setting with positive sIgE facilitated improvement in symptoms including weight and nutrition while and total IgE values. decreasing abdominal symptoms and anxiety.

Seasonal Allergies, How They Relate to Oral 274 Allergy Syndrome (OAS)?

Nicolle Cascone, RN, Tara Shankar, MD, Andrej A. Petrov, MD, Merritt L. Fajt, MD; University of Pittsburgh Medical Center, Division of Pulmo- nary, Allergy and Critical Care Medicine, Pittsburgh, PA. RATIONALE: Patients with seasonal allergies are more likely to have oral allergy syndrome (OAS) resulting from cross-reactivity between protein in pollens and those in some fruits and nuts. METHODS: We conducted a retrospective chart review of 222 adult patients seen in an Adult University Allergy clinic from June 15, 2004 through June 15, 2014 with self-reported food allergies. RESULTS: In 222 patients seen for food allergies, 81% (179) had environmental allergies. Fruit allergy was reported in 37% (n582 patients), tree nut allergy in 36% (n579), and peanut in 25% (n555). Patients with seasonal allergies had an increased frequency of reported fruit allergy and tended to have an increased frequency of tree nut allergy vs. patients without seasonal allergies (41% vs. 21%, p50.015 and 39% vs. 23%, p50.06, respectively) but no difference in peanut allergy frequency (p50.36). In the 179 seasonal allergy patients, OAS symptoms were reported in 45% (n580). In these OAS patients, 74% reported fruit allergy, 45% tree nut allergy and 20% peanut allergy. In these 80 OAS patients, All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. AB84 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2016

Pooled Analysis of Patient Treatment Satisfaction F test with stepwise regression was used to evaluate the significance of OAP 276 from Five Hizentra Studies levels on day of ED visit and mean exposure over the previous week. RESULTS: 67,898 visits were included (mean + SD age of 40.3 + 25.2 Mikhail Rojavin, PhD1, Hirokazu Kanegane, MD, PhD2, Michael Borte3, years, 25.6% African American, 59.6% female). There was a direct Kohsuke Imai, MD, PhD4, Alphonse P. Hubsch5, Helena Soop5, Stephen association between levels of nitrogen dioxide (p<0.001) levels on both R. Jolles, MD, PhD6; 1CSL Behring, King of Prussia, PA, 2Department of day of and week prior to ED visit for acute exacerbations of respiratory Pediatrics and Developmental Biology, Graduate School of Medical and diseases. There was no significant association between ozone, PM2.5, car- Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan, bon monoxide, sulfur dioxide or lead and ED visits. 3Hospital St. Georg GmbH Leipzig, Academic Teaching Hospital of the CONCLUSIONS: Elevations of nitrogen dioxide were retrospectively University of Leipzig, Leipzig, Germany, 4Department of Community Pe- associated with ED visits for acute exacerbations of respiratory diseases. diatrics, Perinatal and Maternal Medicine, Tokyo Medical and Dental Uni- Future efforts need to disseminate these results to local public health versity, Tokyo, Japan, 5CSL Behring AG, Berne, Switzerland, 6University officials and ultimately improve health outcomes. Hospital of Wales, Cardiff, United Kingdom. RATIONALE: To investigate patient treatment satisfaction (TS) and Patient Use Online Resources and Social Media health-related quality of life (HRQoL) in Caucasian and Japanese patients 278 for Food Allergy Information

with primary immunodeficiency (PID) upon switching from intravenous 1 2 SATURDAY Beth D. Strong, RN, CCRC , Jaime Ross, RN, MSN , Jennifer (IVIG) or subcutaneous immunoglobulins (SCIG) to 20% SCIG 3 4 5 (HizentraÒ), and during long-term HizentraÒtreatment. Fishman, RN, BSN , Sally A. Noone, RN, MSN , Zara Atal , Carly Ehritz, RN, MSN5, Jessica Gau, NP, CRC6, Julie Wang, MD, FAAAAI2; METHODS: Pooled analyses were based on five Phase III studies of 1 2 HizentraÒ(two pivotal; three extension/follow-up) conducted in the EU, Icahn School of medicine at Mount Sinia, New York, NY, The Icahn School of Medicine at Mount Sinai, New York, NY, 3Ichan School of Japan, and the US. Life Quality Index (LQI) and Short Form 36, version 4 2 (SF36v2) questionnaires were used to assess TS and HRQoL, respec- Medicine at Mount Sinai, New York, NY, Icahn School of Medicine at Mount Sinai, New York, NY, 5Icahn School of Medicine at Mt. Sinai, tively, at baseline and every 6–24 weeks thereafter (or at baseline and 60 6 weeks for TS in the US extension study). Mt. Sinai School Medicine, New York, NY. RESULTS: EU and Japanese pivotal studies demonstrated significant RATIONALE: Families of food allergic children seek information is a improvements in mean LQI score by sum of all questions (from 4.87 at variety of ways. Use of online resources is a popular way of gathering baseline to 5.70 at Week 40; p <0.001), largely driven by patients switching information. This survey was done to examine the usage of online from previous IVIG therapy. Extension studies, where patients continued resources and social media in this population. steady-state HizentraÒ dosing for up to 3 years, showed no relevant mean METHODS: An anonymous online Qualtrics survey was emailed to our LQI score changes from extension baseline to study end by sum of all ques- Food Allergy Institute email list. tions (5.75 vs. 5.87; p50.26) or by individual questions. Median SF36v2 RESULTS: There were 276 responses; of those, 90% use online resources scores did not change upon switching to HizentraÒin the EU pivotal study, or social media to obtain information on food allergy. 76% found their possibly reflecting low sensitivity of the instrument. Long-term extension resources through a web search, and the rest through a physician, family/ HRQoL studies provided limited conclusions due to the small number of friend or other support groups. The majority of people (90%) found the patients. resources somewhat to very helpful. Of those that use online resources or CONCLUSIONS: Patient TS in Caucasian and Japanese patients with social media, 47% use it monthly and weekly. Most people (80%) are using PID significantly improves upon switching from previous IVIG treatment it for food allergy management and 85% report following the advice they to HizentraÒ and is maintained for up to 3 years under clinical study find online. The majority (74%) found the online advice matched the conditions. advice their physician provided and 71% primarily followed their physician’s advice. Association Between Outdoor Air Pollution and CONCLUSIONS: The majority of families of food allergic children are 277 Acute Exacerbations of Respiratory Diseases in using online resources and social media for information. With better Pittsburgh understanding of how families are using online resources for food allergy management, we can better provide guidance to our patients and their Nicole Pleskovic, BS1, Arvind Venkat, MD2, Albert Presto, PhD3, families. Gajanan Hedge, PhD4, Jennifer Shang, PhD4, Sunde Kekre4, Paige E. Dewhirst, MPH1, Deborah A. Gentile, MD5; 1Allegheny Singer Research Institute, Pittsburgh, PA, 2Allegheny Health Network, 3Carnegie Mellon Univesity, 4University of Pittsburgh, 5Allegheny Health Network, Pitts- burgh, PA. RATIONALE: Pittsburgh lags behind other major cities in improving outdoor air quality. Contributing factors include the perception that Pittsburgh air is cleaner than in past decades and lack of public awareness that regional levels of outdoor air pollution (OAP) are associated with adverse health effects. The purpose of this study was to evaluate the association between OAP and acute exacerbations of respiratory diseases in the Pittsburgh region. METHODS: This study was approved by the Allegheny Singer Research Institute-Allegheny Health Network Institutional Review Board. Retrospective analysis of emergency department (ED) visits to the health- care system was conducted from 07/01/2008 to 06/30/2013 to identify primary discharge diagnoses for acute exacerbations of respiratory diseases. Corresponding EPA air quality index (AQI) data was downloaded. All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. J ALLERGY CLIN IMMUNOL Abstracts AB85 VOLUME 137, NUMBER 2

Food Allergy Education Session Improves Nurses' intermittent oral symptoms, one 3000mg/day with a reaction with hives/ 279 Knowledge, Confidence, and Attitudes Towards shortness of breath, and one 9000mg/day with intermittent pruritus/ Managing Food Allergic Children in a School throat/chest tightness. All 4 who passed the SU-OFC continued PI: one Environment 1500-3000mg/week with intermittent oral symptoms, one 1800-2100mg/ day with intermittent oral symptoms and a reaction requiring epinephrine Zara Atal1, Kathleen Patrick, RN2, Julie Wang, MD, FAAAAI3; 1Icahn for syncope/vomiting/chest-tightness/hives, and two (2000mg/week and School of Medicine at Mt. Sinai, Haidi Demain, Founder and Medical Di- 4800mg/week) with no symptoms. rector of Allergy Safe Kids, Inc., Denver, CO, 2Assistant Director of CONCLUSIONS: Of the original 21 subjects, eleven were still ingesting Health & Wellness, Colorado Department of Education, Denver, CO, peanut after 27 months. However, two of the eleven experienced reactions 3Icahn School of Medicine at Mount Sinai, New York, NY. requiring epinephrine and nine reported at least intermittent symptoms, RATIONALE: Children with food allergies spend much of their time in underscoring the need for additional long term follow-up studies. the school setting; therefore, trained school staff are needed to ensure the safety of these children. The primary goal of this study was to assess the Improving Asthma Outcomes through Systems effectiveness of a food allergy education session to improve Colorado 281 Change: The Breathe Initiative school nurses’ knowledge, confidence and attitudes regarding management Claudia Guglielmo, MPA, AE-C1, Anne M. Little, MPH, AE-C2, Hadi of food allergic children in the school environment. 3 4 1 METHODS: An anonymous questionnaire was distributed to attendees Jabbar, MD, FAAP , Mary E. Cataletto, MD, FAAP ; Asthma Coalition 5 of Queens/American Lung Association of the Northeast, Hauppauge, NY, (n 261) at the Colorado school nurse training sessions in Spring of 2015. 2 The live training sessions were led by a physician and nurse who used a Asthma Coalition of Long Island/American Lung Association of the Northeast, Hauppauge, NY, 3Asthma Coalition of Queens, Hauppauge, training module developed by Allergyhome.org as part of the educational 4 session. NY, Asthma Coalition of Long Island, Brookville, NY. RESULTS: 124 (47.5%) completed pre- and post-surveys were used for RATIONALE: Despite advances in diagnostics and pharmacotherapy to analysis. From baseline to post-training, the median knowledge score improve asthma care, adherence to evidence- based guidelines (EPR-3, increased from 76.92% (SD513.72) to 88.46% (SD58.776; p<.0001). GINA) remains suboptimal. Both patient and provider issues contribute to Improvements in knowledge primarily occurred in the areas of how to poor adherence. Community-based asthma coalitions can facilitate a clean hands (23.39% vs 59.68% correct) and surfaces (59.68% vs 70.16% community of practice where multidisciplinary team practice can improve correct), when to report a reaction to the Department of Education (56.45% outcomes. vs 87.10% correct), and when to take someone to the hospital by METHODS: Community needs assessments were performed utilizing ambulance (79.03% vs 86.29% correct). The median confidence score SPARCS data from Long Island’s Nassau, Suffolk and Queens Counties. increased from 25 (SD53.021) to 27 (SD52.996; p<.0001) out of a total of Our asthma coalitions brought together stakeholders from key institutions 30. The median attitude score increased from 28 (SD53.495) to 31 offering inpatient care for children with asthma. Based on zip codes hospitals that served catchment areas with high asthma hospitalization (SD53.310, p<.0001) out of a total of 35. SATURDAY CONCLUSIONS: These training sessions significantly improved nurses’ rates for children 0-17 were selected. knowledge, as well as increased their confidence and attitudes towards In each institution a common but unique guidelines-based infrastructure proper food allergy management practices in the school setting. was developed, focusing on outcomes improvement through education. Multidisciplinary teams were established and trained utilizing Physician Long-Term Follow up after Peanut Immunotherapy Asthma Care Education (PACE). Checklists were developed to ensure 280 patient and family education and skills training during hospitalizations with follow up through pediatric and subspecialty referrals, home care Kim Mudd, RN, MSN, CCRP1, Shannon Seopaul, MPH2, Satya visits and school re-entry to close the loop. Narisety, MD3, Corinne Keet, MD, PhD4, Robert A. Wood, MD, RESULTS: To date multidisciplinary teams and over 1500 children with FAAAAI5; 1Department of Pediatrics, Johns Hopkins University School asthma and their families have participated in BREATHE within five urban of Medicine, Baltimore, MD, 2Johns Hopkins University School of Med- and suburban hospital centers. Results from a recent sample of 170 patients icine, Baltimore, MD, 3Rutgers University, New Jersey Medical School, from a single center showed a significant reduction in asthma readmis- Newark, NJ, 4Division of Pediatric Allergy/Immunology, Johns Hopkins sions: 283 admissions one year prior to BREATHE enrollment, 40 School of Medicine, Baltimore, MD, 5Department of Pediatrics, Johns readmissions one year post; p < .0001, using the Wilcoxon signed rank test. Hopkins University School of Medicine, Baltimore, Maryland, USA. CONCLUSIONS: BREATHE (Bringing Resources for Effective Asthma RATIONALE: Little is known about long-term outcomes following Treatment though Health Education) is a successful quality improvement peanut immunotherapy. initiative that has a substantial and sustainable reduction in asthma METHODS: Peanut allergic children (7-13years) participated in a readmission rates. randomized peanut immunotherapy trial. Subjects who completed >_12 months of maintenance underwent a desensitization food challenge (d-OFC), and those passing the d-OFC stopped treatment for 4 weeks with re-challenge to determine sustained unresponsiveness (SU-OFC). Follow-up occurred at 9-month intervals over 27-28 months to assess peanut ingestion (PI) and adverse reactions. RESULTS: 14/21 subjects completed maintenance. 4/14 failed the d-OFC but continued with individually prescribed PI. Of these 4, one returned to avoidance due to aversion/intermittent oral symptoms; three continued PI: one 300-500mg/day with intermittent oral symptoms and a reaction requiring epinephrine, one 300-900mg/day with intermittent oral symp- toms, and another 3900mg/day with intermittent coughing. 6/10 subjects failed the SU-OFC but continued PI. Two returned to avoidance, one with severe anxiety and one after a reaction requiring epinephrine. Four continued PI: one 1400mg/day with intermittent wheezing/pruritus and a reaction with wheezing/hives/abdominal pain, one 3000mg/day with All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. AB86 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2016

Suppression of Lipid Mediators By the Humanized were pooled and change from baseline in the annual frequency of CAE at 282 Anti-IgE Antibody Omalizumab in Aspirin- week 52 for CSwNP was analyzed. Exacerbated Respiratory Disease RESULTS: Of 953 patients randomized, 150 (16%) had CSwNP and 252 (26%) had CS. Patients with CSwNP receiving reslizumab (n578) had an Hiroaki Hayashi, MD1,2, Chihiro Mitsui, MD1, Yuma Fukutomi, MD, 83% reduction in the annual rate of CAE versus placebo (RR 0.17 [95% CI: PhD1, Keiichi Kajiwara, BSc1, Kentaro Watai, MD1, Arisa 0.10, 0.32]; p50.0002). Similarly, patients identified as having CS only Kinoshita, MD1, Yosuke Kamide, MD, PhD1, Kiyoshi Sekiya, MD1, Taka- who received reslizumab (n5123) had a 70% reduction in the annual rate hiro Tsuburai, MD, PhD1, Akio Mori, MD, PhD1, Kazuo Akiyama, MD1, of CAE versus placebo (RR 0.30 [95% CI: 0.20, 0.44]; p50.0103). Both 2 1 1 Yoshinori Hasegawa, MD, PhD , Masami Taniguchi, MD, PhD ; Clinical groups also had substantial improvements in FEV1 over 52 weeks. Research Center for Allergy and Rheumatology, Sagamihara National CONCLUSIONS: Patients with inadequately controlled asthma and CS Hospital, Sagamihara, Japan, 2Department of Respiratory Medicine, Na- with or without NP received significant therapeutic benefit with reslizu- goya University Graduate School of Medicine, Nagoya, Japan. mab, providing further support for the use of reslizumab in asthma patients RATIONALE: Research suggests that omalizumab is a potential treat- with eosinophil-mediated disease. ment for severe allergic asthma. Aspirin-exacerbated respiratory disease _ (AERD) causes serious eosinophilic airway inflammation and mast cell Efficacy of Reslizumab in Older Patients (>65 activation. Compared with other types of severe asthma, omalizumab may 284 years) with Asthma and Elevated Blood SATURDAY have distinct therapeutic properties in AERD. This study investigated the Eosinophils: Results from a Pooled Analysis of efficacy of omalizumab for AERD, including changes in mast cell Two Phase 3, Placebo-Controlled Trials

activation, urinary leukotriene E4 (LTE4) and prostaglandin D2 metabolite 1 2 a b David I. Bernstein, MD, FAAAAI , Lyndon Mansfield , James Zan- 9 ,11 -prostaglandin F2 (PGD2M). 3 3 1 5 grilli , Margaret Garin ; University of Cincinnati College of Medicine, METHODS: Japanese adults (n 21) with AERD were enrolled at 2 3 Sagamihara National Hospital between July 2009 and September 2013. All Cincinnati, OH, Western Sky Medical Research, TX, Teva Pharmaceuti- patients had received their usual asthma treatment for at least 12 months, cals, PA. and none of the patients had previously received omalizumab. The RATIONALE: Reslizumab was recently shown to improve multiple following parameters were measured at baseline and after 12 months of measures of asthma control in patients aged 12-75 years with inadequately _ m omalizumab treatment: urinary LTE and PGD M concentrations; controlled asthma and blood eosinophils >400cells/ L (Castro et al., 4 2 _ peripheral blood eosinophil count; respiratory function; and nasal and Lancet Resp Med. 2015). The influence of older age (>65 years) on asthma-related symptom scores. The number of asthma exacerbations reslizumab efficacy is unknown. and hospitalizations, and daily systemic corticosteroid doses were also METHODS: Pooled results from two duplicate, 52-week, placebo- evaluated. controlled studies of reslizumab (3mg/kg IV Q4W) for asthma were _ RESULTS: Omalizumab significantly diminished median urinary con- stratified by age: 18-64 years (‘younger adults’) and >65 years. Efficacy assessments included: rate of clinical asthma exacerbations (CAE) and centrations (pg/mg of creatinine) of both LTE4 (703.2 [IQR: 234.9-2245.4] versus 167.7 [IQR: 72.3-296.5], reduction rate 76.2%; p50.001) and change from baseline in FEV1, ACQ-7 and AQLQ. _ PGD M (55.5 [IQR: 14.8-96.5] versus 6.1 [IQR: 4.3-13.6], reduction RESULTS: 77 patients were >65 and 851 patients were 18-64 years old. 2 _ rate 89.0%; p50.002). Nasal and asthma-related symptom scores, the The reduction in CAE frequency for patients >65 years was 67% (95% number of exacerbations and hospitalizations, and daily corticosteroid CI:29%, 85%) versus 53% in younger adults (95% CI:40%, 64%). The doses were also substantially reduced after omalizumab treatment. mean change in FEV1, ACQ-7 and AQLQ for reslizumab relative to pla- _ CONCLUSIONS: Omalizumab was an effective treatment in AERD cebo at 52 weeks in patients >65 and in younger adults was: 150mL patients with severe asthmatic and nasal symptoms, and reduced mast cell (95% CI:17, 283) and 126mL (95% CI:67, 184); -0.997 (95% CI:-1.447, activation and leukotriene overproduction. -0.547) and -0.305 (95% CI:-0.438, -0.173); and 0.876 (95% CI:0.417, 1.336) and 0.316 (95% CI:0.169, 0.462), respectively. Efficacy of Reslizumab with Asthma, Chronic CONCLUSIONS: Reslizumab was effective at reducing the frequency of 283 Sinusitis with Nasal Polyps and Elevated Blood asthma exacerbations, and in improving lung function, asthma control and Eosinophils quality of life in patients >_65 years old. The observed improvements in this subgroup were numerically larger than for younger adults, with changes in Steven F. Weinstein, MD, FAAAAI1, Matthew Germinaro2, Philip ACQ-7 and AQLQ both exceeding the minimally important difference for the Bardin3, Stephanie Korn4, Eric Donn Bateman, MD5; 1Allergy and measure. Asthma Specialists Medical Group and Research Center, CA, 2Teva Phar- maceuticals, PA, 3Monash University and Medical Centre, 4University Medical Center, Johannes Gutenberg University of Mainz, Germany, 5University of Cape Town, South Africa. RATIONALE: Nasal polyps (NP) are frequently linked to chronic sinusitis (CS) and asthma, conditions often associated with elevated eosinophils. Reslizumab was shown to improve asthma control in patients with NP (Castro et al., AJRCCM, 2011). The aim of this evaluation was to determine the effect of reslizumab on clinical asthma exacerbations (CAE) for patients with inadequately controlled asthma and CS with NP (CSwNP). METHODS: The methodology and primary results of studies 3082 and 3083 (NCT01287039/NCT01285323) have been reported (Castro et al., Lancet Resp Med. 2015). Patients with asthma and elevated blood eosinophils (>_400cells/mL) who remained inadequately controlled on at least medium-dose ICS were randomized to placebo or reslizumab (3mg/ kg [IV] Q4W) for 52 weeks. In the current analysis, results from 3082/3083 All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. J ALLERGY CLIN IMMUNOL Abstracts AB87 VOLUME 137, NUMBER 2

Exploratory Analysis of the Roles of Multiple hypothesized that omalizumab treatment would decrease weeks with 285 Biomarkers in Predicting Response to symptomatic upper respiratory illnesses. Omalizumab in Allergic Asthma METHODS: The Preventative Omalizumab or Step-up Therapy for Severe Fall Exacerbations (PROSE) study was a randomized trial of William W. Busse, MD, FAAAAI1, Karin Rosen, MD, PhD2, Volkan guidelines-based asthma care vs. add-on fluticasone boost vs. add-on Manga, MD3, Benjamin Trzaskoma, MS2, Theodore A. Omachi, MD, omalizumab in 478 asthmatic children (6-17 years) from low-income MBA2; 1University of Wisconsin School of Medicine and Public Health, census tracts. Cold symptom scoring sheets were collected weekly over the Madison, WI, 2Genentech, Inc., South San Francisco, CA, 3Novartis. 4-month treatment period during the fall seasons of 2012 or 2013. Colds RATIONALE: Biomarkers of Type-2 (Th2-high) inflammation, such as were identified as increased symptoms (runny nose, stuffy nose, sneezing, fractional exhaled nitric oxide (FeNO) and peripheral blood eosinophils cough, sore throat) compared to baseline. Adjusted illness rates (colds per (EOS), appear to predict response to biologic treatments in patients with sample) by treatment arm were calculated using an over-dispersed Poisson severe asthma. However, the relative value of assessing multiple bio- regression. markers simultaneously in predicting response to biologics in allergic RESULTS: In total, 5873 cold assessments were completed and 1034 asthma has not been established. (18%) symptomatic illnesses were detected. Rates of colds (per sample) METHODS: Predictive properties of FeNO, within high and low EOS were significantly reduced (p50.01) in participants treated with add-on subgroups, were evaluated in patients with severe allergic asthma in this omalizumab (0.15, n5259) compared to guidelines-based asthma care post-hoc analysis of the 48-week EXTRA study of omalizumab (Hanania alone (0.20, n5 89), a decrease of 27%. Interestingly, this reduction was et al, 2011). Patients were divided into predefined subgroups based on seen across asthma treatment steps, with the same rate of reduction cohort median levels of FeNO (low [<19.5 ppb] or high [>_19.5 ppb]) and observed in children with moderate vs. severe persistent asthma. EOS (low [<260/mL] or high [>_260/mL]). Treatment effect was evaluated Fluticasone boost had no significant effect on cold rates (0.17, n5130). as the number of observed protocol-defined exacerbations, controlling for CONCLUSIONS: Omalizumab significantly decreases rates of cold pre-specified protocol-defined covariates. symptoms in children with allergic asthma. These findings indicate that RESULTS: Patients with higher FeNO and treated with omalizumab IgE contributes to the frequency and/or duration of upper respiratory demonstrated clinically relevant mean reductions in exacerbation fre- illnesses in this population. quency vs placebo whether or not their EOS were high (53.1% [95%CI: 18.7%, 72.9%]; n5120; p50.007) or low (51.0% [95%CI: 22.8%, Nasal Influenza Immunisation with LAIV (FluMist) 76.7%]; n568; p50.059). Among patients with lower FeNO, exacerbation 287 Is Safe in Egg-Allergic Children with Asthma or reduction response to omalizumab appeared less pronounced (7.1% [95% Recurrent Wheeze: Data from the Sniffle-2 Study 2 5 5 CI: 102%, 57.4%]; n 70; p 0.85) among EOS high and (18.0% [95% 1,2 3 2 5 5 Paul J. Turner, FRACP, PhD , Jo Southern, PhD, MFPH , Nick CI: 44.9%, 53.6%]; n 108; p 0.50) among EOS low. 3 3 CONCLUSIONS: These findings suggest that multiple biomarkers of T2 Andrews, PhD , Elizabeth Miller, FRCPath , Michel Erlewyn-Lajeunesse, FRCPCH, DM4; 1Section of Paediatrics, Imperial College London, United may be important in optimally stratifying patients according to possible SATURDAY Kingdom, 2Imperial College London, United Kingdom, 3Public Health biologic treatment responses. Caution must be used in interpretation of 4 results, given their post-hoc nature and the availability of both FeNO and England, United Kingdom, University Hospital Southampton NHS Foun- EOS data in only a single omalizumab clinical trial. dation Trust, Southampton, United Kingdom. RATIONALE: Live Attenuated Influenza Vaccine (LAIV; FluMistÒ; Omalizumab Decreases Rates of Cold Symptoms in FluenzÒ) is an intranasal vaccine widely available in USA and recently 286 Inner-City Children with Allergic Asthma incorporated into the UK National Immunization Schedule. However, CDC guidelines recommend against its use in children under 5yrs with a Ann T. Esquivel, MD1, William W. Busse, MD, FAAAAI2, Agustin history of asthma or recurrent wheezing. We sought to assess the safety of Calatroni, MA, MS3, Peter J. Gergen, MD, MPH4, Kristine Grindle5, Re- LAIV in egg-allergic children with asthma or recurrent wheeze. becca S. Gruchalla, MD, PhD, FAAAAI6, Meyer Kattan, MD7, Carolyn METHODS: Multi-centre phase IV study in egg-allergic children with a Kercsmar, MD8, Gurjit K. Khurana Hershey, MD, PhD, FAAAAI9, Haejin physician-diagnosis of asthma or recurrent wheeze, in whom symptoms Kim, MD10, Petra Lebeau11, Andrew H. Liu, MD, FAAAAI12, Stanley J. were well-controlled. LAIV was administered under medical supervision Szefler, MD, FAAAAI13, Stephen J. Teach, MD14, Jacqueline A. in hospital. Respiratory symptoms were monitored pre- and post-LAIV Pongracic, MD, FAAAAI15, Joseph B. West, MD16, Jeremy Wildfire17, through a validated questionnaire (Asthma Control Test, ACT). Local James E. Gern, MD, FAAAAI18; 1University of Wisconsin, Madison, ethical and regulatory approval was granted, and informed consent was 2University of Wisconsin, Madison, WI, 3Rho Federal Systems Division obtained. Inc., Chapel Hill, NC, 4AAIB/DAIT/NIH, Bethesda, MD, 5University of RESULTS: The cohort included 445 children (median 6.5yrs, range 2- Wisconsin, Madison, WI, 6UT Southwestern Medical Center, Dallas, 18yrs) with asthma or recurrent wheeze. 81% received regular inhaled TX, 7NewYork-Presbyterian/Columbia, New York, NY, 8Cincinnati Chil- corticosteroids while 32% received multiple preventer therapy. There were dren’s Hospital Medical Center, Cincinnati, OH, 9Cincinnati Children’s no systemic allergic reactions. 48/445 children (10.8%, 95%CI:8.1-14.1%) Hospital, Cincinnati, OH, 10Henry Ford Health System, Division of Al- experienced lower respiratory symptoms within 72hrs, including 27 with lergy and Clinical Immunology, Detroit, MI, 11Rho, 12National Jewish parent-reported wheeze (6.1%, 95% CI:4.0-8.7%). Children under 5yrs Health, Denver, CO, 13The Breathing Institute, Children’s Hospital Colo- were slightly more likely to develop lower respiratory symptoms, although rado, Aurora, CO, 14Children’s National Health System, Washington, DC, this did not reach statistical significance (22/149 (15%) vs 26/296 (8.7%), 15Ann and Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL, OR 1.8 (95% CI:0.98-3.3), P50.07). Paired data for ACTwas available for 16Boston University Medical Center, Boston, MA, 17Rho, Inc., Chapel 394/445 (89%) children. There was no significant change in lower airway Hill, NC, 18University of Wisconsin-Madison, Madison, WI. symptoms (assessed using ACT) following LAIV in participants over RATIONALE: Omalizumab can reduce virus-induced asthma exacerba- 12yrs, while those aged 2-5yrs and 2-12yrs reported a small but significant tions, however little is known about its effects on colds. Our previous data improvement (P<0.001). show that omalizumab treatment reduces duration of viral detection, and CONCLUSIONS: LAIV is safe for use in egg-allergic children, including that omalizumab can improve interferon/antiviral responses. Thus, we those with controlled asthma or recurrent wheeze. All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. AB88 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2016

Maternal DNA Methylation of TH17 Cytokine vs 271561025 Bethesda Units/mL, p50.041). Likewise, following 288 Genes in Second Half of Pregnancy Changes stimulation of splenocytes, numbers of IL-10+CD4+ T cells were greater with Parity in mice exposed to pdFVIII-patches than in sham animals (13.265.4 vs 7.161.6 cells/106 splenocytes, p50.031). Orpita Nilormee1, Gabrielle A. Lockett, PhD2, Sabrina Iqbal3, John W. CONCLUSIONS: Epicutaneous exposure to pdFVIII of hemophilic mice Holloway, PhD2, Syed H. Arshad, DM, FRCP4,5, Hongmei sensitized to FVIII, reduces the immune response to therapeutic FVIII Zhang, PhD1, Wilfried Karmaus, MD, Dr.med, MPH6; 1University of during replacement therapy. Further experiments are required to optimize Memphis, Memphis, TN, 2University of Southampton, Southampton, the dose and duration of epicutaneous FVIII exposure, and to investigate United Kingdom, 3University Of Memphis, Memphis, TN, 4The David the potential regulatory role of the induced splenic IL-10+CD4+T cells. Hide Asthma and Allergy Research Centre, United Kingdom, 5University of Southampton, United Kingdom, 6Division of Epidemiology, Biostatis- Antiviral Cytotixic T Lymphocytes Can be Rapidly tics, and Environmental Health, School of Public Health, University of 290 Generated Against an Extended Spectrum of Memphis, Memphis, TN. Viruses

RATIONALE: Pregnancy is an immunological condition with a series of 1 2 1 changes. To explore whether DNA-Methylation (DNA-M) is related to Michael Keller, MD , Patrick Hanley, PhD , Haili Lang , Catherine Bollard, MD2; 1Children’s National Medical Center, Washington, DC, these changes in consecutive gestations, we analyzed the DNA-M of TH1, 2 SATURDAY Children’s National Medical Center. TH2, TH17 and Treg pathway genes in two consecutive pregnancies of multiparous women. RATIONALE: Adoptive immunotherapy using virus-specific cytotoxic METHODS: Blood samples were collected in first (weeks 8-21) and T-lymphocytes (VST) has been successful in restoring antiviral immunity second (weeks 22-38) halves of pregnancy from the Isle of Wight birth in patients with primary immunodeficiency. We hypothesized that ex vivo cohort to measure DNA-M using Illumina Infinium Human expanded VST generated using a rapid GMP compliant protocol will be (i) Methylation450 beadchip. DNA-M was obtained in first (13 mothers) polyclonal and polyfunctional and (ii) elicit broad activity against multiple and second (8 mothers) halves for two consecutive pregnancies. First, viral antigens in a single culture. mixed linear models were used to compare DNA-M across two consecutive METHODS: VST were cultured by stimulating peripheral blood mono- pregnancies, separately for first and second halves, to detect cytosine- nuclear cells from 5 healthy donors with overlapping peptide pools _ encompassing 17 epitopes from 8 viruses (CMV, EBV, adenovirus, BK phosphate-guanine (CpG) sites with significant changes (p<0.05) in TH1 virus, human herpesvirus 6B, RSV, influenza (H3N2), and varicella), (155 CpGs, 19 genes), TH2 (77 CpGs, 12 genes), TH17 (106 CpGs, 15 followed by 10-12 days of culture with cytokines. VSTwere tested via flow genes) and Treg (10 CpGs, 2 genes). Then we compared the proportion cytometry, IFN-g ELISpot against viral epitopes, and for non-alloreactivity of significant CpGs to determine whether T cell pathway CpGs were 51 more often different than 20 random samples each containing 348 CpGs. via Cr cytotoxicity assays using HLA-mismatched PHA blasts. RESULTS: VST predominantly expressed CD3+ (mean 92%, range 88-95%) RESULTS: Only Th17 CpGs in the second half of pregnancy were + + differentially methylated in two consecutive pregnancies. Among the 28 and CD4 (mean66%)orCD8 (mean 29%), with few B-cells or natural killer significantly differentially methylated Th17 CpGs, 24 belong to IL17-fam- cells (<1%). Central memory T-cells (CD3+/CD45RA-/CCR7+) were present ily and four to IL21-family. Compared to changes in random samples in all VST lines (mean 14.6%, range 9-19%). Viral specificity was seen against a median of 7 viruses (range 3-8), with T-cells responding to a median of 12 (14.1-17.8%), the methylation of more CpGs in TH17 (26.4%) were signif- icantly more often changed in the second half of pregnancy. epitopes tested on Inf-g elispot (range 5-17). VST demonstrated no killing (<5% specific lysis) of mismatched PHA blasts in cytotoxicity assays. CONCLUSIONS: Significant more methylation changes in TH17 genes in the second half of gestation comparing consecutive pregnancies may sug- CONCLUSIONS: VST can be rapidly expanded with specificity against 8 gest changes in methylation with parity. viruses, with CD4, CD8, and central memory populations suggesting polyclonality. VST are non- alloreactive in vitro, and may be beneficial for Epicutaneous Immunotherapy Using Plasma- prevention and treatment of a multitude of viral infections in patients with 289 Derived Factor VIII Reduces the Inhibitory primary immunodeficiency. Immune Response to Therapeutic Factor VIII in Experimental Hemophilia a

Sebastien Lacroix-Desmazes1, Adeline Porcherie2, Sandrine Delignat1, Mathieu Ing1, Pierre-Henri Benhamou, MD2, Lucie Mondoulet, PhD2; 1Centre de Recherche des Cordeliers - Equipe 16 INSERM UMRS 1138, Paris, France, 2DBV Technologies, Bagneux, France. RATIONALE: Hemophilia A is a rare X-linked bleeding disorder that results from a lack of functional pro-coagulant factor VIII (FVIII). Treatment of bleeding by administration of exogenous FVIII is compli- cated by the onset of inhibitory anti-FVIII antibodies in up to 30% of the patients. Here, we hypothesized that the epicutaneous delivery of FVIII imposes immune tolerance to FVIII. METHODS: FVIII-deficient C57BL/6 mice were sensitized by intrave- nous administration of recombinant human FVIII (2 mg/mouse, rFVIII) once a week for 3 weeks. Mice were then treated with epicutaneous patches containing PBS (sham) or 25 mg of plasma-derived FVIII (pdFVIII) once a week for 48 hours over 8 weeks. Two weeks after the last treatment, mice were injected intravenously once a week for 4 weeks with rFVIII (0.5 mg/ mouse) to mimic replacement therapy. Plasma levels of FVIII inhibitory antibodies were measured in a coagulation assay. FVIII-specific cellular responses were evaluated in spleen following in vitro stimulation. RESULTS: Mice exposed to pdFVIII-containing patches developed significantly lower levels of FVIII inhibitors than sham mice (10346356 All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. J ALLERGY CLIN IMMUNOL Abstracts AB89 VOLUME 137, NUMBER 2

Siglec-Engaging Tolerance-Inducing Antigenic Future studies may want to focus on the mechanistic role of high number 291 Liposomes (STALs) in the Prevention of Peanut of URI, ragweed sensitization early in life and asthma risk. Allergy Rhinovirus C Targets Ciliated Respiratory Kelly Orgel, BS1, Shiteng Duan, BS2, James C. Paulson, PhD3, A. Wesley 293 Epithelial Cells 1 1 Burks, MD, FAAAAI , Brian P. Vickery, MD, FAAAAI , Michael D. 1 2 4 2 1 Theodor F. Griggs, PhD , Yury A. Bochkov, PhD , Thomas R. Kulis, Jr, PhD , Matthew S, Macauley, PhD ; University of North Car- 1 2 2 Pasic, MD , Rebecca A. Brockman-Schneider, MS , Ann C. olina at Chapel Hill, Chapel Hill, NC, The Scripps Research Institute, 3 2 1 3 4 Palmenberg, PhD , James E. Gern, MD, FAAAAI ; University of Wis- The Scripps Research Institute, La Jolla, CA, University of North 2 3 Carolina School of Medicine, Chapel Hill, NC. consin, University of Wisconsin-Madison, Madison, WI, University of RATIONALE: Peanut-specific B cells are the ultimate source of anti- Wisconsin, Madison, WI. peanut antibodies that drive peanut allergy. Sialic acid-binding immuno- RATIONALE: The Rhinovirus C (RV-C) produce high symptom burdens globulin-like lectins (siglecs) such as CD22 have been targeted to in children and asthmatics, however, their primary target host cell in the successfully induce apoptosis of antigen-specific B cells for induction of airways remains unknown. We hypothesized that the RV-C target ciliated B cell tolerance. We hypothesized that treatment with STALs displaying respiratory epithelial cells (RECs), and that cell specificity is determined the CD22 ligand (BPA-NeuAc) and the major peanut allergen, Ara h 2 by restricted and high expression of the only known RV-C cell-entry factor, (Ah2) prior to sensitization would mitigate Ah2-induced anaphylaxis. cadherin related family member 3 (CDHR3). We further hypothesized that METHODS: BALB/cJ mice received intravenous injections of either PBS ciliated tissues are required for susceptibility to the RV-C in the upper (n56), 100 uM antigenic liposome displaying Ah2 only (n58), 20 uM Ah2 respiratory tract. STALs (n56), or 100 uM Ah2 STALs (n57). After two weeks, mice were METHODS: RV-C15 infection and target cell morphology were assessed sensitized by gavage with crude peanut extract and cholera toxin once using immunofluorescent and time-lapse epifluorescent imaging in REC weekly for 4 weeks. Mice were bled and challenged with intraperitoneal cultures, and immunohistochemistry and flow cytometry of differentiated Ah2. Serology and challenge results were compared between groups. RECs, sinus, adenoid, and tonsil epithelium, respectively. RESULTS: Compared to PBS controls, injection with 100 uM STALs led to RESULTS: RV-C15 produced a scattered pattern of infection, and infected lower Ah2-specific IgG1 (p50.002) and IgE (p50.008). Ah1-specific IgE epithelial cells were shed. RV-C15 inoculation resulted in the infection of (p50.008) and IgG2a (p50.006) were also lower in mice treated with 100 uM 1.4-12% of cultured cells. Infected cells stained positively for acetylated- STALs compared to placebo. Treatment with 20 uM Ah2 STALs had no alpha-tubulin (aat, p<0.001) but not wheat germ agglutinin or Muc5AC 5 significant effect on Ah2- or Ah1-specific IgG1, IgG2a, or IgE, suggesting a (p ns). The uninfected ciliated cell population expressed 2.2-fold more dose effect. Upon challenge, the group pre-treated with 100 uM Ah2 STALs CDHR3 than other epithelial cell populations (p<0.001). RV-C15 inocu- maintained a stable body temperature (slope parameter [6SD] -0.04060.025; lation reduced the CDHR3 expressing ciliated cell population from 70 to p50.122 for a non-zero slope) unlike mice treated with PBS, that displayed the 58% (p<0.001). RV-C15 replicated in sinus and adenoid, but not tonsil epithelium following inoculation. expected anaphylactic response (-0.09960.031; p50.006). ex vivo SATURDAY CONCLUSIONS: Pre-treatment with 100 uM tolerogenic Ara h 2-loaded CONCLUSIONS: In summary, the RV-C replicate only in ciliated RECs STALs leads to lower Ah2- and Ah1-specific IgE and protects from in vitro and CDHR3 expression is largely confined to ciliated RECs. experimental peanut anaphylaxis. Accordingly, sinus and adenoid tissues (ciliated epithelium) but not tonsils (nonciliated epithelium) were susceptible to RV-C infection ex vivo. These Upper Respiratory Infections during Infancy and findings suggest that factors regulating ciliary differentiation and CDHR3 292 Childhood Aeroallergen Sensitization and Asthma expression may be important determinants of RV-C illness severity.

Leilanie Perez Ramirez, MD, MS1, Heepke Wendroth1, Jocelyn Biagini- Myers, PhD1, Grace K. LeMasters, PhD2, Patrick Ryan, PhD1, James E. Lockey, MD, MS, FAAAAI2, David I. Bernstein, MD3, Gurjit K. Khurana Hershey, MD, PhD, FAAAAI1; 1Cincinnati Children’s Hospital, Cincin- nati, OH, 2University of Cincinnati College of Medicine, Cincinnati, OH, 3Division of Immunology, University of Cincinnati, Cincinnati, OH. RATIONALE: While early upper respiratory infections (URI) have been associated with aeroallergen sensitization and asthma, data are contradictory. METHODS: Data from the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS) prospective cohort was assessed to determine the association between the frequency of URIs in the 1styear and subsequent development of allergic sensitization and asthma. CCAAPS is a high-risk birth cohort of one or more confirmed allergic parents. Early sensitization was defined as at least one positive skin prick test (SPT+) from ages1-3, and late sensitization as negative SPTs during 1-3yrs but positive at 7y. High frequency of URI was defined as >6 infections by age 1. RESULTS: Among CCAAPS children (n5 710), 59% and 10% had early and late sensitization, respectively. There were 96% children with >6URI during their first year. A high number of URI was significantly associated with almost a two fold increased risk for early sensitization to ragweed, after adjustment for pets, breastfeeding, daycare and antibiotic use (aOR51.8, 95% CI 1.01-3.1, p50.046). No association was found between high number of URIand late sensitization to any aeroallergen. Early aeroallergensensitization (aOR52.7, 95%CI 1.5-4.7, p50.001) and high number of URI (aOR 2.33, 95%CI 1.4-3.9, p50.002) were associated with asthma at 7yrs. CONCLUSIONS: These data demonstrate that a high number of 1st year URI increases the risk for early ragweed sensitization and asthma at 7y. All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. AB90 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2016

Rhinovirus Infection Results in Increased and and treated with either an anti-TSLP neutralizing antibody or an isotype 294 More Persistent Dysregulation of Gene Expression control. On day 4 post-infection, lungs were collected for evaluation of ILC2 numbers. TSLPR-deficient mice were infected to evaluate patho- Huyen-Tran Nguyen, MD1, Peter W. Heymann, MD2, Mark Lindsey3, physiology. The appropriate institutional review boards approved all Umasundari Sivaprasad, PhD3, Mario Medvedovic, PhD4, Naim Mahi4, experiments. Thomas A. E. Platts-Mills, MD, PhD, FAAAAI FRS2, Ronald B. RESULTS: Neutralization of TSLP at 6 hours or 36 hours post-infection Turner, MD5, John W. Steinke, PhD, FAAAAI6, Judith A. decreased the total number of IL-13-producing ILC2 on day 4 post- Woodfolk, MBChB, PhD, FAAAAI2, Larry Borish, MD, FAAAAI2, infection with RSV strain 01/2-20 compared to isotype treated mice. Gurjit K. Khurana Hershey, MD, PhD, FAAAAI7; 1Cincinnati Children’s Similarly, TSLP neutralization attenuated IL-13-producing ILC2 on day 4 Hospital Medical Center, Division of Allergy and Immunology, Cincin- post-infection in mice inoculated with the INSPIRE strains. Deficiency of nati, OH, 2Division of Asthma, Allergy & Immunology, University of Vir- TSLPR in mice led to attenuated weight loss, decreased IL-13 production, ginia Health System, Charlottesville, VA, 3Cincinnati Children’s Hospital and reduced airway mucus accumulation without a negative impact on viral Medical Center, Division of Asthma Research, Cincinnati, OH, 4Univer- load. sity of Cincinnati, Department of Environmental Health, Cincinnati, CONCLUSIONS: TSLP neutralization attenuated the IL-13-producing OH, 5University of Virginia Health System, Division of Infectious Dis- ILC2 response induced by multiple clinical isolates of RSV, including eases, Charlottesville, VA, 6Asthma and Allergic Disease Center, Carter strains isolated as recently as 2012 that have known human pathogenic SATURDAY Center for Immunology Research, University of Virginia, Charlottesville, potential. These data suggest TSLP as an important therapeutic target VA, 7Cincinnati Children’s Hospital, Cincinnati, OH. during RSV infection. RATIONALE: Rhinovirus is associated with 50-90% of asthma exacer- bations in adults and children. We hypothesized that gene expression in Interrogation of the Effects of Rhinovirus on Th2 asthmatics would be significantly dysregulated compared to non-asth- 296 Promoting Pathways in Allergic Asthma matics following Rhinovirus infection. Rachana Agrawal, PhD1, Peter W. Heymann, MD2, Thomas A. E. Platts- METHODS: Adults (20-33 years old), 5 with allergic asthma and 6 1 without (controls), were inoculated with Rhinovirus-16 and nasal epithelial Mills, MD, PhD, FAAAAI, FRS , Judith A. Woodfolk, MBChB, PhD, FAAAAI1; 1Division of Asthma, Allergy & Immunology, University of samples were obtained 7 days prior to (T0), 2 days after (T1), and 7 days 2 after inoculation (T2). RNA was extracted and used for RNA-seq analysis. Virginia Health System, Charlottesville, VA, University of Virginia Differential gene expression analysis was performed based on the Asthma and Allergic Diseases Center and the Department of Pediatrics negative-binomial statistical model of read counts as implemented in the Division of Respiratory Medicine, Charlottesville, VA. edgeR Bioconductor package. RATIONALE: The cellular mechanisms involved in rhinovirus (RV) RESULTS: At baseline, 57 genes were differentially expressed in induced asthma exacerbations in allergic subjects remain unclear. asthmatics compared to controls (p adj < 0.05). In non-asthmatic controls, Basophils and dendritic cells (DCs) are key players in promoting Th2- 62 genes were significantly altered from T0 to T1, including 27 genes driven inflammation in allergic asthma. We recently reported increased IgE whose expression changed at least 3-fold. Strikingly, in asthmatics, 1329 responsiveness in circulating basophils of allergic asthmatics following RV genes were significantly altered from T0 to T1, including 550 genes whose exposure. Thus, we aimed to explore how RV infection impacts Th2- expression changed at least 3-fold. In controls, only 3 genes remained at associated pathways in basophils and DCs. 5 least 3-fold dysregulated at T2, while in asthmatics, 50 genes still METHODS: Allergic asthmatics (n 9) were challenged intranasally with demonstrated at least a 3-fold change in expression even 7 days later. human rhinovirus 16. Flow cytometry was employed to capture global CONCLUSIONS: Healthy individuals with asthma have a substantially changes and extensively immunophenotype circulating basophils, myeloid different response to Rhinovirus infection than non-asthmatic healthy DCs (mDCs) and plasmacytoid DCs (pDCs) in fresh whole blood obtained controls. The quality of the response was significantly altered, and the pre-inoculation (day 0), and during acute (day 4) and convalescent (day 21) magnitude of the response was increased in asthmatics. Further, the phases post-inoculation. The multi-dimensionsal data analysis software, response persisted longer in asthmatics versus controls. Thus, in patients viSNE, was used to generate cell clusters of similar phenotypes. with asthma, the ability to sense Rhinovirus and the ensuing immune RESULTS: During the acute phase, viSNE analysis revealed enhanced response is inherently altered. expression of activation markers on mDCs and pDCs including HLA-DR and CD86, in conjunction with unconventional markers on mDCs TSLP Neutralization Inhibits ILC2 Activation including CD63 and prostaglandin D2 receptor (CRTH2). Furthermore, 295 Induced By Multiple Pathogenic Clinical Isolates expression of intracellular Syk increased both in mDCs and pDCs, with of RSV little change in FcεRIa. By contrast, basophils displayed increased expression of FcεRIa, Syk and CD63, and levels of FcεRIa and CD63 Matthew T. Stier, BS1, Shinji Toki, PhD2, Dawn C. Newcomb, PhD1,2, remained elevated at day 21. At baseline, asthmatics segregated into IL-4hi Melissa H. Bloodworth, BS1, Tina V. Hartert, MD, MPH2,3, Martin L. (n56) and IL-4lo (n53) subgroups based on the percentage of IL-4+ baso- Moore, PhD4, R. Stokes Peebles, MD1,2; 1Department of Pathology, phils, mDCs and pDCs. Paradoxically, IL-4lo asthmatics developed more Microbiology, and Immunology, Vanderbilt University, Nashville, TN, severe respiratory symptoms than the IL-4higroup. 2Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt CONCLUSIONS: Collectively these findings highlight complex cellular University, Nashville, TN, 3Center for Asthma Research, Vanderbilt Uni- changes induced by RV infection in allergic asthmatics that do not fit a versity, Nashville, TN, 4Department of Pediatrics, Emory University, GA. simple Th2 amplification model. RATIONALE: RSV infection is a major pediatric health burden and is associated with an increased risk of asthma. Data suggest that type 2 immune responses contribute to the severity of RSV illness. ILC2 can be activated by TSLP and are potent producers of type 2 cytokines in the lungs. METHODS: RSV clinical isolates were collected from the Vanderbilt Vaccine Clinic in 2001 (01/2-20) or from infants hospitalized with severe RSV illness as part of the Infant Susceptibility to Pulmonary Infections and Asthma Following RSV Exposure (INSPIRE) study in 2012 (12/11-19 and 12/12-6). Wild type mice were infected with individual RSV isolates All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. J ALLERGY CLIN IMMUNOL Abstracts AB91 VOLUME 137, NUMBER 2

Beneficial Outcomes of an Inpatient Penicillin unclear. Further investigation exploring the therapeutic utility of omalizu- 297 Allergy Testing Protocol mab in AERD patients undergoing AD is indicated based on these data.

Justin R. Chen, MD1, Scott A. Tarver, PharmD2, Kristen S. Intravenous Iron Hypersensitivity Evaluation and Alvarez, PharmD2, Trang Tran, PharmD2, David A. Khan, MD, 299 Desensitization 1 1 FAAAAI ; University of Texas Southwestern Medical Center, Dallas, 1 2 3 2 Joyce T. Hsu, MD , Grace Y. Chan, MD , Donna-Marie Lynch, NP , Ma- TX, Parkland Health and Hospital System, Dallas, TX. 4 1 RATIONALE: More than 90% of patients reporting a penicillin allergy riana C. Castells, MD, PhD, FAAAAI ; Brigham and Women’s Hospital, Boston, MA, 2Tan Tock Seng Hospital, Singapore, 3Brigham and Womens are not actually allergic. We present the findings of a protocol aimed at 4 systematically evaluating penicillin allergy in hospitalized patients. Hospital, Boston, MA, Division of Rheumatology, Allergy and Immu- METHODS: Our approach employed a dedicated clinical pharmacist to nology, Department of Medicine, Brigham and Women’s Hospital, Har- test inpatients with penicillin allergy documented in the electronic medical vard Medical School, Boston, MA. record (EMR). Potential subjects were flagged daily through the EMR or RATIONALE: Patients receiving intravenous iron replacement may have referred by their primary physician. A cohort deemed likely to benefit from systemic hypersensitivity reactions during the infusion. We investigate the penicillin therapy was prioritized for inpatient testing. These patients role of intravenous iron skin testing and the safety of intravenous iron received skin prick (SPT) and intradermal testing with benzylpenicilloyl desensitization with multiple formulations. polylysine (Pre-Pen) and penicillin G followed by oral amoxicillin METHODS: Patients with a history of iron hypersensitivity were challenge if both were nonreactive. Those with a negative evaluation had evaluated in the Brigham and Women’s Hospital Allergy Clinic. Their the penicillin allergy label removed from their EMR. All patients were records were reviewed and analyzed for skin testing results and the individually informed of their result. outcome of desensitization to intravenous iron. RESULTS: Over 9 months approximately 800 applicable charts were detected RESULTS: 12 patients with history of intravenous iron hypersensitivity by our system leading to 135 formal tests. 119 of 135 subjects (88.1%) had were evaluated and desensitized between January 1, 2010 and July 31, their listed penicillin allergy removed. Of the remainder, only 2 (1.5%) had 2015. Reactions ranged from itching to respiratory distress and hypoten- positive skin test results to penicillin, 8 (5.9%) did not react to a histamine sion. 8/12 patients reacted to more than one formulation. Skin testing was control, 2 were not challenged due to b-blocker use, and 4 (3%) did not performed with sodium ferric gluconate, with 6/12 patients positive. 5 of subsequently complete the challenge due to personal or physician preference. those 6 patients reacted to more than one formulation. Patients were treated CONCLUSIONS: An inpatient penicillin skin-testing protocol can lead to with sodium ferric gluconate, iron sucrose, iron dextran, or ferumoxytol in removing the penicillin allergy label in the vast majority of patients and this cohort. All 12 patients were able to complete treatment with full doses serves to educate clinicians and patients alike. Widespread implementation of intravenous iron replacement using a 12-step or 16-step protocol. One of of this practice may potentially benefit healthcare systems by reducing the the 12 patients initially failed desensitization to iron dextran and iron expense of alternative antibiotics and the risk of antimicrobial resistance. sucrose before completing ferumoxytol by desensitization protocol. CONCLUSIONS: Patients who reacted to more than one formulation of SATURDAY Omalizumab Inhibits Aspirin-Provoked Respiratory IV iron were more likely to have positive skin testing to sodium ferric 298 Reaction in Patients with Aspirin Exacerbated gluconate. All the patients were able to receive at least one formulation of Respiratory Disease intravenous iron replacement safely. Intravenous iron replacement can be safely given using the 12-step and 16-step desensitization protocols. David M. Lang, MD1, Mark A. Aronica, MD2, Elizabeth Maierson, BA, RRT2, Xiaofeng F. Wang, PhD3, Dorothy C. Vasas, RN4, Stanley Hazen, MD, PhD2; 1Cleveland Clinic, Respiratory Institute, Department of Al- lergy and Clinical Immunology, Cleveland, OH, 2Cleveland Clinic, Cleve- land, OH, 3Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, 4Cleveland Clinic Foundation, Cleveland, OH. RATIONALE: Omalizumab has anti-inflammatory properties beyond having an impact on IgE (AJRCCM 2004;170:583-93). We performed a double-blind randomized trial to evaluate the hypothesis that omalizumab can attenuate aspirin-provoked respiratory reaction in patients with aspirin exacerbated respiratory disease (AERD). METHODS: Subjects with AERD who fulfilled FDA-label criteria for omalizumab were randomized 2:1 to receive omalizumab:placebo based on body weight and IgE level for 16 weeks, prior to undergoing aspirin desensitization (AD). The primary outcome was respiratory reaction (decline in FEV1) during AD; urinary LTE4 levels were also assessed. RESULTS: Of 72 potential subjects, 56 were excluded mainly based on non- fulfillment of criteria for AERD or FDA-label. Of 16 enrolled, 11 completed participation. For placebo:omalizumab groups, mean age (42.7 vs. 45.7 years) and IgE level (65 vs. 121 IU/ml) did not differ significantly (p5NS). All 4 randomized to placebo had respiratory reactions, including 2 with broncho- spasm (FEV1 decline >_ 20%); 2 of 7 randomized to omalizumab had isolated upper airway reactions, 5 had no respiratory reaction (p 5 0.036, Fisher Exact Test). Assuming a ‘‘false-negative’’ rate of 16% (JACI 1983;71:574-9), the probability these 5 subjects were non-AERD patients and were all randomized to omalizumab is 0.0017 (Exact Binomial Test). No remarkable differences were observed in urinary LTE4 levels (p5NS). CONCLUSIONS: This is the first randomized trial describing a pharma- cologic agent that can completely inhibit aspirin-provoked respiratory reaction in AERD patients. The mechanism for this protective effect is All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. AB92 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2016

Desensitization to Platinums: Our Experience with subjects. Genotype-phenotype association was examined by logistic 300 153 Desensitizations regression analysis adjusting for gender and age. RESULTS: In rs2070424 (Ivs3-251A/G) of SOD1, the frequency of Meaghan R. Misiasz, MD1,2, Jessica W. Hui, MD3, Mahboobeh genotype carrying the minor allele (GA + GG) was higher in patients Mahdavinia, MD, PhD1,2, Mary C. Tobin, MD1,2; 1Department of Immu- with ATD-induced MPE compared with ATD-tolerant controls nology and Microbiology, Allergy/Immunology Section, Rush University (P 5 0.018, OR 5 2.42, 95% CI 1.16-5.05). The other polymorphisms Medical Center, Chicago, IL, 2Department of Pediatrics, Division of in SOD2 and SOD3 did not show significant difference of genotypes be- Allergy and Immunology, John H. Stroger, Jr. Hospital of Cook County, tween case and control group. Chicago, IL, 3Department of Pediatrics, Internal Medicine/Pediatrics CONCLUSIONS: Intron SNP rs2070424 of SOD1 (Ivs3-251A/G) Division, Rush University Medical Center, Chicago, IL. showed significant association with ATD-induced MPE. These findings RATIONALE: Many patients with gynecological malignancies require suggest that this SOD1 genetic variant may increase the risk of ATD- platinum based chemotherapy for treatment. Frequently, patients develop induced MPE. hypersensitivity reactions to these agents necessitating their administration via a desensitization protocol. This study presents our experience utilizing Comparison of Food Allergy Awareness and Self- a 12-step, 3-bag desensitization protocol. 302 Management Among College Students at 3 Large METHODS: We performed a retrospective chart review of patients with US Universities SATURDAY gynecological malignancies undergoing desensitizations to cisplatin and 1 2 carboplatin from 1/1/2010 to 3/31/2015. Data was collected regarding the Marilyn R. Karam, MD , Rebecca Scherzer, MD, FAAAAI , Princess U. Ogbogu, MD, FAAAAI3, Todd David Green, MD, FAAAAI4, Matthew J. original reaction and each desensitization. Reaction severity was graded. 5 1 RESULTS: A total of 153 infusions were given via a desensitization Greenhawt, MD, MBA, MSc ; University of Michigan, Division of Al- lergy and Clinical Immunology, Ann Arbor, MI, 2Nationwide Children’s protocol in 33 patients. Of note, 82 patients were identified with gyneco- 3 logical malignancies and a platinum allergy; of these 33 (40%) were Hospital, Columbus, OH, Wexner Medical Center at the Ohio State Uni- versity, Columbus, OH, 4Children’s Hospital of Pittsburgh of UPMC, desensitized. Eighteen patients (55%) had reactions during at least one 5 desensitization with 38 total reactions (25% of all desensitizations). Eight Pittsburgh, PA, Department of Internal Medicine, The University of patients reacted during initial desensitization and ten reacted during Michigan Medical School, Division of Allergy and Clinical Immunology, subsequent infusions. Seven patients had more severe reactions during Ann Arbor, MI. desensitization than their original reaction. Most reactions (84%) occurred RATIONALE: Food allergy (FA) awareness and self-management during infusion of the final concentration. Reactions were managed with behaviors in college students are poorly understood. We compared FA medications and infusion rate adjustments. Infusion protocol rate adjust- awareness between University of Pittsburgh (PITT), University of ments were made in 28% of desensitizations. Desensitization was discon- Michigan (UM), and the Ohio State University (OSU) students. tinued in four patients, two were later successfully desensitized. METHODS: An online survey was distributed by e-mail to undergraduate Preadmission treatment with antihistamines and/or glucocorticoids was students. 5 not associated with a significantly lower occurrence of reactions. RESULTS: Among respondents, 43.2% (n 748/1772) reported FA, and 5 CONCLUSIONS: Our experience with desensitizations to platinums 59.2% (n 394) reported symptoms consistent with NIAID anaphylaxis indicates the risk of reaction to these medications during desensitization criteria. Tree nut (28.9%), peanut (23.4%), and milk (18.5%), allergy were 5 remains high even after the patient has tolerated an initial desensitization most commonly reported. 81% (n 605) reported a close campus contact 5 and the patient’s initial reaction does not predict the severity of subsequent was aware of their FA. Only 40.1% (n 300) reported maintaining reactions. emergency medication, including self-injectable epinephrine (SIE) in 79.6% (n5239), and only 57.4% (139/239) reporting always carrying SIE. Increased Risk of Antituberculosis Drugs-Induced Only 48.8% reported (n5362) always avoiding their food allergen. Past 301 Maculopapular Eruption in Patients with anaphylaxis was associated with increased odds of medication mainte- Superoxide Dismutase 1 Gene Mutation nance and SIE carriage. Among students not preparing their own food, 31.2% (n5238) reported their food preparers were aware of their FA, Sang-Heon Kim1, Sang-Hoon Kim2, Ji-Yong Moon1, Dong Won Park1, 21.5% (n5161) reported foods in the dining hall were always labeled for Jang Won Sohn1, Ho Joo Yoon, MD, PhD1, Suk-Il Chang3, Young-Koo allergen content, and 32.2% (n5241) reported that allergen-free alterna- Jee, MD, PhD4; 1Department of Internal Medicine, Hanyang University tives were available. Comparatively, significant differences in reported FA College of Medicine, Seoul, South Korea, 2Department of Internal Medi- rates, dining hall labeling, and rates of campus contact awareness were cine, Eulji University School of Medicine, Seoul, South Korea, 3Depart- seen between campuses. However, no differences among the campuses ment of Internal Medicine, Sungae General Hospital, Seoul, South were noted in reported rates of students with past anaphylaxis, maintaining Korea, 4Department of Internal Medicine, Dankook University College SIE, always carrying SIE, food preparer awareness, or always avoiding of Medicine, Cheonan, South Korea. their allergen. RATIONALE: Of various adverse reactions to antituberculosis drugs CONCLUSIONS: Reported FA rates, levels of campus awareness, and (ATD), maculopapular eruption (MPE) is the most common cause leading food labeling vary significantly among students at 3 Universities. However, to discontinuation of the medication. The pathogenesis of ATD-induced poor compliance rates with SIE carriage, food preparer awareness, and MPE is poorly understood, but oxidative stress induced by the ATD allergen avoidance are similar. metabolites might play a role in the development of MPE. This study aimed to examine the associations between genetic polymorphisms in superoxide dismutase genes (SOD1, SOD2 and SOD3) and ATD-induced MPE. METHODS: From the patients receiving the first line ATD including isoniazid, rifampicin, ethambutol and pyrazinamide, 75 patients with ATD-induced MPE and 237 ATD-tolerant control were included in this study. Four single nucleotide polymorphisms (SNP) in SOD1 (rs2070424), SOD2 (rs4880) and SOD3 (rs2536512 and rs1799895) were selected based on the previously reported roles in the literature and genotypes in the study All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. J ALLERGY CLIN IMMUNOL Abstracts AB93 VOLUME 137, NUMBER 2

Quality of Facebook Pages on Food Allergy: Many Educational Needs Assessment of US Allergy/ 303 Food Ingredient Alerts and Event Announcements 305 Immunology Fellowship Programs: Assessment but Little Research News and Patient Education Methods for Determining Competency of Fellows in-Training Mosaab Mohameden, Ves Dimov, MD, Frank J. Eidelman, MD, FAAAAI; Cleveland Clinic Florida, Weston, FL. Lily C. Pien, MD, MHPE, FAAAAI, Erica J. Glancy, MD, Katrina Zell, RATIONALE: Facebook is the most popular and frequently used social Colleen Y. Colbert, PhD; Cleveland Clinic, Cleveland, OH. media website in US. One third of American adults reported using social RATIONALE: ACGME introduced a milestone framework to assist in network sites, such as Facebook or Twitter as a source of health competency development in GME trainees. Little is known about current information. Our study aimed to determine the quality of health informa- use of assessment methods in U.S. Allergy/Immunology (A/I) Fellowship tion on Facebook pages dedicated to food allergy. programs. A recommendation by the A/I Milestone Working Group was METHODS: Facebook main page was searched for ‘‘food allergy’’ to that programs ‘‘should make use of all available data’’ from a wide variety retrieve top ten pages dedicated to the topic. A 0-9 score for quality content of assessment sources. was developed based on the guidelines by National Library of Medicine, METHODS: IRB approval was obtained for a prospective survey study focusing on 9 domains: author/organization, reviewer, contact info, authen- designed as a needs assessment. A link to a REDcap questionnaire, ticity, language used (simple vs scientific), evidence-based vs. opinion, previously piloted, was e-mailed to 74 U.S. Program Directors (PDs) to references vs. testimonials, current information, sponsorship, commercial identify currently used assessment methods. We were also interested in the interest. The score was used to analyze the last 10 posts of each Facebook page. provision of feedback to trainees. Program characteristics were examined Posts were categorized into 5 groups: food ingredient alerts, patient education, for continuous and categorical variables. research news, event announcements, legislation updates. RESULTS: Twenty-one of 74 PDs (28%) responded, with 19 completing RESULTS: 37% of posts were announcements/advertisements, 29% were questions regarding assessment methods. Thirteen PDs completed all related to patient education, 9% legislation updates, only 5% were research questionnaire items. The most commonly used assessment methods were news. Quality score was relatively high with an average of 7.1 (0-9). Most the ITE (100%), direct observation of trainees (95%), faculty assessments pages were by patient advocate organizations. Only one was by a physician (89%), and 360-degree assessments (89%). Commonly used methods (>50% specialty organization, and one by an allergy practice. of programs) included self-assessments, portfolios, and patient surveys. More CONCLUSIONS: In spite of the wide popularity of Facebook, only a information about multiple choice examinations (23%), teamwork assess- minority of the pages on food allergy contained patient education ments (15%), chart-stimulated recall (15%), and OSCEs (15%) was wanted. information. A paucity of research news was likely related to low Feedback, verbal and written, was typically provided to trainees every six engagement by allergists/immunologists. Professional use of Facebook months and classified as both formative and summative in nature. by allergists/immunologists for patient education and sharing research CONCLUSIONS: Our results indicate consistency in the type of news should be encouraged and its implications explored. assessment methods used in respondents’ training programs. Peer assess-

ments and OSCEs, while recommended, were less commonly used in this SATURDAY Level of Knowledge, Concerns and Healthcare sample. Faculty development regarding recommended methods may 304 Practices Among Physicians Regarding E-Cigarettes increase their use and provide additional valuable feedback to trainees.

Venkatkiran Kanchustambham, MD1, Jonathan Rodrigues, Fellow-in- Immunotherapy Guide Increases Dosing Accuracy Training2, Abhishek Krishna, Fellow in training3, Sadashiv Santosh, As- 306 sistant professor3; 1Saint Louis University School of Medicine, St. Louis, MO, 2Saint Louis University School of Medicine, Saint Louis, MO, 3Saint Jared I. Darveaux, MD1, Sameer K. Mathur, MD, PhD, FAAAAI2, Su- Louis University, Saint Louis, MO. jani Kakumanu, MD2, Diane Dierdorff, CPhT3; 1Gundersen Health Sys- RATIONALE: Electronic cigarettes (e-cigarettes) are battery-powered tem, Onalaska, WI, 2University of Wisconsin School of Medicine and devices that deliver aerosolized nicotine. With easy access and over the Public Health, Madison, WI, 3University of Wisconsin Hospitals and Clinics. counter availability, many patients consider using e-cigarettes for smoking RATIONALE: Immunotherapy (IT) is an effective therapeutic tool used cessation. Few studies have looked at long-term safety and efficacy of to treat allergic disease. Proper dosing of IT is important for optimizing e-cigarettes. Physicians have insufficient guidelines for advising their patients. patient results and minimizing the risk of shot reactions/anaphylaxis. In METHODS: An anonymous online questionnaire was sent to all 2011, practice parameters (PP) were published with dosing recommenda- residents, fellows and faculty in the departments of internal medicine tions for standardized and non-standardized antigens. We launched a and surgery at Saint Louis University. quality improvement initiative to study current prescribing practices and RESULTS: We received 114 responses (51%). 57 % of respondents develop a decision support tool (DST) to improve dosing accuracy. knew what ‘‘vaping’’ meant. 9% reported being ‘‘very familiar’’ with METHODS: Developed a DST to provide a dosing guide based on PP e-cigarettes, while 26 % reported no familiarity. 15% of physicians would guidelines. Education was provided in the form of 1:1 coaching, didactic advise e-cigarettes as nicotine replacement therapy, if asked by patients. training sessions and real time guidance. Prior to implementing the DST, 50 91% were aware of the nicotine content of e-cigarettes, but seem to be most recent new IT prescriptions were reviewed (excluding venom) and were unaware of the presence of carcinogens (19%) and polyethylene glycol categorized as either accurate (in accordance with PP guidelines), high, very (38%). Lack of evidence regarding long-term safety (76%), e-cigarettes as high, low, or very low. The DST was then placed in clinics for optional use by starter products for nonsmokers (50%), absence of FDA regulations (51%) providers. After 4 months, the 49 most recent prescriptions were reviewed and and marketing to youth (42%) were major concerns. Stricter regulations compared to pre-implementation values using chi-square analysis. (54%), warning labels similar to tobacco products (53%), restricting RESULTS: Prior to DST use, 28% of prescriptions were accurately dosed. advertising (36%), banning sales to minors (34%) and banning use in The majority of prescriptions (38%) were dosed very low (less than ½ public spaces (25%) were favored as regulatory measures. 50% of lowest recommended dose). After DST implementation accurate dosing physicians see a role for e-cigarettes as part of ‘‘harm reduction strategy’’. improved by 143% (p 5 < 0.0001). There were also significant reductions Training and familiarity showed no significant correlation. in very high (60%, p 5 <0.0001) and very low (79%, p 5 <0.0001) doses. CONCLUSIONS: Further research is needed to assess whether e- CONCLUSIONS: Implementation a DST dramatically improves the cigarettes could be an effective smoking cessation tool. There is an accuracy of IT dosing. A bundled approach of education, coaching and apparent knowledge gap among physicians and an urgent need for evidence decision support linked to the ordering process leads to better adherence to based guidelines to aid with advising smokers enquiring about e-cigarettes. guideline recommendations. All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. AB94 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2016

A Randomized Placebo-Controlled Trial of adjusted odd ratios (AOR) from 6 prospective studies (n522,184) (AOR 307 Intradermal Grass Pollen Immunotherapy for 5 0.92 [0.64-1.33] for top vs. bottom category of 25OHD). Seasonal Allergic Rhinitis CONCLUSIONS: Available evidence from this meta-analysis suggests that the 25OHD level may not relate with neither the prevalence of the Anna D. Slovick, MRCS, DOHNS, MBBS, BSc1, Abdel Douiri, PhD1, current AR nor the development of AR. Since these studies were very Rachel Muir, PhD2, Andrea Guerra, MD1, Kostas Tsioulos, MD1, Evie heterogeneous and the retrospective or the observational cohort studies, Haye, BSc1, Emily Lam, MSc1, Joanna Kelly1, Janet Peacock, PhD1, large randomized controlled trials are needed to determine whether vitamin S. Ying, MD, PhD1, Mohamed H. Shamji, BSc, MSc, PhD, FAAAAI3, D supplementation may be beneficial in the prevention of AR. David Cousins, PhD1, Stephen R. Durham, MA, MD, FRCP3,4, Stephen Till, MD, PhD1; 1King’s College London, London, United Kingdom, Nasal Challenge with Ragweed Pollen Extract 2GSTT, London, United Kingdom, 3MRC & Asthma UK Centre in 309 (RWPE) Increases the Level of Fortilin in Nasal Allergic Mechanisms of Asthma, London, United Kingdom, 4National Lavage Fluid from Subjects with Allergic Rhinitis

Heart and Lung Institute, Imperial College London, United Kingdom. 1 1 1 RATIONALE: We previously reported that repeated intradermal injection Julia W. Tripple, MD , Koa Hosoki, MD, PhD , Istvan Boldogh, PhD , David Rogers Redding, MD2, Sanjiv Sur, MD1, Ken Fujise, MD1; 1Uni- of grass pollen (nanograms of allergen) almost completely suppresses 2 allergen-induced cutaneous late phase responses (JACI 2012 130(4):918- versity of Texas Medical Branch, Galveston, TX, Redding Allergy and SATURDAY 24). Similar suppression of late responses is seen after high dose subcutaneous Asthma Center, Atlanta, GA. and sublingual immunotherapy. We therefore evaluated the efficacy of grass RATIONALE: Fortilin, also known as histamine-releasing factor [HRF] pollen intradermal immunotherapy (IDIT) for treatment of allergic rhinitis. and translationally controlled tumor protein, has been studied as a HRF and METHODS: 93 adults with grass pollen allergic rhinitis were randomized implicated as a mediator in late phase allergic reactions. It has a to receive 7 pre-seasonal IDIT injections (7 ng of Phl p 5 major allergen) or proinflammatory role in murine asthma and skin immediate hypersensi- histamine control at 2-weekly intervals. The primary end point was tivity. However, the ability of allergen challenge to modulate the levels of combined daily symptom/medication scores (CSMS) during 2013 pollen fortilin in the nasal secretion of subjects with allergic rhinitis has not been season. Skin biopsies were taken after the pollen season following reported. intradermal allergen challenges. Cutaneous late responses were measured METHODS: Nine adult subjects with allergic rhinitis and positive skin 4 and either 7, 10 or 13 months post-treatment. prick testing to ragweed pollen extract (RWPE) were recruited for this RESULTS: No difference in CSMS was observed between treatment study. The mean age of the subjects was 41.6 years. Intranasal challenge arms. Paradoxically, amongst secondary endpoints, nasal symptoms with saline and provoking doses of RWPE solution were performed on two measured with daily scores (P50.03) and visual analog scales (P50.05) different days. During nasal challenge, symptom scores were recorded at were higher in the IDIT group. IDIT also increased serum Phl p-specific baseline, 30 min, and hourly for a total of 6 hours. Nasal lavage was IgE (P50.001) compared to the control arm. T cells cultured from skin performed at baseline, 30 min and 5 hours post-challenge, and the collected biopsies of IDIT subjects showed higher and lower expression of surface nasal fluid was analyzed for fortilin levels by ELISA. markers for Th2 (P50.04) and Th1 (P50.01) cells, respectively, together RESULTS: Compared to saline challenge, RWPE challenge rapidly with higher expression of IL-5 mRNA measured by microarray. Late increased congestion, drainage, sneezing, and total symptom scores at 30 responses to grass pollen were still inhibited 7 months after IDIT (P50.03). min post-challenge (p<0.05). These scores decreased 2 hours post- CONCLUSIONS: Although grass pollen IDIT suppressed skin late challenge. Compared to saline challenge, ragweed extract increased the responses, it was not clinically effective but resulted in immunological level of fortilin 5 hours after challenge (p<0.05), but not at 30 min post priming and worsening of allergic rhinitis symptoms. challenge. CONCLUSIONS: Exposure to ragweed pollen induces a delayed Vitamin D Level in Allergic Rhinitis: A Systemic secretion of fortilin in the nasal airway of ragweed-IgE skin test positive 308 Review and Meta-Analysis subjects with allergic rhinitis. Fortilin may play a role in the pathophys- iology of allergic rhinitis. Yoon Hee Kim, Min Jung Kim, MD, In Suk Sol, Seo Hee Yoon, Young A. Park, MD, Kyung Won Kim, Myung Hyun Sohn, MD, PhD, Kyu-Earn Kim, MD, PhD; Department of Pediatrics, Severance Hospital, Institute of Allergy, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea. RATIONALE: Vitamin D has emerged to play a key role in the allergic disease by influencing to the immune system. 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 searched MEDLINE, EMBASE, the Cochrane Library and KoreaMed to February 28, 2015. Two reviewers completed in duplicate and independently study selection, data abstraction, and assessment of risk of bias. 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 (n542,925) (odd ratio [OR] 5 0.95 [0.76-1.20] for top vs. bottom category of 25OHD) and 6 prospective studies (n522,184) (OR 5 0.89 [0.70-1.15] for top vs. bottom category of 25OHD). The prospective studies analyzed additionally with adjusting of the general epidemiologic characteristics. Meta-analysis was performed to pool All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. J ALLERGY CLIN IMMUNOL Abstracts AB95 VOLUME 137, NUMBER 2

IL-2 Mediates Generalized Tfh Downregulation comorbidity. A reminder push to track and treat is an included option. 310 during Allergen-Specific Immunotherapy VAS scores are logged and plotted over time and control assessed by pre- defined cut-offs as well-controlled: VAS <20 mm; partly-controlled VAS Veronique M. Schulten, PhD1, Shane Crotty, PhD2, Alessandro >20 mm <50mm; uncontrolled VAS >50 mm. This VAS has been inte- Sette, Dr. Biol. Sci.1, Bjoern Peters, PhD1; 1La Jolla Institute for Allergy grated into the MACVIA ARIA AR CDSS, a simple treatment algorithm and Immunology, La Jolla, CA, 2La Jolla Institute for Allergy & Immu- for physicians. nology, La Jolla, CA. CONCLUSIONS: Allergy Diary is a simple way to assess AR symptom RATIONALE: A key factor in mediating allergic disease is allergen- control, is expected to improve treatment compliance, fully integrates specific IgE, which is significantly impacted by IgG4 blocking antibodies with the updated ARIA guideline (i.e. AR CDSS) and will allow physicians induced during allergen-specific immunotherapy (AIT). T follicular helper and patients to better manage AR. (Tfh) cells are CD4+ T cells specialized in helping B cell differentiation and maturation. To date, no data is available on the impact of Tfh cells in Monitoring Circulating Virus-Specific CD4+ T Cells allergic disease. 312 and Probiotic Effect in an Experimental Rhinovirus METHODS: The frequency of total Tfh cells (CD4+CD45RO+CXCR5+) Challenge Model

in allergic, non-allergic and AIT-treated patients was assessed by flow 1 1 cytometry. The effect of IL-2 production after a 5-day culture with anti- Lyndsey M. Muehling, MS , Ronald B. Turner, MD , Rachana Agrawal, PhD1, Paul W. Wright, BS1, James T. Patrie, MS1, Sampo J. CD3/28 or antigenic stimulation on CXCR5 was assessed alongside CD25 2 2 3 expression and IL-2 levels in the supernatant. Lahtinen, PhD , Markus J. Lehtinen, PhD , William W. Kwok, PhD , Judith A. Woodfolk, MBChB, PhD, FAAAAI1; 1University of Virginia, RESULTS: Assessment of total Tfh cell frequency in different cohorts 2 3 revealed that CXCR5 expression is broadly down-regulated during AIT Charlottesville, VA, DuPont Nutrition and Health, Kantvik, Finland, Be- compared to untreated patients. Furthermore, a generalized down-regula- naroya Research Institute at Virginia Mason, Seattle, WA. tion was observed in response to IL-2 after TCR stimulation, which was RATIONALE: Rhinovirus (RV) is a major cause of common cold and an partially reversed by anti-IL-2. important trigger of asthma exacerbations. T-cell responses to RV are CONCLUSIONS: Investigating Tfh populations in different donor poorly understood and no preventive strategies exist. We sought to cohorts revealed that AIT treatment reduced CXCR5 expression in Tfh determine whether circulating RV-specific CD4+ T-cell responses were cells. This down-regulation is associated with IL-2 production in an in vitro modulated in subjects who received probiotic supplementation. setting. Decreased CXCR5 expression could have drastic effects on the METHODS: Our substudy included sixteen HLA-DRB1*0401+ subjects motility of Tfh cells in vivo and may impact their homing to germinal cen- who tested seronegative for RV-39, and who were enrolled in a double- ters, where they co-localize with B cells. This may reduce B cell help and blind placebo-controlled trial of Bifidobacterium lactis Bl-04 supplementa- affect antibody production. Elucidating the exact mechanism by which IL- tion. After 4 weeks of supplementation, subjects received intranasal RV-39. 2 is involved in CXCR5 down-modulation and to what extend Tfh cell PBMCs isolated on days -28 (pre-supplementation), 0 (pre-inoculation), 5 and 21 (post-inoculation) were stained with HLA-DRB1*0401 tetramers mobility and functionality is affected could give new insights into the SATURDAY mechanisms by which AIT modulated antibody responses. presenting two RV-39 capsid peptides, and analyzed by flow cytometry. RESULTS: RV-specific CD4+ T-cell frequencies and phenotypes were A New Digital Tool to Assess Allergic Rhinitis comparable among probiotic (n511) and placebo (n55) groups. Among 311 Symptom Control infected subjects (n512), RV-specific CD4+ T-cells were expanded during the effector phase (day 5) and displayed an activated effector memory Jean Bousquet, MD, PhD1,2, David Price, MD, FRCGP, MRCGP, phenotype. This expansion was absent in 2 infected subjects who lacked DRCOG3,4, Sarah Acaster, BSc5, Anna Bedbrook, BSc6, Davide neutralizing antibodies, and in 4 non-infected subjects. Pre-existing RV- Caimmi, MD2, Claus Bachert, MD, PhD7,8; 1MACVIA-LR, Contres les specific memory cells recognized epitopes conserved across RV strains, Maladies Chronique pour un Vieillissement Actif en Languedoc Roussi- comprised a mixture of T helper (CXCR5neg) and T follicular helper lon, EIP on AHA, France, 2University Hospital, Montpellier, France, (CXCR5+) populations, and were predominantly IFN-g+IL-4neg, with mi- 3Research In Real Life, Cambridge, United Kingdom, 4University of nor IL-17+ and IL-21+ populations. Moreover, they were cross-reactive Aberdeen, Aberdeen, United Kingdom, 5Acaster Consulting, London, with a corresponding epitope of RV-16. High pre-existing RV-specific United Kingdom, 6MACVIA-LR, Contre les Maladies Chronique pour T-cell frequencies were linked to reduced viral infection (p<0.05); un Vieillissement Actif en Languedoc Roussilon, EIP on AHA Reference however this effect was attenuated after accounting for probiotic Site, France, 7Division of ENT Diseases, Karolinska Institute, Stockholm, supplementation (p50.11). Sweden, 8Upper Airway Research Laboratory (URL), Ghent University CONCLUSIONS: Circulating RV-specific CD4+ T cells display attri- Hospital, Ghent, Belgium. butes that might be harnessed for the treatment or prevention of common RATIONALE: MASK-rhinitis (MACVIA-ARIA Sentinel NetworK for cold. allergic rhinitis) is a simple patient-centered-system using information and communications technology tools and a clinical decision support system (CDSS) based on the ARIA 2015 revision. A cell phone-based daily visual analogue scale (VAS) assessment of disease control is one of these tools and is described here. METHODS: App content was developed by ARIA and experts in patient reported outcomes. Wireframes were generated, and a prototype developed and tested (in both patients and physicians). RESULTS: The final app called Allergy Diary was produced (for apple and android platforms) and translated into 14 languages by ARIA Executive Committee members. It collects information on symptom type and duration (intermittent/persistent), disease impact and AR medica- tion(s) (country-specific) used. Users assess daily symptom control using a VASin response to the question ‘overall are much are your allergic symp- toms bothering you today?’, from ‘not at all bothersome’ to ‘extremely bothersome’. An asthma VAS is included for those with asthma All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. AB96 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2016

Viral Infections and Their Impact on the Clostridium (log2 fold change -2.55, p50.04) were underrepresented 313 Respiratory Microbiome in Pediatric Patients among subjects with food allergy. with Cystic Fibrosis CONCLUSIONS: The temporal association between bacterial taxa and food sensitization and allergy suggest that the microbiome may have a Gina T. Coscia, MD, Paul Planet, MD, PhD, Hannah Smith, Melanie Har- causal role in the development of food allergy. Our findings have asym; Columbia University Medical Center, New York, NY. therapeutic implications for the prevention and treatment of food allergy. RATIONALE: Viruses are known to impact clinical status in patients with cystic fibrosis (CF); however their effects on the respiratory microbiome Features of the Bronchial Bacterial Microbiome are unclear. The goal of our study is to assess changes in the lung 315 Associated with Allergy and Mild Allergic microbiome of pediatric patients with CF during periods of wellness and Asthma. exacerbation, with a focus on the impact of viral infection, using Juliana Durack, PhD1, Susan V. Lynch, PhD1, Avraham Beigelman, MD, culture-dependent and independent techniques. Our hypothesis is that 2 2 viruses impact the respiratory microbiome leading to worse clinical MSCI, FAAAAI , Mario Castro, MD, MPH , Elliot Israel, MD, FAAAAI3, Monica Kraft, MD4, David Mauger, PhD5, Richard sequelae during exacerbation. 6 7 8 METHODS: In this prospective, longitudinal study we recruited 101 pe- Martin, MD , Snehal Nariya, BS , Steven R. White, MD , Homer A. Boushey, Jr, MD1, Yvonne Huang, MD7; 1University of California San diatric patients with CF, ages 0-22 years. We collected oropharyngeal 2 SATURDAY swab, sputum, and BAL samples from subjects during their clinical base- Francisco, San Francisco, CA, Washington University, Saint Louis, MO, 3Brigham and Women’s Hospital, Boston, MA, 4University of Ari- line and exacerbation states. We used Illumina sequencing and standard 5 culture for bacterial detection and quantitative RT-PCR techniques for viral zona, Tuscon, AZ, Penn State University College of Medicine, Hershey, PA, 6National Jewish Health, Denver, CO, 7University of Michigan, Ann detection. 8 RESULTS: We collected 380 samples from 102 subjects between March, Arbor, MI, University of Chicago, Chicago, IL, 2013 and June, 2014. Seventy-three samples are virus positive and 307 are RATIONALE: While the composition of lower airway microbiota has virus negative. The most prevalent viruses in our cohort are rhinovirus/ been reported to differ in subjects with asthma compared to healthy enterovirus and coronavirus. Virus (+) samples are associated with a controls, it is unclear whether these differences are a function of asthma or greater prevalence of traditional CF pathogens (p 5 0.0018). We found are related to allergy. Here we dissect the specific bacterial taxa associated no clear relationship between viral infections and clinical status or lung with mild allergic asthma and those associated with allergy alone, in an function. Using deep-sequencing, we defined 1,772 OTUs rarified to attempt to identify potential bacterial contributors to asthma pathogenesis. 10,000 reads and found some changes in relative abundances of organisms METHODS: Bacterial composition in protected bronchial brushings, € in virus (+) compared to virus (-) samples, particularly prevotella species. from 28 mild corticosteroid-naıve allergic asthmatics (AA), 15 allergic CONCLUSIONS: Detection of viruses in pediatric patients with CF may non-asthmatics (AN) and 13 non-allergic non-asthmatics healthy controls predict subsequent infection with traditional CF pathogens. Viruses may (HC), was profiled using 16S rRNA sequencing on the Illumina MiSeq also be associated with subtle changes in the microbiome but further platform. analysis is needed. RESULTS: Compared to AN and HC, AA exhibited a loss of bacterial taxa, such as Lactobacillus, and Methylobacterium, which were predicted A Prospective Microbiome-Wide Association to encode putatively protective functions, and increased relative abundance 314 Study of Childhood Food Sensitization and Allergy of Haemophilus, Neisseria, Porphyromonas and Sphingomonodaceae.A number of these taxa were significantly correlated with systemic eosino- Jessica Rabe Savage, MD, MHS1, Joanne Sordillo, ScD2, Erica Soderg- philia and elevated serum IgE, implicating these organisms as potential ren3, George Weinstock3, Diane R. Gold, MD, MPH4, Scott T. Weiss, MD, contributors of eosinophilic inflammation in allergic asthma. A number MS5, Augusto A. Litonjua, MD, MPH2; 1Brigham and Women’s Hospital, of taxa, including Fusobacterium, Actinomyces and Treponema, which Division of Rheumatology, Immunology and Allergy, Boston, MA, were enriched in AA compared to HC airways were also enriched in AN 2Channing Division of Network Medicine, Brigham & Women’s Hospital, compared to HC, and were considered as allergy-associated. Harvard Medical School, Boston, MA, 3Jackson Laboratory, 4Channing CONCLUSIONS: This study distinguishes taxa associated with allergy Laboratory, Brigham and Women’s Hospital, Boston, MA, 5Channing from those which are potential contributors to asthma pathogenesis. Laboratory, Harvard Medical School, Boston, MA. Understanding which specific members of the airway microbial commu- RATIONALE: Alterations in the intestinal microbiome are prospectively nity associated with allergy and which are associated with asthma may associated with the development of asthma; it is unknown whether these prove crucial for development of targeted therapeutics to control, or differences occur in food allergy. ideally, to prevent the development of disease. METHODS: Child intestinal microbiome samples were collected at age 3-6 months in children participating in the follow-up phase of an interventional trial of high dose Vitamin D given during pregnancy. At age 3, sensitization to foods (milk, egg, peanut, soy, wheat, walnut) was assessed. Food allergy was defined as caretaker report of healthcare provider-diagnosed allergy to the above foods prior to age 3 years with evidence of IgE sensitization. Analysis was performed using phyloseq and DESeq2; p-values are adjusted for multiple comparisons. RESULTS: Complete data were available on 225 children; there were 87 cases of food sensitization and 14 cases of food allergy. Microbial diversity measures did not differ between food sensitization and food allergy cases

and controls. The genera Haemophilus (log2 fold change -2.10, p50.003), Clostridium (log2 fold change -1.57, p50.007), and Dorea (log2 fold change -1.57, p50.03) were underrepresented among subjects with food

sensitization. The genera Oscillospira (log2 fold change -2.85, p50.02), Citrobacter (log2 fold change -3.40, p50.02), Lactococcus (log2 fold change -3.33, p50.03), Dorea (log2 fold change -3.05, p50.03), and All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. J ALLERGY CLIN IMMUNOL Abstracts AB97 VOLUME 137, NUMBER 2

A Rationally Designed Microbial Consortium tolerance. Immunological changes were evaluated by monitoring sIgE and 316 Attenuates Allergic Asthma in a Murine Model sIgG4 levels and basophil reactivity. RESULTS: After one year of SLIT, the wheal area in SPT significantly Nikole E. Kimes, PhD, Ricardo B. Valladares, PhD, Din L. Lin, PhD, decreased and there was a significant increase in the amount of peach Susan V. Lynch, PhD; University of California, San Francisco. tolerated in treated patients (p<0.001). Patients in Group A showed a RATIONALE: Lactobacillus supplementation provides partial attenua- significant decrease in peanut SPTwheal area and an increase in amount of tion of allergic responses in the airway and alters the composition of the peanut tolerated (p<0.001). Immunological changes were observed in gastrointestinal microbiota. Using microbial profiling data from clinical treated patients only, with a significant decrease of sIgE and a parallel studies, we designed a bacterial consortium based on enriched taxa and increase of sIgG4, sIgG4/sIgE and basophil reactivity for both Pru p 3 and functional pathways associated with Lactobacillussupplementation. We Ara h 9. hypothesized that intervention using a microbial consortium would pro- CONCLUSIONS: After one year Pru p 3 SLIT induces both clinical and vide improved protection against allergic asthma due to the functional syn- immunological changes not only for peach but also for other food allergens ergism of the consortium members. relevant in the induction of severe reactions such as peanut. METHODS: To investigate the protective effects of supplementation, C57BL/6 mice were intratracheally sensitized and challenged with Immune Tolerance Induction Following AIT Is cockroach allergen (CRA). The mice were concurrently supplemented 318 Associated with Induction of Circulating with Lactobacillus johnsonii, the microbial consortium, or both over a CD4+CXCR5+PD-1+FoxP3+ T Follicular Regulatory three-week period. We evaluated allergic responses and potential mecha- Cells nisms of protection using flow cytometry, qPCR, 16S rRNA gene Hjh Hanisah Hj Awg Sharif, BHSc, MSc1,2, Rebecca Parkin, BSc1,2, sequencing, and histology. 1,2 2 RESULTS: Supplementation with the microbial consortium and L. john- Constance Ito, MSc , Guy Scadding, MRCP , Stephen R. Durham, MA, MD, FRCP1,2, Mohamed H. Shamji, BSc, MSc, PhD, soniicombined provided the most robust protection against allergic asthma, 1,2 1 including significant decreases in lung mucin hyperplasia and Muc5 gene FAAAAI ; Immunomodulation and Tolerance Group, Immune Toler- expression, as well as decreases in Th2-related cytokines. These responses ance Network (ITN) Distributed Centre of Excellence for Allergy & were correlated with systemic increases in IL-17 secreting leukocytes. Asthma, Allergy & Clinical Immunology Inflammation, Repair and Development National Heart & Lung Institute, Imperial College London, CONCLUSIONS: The gut microbiota forms a complex functional 2 network that influences both individual microbial members and host United Kingdom, MRC & Asthma UK Centre in Allergic Mechanisms of immune responses. Here we show that a rationally designed microbial Asthma, London, United Kingdom. consortium can provide greater attenuation of allergic asthma than an RATIONALE: Circulating T follicular regulatory cells (CD4+CXCR5+PD-1+FoxP3+ Tfr) are a newly identified subset of individual probiotic species. Future research will be aimed at character- + izing functional interactions and determining the mechanism of improved CD4 T cells with regulatory properties. We hypothesised that Tfr cells are dysregulated in patients with seasonal allergic rhinitis (SAR) compared protection. SATURDAY to non-atopic controls (NA). Furthermore, grass pollen immunotherapy The Clinical and Immunological Effects of Pru p 3 (AIT) is associated with the induction of Tfr cells which may play a role 317 Slit on Peach and Peanut Tolerance in Patients in tolerance induction during AIT. with Systemic Allergic Reactions METHODS: In a cross-sectional study of AIT, PBMCs were isolated from SAR (n513), NA (n513) and AIT (subcutaneous, SCIT (n510) and Francisca Gomez, MD, PhD1, Gador Bogas, MD2, Miguel Gonzalez3, sublingual, SLIT (n58) immunotherapy)-treated group. Circulating Paloma Campo, MD, PhD1, Maria Salas, MD, PhD1, J. A. Huertas1, Ara- CD4+CXCR5+PD-1+FoxP3+ Tfr, CD4+CXCR5+PD-1+FoxP3-T follicular celi Diaz-Perales, PhD, Prof4, Domingo Barber, MD5, Marıa J. Rodri- helper (Tfh) cells were enumerated by flow cytometry. Allergen-induced guez3, Miguel Blanca, MD, PhD6, Cristobalina Mayorga, PhD7, Marıa Tfr and Tfh cell proliferation were also assessed. Jose Torres, MD, PhD8; 1Allergy Unit, IBIMA-Regional University Hos- RESULTS: Symptom scores were lower in SCIT (p<0.0001) and SLIT pital of Malaga, Malaga, Spain, 2Allergy Unit, Regional University Hos- groups (p<0.05) compared to SAR. The frequency of circulating pital of Malaga-IBIMA, UMA, Malaga, Spain, 3Research Laboratory, CD4+CXCR5+PD-1+FoxP3+ Tfr cells were lower in SAR compared to IBIMA-Regional University Hospital of Malaga, Malaga, Spain, 4Centre NA (median (IQR):13.90(4.42-18.50);p<0.05) and were elevated in for Plant Biotechnology and Genomics (UPM-INIA), Campus de SCIT (24.15(13.10-34.24);p<0.05) and SLIT (26.00(20.70- Montegancedo, Pozuelo de Alarcon, Madrid, Spain, 5Universidad San 36.49);p<0.05). Conventional FoxP3+ Tregs were elevated in SCIT Pablo-CEU, Madrid, Spain, 6Allergy Service, IBIMA-Regional (6.83(4.83-7.92);p<0.01) and SLIT (6.64(5.48-7.92); p<0.001) compared University Hospital of Malaga-UMA, Malaga, Spain, 7Research to SAR (4.06(2.50-4.60). We also confirmed that Tfh cells were higher in Laboratory, IBIMA-Regional University Hospital of Malaga-UMA, SAR (86.10(81.50-95.58) compared to SCIT (75.58(65.76- Malaga, Spain, 8Allergy Unit, IBIMA, Regional University Hospital of 86.90);p<0.05), SLIT (74.00 (63.51-79.30);p<0.001) and NA Malaga, UMA, Malaga, Spain. (77.60(49.25-85.15); p<0.05) groups. In addition, Tfh but not Tfr cells RATIONALE: The peach non-specific lipid transfer protein (nsLTP), Pru showed increased proliferative capacity in response to in vitrograss pollen p 3, is the primary sensitizer in fruits and responsible for severe reactions in allergen stimulation. the Mediterranean area. Peach allergy is frequently accompanied with CONCLUSIONS: For the first time, we show that Tfr and Tfh cells are other allergies as peanut. Specific immunotherapy to Pru p 3 could affect dysregulated in patients with seasonal allergic rhinitis. AIT induces both peach and peanut tolerance. The aim is evaluate peach and peanut circulating Tfr cells and these cells may potentially be associated with tolerance and immunological changes after one year of Pru p 3 sublingual tolerance induction during AIT. immunotherapy (SLIT) in patients with systemic allergic reactions to peach and/or peanut. METHODS: Forty-eight peach allergic patients, 36 treated with SLITand 12 non-treated, were monitored for 12 months. Treated patients were sub- classified as peanut allergic (Group A), sensitized (Group B) or tolerant (Group C). SLIT efficacy was evaluated by skin test reactivity and food All abstracts are strictly embargoed until the date of presentation at the 2016 Annual Meeting. AB98 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2016

Early Introduction of Egg for Infants with Atopic farm children had increased numbers of viral respiratory illnesses/child/ 319 Dermatitis to Prevent Egg Allergy: A Double- year (mean 2.69, 95% CI, 1.79-4.04) compared to farm children (mean Blind Placebo-Controlled Randomized Clinical 1.45, 95% CI 0.94-2.25), a 1.85-fold increase (95% CI 1.02-3.35, p50.04). Trial CONCLUSIONS: Despite similar rates of viral infection, farm versus non-farm children have significantly decreased rates of respiratory viral Osamu Natsume, MD1, Shigenori Kabashima, MD, PhD1, Junko illnesses. Early-life farming exposures may impact anti-viral immune Nakasato, MD, PhD1, Kiwako Yamamoto-Hanada, MD1, Masami maturation. Narita, MD, PhD1, Mai Kondo, MD1, Mayako Saito, MD1,Ai Kishino, MD1, Eisuke Inoue, PhD2, Wakako Shinahara, PhD3, Hiroshi Could Allergen Immunotherapy be a Therapeutic Kido, MD, PhD3, Hirohisa Saito, MD, PhD4, Yukihiro Ohya, MD, 321 Intervention in Eosinophilic Oesophagitis? PhD1; 1Division of Allergy, National Center for Child Health and Development, Tokyo, Japan, 2National Center for Child Health and Moises A. Calderon, MD, PhD; Imperial College London, London, Development, Tokyo, Japan, 3The University of Tokushima, Japan, United Kingdom. 4Department of Allergy and Clinical Immunology, National Research RATIONALE: Eosinophilic esophagitis (EoE) is characterized by Institute for Child Health and Development, Tokyo, Japan. esophageal dysfunction and, histologically, by eosinophilic inflammation. RATIONALE: We investigated whether an early introduction of a small Although different therapeutic interventions are used to improve EoE, SATURDAY amount of egg for infants with atopic dermatitis would prevent egg allergy there is no aetiological treatment and diet exclusion is difficult. in the first year of life. OBJECTIVE: Component resolved diagnostic (CRD) may be useful in METHODS: This intervention was carried out as a double-blind, placebo- detecting the allergens that might be involved in this inflammatory process. controlled, parallel-group, randomized clinical trial (DBPCRCT). Infants This will allow the selection of a proper diet and allergen immunotherapy with atopic dermatitis were randomly assigned to one of the two groups: (AIT) to treat EoE. placebo or egg consumption. The infants were enrolled between four to five METHODS: 55 patients with clinical and histological diagnosis of EoE months of age, and started taking egg powder or placebo daily from six were tested for environmental and food allergens. CRD analysis with months until 12 months of age. Participants of the intervention arm (egg microarray technology was performed. Clinical evolution, including group) took 50 mg of heated egg powder from six to nine months and 250 adjusted symptom scores and endoscopic biopsy, were performed every mg from nine to 12 months of age. The primary outcome was a prevalence six months for 2 years. 50 healthy patients served as control group. of hen’s egg allergy confirmed by oral food challenges at 12 months of age. Subcutaneous AIT (SCIT- ALK Abello) was administered in 39 patients RESULTS: This trial was completed based on the result of a scheduled with EoE. Exclusion diet was indicated according to CRD (only 1 or 2 interim analysis which showed a significant difference between the two group of food avoidance). groups. A total of 121 participants were in the intention-to-treat analysis RESULTS: Allergy was detected in 88% of patients with EoE. The (placebo group n561; egg group n560). The prevalence of egg allergy was predominant allergens were grasses group 1 and, in particular, nCyn d 1 37.7% in placebo group and 8.3% in egg group (p50.0013). There was no (Cynodon dactylon) or Bermuda grass pollen, followed by lipid transfer significant difference in adverse events between the two groups. proteins (LTP) of peach and mugwort, hazelnuts and walnuts. After two CONCLUSIONS: The introduction of a small amount of heated egg at six years of the array-guided exclusion diet and SCIT, patients with EoE months old followed by stepwise increasing in intake is effective and safe showed a significant clinical improvement and 68% of patients were for infants with atopic dermatitis to prevent hen’s egg allergy in the first discharged from clinic (cure based on negative biopsy, no symptoms, no year of life. The trial registration is UMIN-CTR 000008673. medication intake). CONCLUSIONS: In patients with EoE, sensitization to plant foods and Farm Exposure Is Associated with Reduced Rates pollen is important. AIT seems to be efficacious and well tolerated in 320 of Viral Respiratory Illnesses in Early Life patients with EoE.

Jamee R. Castillo, MD1, Christine M. Seroogy, MD, FAAAAI1, Matt Keifer, MPH, MD2, Iris A. Reyes, MPH2, Jeffrey Van Wormer, PhD2, Jen- nifer Meece, PhD2, Michael D. Evans, MS1, James E. Gern, MD, FAAAAI3; 1University of Wisconsin School of Medicine and Public Health, Madison, WI, 2National Farm Medicine Center, Marshfield Clinic Research Foundation, Marshfield, WI, 3University of Wisconsin-Madison, Madison, WI. RATIONALE: Early-life exposure to farm animals is associated with reduced allergic diseases. The aim of this study is to determine effects of farm exposure on rates of viral infections and illnesses through age 2 years. We hypothesized that the rate of viral infections will be the same between farm and non-farm children, while the rate of illnesses will be lower in farm children. METHODS: In a prospective birth cohort study, nasal mucous samples were collected from farm and non-farm children at scheduled intervals (2, 9, 12, and 18 months of age), and during respiratory illnesses (at least mild symptoms>_2 days). Farm children were born to women who reside or work on cattle or dairy farms. Infection rates were determined by viral detection (multiplex PCR) at scheduled visits. RESULTS: 210 nasal specimens from 28 farm children and 24 non-farm children were analyzed. Mean length of time for follow-up was 10.1 months for farm children and 10.3 months for non-farm children. Viral detection rates were similar in farm and non-farm children at scheduled visits (2 months: 8/28 vs. 9/24, p50.49; 9 months: 7/15 vs. 8/15, p50.72; 12 months: 3/11 vs. 4/6, p50.11; 18 months: 1/3 vs. 1/3, p51.00). Non-