J ALLERGY CLIN IMMUNOL Abstracts AB99 VOLUME 147, NUMBER 2

Needs Assessment for an Infant and Toddler participants were unaware of the LEAP study and 51 (61%) did not know 313 Food Allergy Curriculum for Pediatric Residents about the addendum guidelines. CONCLUSIONS: This preliminary data demonstrates that there is a Marielle Young1, Ariel Frey-Vogel, MD1, Kristina Dzara, PhD, MMSc1, knowledge gap in pediatric residents and more education is necessary. This Michael Pistiner, MD MMSc2; 1MassGeneral Hospital for Children, is an ongoing project that will use didactic tools to ensure future 2MassGeneral Hospital for Children, Harva. implementation of the guidelines. RATIONALE: The prevalence of pediatric food allergies is increasing. Approximately 6% of children ages 0 to 2 years have a food allergy. A Quality Improvement Initiative to Improve Pediatric residents are frontline providers for children with food allergies, 315 Resident- Physician Practices Regarding Flu but little is known about their educational experiences and comfort Vaccine Administration in Individuals with Egg managing infant/toddler food allergies. Allergy

METHODS: An anonymous online needs assessment survey was created 1 1 2 and distributed to pediatric residents in one residency program. The survey Aishwarya Navalpakam , Shweta Saini, MD , Chi- Lan Tran , Jenny Huang, MD1, Divya Seth2, Pavadee Poowuttikul, MD FAAAAI2; 1Chil- explored residents’ knowledge sources, experience and comfort diag- 2 nosing, treating and counseling patients regarding infant/toddler food dren’s Hospital of Michigan, Wayne State University. allergies. RATIONALE: Individuals with any severity of egg allergy, including RESULTS: Forty-nine pediatric residents (77%) responded. Prior to anaphylaxis, should receive the influenza vaccine annually per CDC residency, most residents (94%) did not have any formal training on infant/ guidelines. This recommendation has evolved over the past ten years. We toddler food allergies. The most common sources of information on infant/ performed a quality improvement initiative to assess and improve resident toddler food allergies included outpatient pediatric clinicians (74%), other physician practices regarding flu vaccine administration in egg allergic pediatric residents (59%) and emergency department clinicians (55%). individuals. Nearly all residents were uncomfortable (69%) evaluating food allergies. METHODS: Residents rotating through the allergy clinic of a free- Most residents were very uncomfortable (20%) or uncomfortable (65%) standing children’s hospital were provided with a pre-survey, educational managing food allergies. Most residents were very uncomfortable (16%) or intervention, and post-survey over the course of a year. The educational uncomfortable (65%) counseling families about food allergy diagnosis. intervention was a brief informational session on influenza vaccine by the The majority of residents were very uncomfortable (14%) or uncomfort- allergy fellow in clinic. Data was analyzed using descriptive statistics. Chi- able (53%) counseling families about food allergy prevention. In contrast, square test was performed. most residents were very comfortable (16%) or comfortable (53%) RESULTS: Pre-intervention survey was completed by 34 residents and diagnosing anaphylaxis. Similarly, most were very comfortable (20%) or post-intervention survey by 22 residents. Prior to the intervention, 14% of comfortable (49%) treating anaphylaxis. residents believed that the flu vaccine is contraindicated in patients with CONCLUSIONS: While pediatric residents feel comfortable diagnosing history of anaphylaxis to egg. After receiving education, none of the and treating infant/toddler anaphylaxis, there is a lack of comfort residents believed that the flu vaccine was contraindicated in these patients 5 surrounding infant/toddler food allergy evaluation, management, and (p 0.16). Only 44% of residents pre-intervention would administer the counseling for families. Pediatric residents may benefit from a compre- vaccine in the usual manner with egg allergic patients intervention when hensive infant/toddler food allergy curriculum which focuses on these compared to 90% post- intervention (p <0.005). specific areas of need. CONCLUSIONS: This study revealed room for improvement in resident training and practice in influenza vaccine administration in egg allergic Assessment of Early Peanut Introduction individuals. A focused educational intervention led to increased resident 314 Guidelines Among Pediatricians In An Inner- knowledge and better adherence to influenza vaccine administration city Hospital guidelines.

Sumeet Sandhu, MD1, Monique Hanono, MD2, Carly Rabin, MD2, Rob Harriz, MD2, Sairaman Nagarajan, MD MPH1, Maria-Anna Vastardi, MD1; 1Center for Allergy and Asthma Research, SUNY Brooklyn Health Sciences University, 2SUNY Downstate Medical Center. RATIONALE: Peanuts are the leading cause of death from food-induced anaphylaxis. The 2015 Learning Early About Peanut Allergy (LEAP) landmark study led to the 2017 Addendum Guidelines, which recommends early peanut introduction to infants at increased risk of developing peanut allergy. It is unclear to what extend general pediatricians follow these guidelines. Educating pediatric residents and attendings will result in an increased knowledge of these evidence-based early peanut introduction guidelines, leading to reduced development of peanut allergy in the pediatric population. METHODS: In this multicenter study, an anonymous voluntary survey was used to assess knowledge and practice of early peanut introduction in pediatric house staff and attendings. RESULTS: Currently, we have collected 83 completed surveys. Of these, 73 (88%) survey participants were residents. 43 (52%) participants start discussing peanut introduction at age 6 months and 73 (88%) participants have never ordered serum specific peanut IgE. Only 5 (6%) participants were comfortable with interpreting lab results to diagnose peanut allergy, 42 (51%) were somewhat comfortable and 36 (43%) were not comfortable. Most common reason parents reported to doctors for not introducing peanuts early was that they were unaware (23 participants). 35 (42%) AB100 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Dietary Normalization Following A Successful guardians screened positively for worry (82%, N518) or stress (59%, 316 Oral Food Challenge In Children With Food N513). Of those who screened positively for worry or stress, 11% (N52) Allergies and 8% (N51) responded that their child had been bullied/teased, respectively. Elizaveta Rakhmanova, BSc1, Kuang-Chih Hsiao, MBChB2; 1Univer- CONCLUSIONS: Based on the results of this survey study, allergists and sity of Auckland School of Medicine, Auckland, New Zealand, 2Starship pediatricians are infrequently screening for food allergy-related bullying/ Hospital, Auckland District Health Board, Auckland, New Zealand. teasing and parents are receptive to screening and resources. RATIONALE: Oral food challenge (OFC) is a resource-intensive yet invaluable investigation for diagnosing food allergy (FA) and confirming Systematic Development of a Patient-centered FA resolution. Some recent case series report low rates of regular dietary 318 Outcomes Measure to Assess the Psychosocial consumption of previously implicated allergen despite successful OFC, Impact of Food Allergy in Routine Clinical with no local data available to date. We hypothesized that continued Practice ingestion rates post successful OFC may be influenced by patient and 1 2 procedure-related factors Katherine Tison , Kaitlin Proctor, PhD , Hayley Estrem, PhD, MSN, RN3, Jinhee Park, PhD, RN4, Brian Vickery, MD FAAAAI1, William METHODS: We identified 195 children who passed an OFC (peanut, 1 1 2 mixed/multiple tree nuts, baked egg, baked milk, hen’s egg, cow’s milk) Sharp, PhD ; Emory University School of Medicine, Center for Advanced Pediatrics, Children’s Healthcare of Atlanta, 3UNCW School and were followed up by the paediatric immunology service at a university- 4 affiliated tertiary hospital in Auckland, New Zealand, from March 2016 of Nursing, Boston College. through February 2019. Relevant data were retrieved from a prospectively RATIONALE: A recently conducted patient-centered outcomes study maintained OFC service database and patients’ electronic medical records. identified assessment and treatment of food allergy (FA)-related psycho- Effects of exposure variables on ingestion status were examined using Chi- social issues a top research priority. Most currently available instruments Square tests. are designed for use in research settings and focus primarily on FA-related RESULTS: Passing an OFC enabled continued ingestion in the majority quality of life. Our team sought to systematically develop a measure of FA (86%,169/195) of our population at a median follow-up of 10.95 psychosocial impact on caregivers that is sensitive to change with (IQR:5.95-14.76) months. Ingestion status post-OFC was associated with treatment. the allergen tested but not with past atopy, gender, ethnicity, or age at OFC METHODS: Eighteen caregivers of children with FA recruited from the and follow-up. The rate of ongoing consumption was significantly lower CHOA Food Allergy Center participated in focus groups centered on (p50.002) in those who passed mixed nut OFC (69.7%,23/33) as compared exploring caregiver perception of the psychosocial impact FA had on to other challenged foods (90.1%,146/162). themselves and their families. Interviews were transcribed and entered into CONCLUSIONS: In our experience, successful OFC enabled dietary ATLAS.ti for analysis. Analysis was completed using a multi-step, incorporation of allergens in most patients. However, children with iterative process. The initial coding system was based on relevant multiple nut allergies may require additional support to aid dietary literature. Eight members of the research team independently coded normalization. Further work examining the links between type/amount data. The team then discussed discrepancies and reached consensus. of allergen challenged, long-term ingestion status, and quality of life Codes were then reviewed to identify key themes that captured why each impact, is underway. code was assigned. RESULTS: Seventeen codes were derived from the first round of coding. Parental Perspectives on Food Allergy-Related The most frequent codes included caregiver adjustment, allergy specific 317 Bullying/Teasing Screening Practices by knowledge, integration of daily adaptations, and communication both Allergists and Pediatricians within and outside the family. The second round of coding is underway. Based on key themes identified, measure items will be generated. Dana O’Toole, MD1, Charlene Thomas1, Linda Gerber, PhD1, Elizabeth CONCLUSIONS: This study generated an emerging understanding of Feuille, MD1, Edith Schussler, MD1, Lisa Bartnikas, MD2, Perdita Per- caregiver’s perception regarding the unique psychosocial impact of FA on maul, MD FAAAAI1; 1Weill Cornell Medicine, 2Boston Children’s patients and caregivers. With this foundation in place, continued measure Hospital. development will support outcomes research, including a manual-based, RATIONALE: Studies have demonstrated that children with food psychosocial intervention to support patients and their caregivers impacted allergies are bullied/teased, impacting child and parent quality of life. by FA. We hypothesized that allergists and pediatricians infrequently ask parents/ guardians about food allergy-related bullying/teasing. METHODS: The Division of Pediatric Allergy/Immunology at NewYork- Presbyterian Hospital/Weill Cornell Medical Center surveyed the parents/ guardians of 22 pediatric patients with food allergies, ages 5-18 years, followed by an allergist. Parents/guardians completed an anonymous survey in the waiting room of their child’s normally scheduled allergy or primary care appointment, including an original survey on screening for bullying/teasing and validated surveys on worry (The Penn State Worry Questionnaire) and stress (Perceived Stress Scale). The patient’s de- mographics and food allergy history were collected. RESULTS: 18% (N54) of parents/guardians responded that their child had been bullied/teased about his/her food allergies. 91% (N520) and 86% (N519) of parents/guardians identified that their allergist or pediatrician never or almost never asks about food allergy-related bullying/teasing, respectively. Of the 4 who reported their child had been bullied/teased, none reported having been asked by their allergist or pediatrician about bullying/teasing. All parents/guardians surveyed were comfortable being screened by their child’s allergist and pediatrician. 59% (N513) of parents/guardians were interested in educational materials. Parents/ J ALLERGY CLIN IMMUNOL Abstracts AB101 VOLUME 147, NUMBER 2

A Quality Improvement Initiative to Improve differ. While caregivers find seeking educational information and con- 319 Resident-Physician Practices Regarding Peanut necting with others helpful, children utilize fewer coping strategies to Introduction in Infancy manage their FA-related emotions. Caregivers overwhelmingly expressed interest in testing new coping interventions for their children with FA, Shweta Saini, MD1, Chi-Lan Tran2, Jenny Huang, MD1, Divya Seth1,Pa- indicating a need for mental health professionals to address this gap in vadee Poowuttikul, MD FAAAAI1; 1Children’s Hospital of Michigan, De- psychosocial support for FA families. troit, MI, 2Wayne State University School of Medicine, Detroit, MI. RATIONALE: In 2017, the National Institute of Allergy and Infectious Addressing food insecurities in clients with Diseases (NIAID) developed addendum guidelines for peanut allergy 321 food allergies in underserved communities prevention giving recommendations regarding peanut introduction in at- with a prescription food program risk infants. However, recent data has suggested that these recommenda- 1 1 1 tions have not yet been fully implemented in primary care setting. We Andrea D’Mello, MD , Amara Seng , Marissa Love, MD , Erin Martinez, MS2, Emily Brown2; 1University of Kansas Medical Center, undertook a quality improvement initiative to improve resident-physician 2 practices regarding peanut introduction in infancy. The Food Equality Initiative. METHODS: Pediatric residents rotating through allergy clinic at a RATIONALE: Food insecurity affects 11% of American households and children’s hospital were surveyed from 08/2019- 07/2020. Survey was people with food allergies are at a higher risk of food insecurity due to conducted before and after an educational session (intervention) based on dietary restrictions. Food Equality Initiative (FEI) is a novel prescription the 2017 NIAID addendum guidelines, run by allergy fellows. Data was food program for clients with food allergies and celiac disease in analyzed using descriptive statistics and statistical significance was underserved populations. In this study, we describe the demographics of determined using chi-square test. the clients with food allergies who have benefited from this innovative RESULTS: A total of 56 survey questionnaires were collected (pre- prescription food program. intervention N534, post-intervention N522). For infants with moderate- METHODS: A retrospective study assessed data from de-identified FEI severe eczema or egg allergy, only 14.71% of the pre-intervention clients regarding specific food allergies, food insecurity, and general responders recommended peanut feeding at 4-6 months, 23.53% recom- demographics. Data from clients with celiac disease and clients with mended serum IgE or referral to an allergist before peanut introduction missing survey data were omitted from analysis. Data was analyzed using while 5.88% recommended delayed peanut feeding. After the intervention, Prism GraphPad. 72.73% of the participants answered the question correctly (P50.025). For RESULTS: From 2016 to 2019, FEI served over 100 clients. The average peanut introduction in infants without moderate-severe eczema or egg annual cost of providing food per client was $1800. An overwhelming 84% allergy, 58.82% of the responders in the pre-intervention group recom- of clients with food allergies felt food insecure, and 74% of those patients mended peanut introduction at 4-6 months or recommended peanut had an annual income of less than $50,000. About 79% of clients needed to introduction in accordance with the cultural practices of the family. avoid more than one food to manage their condition. About 40% of clients After the intervention, 86.36% of the participants answered the question were not Caucasian. The common food triggers that clients reported correctly. avoiding were cow’s milk, wheat, and peanut. CONCLUSIONS: The results of our survey study show significant CONCLUSIONS: These data demonstrate the utility of prescription food improvement in the residents’ knowledge regarding peanut introduction assistance and the demographics of the clients who benefit from them. in at-risk infants by increasing awareness about addendum guidelines for Prescription food programs, like FEI, are a valuable resource for people peanut allergy prevention. with food restrictions living in underserved communities. 320 Exploring psychosocial coping with food allergy

Lisa Lombard, PhD1, Gwen Holtzman, BA1, Madeleine Kanaley, BA1, James Lawson1, Hannah Safron1, Ruchi Gupta, MD MPH2; 1North- western University, 2Northwestern Medicine. RATIONALE: This study aims to better understand the emotional experiences and related coping strategies of food-allergic children and their caregivers, so that effective psychosocial interventions can be designed to support this population. METHODS: An online cross-sectional, population-based survey was sent to caregivers of children with food allergies. Questions assessed care- givers’ and their children’s emotions about FA, their current coping strategies, and their interest in testing new coping strategies to manage their FA-related emotions. RESULTS: 472 surveys were completed. Respondents were predomi- nantly female, non-Hispanic white, and living in a suburban location. Caregivers and children shared 4 of the top 5 endorsed emotions, ‘‘anxious’’, ‘‘scared’’, ‘‘sad’’, and ‘‘frustrated’’ when asked how they felt about living with FA. Caregivers’ most helpful coping strategies included reading articles about FA (80.8%), talking with a doctor (78.3%), and talking with friends and family (64.1%), while children’s most helpful strategies were speaking with trusted adults (30.3%) and doctors (11.6%), followed by ‘‘nothing’’ (10%) and ‘‘I don’t know’’ (8.1%). When asked if they were interested in trying new coping interventions, over half (66%) of respondents said ‘‘yes’’. CONCLUSIONS: Results suggest emotional experiences related to FA overlap between caregivers and children, though their coping strategies AB102 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

The impact of COVID-19 on patients with food unique longitudinal perspective on the influence of allergic diseases on 322 protein-induced enterocolitis syndrome (FPIES) growth trajectories throughout childhood and adolescence. and their caregivers. Assessment of Anxiety, Depression and Brit Trogen, Hope Jin, MD1, Antonella Cianferoni, MD PhD FAAAAI2, 324 Resilience in Food-Allergic Adolescents and Fallon Schultz, MSW, LCSW, CAM3, Amity Chavez4, Anna Nowak- Primary Caregivers During the COVID-19 Wegrzyn, MD, PhD1; 1NYU Langone Health, 2Children, 3FPIES, 4Int. Pandemic RATIONALE: To assess the burden of COVID-19 on patients with food Ashton Rogers1, Emily Seminara2, Caitlan Murphy, MD3, Diana Munoz- protein-induced enterocolitis syndrome (FPIES) and their caregivers. 4 5 3 METHODS: An anonymous survey was distributed online to subscribers Mendoza, MD , Amika Sood, MD , Ellen Manegold, PhD , Brandi Whitaker, PhD3, Stacie Jones, MD FAAAAI6, Amy Scurlock, MD of the International FPIES Association website, https://www.fpies.org, 7 1 2 from March-July, 2020. FAAAAI ; Arkansas Children’s Research Institute, Arkansas Chil- dren’s, 3UAMS, 4University of Arkansas for Medical Scien, 5Arkansas RESULTS: 147 surveys were completed, 142 of which were submitted by 6 7 mothers of children affected by FPIES with mean age of 3.3 years (Range: Children, UAMS/Arkansas Children, UAMS/AR Children’s Hospital. 2mo-16yrs). No cases of COVID-19 were reported by respondents or their RATIONALE: Food allergy has significant psychosocial impacts, which children. Increased stress during the pandemic was widespread with 57.1% may be intensified during times of stress. We evaluated mental health and reporting difficulty buying safe, nutritious food, 82.3% utilizing multiple resilience in food allergic adolescent- caregiver dyads during the COVID- retailers to buy safe foods, and 80.3% spending more money on food during 19 pandemic. the pandemic. Among respondents, 59.1% reported stress of 7 or greater on METHODS: Food-allergic adolescents (13-17 years) and caregivers were a 10-point scale due to inability to safely obtain adequate nutrition during recruited from the Arkansas Children’s Food Allergy Program. Dyads COVID-19. 64.6% reported significant worry that FPIES/food allergies participated in structured telephone interviews including demographics, would result in more severe symptoms in the case of COVID-19 infection. adolescent medical and mental health history and responses to the 74.1% reported worries about managing FPIES or anaphylactic reactions following validated assessments: 1) Generalized Anxiety Disorder-7 during COVID-19, and 82.3% reported significant worries about having to (GAD-7); 2) Patient Health Questionnaire-9 (PHQ-9); 3) Connor- go to the emergency department for these reactions during the pandemic. Davidson Resilience Scale (CD-RISC) and 4) COVID-19 Exposure and Among respondents, 16.3% consulted with a registered dietitian to develop Family Impact Scale (CEFIS, CEFIS-AYA). Psychology contacted all a meal plan during COVID-19, and 36.1% contacted a physician with individuals reporting concerning symptoms. questions regarding managing FPIES or food allergies during the RESULTS: Fifty-four adolescent-caregiver dyads (median adolescent 5 pandemic. 59.9% reported having a physician office visit canceled during age 14 years) completed interviews. Participants were 68.5% male and COVID-19, and 58.5% reported utilizing telemedicine to contact their 72% reported multiple food allergies. Comorbidities included allergic physician during this period. rhinitis (54%), asthma (65%), and atopic dermatitis (46%). Self-reported CONCLUSIONS: Families affected by FPIES experienced increased mental health conditions were observed in 46% of adolescents, including stress during the pandemic even in the absence of acute COVID-19 anxiety (48%), depression (24%), and ADHD (48%). PHQ-9 scores were infection in this population. above clinical cut-offs for depression in 7% of adolescents and 9% of caregivers. GAD-7 scores were above clinical cut-offs for anxiety in 13% Early Growth in Children with IgE and Non-IgE- of adolescents and caregivers. CD-RISC scores in the lowest two quartiles 323 Mediated Food Allergy in a Healthy Infant were observed in 76% of adolescents, compared with 44% of caregivers. Cohort Mean adolescent self-reported distress due to COVID-19 (CEFIS-AYA)5 3.98 62.25 vs. caregiver-reported 5.2662.32; caregiver self-reported Rachael Rosow1, Yamini Virkud, MD FAAAAI1, Victoria Martin, MD1, stress due to COVID-19 (CEFIS)55.69 62.20. Wayne Shreffler, MD PhD FAAAAI2, Qian Yuan, MD PhD1; 1Massachu- CONCLUSIONS: Food-allergic adolescents reported poorer resilience, setts General Hospital, 2Massachusetts General Hospital / Harvard. but better COVID-19 coping than caregivers, with rates of depression and RATIONALE: There are conflicting reported associations between food anxiety comparable to other chronic illnesses. Improving resiliency and allergies and poor growth, with some indication that children with multiple mental health is an important consideration in comprehensive food allergy food allergies are at highest risk. We used longitudinal weight data from management. our healthy cohort to evaluate associations between IgE-mediated food allergy (IgE-FA), cow’s milk protein intolerance (aka Food Protein Induced Allergic Proctocolitis, FPIAP) and weight. METHODS: The Gastrointestinal Microbiome and Allergic Proctocolitis (GMAP) study is an observational cohort of 1003 healthy newborn infants designed to prospectively evaluate the development of pediatric food allergies. We used longitudinal mixed effects modeling to compare differences in weight among children with IgE-FA and FPIAP, compared to children without, through age 4. RESULTS: 805 subjects (age 0-4 years) met inclusion criteria, with a cumulative IgE-FA incidence of 6.2%, multiple IgE-FA of 2.2%, and FPIAP of 16.6%. There were no significant differences in weight in children with IgE-FA compared to unaffected children (p 5 0.13), or in children with FPIAP compared to unaffected children (p 5 0.69). There was a significant association between multiple IgE-FAs and decreased weight over time (p < 0.001). CONCLUSIONS: Our findings support an association between multiple IgE-FAs and decreased weight gain over time, but no association between overall IgE-FA or FPIAP and weight were seen in this population. Analyses of linear growth and weight-for-length are ongoing which will offer a J ALLERGY CLIN IMMUNOL Abstracts AB103 VOLUME 147, NUMBER 2

Yellow Fever Vaccine in 435 Egg Allergic Identification Is Key: Barriers To Regular Usage 325 Children During 2018-2019 Yellow Fever 327 Of Allergy Identifiers Epidemic in Brazil Sebastian Sylvestre1, Doerthe Andreae, MD PhD1; 1Penn State Hershey Wilson Rocha1, Fernanda Lopes1, Livia Oliviera1; 1Hospital Infantil Jo~ao Medical Center. Paulo II. RATIONALE: Prompt administration of epinephrine is paramount in the RATIONALE: During the 2018-2019 Yellow fever (YF) epidemic in management of anaphylaxis and allergy identifiers may help promote Brazil there was an urgent need for vaccination in egg allergic children recognition of this life-threatening condition. However, few pediatric METHODS: Children were referred to the Food Allergy Clinic of our patients with food allergies wear allergy identifiers. We inquired why institution for supervised YF vaccination. The diagnosis of egg allergy was patients do not wear allergy identifiers and investigated social determinants made by history and sIgE to egg. Children were classified as probably non- of health that may impact patients’ usage. allergic or probably allergic to egg. Those with a history of anaphylactic METHODS: Penn State Hershey Medical Center’s Pediatric Allergy/ reaction were submitted to a prick-test with the vaccine. If positive, 2 doses Immunology clinic collected and analyzed surveys answered by 27 of 0,25 ml SC, 30 minutes apart, were applied. All the others received a caregivers and their children diagnosed with IgE-mediated food allergies single dose of 0,5 ml SC of the YF vaccine. Children were observed for 1 for a prospective observational study. The survey investigated barriers to hour after vaccination. The primary end-point was the need for epinephrine wearing allergy identifiers as well as patient demographics. Measures of injection. The secondary end point was the incidence of YF vaccine central tendency were used in our analyses. reaction. RESULTS: Though a significant portion of children diagnosed with food RESULTS: We study 435 egg allergic children; 83 (19%) children were allergy required epinephrine administration (53% for <10 years of age; classified as probably non-allergic and 352 (81%) as probably allergic to 25% for >10 years of age), only about 20% of children wear allergy egg, of which 91 (26%) were considered to have severe egg allergy identifiers. Socioeconomic status is a strong predictor of allergy identifier (anaphylaxis to egg). 422 (97%) patients had no YF vaccine reaction; usage. Decreased usage is associated with having public insurance (7%) 21(18%) received the fraction schedule. Twenty patients react to YF and household income of less than $50,000 (0%) as compared to having vaccine; 11 (55%) had mild local reactions and 9 (45% ) had diffuse skin private insurance (48%) and household income of greater than $50,000 rash. Only 1(0,2%) patient with a negative prick test to the vaccine needed (25%), respectively. Families consider allergy identifiers unnecessary, epinephrine. unattractive, and/or associated with social stigma, while others (22%) were CONCLUSIONS: YF vaccine is safe in egg allergic children. Skin test did never offered one. Most respondents (56%) reported preference for not predict the reaction and can probably be abandoned as a screening wearing bracelets among available allergy identifier options. method in children with anaphylactic reaction to egg. CONCLUSIONS: This prospective observational survey supports exist- ing evidence that few patients with food allergies wear allergy identifiers. Screening for Anti-Food Immunoglobulin G of Lower socioeconomic status, perceived social stigma, and/or aesthetic 326 Human Plasma and an Intravenous displeasure significantly impact usage. Bracelets are the allergy identifier Immunoglobulin Preparation (Gammagard most likely to be worn by patients. Liquid)

Alfred Weber1, Andrea Engelmaier2; 1Baxalta Innovations GmbH, now part of Takeda, 2Baxalta Innovation Gmbh, Member of Taked. RATIONALE: Chronic reactions to food antigens triggered by specific immunoglobulin G (IgGs) have been described. In contrast to the imme- diate reaction characteristic for IgE-mediated allergy, IgG-driven symp- toms take longer to appear. We here screened a human normal reference plasma pool and two lots of the intravenous IgG preparation Gammagard Liquid for the presence of IgG antibodies against 108 Mediterranean food antigens. METHODS: The commercially available semiquantitative kit ‘‘Mediterranean Food IgG’’ (Genesis Diagnostics) was applied to screen one lot of the normal reference plasma preparation CRYOCheck (Precision BioLogics) and two lots of GGL for the presence of anti-food IgG. The assay and the data evaluation were carried out according to instructions of the manufacturer. RESULTS: The reference plasma preparation showed borderline/positive binding to two of the 108 antigens tested. Thus, a positive reaction (16 units, defined range 12.5 to 25 U) was found for cow milk antigen, while binding to egg white was borderline (10 U, range 8 to 12.5). The two GGL lots, measured at the same total IgG concentration, showed clearly lower binding with borderline binding to cow milk (8 U) in only one GGL lot. Weak binding to the food antigens almond, hazelnut, lemon and corn was observed for at least one lot GLL, but binding was below the assay cut-off (8 U). CONCLUSIONS: The data obtained do not indicate the presence of significant levels of anti-food IgG in GGL. Thus, a passive transfer of anti- food IgG during IgG substitution therapy is unlikely to occur. AB104 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

N-terminal Leader Sequence of Vicilin Storage Characteristics of Baked Cheese Challenge 328 Proteins Potentially Contribute to Cross-reactivity 330 Between Evolutionarily Distant Plant Species. Jeehyun Rha1, Bruce Lanser, MD FAAAAI2; 1University of Colorado/ Alexander Foo1, Jacqueline Nesbit, PhD2, Stephen Gipson3, Eugene National Jewish Health, 2National Jewish Health. DeRose1, Barry Hurlburt, PhD2, Soheila Maleki, PhD FAAAAI4, Geof- RATIONALE: Cow’s milk (CM) is the most common food allergy in frey Mueller, PhD1; 1NIEHS, 2USDA, 3USDA SRRC, 4USDA-Agricul- young children. While commonly outgrown, avoidance is difficult, and tural Research Service. causes significant deficits in quality of life. Baked milk (BM) may hasten RATIONALE: Peanut (PN) allergy is frequently comorbid with allergy to outgrowing CM allergy, but little is known about baked cheese (BC) tree-nuts (TN) such as walnuts (WN), cashews (CS) and pistachios (PS). Vicilin tolerance, which can be an intermediate step between baked milk and CM. seed storage proteins from both PN and TN are expressed with an N-terminal METHODS: We performed a 3-year retrospective review of all BC oral leader sequence (LS) consisting of a repeated CxxxC helical-hairpin motif, the food challenges (OFCs) performed in children diagnosed with CM allergy structural and immunological characterization of which may provide insights and BM-tolerant. All associated clinical and laboratory data was evaluated. into the cross-reactivity observed between these evolutionarily distant species. Negative/positive (pass/fail) determination was made by the individual METHODS: The structure of the individual CxxxC motifs from PN provider performing the OFC. (AH1), WN (JR21, JR22, JR23), CS (AO1, AO2), and PS (PV1, PV2) were RESULTS: There were 25 open OFCs conducted in 24 children. Twenty- solved using solution-NMR, while simulated gastric digestion and circular three OFCs were negative (96% passed). The median CM sIgE was 2.64 dichroism were used to assess biophysical stability. Peptide microarrays kUA/L (range 0.34-95.5), and mean CM skin prick test was 12 mm (range were used to identify and map IgE epitopes onto the resulting structures to 6-23) among all 24 children. The cohort was predominantly male (60%) identify regions responsible for both immunogenicity and cross-reactivity. and highly atopic, with asthma in 60%, allergic rhinitis in 80%, atopic RESULTS: PN and TN CxxxC motifs adopted a common a-helical dermatitis in 70%, and all had multiple food allergies. One child who hairpin fold with a high degree of structural similarity. Numerous PN-TN had a positive OFC, experienced multiple hives, which resolved with and TN-TN cross-reactive epitopes were identified within the structured oral cetirizine. BC OFC was repeated 1 year later, and it was negative, regions. However, their distribution across the individual CxxxC motifs while CM OFC was positive. The other positive OFC involved pruritic was uneven. Proteolytic resistance was similarly variable, suggesting that rash and abdominal pain that resolved without intervention. structural similarity and biophysical stability are both major determinants CONCLUSIONS: Among patients with CM allergy, BC is likely to be of immunogenicity and cross-reactivity within these regions. tolerated or result in only mild reactions. OFCs or home introduction CONCLUSIONS: Despite the lack of sequence identity, vicilin LS may should be considered for BM-tolerant children remaining allergic to CM to contribute to PN-TN cross reactivity. However, the immunogenicity of increase dietary consumption of CM and limit social isolation. individual CxxxC motifs is difficult to predict using traditional bioinfor- matics techniques. Given the widespread prevalence of vicilin LS in other Providing Breast Milk to Infants and Toddlers food allergens, similar interactions may contribute to cross-reactivity 331 with IgE-Mediated Food Allergies across a wide range of seemingly unrelated species Hannah Wangberg, MD1, Kathleen Luskin, MD1, Samantha Spierling Epinephrine Administration in Pediatric Patients Bagsic, PhD, MSE1, John Kelso, MD FAAAAI1, Cathleen Collins, 329 with Food-Related Anaphylaxis MD2; 1Scripps Clinic, 2University of California San Diego/Rady Chil- dren’s Hospital. Isma Shah1, Benjamin Prince, MD MCSI FAAAAI1, Rebecca RATIONALE: There is a paucity of research investigating the provision Scherzer, MD FAAAAI2, Elizabeth Erwin, MD2, Irene Mikhail, MD2; of breast milk to infants and toddlers with IgE-mediated food allergies. The 1Nationwide Children’s Hospital, 2Nationwide Children. purpose of this study was to determine what advice mothers who were RATIONALE: Current food allergy (FA) guidelines suggest children breastfeeding their children with IgE-mediated food allergy had been given present to the emergency department (ED) following administration of about this practice. epinephrine for food-related anaphylaxis (FRA). METHODS: Avoluntary and anonymous REDCap survey was distributed METHODS: A retrospective chart review was conducted looking at electronically to mothers who provided breast milk to children with IgE- patients that presented to the ED of a tertiary care pediatric hospital mediated food allergies as diagnosed by an allergist prior to the age of 2. A between December 2019 and May 2020. Patients younger than 18 years of total of N 5 133 mothers met inclusion criteria and completed the survey. age who received epinephrine prior to ED arrival for FRA and had a known RESULTS: The majority of children with IgE-mediated food allergy were FA or exposure to one of the common eight food allergens were included. diagnosed before 12 months of age (86%, n 5 114). After their child was Patients who developed anaphylaxis to an uncommon food allergen, had diagnosed with a food allergy, 17.3% (n 5 23) of nursing mothers reported reaction details inconsistent with FRA, or received their first dose of their physician advised them to avoid eating the food(s) their child was epinephrine in the ED were excluded. allergic to, while 28.6% (n 5 38) reported their physician did not address RESULTS: Of the 148 patients who presented to the ED for FRA, only 47 this issue at all. A minority (12%, 16/133) of mothers reported their child met inclusion criteria. The median age was 5.3 years, 57% were male, 85% experienced an adverse reaction to maternal breast milk while the mothers had known diagnosis of FA, 47% of reactions were to peanuts or tree nuts, consumed food(s) their child was allergic to. A blinded allergist assessed and 64% patients received epinephrine at site of reaction. Five (10%) most of the reactions described (75%, 12/16) were not likely to be IgE- patients were admitted to the hospital and 8 (17%) required repeat mediated. epinephrine dosing after presenting to the ED. Patients who required CONCLUSIONS: This survey exposed inconsistent recommendations admission or repeat epinephrine were similar to those who did not. for mothers providing breast milk to children with IgE-mediated food However, patients who had resolution of symptoms prior to ED arrival allergies. The majority of women were able to consume the food their child were 19.6 times more likely not to require additional intervention (95% CI was allergic to with no adverse sequelae. Standardized evidence-based 2.2-176.1, p5.008). recommendations would enhance the well-being of these unique mother/ CONCLUSIONS: Patients who do not have complete resolution of infant dyads. symptoms following epinephrine administration will benefit most from seeking ED evaluation. However, home monitoring could be considered in patients who have resolution of their symptoms with epinephrine. J ALLERGY CLIN IMMUNOL Abstracts AB105 VOLUME 147, NUMBER 2

Time To Resolution Of Egg Allergy Utilizing A Do Age and Baseline Peanut-specific IgE Levels 332 Baked Egg Diet: A Community-Based Practice 334 Predict Oral Immunotherapy Outcomes? Analysis Katharine Guarnieri, MD1, Ian Slack, MD1, Amy Eapen, MD, MS1,Va- Jeff Zavala, Resident1, Erin Rasmussen, MD1; 1University of Iowa. nessa Gadoury-Levesque, MD2, Sandra Andorf, PhD1, Michelle Lierl, RATIONALE: Sparse studies have investigated the issue of time to MD FAAAAI1; 1Cincinnati Children’s Hospital Medical Center/Univer- tolerance of egg allergy with the use of baked-egg diets. It has been sity of Cincinnati College of Medicine, 2Montreal Children’s Hospital/ reported that fifty percent of baked-egg diet followers achieve fresh-egg McGill University. tolerance in approximately 36 months, while, 47% of infants with egg RATIONALE: Additional information is needed regarding optimal allergy in the first year of life achieved fresh-egg tolerance by two years patient selection for peanut oral immunotherapy (OIT). We analyzed a with trend of frequent baked egg consumption increasing the chance of real-world peanut OIT cohort to determine how patient age and peanut- tolerance. Tolergenic immune changes occur at 3 months in numerous specific IgE (sIgE) at OIT initiation correlate with outcomes. studies on baked-egg diets and our own clinical experience suggests that METHODS: Records were reviewed for 199 children undergoing peanut egg allergy resolution on baked-egg diet occurs sooner than the above OIT at a pediatric allergy clinic 2011-2020. Patients advanced through reported data. The goal of our study is to provide an analysis of a updosing to long-term daily maintenance with goal dose of 1-2 teaspoons community-based practice and add to the scant data in this area. of peanut butter equivalent. METHODS: This was an IRB-approved retrospective chart review of an RESULTS: To date, 144 patients have achieved maintenance dosing and EMR between 2008-18, aged 6 to 96 months (median 14 months). Sixty- continue to tolerate peanut ingestion; 25 are still updosing; 30 discontinued one egg-allergic patients were analyzed for time to tolerance, percent OIT. Eighty-six percent (59/69) aged 0.5 to <5 years reached and passage of fresh-egg challenge, and atopic disease burden. continued maintenance OIT compared to 73% (62/85) of those 5 to <11 RESULTS: Fifty percent of baked-egg diet patients passed a fresh-egg years and 51% (23/45) 11 to <18 years (p50.00038), though 7%, 9%, and challenge in approximately 20 months from starting baked egg diet. The 27% of these age groups respectively are still updosing. Age was not signif- fresh-egg challenge passage rate with and without a baked-egg diet was icantly correlated with initial reaction threshold (p50.77), number of reac- 100% and 87% respectively (p50.02) A trend for increased atopic score tions during updosing (p50.35) or maintenance phase (p50.2), or time was noticed for those who failed fresh challenge. spent updosing (p50.58). Mean baseline peanut-sIgE was 33.48 kUA/L CONCLUSIONS: Time to resolution of fresh-egg allergy utilizing a (0->100). Baseline peanut-sIgE was not significantly different in those baked-egg diet in a wide-age range cohort is sooner than previously who achieved successful maintenance versus those who discontinued reported. Baked-egg diet seemed to have a significant effect on passing OIT (p50.098). Baseline peanut-sIgE negatively correlated with initial re- fresh-egg challenge. action threshold (p<0.0001) and positively correlated with number of reac- tions during updosing (p<0.0001) and maintenance (p50.0011). Early Anticipatory Guidance and Sensitization to CONCLUSIONS: Although older age correlated with reduced rates of 333 Tree Nuts in At-risk Infants successful maintenance phase achievement and higher baseline peanut- sIgE with increased reactions during OIT, this study demonstrates that Priyanka Seshadri, MD1, Sharon Hwang, MD2, Trong Le, MD3; 1 2 these children can successfully undergo OIT and should not be excluded Thomas Jefferson University Hospital, Nemours AI DuPont Hospital from this management option based on these characteristics alone. for Children, 3Nemours/Sidney Kimmel Medical College Th. RATIONALE: Toit et al identified increased sensitization to certain tree nuts (TN) in infants in the Learning Early About Peanut Allergy trial suggesting that peanut consumption is not protective in reducing allergic disease. Currently, there are no guidelines specific to TN introduction. METHODS: Of 52 eligible patients identified, 39 families responded to telephone surveys. The patients ranged from 27 to 53 months old at the time of the survey, and all patients had passed a supervised peanut challenge (median age 8 months old). At the time of peanut challenge, patients had eczema (87.1%) and/or egg allergy (71.7%) with medians of peanut skin prick test and sIgE of 2.17mm and 1.70kU/L, respectively. Anticipatory guidance on TN introduction, frequency, and outcomes of introductions were assessed. The rationale for TN avoidance was determined based on family preference, evidence of sensitization, or adverse reaction to TN. RESULTS: 38.5% of families recalled receiving instructions on intro- ducing TN. 76.9% introduced TN into the diet, and 56.4% maintained TN in the diet at least monthly. Three patients (7.6%) developed adverse reactions, and an additional 4 (10.2%) avoided TN due to positive testing or subsequent reactions to peanut without a history of TN reaction. Four families (10.2%) had not introduced TN solely because of family preference. CONCLUSIONS: These results demonstrate a lack of standardization on counseling for TN introduction and a significant rate of sensitization (either due to reaction or positive testing) in 17.9% of patients. These findings highlight the importance of early anticipatory guidance to TN introduction in high-risk infants. AB106 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Safety of Peanut (Arachis Hypogaea) Allergen peanut consumption once meeting predefined clinical and laboratory 335 Powder-dnfp in Children and Teenagers With criteria. Peanut Allergy: Pooled Analysis From METHODS: Data were collected for 199 patients initiating peanut oral Controlled and Open-Label Phase 3 Trials immunotherapy (OIT) at a pediatric Allergy clinic between 2011-2020. Patients proceeded through clinic updosing to daily maintenance dose of 2 Thomas Casale, MD FAAAAI1, A. Wesley Burks, MD FAAAAI2, James teaspoons peanut butter, or lower dose for toddlers or those with severe Baker, MD FAAAAI3, Jonathan O’B Hourihane4, Kirsten Beyer, MD5, peanut aversion. Patients were permitted to transition to ad lib peanut con- Brian Vickery, MD FAAAAI6, Stacie Jones, MD FAAAAI7, George Du sumption once meeting the following criteria: (1) tolerance of a full- Toit, MD FAAAAI8, J. Andrew Bird, MD FAAAAI9, Alex Smith10, serving of peanut (7000mg peanut protein) in oral food challenge, (2) Kari Brown, MD10, Stephen Tilles, MD10; 1University of South Florida, Skin prick wheal <8mm, and (3) serum peanut-specific IgE level <1 2 Tampa, FL, USA, University of North Carolina Food Allergy Initiative, kUA/L. Patients were advised to continue peanut consumption at least Division of Allergy, Immunology and Rheumatology, University of North twice weekly during ad lib regimen. Clinical outcomes were monitored Carolina at Chapel Hill, Chapel Hill, NC, USA, 3Mary H Weiser Food Al- by clinic visits or telephone contact. lergy Center, University of Michigan, Ann Arbor, MI, USA, 4Paediatrics RESULTS: Fifty-one of 199 patients transitioned to ad lib consumption and Child Health, Royal College of Surgeons in Ireland, Dublin, Ireland, after a median of 285 days since reaching daily maintenance (91-1183 5Charite Universt~atsmedizin Berlin, Berlin, Germany, 6Emory University days). Median time on ad lib status was 581 days (20-2,275 days). Two School of Medicine, Atlanta, GA, USA, 7University of Arkansas for Med- grade I reactions–oral itching and perioral rash–occurred after lapse in pea- ical Sciences and Arkansas Children’s Hospital, Little Rock, AR, USA, nut intake for 2 weeks and 2 months, respectively. Eight patients (16%) 8Guy’s and St. Thomas’ NHS Foundation Trust, London, United continued to self-report peanut allergy, and 24 (48%) continued to carry Kingdom, 9Department of Pediatrics, Division of Allergy and Immu- epinephrine injectors. nology, University of Texas Southwestern Medical Center, Dallas, TX, CONCLUSIONS: Peanut OIT patients identified prospectively by USA, 10Aimmune Therapeutics, Brisbane, CA, USA. clinical and laboratory criteria can successfully transition from daily RATIONALE: PeanuT (Arachis Hypogaea) allergen powder-dnfp maintenance dosing to intermittent ad lib peanut consumption. (PTAH; previously known as AR101) is a once-daily oral immunotherapy recently approved by the FDA (PALFORZIAä) to mitigate allergic reac- Tolerance of Pistachio and Pecan in Patients tions following accidental peanut exposure in peanut-allergic individuals 337 Desensitized to Cashew and Walnut aged 4-17 years. Longer-term data will further characterize the PTAH 1 1 adverse event (AE) profile. Madison Lee, Jeffrey Factor, MD ; CT Asthma and Allergy Center, METHODS: Safety data from six PTAH clinical trials (n53, controlled; LLC. n53, open-label extension) were pooled and assessed (cut-off date, RATIONALE: Cross-reactivity of cashew and pistachio and pecan and 31Jul2020). walnut has been reported in the past. We hypothesized that cashew and RESULTS: Of the 1182 individuals receiving >_1 PTAH dose, totaling walnut oral immunotherapy (OIT) lead to pistachio and pecan desensiti- 1886 exposure-years, most participants experienced >_1AE(n51132; zation, respectively. 95.8%). Maximum severity was predominantly mild (n5417; 35.3%) or METHODS: Chart review was done on patients who underwent cashew or moderate (n5657; 55.6%). Serious AEs (SAEs) occurred in 41 (3.5%) walnut OITusing a previously published protocol at the New England Food participants; nine (0.8%) experienced treatment-related SAEs. Overall, Allergy Treatment Center from 2014 to 2019. Following the protocol, 152 (12.9%) participants discontinued due to AEs; most experienced a every patient was offered a pistachio or pecan challenge after reaching gastrointestinal symptom and discontinued during the first 6 months. When maintenance doses of cashew or walnut. The number of patients who adjusted for exposure, AEs and treatment-related AEs occurred at a rate of passed the challenge was recorded. 71.0 and 54.5 events/exposure-years, respectively, during updosing and RESULTS: One hundred fifty-eight charts were reviewed. Patient ages decreased to 17.0 and 10.0 events/exposure-years, respectively, during ranged from 3 to 23 years, and 67% were males. Ninety-two patients went 300-mg maintenance. Exposure-adjusted rates of anaphylactic reactions through OIT to cashew with a maintenance dose of 3 cashews/day. Mean (eg, systemic allergic reactions of any severity) and epinephrine use were cashew and pistachio IgE levels were 13.2 ku/l and 14.0 ku/l, respectively. low during Year 1 (0.26 and 0.25) and decreased in Years 2 (0.21 and 0.16) Seventy-seven patients were challenged to 6 pistachios, and 77 patients and 3 (0.13 and 0.10). (100%) passed the challenge. Sixty-six patients were desensitized to CONCLUSIONS: With 1886 exposure-years, PTAH safety profile is well walnut with a maintenance dose of 4.2 grams. Mean walnut and pecan IgE characterized. Mild-to-moderate AEs are anticipated early in treatment, levels were 19.5 ku/l and 9.9 ku/l, respectively. Thirty-seven patients were declining in frequency and severity with continued treatment. challenged with 6.5 grams of pecans, and 37 patients (100%) passed the Anaphylactic reactions are rare and occur less frequently with continued challenge. treatment. These data summarize the PTAH safety profile over 3 years and CONCLUSION: Cashew and walnut oral immunotherapy confer pista- can aid clinicians in managing safety and shared decision-making. chio and pecan desensitization, respectively.

Predefined Clinical and Laboratory Criteria 336 Predict Successful Transition from Peanut Oral Immunotherapy Daily Maintenance Dosing to Ad Lib Consumption

Ian Slack, MD1, Katharine Guarnieri, MD1, Amy Eapen, MD, MS1,Va- nessa Gadoury-Levesque, MD2, Sandra Andorf, PhD1, Michelle Lierl, MD FAAAAI1; 1Cincinnati Children’s Hospital Medical Center/Univer- sity of Cincinnati College of Medicine, 2Montreal Children’s Hospital/ McGill University. RATIONALE: Peanut oral immunotherapy has been shown to effectively decrease sensitization in peanut-allergic individuals; however, clinical endpoints for completion of therapy remain unclear. We followed long- term outcomes in a real-world peanut OIT cohort that transitioned to ad lib J ALLERGY CLIN IMMUNOL Abstracts AB107 VOLUME 147, NUMBER 2

Identifying Candidates for Real-World Peanut the frequency of IL-4+ and IL-13+ILC2 and inducing the regulatory 338 Oral Immunotherapy in the Allergy Clinic response by increasing the frequency of IL-10+ILC2 in LTP-AP. CONCLUSIONS: For the first time, ILC2 are described to be involved in Andrea Blackman, MD1, Aikaterini Anagnostou, MD MSc PhD FAAAAI2; food allergy to LTP suggesting them as potential therapeutic targets and 1Baylor College of Medicine, Texas Children’s Hospital, 2Texas Children. biomarkers to predict the food immunotherapy responses. RATIONALE: Peanut oral immunotherapy (POIT) has a key role as a treatment option in peanut-allergic patients, with demonstrated safety and Subcutaneous Immunotherapy for Pollen Food efficacy in research trials. 340 Allergy Syndrome: A Systematic Review

METHODS: We assessed the eligibility of patients who expressed an 1 1 1 interest in undertaking POIT in our allergy clinic over a period of 2.5 years. Abigail Finley , Evan Atkinson, MD MS ; Tulane University. Our goal was to identify appropriate candidates for this therapy and RATIONALE: Pollen food allergy syndrome (PFAS) presents classically examine reasons for non-participation. as oropharyngeal pruritus, though systemic reactions have also been RESULTS: One hundred and seventy-four patients were evaluated over a reported. Treatment for PFAS varies widely. Whether pollen immuno- period of 2.5 years (January 2018 - July 2020). Median age was 8 years therapy provides substantial improvement in PFAS symptoms has been (IQR 5.25-11), 104 were male (60%) and 70 (40%) were female. Of these, studied with varying results. We sought to systematically review all studies 138 (79%) had concomitant food allergy, with 36 (21%) having peanut evaluating the effect of subcutaneous immunotherapy (SCIT) on PFAS. allergy only, 136 (78%) had associated atopic dermatitis (AD), 79 (45%) METHODS: A systematic search of PubMed, CINAHL, Web of Science, asthma, and 145 (83%) allergic rhinitis (AR). Cochrane Libraries, and EMBASE was performed following PRISMA A total of 24 patients were not eligible for POIT. The main reasons included: guidelines, focusing on studies assessing PFAS (or ‘‘oral allergy syn- uncontrolled asthma (1), uncontrolled allergic rhinitis (1), aeroallergen drome’’) symptoms after SCIT. Studies published only in abstract form immunotherapy build-up period (1), severe atopic dermatitis (1), Crohn’s were not included. disease (2), undiagnosed abdominal migraines (1), eosinophilic esophagitis RESULTS: Online database searches yielded 506 publications. After (1), undiagnosed chronic gastrointestinal symptoms (2), infant age (1), screening the titles and abstracts, 296 unique articles were identified and 20 concerns over inconsistent epinephrine carriage (1), negative peanut oral full-text articles were reviewed. Nine articles met inclusion criteria for challenge (1), unconfirmed peanut allergy diagnosis (2), inability to adhere analysis. Studies varied in design, including allergen content of SCIT, to exercise restrictions associated with therapy or regular up-dosing treatment duration, and provocation testing. Eight studies demonstrated appointments (2), severe anxiety/depression (2), financial issues (5). improvement in PFAS symptoms after SCIT for most patients (59-88%). CONCLUSION: Identifying appropriate candidates for POIT is crucial The remaining study found improvement of PFAS symptoms in only 10% for the success of this intervention and for ensuring safety of participating of patients. Across all nine studies included, 132/183 (72%) of patients patients. Practicing clinicians should evaluate patients carefully and treated with SCIT had a reduction in PFAS symptoms. thoroughly prior to initiating POIT. CONCLUSIONS: The results from our review suggest SCIT can reduce the severity of PFAS symptoms in a majority of patients. However, given Identification and modulation of the peripheral the small number of randomized placebo-controlled studies, as well as the 339 innate lymphoid cells type 2 in LTP-allergic lack of standardization in symptom assessment, allergen content of SCIT patients treated with Pru p 3 Sublingual and length of therapy, a definitive recommendation for the use of SCIT to Immunotherapy. manage PFAS symptoms cannot be made.

Maria Francisca Palomares Jerez, PhD1, Francisca Gomez2,Gador Bo- Non-Daily OIT Dose Frequency may be Safe and gas3, Marıa Jose Rodrıguez1, Rosa Munoz-Cano~ 4, Marıa Jose Torres3, 341 Effective 5 1 Cristobalina Mayorga, PhD ; Allergy Research Group, Instituto de Inves- 1 1 1 1 tigacion Biomedica de Malaga-IBIMA, Malaga, Spain, 2Allergy Clinical Whitney Block , Barrie Shapiro, PhD , Teresa Neeno, MD ; National Unit, Hospital Regional Universitario de Malaga, Malaga, Spain, 3Allergy Allergy Center. Clinical Unit, Hospital Regional Universitario de Malaga, Malaga, Spain, RATIONALE: Some patients decide not to do OIT because of the long- 4Allergy Section, Institut Clınic Respiratori (ICR), Hospital Clınic de Bar- term daily maintenance dose, however it may be possible to reduce the celona, Barcelona, Spain, 5Allergy Research Group, Instituto de Inves- maintenance dose frequency and remain desensitized. tigacion Biomedica de Malaga-IBIMA, Malaga, Spain. METHODS: A retrospective chart review was conducted of 46 patients RATIONALE: The innate lymphoid cells type 2 (ILC2) are being reported to who completed oral immunotherapy with or without omalizumab in a be involved in different allergies. Studies in animal models have shown that, at private practice clinic. Follow-up food challenges were conducted at specific tissue, the ILC2 play an important role in food allergy (FA); however, approximately 6 month intervals to cumulative protein amounts 6-7 times studies are lacking in humans. Moreover, their activities at the peripheral level greater than the OIT maintenance dose. After 12 months of maintenance are poorly described, as well as their response to food-specific immuno- and a passed OFC, patients were eligible to reduce dosing frequency and therapy. The aim of this study was to identify the ILC2 in lipid transfer protein- return for additional challenges to confirm desensitization. allergic patients (LTP-AP) and analyse the ILC2 modulation during one year RESULTS: Twenty-eight patients (61%) were treated for a single food and of sublingual immunotherapy with Pru p 3 (SLIT-Prup3) in these patients. 18 patients (39%) were treated for multiple foods simultaneously; 24 METHODS: Peripheral blood mononuclear cells (PBMCs) were obtained (52%) used omalizumab in conjunction with their OIT buildup and 22 from LTP-AP (N 5 10), tolerant controls (TC, N 5 10), and a group of (48%) did not. Follow-up challenge allergens included almond, cashew, patients who received SLIT-Prup3 (N 5 7). PBMCs were stimulated with egg, hazelnut, milk, peanut, pecan, pistachio, sesame, soy, and walnut. Of phorbol myristate acetate plus ionomycin and phenotypically character- the 117 follow-up challenges completed, 109 (93%) resulted in a ‘‘pass’’ ised by flow cytometry as ILC2 and T-cells. We also studied the possible defined as either no symptoms or mild symptoms not requiring treatment. relationship of ILC2 with T-cells and clinical parameters. The 8 (7%) failed challenges were to cashew (1 challenge), egg (2 RESULTS: IL-4+ and IL-13+ILC2 present a higher percentage in LTP-AP challenges), peanut (4 challenges), and walnut (1 challenge). None of the vs TC and a positive correlation with Th2-cells producing these cytokines failed challenges followed reduction of dosing frequency. Nine of the 17 (IL-4+ and IL-13+Th2-cells), with skin prick test, and with specific IgE eligible patients (53%) opted to reduce dosing frequency and all passed a levels. SLIT-Prup3 changed the effector pattern of response by reducing repeat OFC approximately six months after their frequency adjustment. CONCLUSION: A reduction from daily maintenance dosing may be safe and desirable for patients who have completed OIT. AB108 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Reduction in Severity Following 12 Months of Mass Cytometry Reveals Immune Signatures 342 Epicutaneous Immunotherapy for Peanut Allergy 344 Associated With Desensitization Through Multi-Food Oral Immunotherapy. Philippe Begin, MD FAAAAI1; 1Universite de Montreal. RATIONALE: Daily epicutaneous immunotherapy (EPIT) for 12 months Ziyuan He1, Diane Dunham1, Xiaoying Zhou1, Shu-Chen Lyu1, Monali with DBV712 250 mg has been shown to be statistically superior to placebo Manohar, PhD1, Sharon Chinthrajah, MD1, Sandra Andorf, PhD2, Kari in desensitizing (increasing reactivity threshold) 4-11-year-old peanut- Nadeau, MD PhD FAAAAI3; 1Stanford University School of Medicine, allergic children in a Phase 3 clinical trial (PEPITES). While decreasing 2University of Cincinnati College of Medicine, Cincinnati Children’s Hos- the likelihood of accidental ingestion reactions through desensitization is a pital Medical Center, 3Stanford Univ School Medicine. major goal of food allergy immunotherapy, caregivers and patients also RATIONALE: Individuals with multiple food allergies represent approx- desire a reduction in reaction severity. imately 30% of all patients with food allergies. Desensitization can be METHODS: Double-blind, placebo-controlled food challenges achieved safely and rapidly with multi-food oral immunotherapy (OIT) in (DBPCFC) were performed at baseline and following treatment (Month- combination with Omalizumab; however the immune mechanism behind 12) to determine eliciting dose (ED) in PEPITES. Standardized DBPCFCs desensitization to multiple foods remains unclear. were stopped only after sufficient objective signs/symptoms, in accordance METHODS: Mass cytometry was used to assess the immune profile of 12 with PRACTALL guidelines. Symptoms in each body system were graded participants from a published trial (Andorf et al., Lancet by prespecified criteria. Maximum severity of symptoms at baseline and eClinicalMedicine, 2019) who were allergic to multiple foods including Month-12 between active and placebo groups was compared post-hoc, in peanut and cashew and were successfully desensitized. PBMCs collected all organ systems (AOS) and five significant symptom domains (5SS) of before and post-OIT were stimulated with peanut or cashew protein or wheezing, cardiovascular, laryngeal, vomiting and diarrhea. medium. Immunophenotyping and functional analysis were performed RESULTS: At baseline, there was a similar proportion of mild/moderate/ through unsupervised clustering and manual gating. Wilcoxon signed-rank severe objective signs/symptoms in AOS systems (P5 0.931) and 5SS sys- test were used to compare cell subset frequencies and functional marker tems (P50.946) between DBV712 250 mg and placebo. At Month-12, expression before and post-OIT, adjusted for multiple comparisons. there was a significant difference between groups in AOS and 5SS organs RESULTS: After treatment with anti-IgE and multi-OIT, the frequency of systems severity, irrespective of ED (P<0.001 and 0.016, respectively). By allergen specific CD25+CD40L+ T cells following peanut and cashew stim- AOS, 16.2% of active subjects had a maximum symptom severity of ‘‘se- ulations was significantly decreased. In contrast, an increased trend of IFN- vere’’ compared with 27.5% in placebo (P50.019). Similarly, at Month- gamma positive allergen specific cells and a significant increase of 12, 20.7% of active subjects had no 5SS symptoms compared with 11% CCR4+CLA+ Th17 in CD4+ T cells were observed post-OIT. We also of placebo (P50.031). observed an increased frequency of CCR4+CLA+ Th2 effector memory CONCLUSIONS: In addition to increasing reactivity threshold in 4-11- cells (Th2EM) post-OIT with diminished activation markers (CD25/ year-old peanut-allergic children, investigational EPIT with DBV712 250 CD40L) expression under peanut and cashew stimulations. mg may also reduce the severity of allergic reactions. CONCLUSIONS: Overall, we observed a decrease of allergen specific T cells and a shift from Th2 immunity toward a Th1/Th17 response in Real World Adoption of FDA-approved Peanut response to both peanut and cashew stimulation after multi-OIT treatment. 343 Oral Immunotherapy with Palforzia Increased frequency of CCR4+CLA+ Th2EM cells post-OIT suggests possible Th2 cell proliferation and tissue homing during OIT. S Shahzad Mustafa, MD1, Sara Patrawala, MD2; 1Rochester Regional Health, 2University of Rochester Medical Center. RATIONALE: Oral immunotherapy with Palforzia (POIT) is the first FDA-approved therapy for food allergy, aimed to mitigate accidental allergic reactions in children and adolescents with peanut allergy (PA). Given the novelty of the therapy, it is unknown what percentage of patients and families will pursue this option versus continued strict avoidance. METHODS: All patients ages 4-17 with a physician diagnosis of PAwere enrolled. Patient demographics, comorbidities, PA diagnostics, and rationale for choice for/against POIT were collected. Descriptive statistics are reported with medians and interquartile ranges. RESULTS: Fifty-seven patients were enrolled, and 40/57 (70%) were male. Median age was 9 (7-12) years old and 39% had concurrent asthma. 74% had at least one additional food allergy, with tree nut being the most common (58%). The median age of diagnosis of PA was 1 (1-2), with anaphylaxis the most common presentation (26%), followed by rash (18%). Median wheal 5 15 mm (5-20), and median peanut sIgE 5 17.9 kU/L (3-100). Of the 57 patients, 4 (7%) pursued POIT, 49 (86%) declined and 4 (7%) were undecided. The most common reason to pursue POIT was protection from future reactions whereas the most common reasons to decline were concerns over side effects (45%) and time commitment required for therapy (31%). CONCLUSIONS: The majority of PA patients (86%) chose not to pursue POIT, citing side effects and time commitment as the most common barriers. Future studies are needed to better understand characteristics of patients and families who pursue POIT, as well as rates of adoption over time. J ALLERGY CLIN IMMUNOL Abstracts AB109 VOLUME 147, NUMBER 2

Oral Immunotherapy in Children with Peanut certain tree nuts, for example, those recognized by cashew or hazelnut, 345 Allergy and Asthma in Clinical Practice but not walnut or pecan-allergic individuals may be valuable for targeted multi-tree nut therapeutics. These results may also help identify those Adam Magier, MS1, Sandra Andorf, PhD1, Christa Mills, RN1, Sandy hazelnut or cashew-allergic individuals who would benefit from walnut Durrani, MD2, Justin Schwartz, MD PhD2; 1Cincinnati Children’s Hospi- OIT due to their recognition of walnut homologous epitopes. tal Medical Center, 2Cincinnati Children’s Hospital Medical Center. Uni- versity of Cincinnati College of Medicine. Cincinnati OH USA. Continuing Peanut Oral Immunotherapy via RATIONALE: Current evidence supports oral immunotherapy (OIT) as 347 Telemedicine During the COVID-19 Pandemic an effective approach to desensitize children with peanut allergy, despite a 1 2 high frequency of mild adverse reactions primarily, gastrointestinal and Anna Schoonover , Anny Uyehara, NP , Michael Goldman, MD FAAAAI3; 1Allergy and Asthma Center of Central Mar, 2Allergy & respiratory. We investigated whether comorbid asthma affected clinical 3 reactions during pediatric peanut OIT in clinical practice. Asthma Center of Central Maryland, Allergy & Asthma Center of Cen- METHODS: We retrospectively collected medical histories and clinical tral Maryl. laboratory data from 100 pediatric patients (0.67–18 years) with peanut RATIONALE: Peanut oral immunotherapy (OIT) is a treatment to allergy undergoing OIT. Baseline Pediatric Asthma Risk Scores (PARS) desensitize patients with peanut allergy. OIT up-doses are typically were retrospectively determined for 48 patients (0.67–6 years) without conducted in the office to ensure tolerance of the next dosing level. Due physician-diagnosed asthma. The asthma group (n539) comprised to the COVID-19 pandemic, we adapted our protocol to enable up-dosing patients having physician-diagnosed asthma (n530), high PARS risk via telemedicine. We sought to determine whether telemedicine up-doses score (n53), or moderate PARS risk score that included history of early are safe, defined as minimal reactions which can be treated at home, under wheeze (n56). Statistical analyses used Fisher’s Exact Test or Wilcoxon provider supervision. Rank Sum Test. METHODS: A retrospective chart review was performed for patients RESULTS: Comparing the asthma and non-asthma groups at baseline, we electing to continue peanut OIT up-doses via telemedicine during COVID- found that patients with asthma were older (P50.048) and had clinical his- 19 (March-August 2020). Cases were assessed for number of up-doses, tories of more severe reactions to peanut (requiring epinephrine, number and type of adverse reactions, and type of treatment administered. P50.0012), whereas peanut-specific IgE, skin prick test wheal size, total Prior to instituting telemedicine up-doses, risks and benefits were IgE, and absolute eosinophil count were similar. During OIT, the starting reviewed. We modified our standard OIT regimen so each up-dose occurred dose, time to reach maintenance, and current maintenance dose were over 2 days. similar between groups, but patients with asthma were significantly more RESULTS: Twenty-one patients, ages 6 months - 17 years, were included. likely to discontinue OIT due to adverse clinical reactions (asthma We conducted 130 up-doses via telemedicine, with doses ranging from 23.1% vs. non-asthma 4.9%, P50.010). 0.5mg to 500mg of peanut protein. Three patients initiated OIT via CONCLUSIONS: Children with asthma can be desensitized to peanut via telemedicine. In total, there were 8 adverse reactions (6.2% of up-doses), in OIT but have increased risk for discontinuing OIT due to adverse clinical 5 patients, all mild. Of these reactions, 6 required no treatment, 2 required reactions. Physicians considering peanut OIT should screen prospective oral antihistamine, and none required injectable epinephrine or emergency children for asthma risk and asthma history to weigh OIT risks and benefits. medical services. All reactions were managed by video call with the provider. Microarray Analysis of Major Epitopes Among CONCLUSIONS: Our findings indicate that modified OIT up-doses via 346 Tree Nut-Allergic Individuals May Explain telemedicine are safe. During COVID-19, this protocol allowed us to Patterns of Cross-Desensitization minimize interruptions in therapy and continue OIT with the convenience of home dosing. This may provide an alternative method of OIT for Stephen Gipson1, Jacqueline Nesbit, PhD1, Hsiaopo Cheng1, Suzanne patients who cannot manage frequent in-office up-doses. Teuber, MD FAAAAI2, Stephen Dreskin, MD PhD FAAAAI3, S Shahzad Mustafa, MD4, Barry Hurlburt, PhD1, Soheila Maleki, PhD FAAAAI1; 1USDA SRRC, 2Univ CA-Davis School of Medicine, 3University of Col- orado Denver, 4Rochester Regional Health. RATIONALE: Oral immunotherapy (OIT) studies have demonstrated decreased sensitization to a target allergic tree nut as well as cross- desensitization with other similar tree nuts. Walnut OIT results in high rates of desensitization to pecan, yet lower rates of desensitization to other tree nuts such as hazelnut and cashew. We hypothesize that OIT driven cross- desensitization occurs more frequently between similar tree nuts due to immunoglobulin E (IgE) binding to sequentially different, yet homologous epitopes. METHODS: We collected serum from patients allergic to walnut, pecan, hazelnut, and/or cashew. We measured IgE binding to tree nut allergens using linear peptide microarrays. We identified the major epitopes recognized by tree nut-allergic individuals and measured their similarity to known and newly identified walnut epitopes using the Structural Database of Allergenic Proteins (SDAP). RESULTS: Common homologous and cross-reactive epitopes were identified, aligned, and compared among walnut, pecan, hazelnut, and cashew. Many walnut epitopes were recognized by pecan, hazelnut and/or cashew-allergic individuals. We identified several epitopes recognized only by hazelnut and/or cashew-allergic individuals. CONCLUSIONS: Walnut epitopes recognized by pecan, hazelnut, and/or cashew-allergic individuals may underlie cross-reactions and cross- desensitization during walnut OIT. Epitopes uniquely shared among AB110 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Biomarkers for Desensitization in Patients A positive perception of treatment and 348 Undergoing Sublingual Immunotherapy for 349 continued adherence to dosing in a long-term Peanut Allergy follow-up study in food allergic participants undergoing multi-food oral immunotherapy Suzanne Barshow1, Barry Hurlburt, PhD2, Jane McBride, MS3, Soheila Maleki, PhD FAAAAI2, Ping Ye4, Quefeng Li, PhD5, A. Wesley Sayantani Sindher, MD1, Divya Kumar, PhD1, Jessica Fitzpatrick1, Shu Burks, MD FAAAAI4, Michael Kulis, PhD4, Edwin Kim, MD MS Cao1, Andrew Long, PharmD2, Margaret Woch1, Tiffany Conn1, Kari FAAAAI4; 1Duke University Medical Center, University of North Car- Nadeau, MD PhD FAAAAI3, Sharon Chinthrajah, MD1; 1Stanford Uni- olina- Chapel Hill, 2USDA, 3USDA Agricultural Research Service, 4Uni- versity - Sean N. Parker Center for Allergy and Asthma Research, 2Stan- versity of North Carolina- Chapel Hill, 5University of North Carolina- ford University, 3Stanford Univ School Medicine. Chapel Hill. RATIONALE: Multi-food oral immunotherapy (mOIT) with adjunct RATIONALE: To identify biomarkers predictive of desensitization to omalizumab has been efficacious for the treatment of food allergy in the peanut in subjects undergoing sublingual immunotherapy (SLIT) for setting of clinical research trials, however, long-term adherence to daily peanut allergy. dosing and quality of life (QoL) after completion of trial remains unknown. METHODS: We included 42 challenge-proven peanut-allergic subjects METHODS: In a pilot study, multi-food allergic participants were between 1-11 years of age who underwent 48 months of peanut SLIT. enrolled in an 18-week trial and initiated low-dose mOIT, that included Double-blind, placebo-controlled food challenges (DBPCFC) to 5000 mg 2-5 food allergens, with 3 doses of adjunct omalizumab. At the end of the of peanut protein were done at completion of SLIT. Plasma from baseline study participants were transitioned to real-food alternatives. Two years and completion of SLIT was assayed for peanut-specific IgE and IgG4 in after the initial trial a long-term follow up survey included questions about addition to IgE to peanut components assayed using the ISAC chip (Ara h ongoing dosing of the allergens, adverse events, and epinephrine use. 1, Ara h 2, Ara h 3, Ara h 6, Ara h 8, Ara h 9). Additional surveys were used to assess quality of life (QoL) of participants. RESULTS: After 48 months of SLIT, 15 subjects (35.7%) passed the RESULTS: Among the 30 participants who were initially enrolled at DBPCFC. The 27 subjects who failed tolerated a mean of 1374 mg of Stanford, 21 participants completed the surveys. Majority of participants peanut protein (range 100-2900). Peanut-specific IgG4 to IgE ratio (IgG4/ (77%) reported extremely positive or positive to the OIT treatment of this IgE) after completion of SLIT positively correlated with amount tolerated study. The QoL score of FAQLQ-PB significantly decreased after study at the 48-month DBPCFC (Kendall’s tau5 0.336, p5 0.004). At 48 (p50.05), indicating an improvement of quality of life. Three participants months, Ara h 2 and Ara h 6 IgE negatively correlated with the tolerated discontinued at least 1 allergen due to adverse events (AEs) and 1 reaction amount (Ara h 2: Kendall’s tau5 -0.277, p5 0.021; Ara h 6: Kendall’s required treatment with epinephrine. tau5 -0.333, p5 0.008). At baseline, only Ara h 2 negatively correlated CONCLUSIONS: Our data suggests that dietary inclusion of multiple with the tolerated amount (Kendall’s tau 5 -0.243, p50.042). Baseline allergens after completion of a mOIT clinical trial is safe and beneficial for IgG4/IgE also positively correlated with amount tolerated at the 48-month most patients and caregivers. A large portion of participants continued DBPCFC (Kendall’s tau 5 0.248, p50.035). dosing with multiple allergens 2 years after completion of study and did not CONCLUSIONS: In our cohort, decreased Ara h 2- and 6-specific IgE report any adverse events secondary to dosing. A better understanding of and increased peanut IgG4/IgE were associated with larger amounts the long-term impact of continued desensitization will aid in proper tolerated during DBPCFC and may be useful biomarkers for desensitiza- counseling. tion in subjects undergoing SLIT for peanut allergy. J ALLERGY CLIN IMMUNOL Abstracts AB111 VOLUME 147, NUMBER 2

Adverse Reactions and Anaphylactic Adverse concentrations in the supernatant were measured. Serum OVA- and 350 Reactions Among Children Undergoing Milk OVM-specific IgE titers were also measured. Oral Immunotherapy (OIT) RESULTS: (1) Oral administration of the 2 digested EW products significantly suppressed OVA- and OVM-specific IgE production. (2) Luca Delli Colli1, Sofianne Gabrielli, MSc2, Bruce Mazer, MD EW and the digested products induced Th2 cytokine production by FAAAAI3, Danbing Ke, PhD4, Christine McCusker, MD MSc5, Liane splenocytes. However, OVA- and OVM-specific IgE titers were hardly Beaudette, RN6, Duncan Lejtenyi, MSc1, Edmond Chan, MD FAAAAI7, detectable following epicutaneous exposure to the digested products. Ingrid Baerg7, Eyal Grunebaum, MD8, Philippe Begin, MD FAAAAI9, CONCLUSIONS: These results suggest that protease-digested EW Ann Clarke10, Moshe Ben-Shoshan, MD FAAAAI5; 1McGill University products contain T-cell epitopes of EW that are able to induce oral Health Center, 2McGill University Health Centre, 3The McGill University tolerance. The digested products also show weaker IgE induction than EW. Health Center, 4McGill University Health Center Research, 5Montreal Children, 6McGill, 7BC Children, 8Hospital for Sick Children, 9Universite A Simplified, Real-World Approach to Safely de Montreal, 10University of Calgary. 352 Inducing Bite-Proof Tolerance in Peanut- RATIONALE: The risk of reaction during milk OIT is an important Allergic Preschool-Aged Children and Babies consideration for many cow’s milk-allergic children, their families and 1 1 1 health care providers. We aimed to assess the clinical characteristics of Sandra Hong, MD FAAAAI , Alice Hoyt, MD , Rachel Whitsel, CNP , 2 1 1 adverse and anaphylactic reactions occurring during milk OIT in a Jaclyn Bjelac, MD , Ahila Subramanian ; Cleveland Clinic Foundation, 2 pediatric population having successfully completed milk OIT protocol. Cleveland Clinic. METHODS: Children with diagnosed milk allergy were recruited at the RATIONALE: When babies and toddlers are identified as peanut-allergic, Montreal Children’s Hospital, British Columbia Children’s Hospital, and especially after identification through LEAP-based recommendations, The Hospital for Sick Children. All patients underwent double-blind, these children should not necessarily wait until age four-years to attempt placebo-controlled milk-challenge prior to OIT. Anaphylaxis was defined induction of tolerance. We sought to safely induce tolerance in these young as involvement of at least 2 organ systems or development of hypotension children by adapting tolerance-inducing protocols to our clinical practice. in response to milk ingestion. Severity of anaphylaxis was graded on a METHODS: Children <4 years-old with peanut allergy are offered early scale previously described Muraro et al. (Allergy, 2007). peanut oral immunotherapy (EPOIT). EPOIT protocols vary by physician ; RESULTS: Among 37 patients who completed the protocol successfully. but start with 8-16mg peanut protein (PP) or with the amount tolerated at ; The median age was 14 (IQR 10, 16) years old, and 56% were male. There a positive challenge, and build up occurs over 3-12 months. Maintenance ; were 704 adverse reactions (19 reactions per patient), of which, 185 were dosing is 500mg PP through 0.5 teaspoons peanut butter (PB). Children classified as anaphylaxis (5 reactions per patient). Anaphylactic reactions continue on this dosing for at least one year before repeat peanut challenge. were defined as mild, moderate, and severe, in 55%, 44%, and 0.5% of RESULTS: 30 children are participating to date. 2/30 (7%) withdrew reactions, respectively. Epinephrine was used to treat 2% of mild, 29% of (reasons unrelated to allergy). 19/28 (68%) are at maintenance and, thus, moderate, and 100% of severe reactions. Most anaphylactic reactions bite-proof; 8/28 (29%) are building up; 1/28 (4%) stopped due to the child (76%) occurred at home. Most anaphylactic reactions occurred during refusing the doses. These 28 children received combined total of 10,315 escalation (89% mild, 87% moderate, and 100% severe). Of mild, doses. Within these doses, there have been 8 reactions, 1 requiring moderate, and severe anaphylactic reactions, 5%, 13%, and 0% respec- epinephrine (initial dose and occurred in office). tively occurred during maintenance. CONCLUSION: Babies and preschool-aged children with peanut allergy CONCLUSIONS: Most adverse anaphylactic reactions were mild and can safely become bite-proof using provider-specific EPOIT protocols. moderate, occurring during escalation phase. Milk OIT may pose a risk, The common practice of our protocols is the slow increase in the amount of however, is generally safe when protocols are followed. peanut protein with the goal maintenance dose being 0.5 teaspoons PB. Further studies exploring protocols are needed to help personalize EPOIT Protease-digested Egg White Products Induce to children while continuing to optimize safety. 351 Oral Tolerance, but Little IgE Production upon Epicutaneous Exposure in Mice

Ayako Yamada1, Takanori Hasegawa, PhD1, Hideaki Morita, MD PhD2, Kenji Matsumoto, MD PhD2; 1NH Foods Ltd., 2National Research Insti- tute for Child Health and Development. RATIONALE: Early egg introduction is effective for primary prevention of egg allergy, but antigen exposure via eczema can cause strong IgE- sensitization if the eczema is inadequately treated. To improve the safety of early egg introduction, we investigated protease-digested egg-white products’ potential for inducing oral tolerance without IgE-sensitization, even after exposure via inflammatory skin lesions. METHODS: Egg white (EW) protein was digested with pepsin or Bacillus sp-produced protease (thermolysin) under optimal conditions. (1) Oral tolerance: Three-week-old female BALB/c mice were intragastrically administered EW or digested product 5 times/week for 2 weeks, followed by intraperitoneal injection of ovalbumin (OVA) or ovomucoid (OVM) with alum twice, 2 weeks apart. Two weeks later, serum anti-OVA or anti-OVM IgE antibody titers were measured. (2) Epicutaneous exposure: The dorsal skin of 6-week-old female BALB/c mice was tape-stripped, and EWor digested product was applied on 3 days/week for 3 weeks. One week later, splenocytes were cultured with OVA for 3 days, and the cytokine AB112 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Retrospective Analysis of Synchronous Adult patients with food allergy and patients with a higher number of 353 Telemedicine Use in Clinical Immunology and allergic diseases are less receptive of teleconsultation. Allergy (CIA): A Population-based Cohort Study in Ontario, Canada Rapid Adoption of Video Visits and Return-to- 355 Clinic Procedures to Maintain Access to Erika Lee1, Christine Song, MD2, Peter Vadas, MD PhD2, Matthew Allergy/Immunology Care Delivery During Morgan, MD3, Stephen Betschel1; 1University of Toronto, 2St. Michael, COVID-19 3Sinai Health System. Lulu Tsao, MD1, Stephanie Anne Villanueva Ferraris, RN1, David Pines1, RATIONALE: There exists a geographic barrier to access CIA care for 1 1 1 patients who live in rural communities; telemedicine may bridge this gap in Eugene Choo, MD FAAAAI , Michele Pham, MD , Monica Tang, MD , Lorianna Leard, MD1, Andrew Gross, MD1, Cameron Ashbaugh, MD1, care. Herein we characterized the use of telemedicine in CIA at a 1 1 1 population-based level and single centre. Lei Choi, MD , Iris Otani, MD FAAAAI ; UCSF. METHODS: Data were collected from the administrative database of RATIONALE: COVID-19 necessitated rapid transitions to novel allergy Ontario Telemedicine Network (OTN) and from electronic medical care models centered around telemedicine. records at a single academic centre during 2015 to 2019. The potential METHODS: Pre-COVID-19, we provided in-person provider visits with distance travelled and time saved by telemedicine visits were calculated on-demand skin testing (ST) and dedicated drug allergy (DA) testing visits. using postal codes. On 03/10/2020, provider visits were converted to video visits (VV). DA RESULTS: During the five-year study period, a total of 952 telemedicine visits were cancelled. During VV, ST and DA tests were ordered for visits was conducted over OTN, with an average of 190 visits per year patients, who were then offered dedicated in-person testing visits starting (range 127-291). The majority of visits were provided by a single academic 05/11/2020. centre, and chart review was performed to better characterize telemedicine Telephone scripts, electronic health record (EHR) patient portal use. In this cohort, 66% were female and the overall mean age was 47616. messaging, and standard work for medical assistants, nurses, and providers The most common diagnosis was immunodeficiency (39%), followed by were rapidly developed and implemented. Standard communication and asthma (14%) and urticaria (10%). Most patients required at least one workflows were continuously updated using rapid improvement cycles. follow-up via telemedicine. The average potential one-way distance Appointment outcomes were measured over time. travelled per visit was 359.3km (range 1.2-4218.0); the average potential RESULTS: Of patients originally scheduled for in-person provider visits time travelled in total was 6.6 hours. between 03/10/2020-04/30/2020, 72.0% (275/382) successfully completed CONCLUSIONS: While telemedicine use in CIA has not been widely a VV. Of patients with STordered between 03/10/2020-06/30/2020, 77.2% practiced in North America, it can be a cost- and time-saving tool to (149/193) scheduled and 66.3% (128/193) completed ST by 07/31/2020. provide longitudinal care for patients with chronic diseases who live in Average volumes per month were comparable between 06/01/2019-07/31/ rural communities. In light of the current pandemic, the study provides 2019 and 06/01/2020-07/31/20120 for provider visits, environmental ST, rationale for more physicians to adopt telemedicine use, and for healthcare and food ST (230.5 and 285, 68 and 53.5, 22.5 and 17, respectively). Only agencies to support telemedicine as a strategic priority. 21.1% (8/38) of patients originally scheduled for DA testing between 03/ 10/2020-04/30/20 rescheduled and completed testing between 05/11/ Patient's perceived quality and satisfaction of 2020-07/31/2020. New allergy/immunology VV orders and external 354 Teleconsultation Services in an Allergy referrals directly scheduled into DA testing visits represented 70.0% (35/ Department during COVID-19 pandemic era 50) of DAvisits between 05/11/2020- 07/31/2020. No COVID-19 in-clinic infections occurred. Aida Bermejo-Becerro1, Filip SkrabskiAllergologist1, Esperanza Perez- CONCLUSIONS: Rapid adoption of VV and return-to-clinic procedures Pallise1, Sandra Rodrıguez-Hermida1, Jose Manuel Zubeldia1, Alberto Al- safely allowed continued access to allergy/immunology services. Further varez-Perea1; 1Hospital General Universitario Gregorio Maran~on. work is needed to remove barriers and provide enabling factors for the RATIONALE: The outbreak of COVID-19 has led to a sudden change patients who could not schedule or complete video/testing visits in this new into Telemedicine in the Allergy field. The aim of this study is to know the delivery system. patient’s perspective on quality of teleconsultation services. METHODS: Patients attended by teleconsultation during April 2020 were selected. After obtaining informed consent, they, or their parents, were surveyed for 9 questions. Clinical and demographic data were recorded. RESULTS: We collected responses from 558 patients were recruited. Women: 54.1%; age (mean6SD) 29.6621.4 years; 53.2% adults, 46.8% children (of whom 80.1% mothers and 18.8% fathers were interviewed). Mean general satisfaction score was 8.6 61.4 out of 10. Mean perception of the level of humanization was 7.562.4 out of 10. No significant differences were found for age, sex or different pathologies. Patients with less than 3 allergic diseases scored their satisfaction with teleconsultation higher than patients with more comorbidities (8.7 vs 8.2, p50.001) When asked about different scenarios, in a pandemic situation, most patients patients preferred teleconsultation (56.8%) instead of face-to-face consultation (33.9%) (p<0.0001). In a non-pandemic scenario, ordinary consultation was the preferred method (53.2%), followed by the combi- nation of face-to-face and teleconsultation (41.2%) (p<0.0001). Adults with food allergy were the only group which preferred physical consul- tation in both situations. CONCLUSIONS: From the Allergy patient’s perspective, teleconsulta- tion is a good clinical alternative in the present COVID-19 pandemic. However, face-to-face consultation remains the preferred option in regular conditions. J ALLERGY CLIN IMMUNOL Abstracts AB113 VOLUME 147, NUMBER 2

How To Care For Errors of Innate Immunity (EII) allergy consultations. Furthermore, a hybrid consultation model could be a 356 Patients During The Pandemic In a Developing potential option for future medical consultation. Country Without Telemedicine? Increased adherence to controller medication Raissa Roque, MD1, Fernanda Vaz, MD2, Rafael Saldanha3, Caroline 358 maintained during the COVID-19 pandemic 4 5 1 6 Ferreira, MD , Nathalia Vital, MD , Pedro Bubach , Mariana Pimentel , 1 2 1 2 ~ 1 1 7 Benjamin Theye , Leanne Kaye , Jared Nagano , Rahul Gondalia, PhD , Rafaela Guimaraes , Luiza Schmid , Candida Rizzo, MD PhD , Carolina 2 1 1 5 1 1 ~ 2 Meredith Barrett, PhD , David Stempel, MD FAAAAI ; Propeller Aranda , Dirceu Sole ; Federal University of Sao Paulo, FEDERAL 2 UNIVERSITY OF SAO~ PAULO, 3Universidade Federal de S~ao Paulo, Health, ResMed. 4UNIFESP- Federal University of S~ao Pau, 5Federal University of Sao RATIONALE: The COVID-19 pandemic highlights the importance of Paulo, 6Federal University of S~ao Paulo, 7UNIFESP. medication adherence for RATIONALE: Clinical immunology has advanced exponentially in those with asthma or COPD. A prior study demonstrated an initial increase recent years. Due to the 2020 SARS-coV-2 pandemic, this year was in medication particularly more challenging and our service needed to make efficient adherence among patients with asthma and COPD in March and April adaptations. Our aim was to describe the strategies we developed to 2020, but it is unknown if provide the best support to our EII patients during this period. this behavior persisted beyond the early months. METHODS: This is a retrospective study to evaluate our e-mail service METHODS: Patients with self-reported asthma or COPD enrolled in a from March to August/2020, with messages between doctors and patients digital self-management in a referral service that assists patients from all over Brazil . platform, which included an electronic medication monitor (EMM) to RESULTS: Our team involves 12 fellows, 4 graduate students and 2 capture the date and time of professors which serves more than 500 EII patients. Telemedicine was not controller inhaler use, and a paired smartphone app providing feedback and a possibility in our service and we found as a challenge the fear of our medication patients to expose themselves, leading to unmarked appointments and even reminders. Data was analyzed from January to May 2020 and assessed infusion of human immunoglobulin (IVIG). During this period, we changes in mean responded to more than 570 demands by email, including 85 prescription controller medication adherence, defined as the mean number of puffs medicines, 36 IVIG renewal process, 39 medical certificates, 20 referral for taken divided by the vaccination, 241 appointment schedules and IVIG infusion, 5 referrals for number of puffs prescribed per day, capped at 100%. stem-cell transplantation, 54 medical reports and 95 responses to patients RESULTS: 17,095 patients with asthma or COPD were included in the questions, much of which involved fear of exposure. analysis (median age CONCLUSIONS: The SARS-coV-2 pandemic is one of the most difficult (IQR): 52 (38-62) years, 72% female, 82% asthma). Mean adherence in the periods facing humanity. The development of strategies that we had to raise last 7 days of was even more challenging in the scenario of a public service without January was 56.2%. Mean adherence for the last 7 days of each month from telemedicine. Brazil had a major disadvantage in relation to health policies February to May compared to most other countries, especially because social distance are were: 56.5%, 58.6%, 59.1%, and 59.4%, respectively. A larger proportion not strongly encouraged by the authorities. of patients maintained 75% or greater adherence for the last weeks of April and May (47.6% and Covid impact in allergy: patients' perceptions of 49.1%, respectively) 357 "virtual'' consultations and preferences for the compared to the first week of January (42.7%). future. CONCLUSIONS: During the COVID-19 pandemic, patients with asthma and COPD initially increased Vince Wu, BSc1, Wardha. Wardha, Bsc1, Vaidehi Bhatt, BSc1, Tyler their use of controller medications and maintained this behavior through Seto1; 1Hamilton Allergy. May 2020. Monitoring RATIONALE: The COVID-19 pandemic has provided challenges for patterns of use throughout the pandemic may help characterize patient healthcare professionals to provide medical care to patients. The recent medication-taking emergence of telemedicine consultation has provided an alternative to ‘‘in behavior. office’’ care. Assessing its impact may provide insight to the future of medical diagnosis and treatment. Methods Telemedicine consultations were provided at an allergy clinic between June and July 2020. Patients (n5207) were provided with a questionnaire after their consultation to assess the following: if healthcare requirements were met when consulted virtually, the consideration of telemedicine for future appointments, and if they would like a hybrid consultation model (initial eConsult and in person follow up). A 7-point scoring system was used to evaluate each question. Scores between 1 to 3 disagreed with varying degrees, a score of 4 was neutral, and scores between 5-7 agreed with varying degrees. RESULTS: Patients scored an average of 5.7 with a standard deviation (SD) of 1.3 with 80% of patients scoring between 5-7 when asked if the virtual consult met all their healthcare requirements. When asked about the use of telemedicine in the future, patients scored an average of 5.3 and a SD of 1.5, with 76% of patients scoring between 5-7. Lastly, patients scored the hybrid consultation model an average of 5.5 with a SD of 1.6, with 79% of patients scoring between 5-7. CONCLUSIONS: The majority of patients believe that virtual consulta- tion provided appropriate medical information and should be used in future AB114 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Allergy & Immunology Involvement on study demonstrates the effectiveness of asthma navigators in maintaining 359 Multidisciplinary Treatment Team During close monitoring. Anecdotally, families expressed how important these COVID-19 Pandemic outreach visits were to them.

Veronica Azmy, MD1, Kelsey Kaman, MD1, Christina Price, MD1; 1Yale Changes in food spending among food allergic School of Medicine. 361 families following the COVID-19 pandemic

RATIONALE: As clinical immunologists, we are experts in immune 1 1 dysregulation as we regularly treat patients with combined immune Michael Golding , Catherine Lemoine-Courcelles, BSc , Elissa Abrams, MD FRCPC1, Moshe Ben-Shoshan, MD FAAAAI2, Edmond deficiency and autoimmunity. This places us in a unique position to 3 4 5 understand the nuances of COVID-19 immune disturbances, including Chan, MD FAAAAI , Derek Chu, MD PhD , Jennifer Gerdts , Harold Kim, MD6, Elinor Simons, MD PhD MS FAAAAI1, Julia Upton, MD7, cytokine release syndrome, and make recommendations regarding 1 1 2 treatment. Jennifer Protudjer, PhD ; University of Manitoba, McGill University, 3University of British Columbia, 4McMaster University, 5Food Allergy METHODS: At our institution, Allergy and Immunology faculty and 6 7 fellows participated on a multidisciplinary COVID-19 treatment team Canada, Western University, The Hospital for Sick Children. whose role was to develop and revise a treatment algorithm for admitted RATIONALE: Efforts to combat the spread of COVID-19 have disrupted patients and review patient charts under a stewardship module in the EMR. food supply chains and shifted consumption patterns leading to increased Outcome data for patients admitted with SARS-CoV-2 infection from food prices and shortages of some products. It is hypothesized that these March 10 to 31, 2020 was analyzed. Severe disease was defined as changes may disproportionately affect food allergic families given their requiring at least 3L of oxygen to maintain SpO2 >93%. restricted diet. RESULTS: A treatment algorithm with recommendation for tocilizumab METHODS: Between 1 May and 30 June 2020, 205 families completed for patients requiring 3L/min of oxygen or greater to maintain SpO2 >93% an online questionnaire that assessed food spending before and after the was developed. The treatment algorithm included consideration of Allergy outbreak of COVID-19. Of these families, 171 had at least one member and Immunology consultation if there was need for repeat or alternative with a physician-diagnosed food allergy, while 34 families reported no biologic agents. A total of 239 patients with PCR-confirmed SARS-CoV-2 food allergic members. Logistic regression analyses were used to assess infection were included. 153 of 239 patients received tocilizumab. Of all changes in food spending among food allergic and non-food allergic patients, 25 of 239 died, for an overall mortality rate of 10.5%. Among families. Pandemic duration and the prevalence of COVID-19 in each tocilizumab-treated patients requiring mechanical ventilation, survival was participant’s province were included as covariates. 75% (95% CI, 64-89). RESULTS: Relative to families without a food allergic member, food CONCLUSIONS: The presence of a multidisciplinary treatment team, allergic families were 2.37 times more likely to report increased spending 5 5 treatment algorithm, and stewardship module involving Allergy and on food following the outbreak of COVID-19 (95%CI 1.08, 5.21, p .03). Immunology was associated with favorable mortality outcomes for An analysis of these families revealed that monthly spending on food 5 patients affected by COVID-19. Involvement of Allergy fellows on the increased by an average of 23% (e.g., $191.28 CAD, SD 31.13) following multidisciplinary team supported learning opportunities for fellows via the pandemic. Moreover, results indicated that among food allergic collaboration with other specialists. families, increased spending on food was associated with a lack of food availability (OR52.63; 95%CI51.28, 5.41, p5.01). COVID-19 Impact on Participant Engagement CONCLUSIONS: Results from the current study suggest that food 360 with a School-centered Asthma Navigator allergic families are particularly affected by changes in the price and Program availability of food that have followed the COVID-19 pandemic. Policy makers should consider this increased burden when developing policies Melanie Gleason, MS PA-C1, Arthur McFarlane2, Mfonobong aimed at lessening the financial impact of COVID-19 on families. Udoko, MD1, Elizabeth Konon3, Stanley Szefler, MD FAAAAI1; 1Univer- sity of Colorado School of Medicine/Children’s Hospital Colorado, 2Chil- dren’s Hospital Colorado, 3University of Colorado School of Medicine. RATIONALE: The COVID-19 pandemic has made an impact on how health care/support services are accessed with up to 60% decline in visits to primary care providers. This study evaluated the impact of COVID-19 on participant engagement with asthma navigators and asthma outcomes in a school-centered asthma program. METHODS: Step Up Asthma program is implemented in 40 Colorado schools. Asthma navigators enrolled 2 cohorts (Cohort 1/2018-2019 and Cohort 2/2019-2020) of students with poorly controlled asthma to participate in a comprehensive asthma navigator program. Study visits were scheduled every 3 months over a 12-month period. Due to COVID-19 school closures, we transitioned to telehealth visits beginning in March 2020. We compared participation rates and indicators of asthma control (ACT score, ED and hospitalizations) before and during the COVID-19 crisis to identify if there was an impact on program engagement. RESULTS: We compared rates for participation at 3-time points: start of school year, mid-year, and end of school year. Cohort 1 (n5113) had participation rates of 100%, 99.1% and 88.5% respectively and Cohort 2 (n5119) had rates of 100%, 87.4% and 70.6%. The results demonstrate an 11.5% decline from start of year to end of year for Cohort 1, compared to a 29.4% decline for Cohort 2 during the COVID-19 crisis. No change in asthma outcomes was noted. CONCLUSIONS: Our school-centered asthma program maintained high levels of participant engagement through telehealth mechanisms. This J ALLERGY CLIN IMMUNOL Abstracts AB115 VOLUME 147, NUMBER 2

Consequences of the COVID-19 pandemic on health T-scores were 54.1 and 53.3, respectively. Hispanic participants 362 grocery shopping habits of food allergic families reported poorer physical (p50.01) and mental health (p50.03) vs. non- Hispanic participants. Participants initially testing negative to COVID-19 Michael Golding1, Catherine Lemoine-Courcelles, BSc1, Elissa (N525) reported better physical health vs. those testing positive Abrams, MD FRCPC2, Moshe Ben-Shoshan, MD FAAAAI3, Philippe (N5131);(p50.02), however mental health T-scores were comparable Begin, MD FAAAAI4, Edmond Chan, MD FAAAAI5, Derek Chu, MD (p5.34). PhD6, Jennifer Gerdts7, Harold Kim, MD8, Elinor Simons, MD PhD CONCLUSIONS: Preliminary data from this diverse cohort of families MS FAAAAI2, Julia Upton, MD9, Jennifer Protudjer, PhD2; 1University impacted by COVID-19, indicate that COVID-19 can lead to substantial, of Manitoba, Children’s Hospital Research Institute of Manitoba, 2Univer- sustained physical and mental health burden—which may be greater sity of Manitoba, 3Montreal Children, 4Universite de Montreal, 5BC Chil- among Hispanic patients. dren, 6McMaster University, 7Food Allergy Canada, 8Western University, 9The Hospital for Sick Children. The Emotional Impact of COID-19 on Residents RATIONALE: Physical distancing requirements during the early months 364 and Fellows of the COVID-19 pandemic changed peoples’ ability and willingness to 1 1 1 access grocery stores. We hypothesize that families with food allergy, who Muhammad Awan , Kristina Antuna, MD ; Nova Southeastern rely on label reading to minimize the risk of accidental exposure to a known University. allergen, were negatively impacted by these changes. RATIONALE: To determine the levels of burnout and anxiety experi- METHODS: Canadian-based families with food allergy completed an enced by residents and fellows during COVID-19. anonymous, online survey on the consequences of COVID-19-related METHODS: Multicentric prospective study. Survey included validated changes on shopping habits and behaviours between 1 May and 30 June tools to evaluate burnout, psychological distress, anxiety, and depression. 2020. We used descriptive and comparative statistics to assess grocery Additionally, we assessed participants’ perception and emotional impact of shopping experiences, and motivation for product choice. COVID-19. We analyzed the prevalence and correlation of the different RESULTS: The unavailability of certain foods had, on average, conse- variables. quences on these families (N5191). The most common consequence was RESULTS: We evaluated 110 residents and fellows. Age range 25-39 greater stress while shopping (n594; 49.2%), but a sizeable minority also years; 42.7% were females. The 90.9% and 83.6% of participants reported reported buying higher priced products (n574; 38.7%), products they fear of losing a loved one and getting sick or dying related to COVID-19. enjoy less (n551; 26.7%), switching types of foods (n544; 23.0%), and Additionally, 88.2% felt uncertain about their future, while 91.8% and buying products that required more preparation (n545; 23.6%). Moreover, 89.1% revealed that COVID-19 is affecting their quality of life and during the pandemic, 12.0% (n523) of food allergic families reported emotional status. The prevalence of psychological distress and burnout was buying foods labeled with ‘‘may contain’’ precautionary allergen labelling 31.8% and 9.1%. Additionally, 20% and 11.8% screened positive for although they avoided such purchases pre-COVID-19. anxiety and depression. Psychological distress, anxiety, and depression had CONCLUSIONS: Food allergic families report that the COVID-19 a significant correlation with being afraid of losing a loved one, being pandemic has had negative consequences on their grocery shopping habits, afraid of getting sick or dying, uncertainty about the future, changes in including the purchase of foods with precautionary allergen labelling. emotional status and quality of life. Burnout had a strong correlation with emotional status, and a weak correlation with being afraid of getting sick or Understanding the impact of the COVID-19 dying, and quality of life. 363 pandemic on physical and mental health CONCLUSION: Medical trainees are at risk of burnout during their training. COVID-19 has added a new component that affects their personal Shu Cao1, Hena Din1, Christopher Warren, PhD1, Jessica Fitzpatrick1, and professional lives. Residents and fellows’ quality of life, emotional Tina Hernandez-Boussard2, Manisha Desai, PhD3, Sharon status and their perception of the future has been affected by COVID-19. Chinthrajah, MD1, Kari Nadeau, MD PhD FAAAAI4; 1Stanford Univer- The outcomes in this paper show us a direct impact in the trainees’ sity - Sean N. Parker Center for Allergy and Asthma Research, 2Stanford psychological distress levels, depression, and burnout risks. University - Biomedical Data Science and of Surgery, 3Stanford Univer- sity - BIOMEDICAL DATA SCIENCE AND, BY COURTESY, OF HEALTH RESEARCH AND POLICY, 4Stanford Univ School Medicine. RATIONALE: The COVID-19 pandemic has contributed to 800,000 deaths and millions of hospitalizations globally. However, little is known regarding long-term symptom trends among recovering patients nor its mental health impact. METHODS: Individuals testing positive for COVID-19 at Stanford Hospital were recruited into a year-long observational study. Recruited individuals were invited to enroll family members irrespective of suspected COVID status. All participants underwent COVID-19 testing and completed questionnaires assessing COVID-19-related symptomatology, testing methods, preventative behaviors, comorbidities, and psychosocial factors. RESULTS: From April 8 to August 20, 156 participants (4-86 years-old) were enrolled a median of 25 days post-COVID-19 testing (55% female, 32% Hispanic, median age542). Most (60%) participants had mild COVID-19 symptoms (i.e. symptoms resolving without clinical interven- tion) while 17% were hospitalized. Median symptom duration was 13 days. Fatigue was most commonly reported (49%). Although symptoms resolved for all patients by 2 months post-initial test, at 4 months symptoms reappeared in 3% of participants, including fatigue, body aches, shortness- of-breath, and trouble breathing. 17% of participants reported greater anxiety due to the pandemic. Median PROMIS global mental and physical AB116 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

A COVID-19 vaccine success? patients protective environmental factors: AD (breastmilk, antibiotics, antacids); 365 perception of Covid vaccination program FA (VD, formula, antibiotics, antacids); asthma and AR (VD, breastmilk, antibiotics, antacids). Wardha. Wardha, Bsc1, Vaidehi Bhatt, BSc1, Tyler Seto1, Vince Wu, BSc1; 1Hamilton Allergy. Neonatal Intensive Care Unit Demographics and RATIONALE: The COVID-19 vaccine began development in early 2020. 367 Subsequent Development of Food Allergies A global vaccine may be available as early as 2021 under emergency use Emily Robbins1, Seleshi Demissie, PhD1, Jonathon Blau, MD1, Courtney protocols. We assessed patient attitudes toward a potential COVID-19 1 1 vaccine and history with past vaccinations. Briggs-Steinberg, DO ; Staten Island University Hospital. METHODS: 220 patients were assessed at an allergy clinic in Ontario RATIONALE: We aimed to determine the association between neonatal from June-July 2020. A COVID-19 questionnaire assessed two questions: intensive care unit (NICU) length of stay (LOS), gestational age (GA) and would patients want to receive the COVID-19 vaccination when available birth weight (BW), and the diagnosis of food allergies later in childhood. and would it make them more comfortable when attending mecdical We hypothesized that infants that had longer NICU LOS and lower GA appointments. A 7-point scoring scale was utilized to assess each question. would have a lower prevalence of food allergies than the control group due 1-3 indicated a disagreement with the statement, 4 was neither agree nor to an incidental finding by a large prospective Swedish study (Mitselou et. disagree and 5-7 indicated an agreement with the statement. An additional al.) along with evidence from studies on early exposure to allergens and question inquired if patients received influenza vaccinations within the past varied microbiota. two years. METHODS: We utilized retrospective chart analysis for eligible patients RESULTS: Patients indicated a mean score of 5.3 with respect to in the Northwell Health System from 2008-2018 for any child born at a receiving the COVID-19 vaccine with a standard deviation (SD) of Northwell hospital who also had an outpatient visit between the ages of 2- 2.0; 65% of patients would want to receive the COVID-19 once developed. 10 years old. The primary outcome variable was the development of food Patients demonstrated a mean score of 5.0, with a SD of 1.9 for comfort allergies.??We used chi-squared analysis to compare NICU patients with with appointments post vaccine; 57% of patients would feel more comfort- newborns admitted to a well baby nursery. Predictive variables included able coming into the office for appointments post-vaccine. 52% percent of NICU LOS, race, insurance type, and BW.??All statistical tests were two- patients reported having received their influenza vaccination in the past 2 sided and P-value <0.05 was considered statistically significant.? years whereas 48% did not. RESULTS: With an N of 29,876, 81% of which were term babies without CONCLUSIONS: Uptake of a future COVID-19 vaccination was NICU admission, there was no statistical difference between term and 5 5 lukewarm despite the current pandemic and would provide reassurance preterm babies (p 0.5626), birth weight (p 0.139) or NICU LOS 5 in the majority of patients seeking medical care. There remained a strong (p 0.686) and later development of food allergies resistance to vaccination. Further patient education is needed to increase CONCLUSIONS: No study has examined NICU LOS and the later uptake of a Covid vaccination. development of food allergies. This study indicates that despite these correlations, there is no statistically significant increase or decrease in food Bioinformatic analysis of electronic birth cohort allergies; regardless of a baby’s GA, BW, or NICU status. 366 reveals distinct associations between early-life environmental factors and childhood allergic The Association Between Family History of outcomes 368 Atopy and Food Allergy in Hispanic Children

1 2 1 1 1 Stephania Lairet, MD , Stanislav Ivanov, MD , Jose Calderon, MD , Stanislaw Gabryszewski, MD PhD , Jesse Dudley, MS , Robert 3 1 2 3 1 Vivian Hernandez-Trujillo, MD FAAAAI ; Nicklaus Children’s Hospi- Grundmeier, MD , David Hill, MD, PhD ; Children’s Hospital of Phila- 2 3 delphia, Philadelphia, PA, 2Children’s Hospital of Philadelphia, Philadel- tal, University of Miami/JFK Medical Center, Allergy and Immunology phia, PA, 3Children’s Hospital of Philadelphia, University of Care Center of So. Pennsylvania, Philadelphia, PA. RATIONALE: The aim of this study is to explore the association between RATIONALE: Environmental factors known to influence the infant family history of allergic conditions and food allergies in children of microbiome, including delivery mode, diet, and early-life exposure to Hispanic ethnicity. We hypothesized that there is an association between antibiotics and/or antacids, have been implicated in the pathogenesis of family history of atopy and food allergy in children; this association has not allergic disease. However, the extent to which they influence the risk of been well studied in the Hispanic population, thus we aim to contribute developing atopic dermatitis (AD), IgE-mediated food allergy (FA), further to the existing food allergy literature. asthma, and/or allergic rhinitis (AR) remains incompletely understood. METHODS: We performed a retrospective cohort study of 355 patients of METHODS: Using an electronic medical record-based cohort of 158,510 Hispanic origin with diagnosis of food allergy in Nicklaus Children’s children, we identified patients with AD, FA, asthma, and AR. We adjusted Hospital Allergy & Immunology clinic. Non-parametric Chi-Square for race and sex and determined hazard ratios (HRs) to assess associations analysis of a 2 by 1 contingency table was performed using SPSS to between environmental factors and allergy development rates. Chart assess the relationship between family history of atopy and food allergy in review was performed to validate exposures and outcomes. children. The data was further stratified via a 2 by 2 contingency table RESULTS: Vaginal delivery (VD) was associated with reduced rates of analysis to derive Chi-Square values by type of family history of atopy and developing FA, asthma, and AR (HR 0.86, 0.85, 0.84, respectively) but had specific type of food allergy in children. no association with AD. Exclusive breastmilk was associated with reduced RESULTS: A difference was found in patients with food allergies and rates of developing AD, asthma, and AR (HR 0.91, 0.58, 0.73) but absence of family history of atopy vs. those with presence of family history increased rate of developing FA (HR 1.58). Formula-supplemented atopy (p-value of <0.05). Furthermore, family history of atopy was found breastmilk exhibited comparable associations for asthma, AR, and FA to be associated with greater odds of egg allergy in Hispanic children (OR: (HR 0.85, 0.95, 1.37). Exposure to antibiotics (HR 1.34, 1.32, 1.53, 1.23) 1.62, CI: 1.029-2.556). and antacids (HR 1.09, 1.11, 1.37, 1.31) during the first six months of life CONCLUSIONS: Based on our findings, family history of atopy cannot were associated with increased rates of developing AD, FA, asthma, and be reliably used as a sole predictor of food allergy in Hispanic children. AR. All reported associations were statistically significant (p<0.05). However, for egg allergy in particular, family history of atopy is associated CONCLUSIONS: Dissecting risk relationships between environmental with increased risk of developing egg allergy. factors and allergic diseases poses ongoing challenges. Our analysis revealed distinct associations between specific allergic outcomes and J ALLERGY CLIN IMMUNOL Abstracts AB117 VOLUME 147, NUMBER 2

Characterization of the Relationship Between knowing the importance of a spacer; and 81% reported knowing the 369 Prenatal Farm Exposures and Allergen importance of a peak flow meter. Sensitization in the First Year of Life CONCLUSIONS: Remote data collection through mHealth interventions may serve as a viable method for conducting clinical trials, especially Joshua Brownell1, Zhumin Zhang1, James Gern, MD2, Christine Sero- during the COVID-19 pandemic. ogy, MD FAAAAI1; 1University of Wisconsin, 2University of Wiscon- sin-Madison. Human dietitians vs. Artificial intelligence: RATIONALE: Early childhood exposure to animal farming environments 371 Which diet design do you prefer for your has been associated with decreased incidence of atopic disease. We children? hypothesize that prenatal farm environment exposure is associated with 1 2 2 2 lower rates of allergen-specific and total IgE in early life. Min Jung , Chiehyeon Lim , Changhun Lee , Soohyeok Kim , Jayun Kim3; 1Kosin Gospel University Hospital, Busan, Korea, 2Ulsan National METHODS: The Wisconsin Infant Study Cohort (WISC) birth cohort 3 enrolled farm and non-farm pregnant woman from central Wisconsin. Institute of Science and Technology (UNIST), Ulsan, Korea, Kosin Uni- Farm and other environmental exposures are surveyed prenatally. Plasma versity Gospel Hospital, Busan, Korea. total IgE, mixed aeroallergen IgE (Phadiatop), and specific food IgE are RATIONALE: Caregivers of children with food allergy should always be measured at 12 months of age. Farm subjects were also grouped by the concerned about the diet design to ensure adequate intake of nutrients and number of animal species (0-2 animals, n515; 3-4, n538; 5-6, n514) elimination of implicated foods. We believe that artificial intelligence (AI) exposed to prenatally. Analysis was performed using the Chi-square test, solutions can help the diet design for them. In this study, we developed the ANOVA, or 2-tailed t-test. two types of AI and compared their utility over human dietitians. RESULTS: Of 240 subjects enrolled in WISC, 169 had 12 month IgE data METHODS: The first one mimics existing records of human-made diets available for analysis. Farm (n570) and nonfarm (n599) participants had using the generative adversarial network (GAN) model. The second one similar total IgE (geomean farm 4.1 kU/L, nonfarm 4.3 kU/L, p50.81), mimics the human’s diet design process using the reinforcement learning aeroallergen IgE (farm510%, nonfarm513.4%, p50.50), and food IgE (RL) framework. Using the database of 1,724 foods and 220 daily diet (farm512.9%, nonfarm513.5%, p50.90) at 12 months of age. Within the plans for the 3-5-years old children, we have trained these AI solutions to farm group, the number of prenatal animal exposures (0-2, 3-4, 5-6) tended produce the daily diet plans. To evaluate the utility of AI solutions, we to be inversely related to total IgE (geomean 4.4 kU/L, 4.3 kU/L, 2.5 kU/L; conducted the two surveys to an expert group consisting of dietitians, p<0.10), while the prevalences of sensitization to aeroallergens (20%, pediatricians, and teachers of day care center, from April 2020 to May 7.89%, 7.14%; p50.39) and foods (13.3%, 15.8%, 0%; p50.29) were 2020. In the first survey! , we asked 41 experts to evaluate the similar. compositional, nutritional, and overall quality of the 45 diet design CONCLUSIONS: Our preliminary analysis suggests that total IgE and outcomes made by the GAN-based AI, RL-based AI, and human dietitians; allergic sensitization at 12 months of age are similar among farm and non- here, we gave them only the menu name information. In addition, we asked farm children but may be reduced by prenatal exposure to farm animals. them to guess which diet outcome is designed by an AI. In the second Additional samples are being analyzed to further test this hypothesis. survey, we asked 27 experts the same questions the other way around; here, we did not give them the menu name but the nutrient information. Remote Data Collection Through the RESULTS: In the first survey, the human-made diet outcomes received 370 ASTHMAXcel Mobile Application, and Lessons 82.44% of positive response in overall evaluation, whereas the diets made Learned During the COVID-19 Pandemic by RL-based AI and GAN-based AI received 43.74% and 35.12%, respectively. In addition, the respondents easily distinguished human- Brian Hsia, MD1, Anjani Singh, MD2, Obumneme Njeze, BS2, Emine made diets and AI-made diets. Interestingly, the result of second survey Cosar2, Savneet Kaur2, Sunit Jariwala, MD FAAAAI3; 1Icahn School of without the menu name information was different to the above. The diets Medicine at Mount Sinai, 2Montefiore Medical Center, 3Albert Einstein/ made by RL-based AI received 86.67% positive response, whereas the Montefiore Medical Cente. human-made diets received 43.70%. RATIONALE: The ASTHMAXcel mobile application has been associ- CONCLUSIONS: The survey results may indicate that the experts (1) ated with improvements in clinical outcomes and healthcare utilization have their own preference to the menu composition of diets, (2) are not through on-site use at designated study visits. Remote testing and data capable to precisely evaluate the nutritional quality of diets, and (3) collection may streamline and transform clinical trials for mobile health become negatively biased if the composition does not fit their preference, (mHealth) interventions. regardless of the nutrient quality. This study shows the possibility and METHODS: ASTHMAXcel is a novel, guideline-based smartphone direction of developing a dietary AI for children with food allergies. application freely available on the iOS/Android app marketplaces. Within the app, users answered surveys on initial (prior to navigating content) use and after first-time use. Pre-intervention questions included user demographics and baseline knowledge. Post-intervention questions addressed attitude changes after completion of all content. RESULTS: Between April 15 and August 13, 2020, 96 users (F: 60%, mean age: 38.8 6 14.9, range: 19-77) completed the pre-intervention survey. 56% of users completed college or a higher program. 83% of users primarily spoke English, 6% primarily Spanish, and 11% another lan- guage. Common comorbidities included seasonal allergies (37%), anxiety/ depression (37%), eczema (16%), food allergies (12%), and diabetes mellitus (9%). At baseline, the following proportion of users reported: 41% had an asthma action plan; 60% knew the difference between a rescue vs controller medication; 32% had a peak flow meter; and 38% had a spacer. 23 users completed the post-intervention survey. 72% reported knowing the importance of an asthma action plan; 81% reported knowing the difference between a rescue vs controller medication; 87% reported AB118 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Mapping Food Allergy Data to a Standard Data in the literature. This indicates a need to address the socioeconomic and 372 Model environmental disparities in big data practices for characterizing asthma and its related triggers. Mark Wlodarski, MS1, Ruchi Gupta, MD MPH2, Lucy Bilaver, PhD MS MA3, Shruti Sehgal, MD(Hom), MS4, Justin Starren, MD, PhD, FACMI5, The Development and Validation of Food Allergy Michael Gurley, BA5, Firas Wehbe, MD, PhD5; 1Northwestern University, 374 Data Dictionary 2 3 Feinberg School of Medicine, Northwestern Medicine, Northwestern 1 2 4 5 Shruti Sehgal, MD(Hom), MS , Ruchi Gupta, MD MPH , Mark University, Northwestern University, Feinberg School, Northwestern 1 2 3 University Feinberg School of Medicine. Wlodarski, MS , Lucy Bilaver, PhD MS MA , Melanie Makhija, MD , Jonathan Spergel, MD, PhD4, Julie Wang, MD FAAAAI5, Christina RATIONALE: Food Allergy (FA) research and treatment would greatly 6 7 benefit from enhanced sharing data across institutions. Over the last few Ciaccio, MD FAAAAI , Dana Ward, MS, MBA , Nicholas Soulakis, PhD1, Justin Starren, MD, PhD, FACMI1; 1Northwestern Uni- years the Observational Medical Outcomes Partnership (OMOP) Common 2 Data Model (CDM) has become the most widely adopted standard for versity, Feinberg School of Medicine, Chicago, IL, Northwestern Univer- storage and sharing of medical data. To support the creation of a FA data sity, Feinberg School of Medicine, Chicago, IL, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL, 3Ann & Robert H. Lurie commons, an OMOP compliant data model was created. 4 METHODS: Other work by our group has created an initial data Children’s Hospital of Chicago, Chicago, IL, Children Hospital of Phil- adelphia, 5Icahn School of Medicine at Mount Sinai, 6The University of dictionary of concepts deemed important to the study and treatment of 7 food allergies. Concepts were mapped to the OMOP standardized vocab- Chicago, Food Allergy Research & Education (FARE). ulary for the OMOP CDM. Gaps were identified and ambiguities resolved RATIONALE: Lack of a comprehensive and widely adopted terminology based on semantic domain. for food allergy (FA) presents a challenge for researchers and clinicians to RESULTS: 977 concepts, in 11 categories, were evaluated. Coverage of improve care and outcomes. There is a discernible need to develop a core the complex Oral Immunotherapy category was found to be most lexicon and ontology for FA concepts which would enable data sharing incomplete, containing 117 unmapped concepts. Of the other categories, across multiple institutions to advance FA research and treatment. 66 concepts did not map to the OMOP standardized vocabulary. The METHODS: During the first phase, clinical artifacts, including, patient placement of some mapped concepts in the OMOP hierarchy was intake forms, templates, clinical notes, and pre-compiled EPIC phrases inconsistent with clinical allergy practice, based on an expert panel. The used across four Food Allergy Research and Education (FARE) Clinical OMOP vocabulary team expressed openness to resolving the gaps and Network (FCN) sites were analyzed and interviews with domain experts inconsistencies. were conducted. Next, we defined high-level FA categories and enumer- CONCLUSIONS: There is definite room for the existing ontologies to be ated clinical concepts into these categories. Finally, the candidate ontology expanded to provide for the unique aspects of food allergies. By working was sequentially validated over a series of iterations with the panel of with the OMOP team to address the discovered inconsistencies, and by experts to include clinical concepts that recorded the highest agreement. continuing to refine our data dictionary we hope to close those remaining The second validation phase involved vetting the dictionary with experts gaps and provide a platform for uniformity of FA data. across 22 FCN Centers of Distinction. RESULTS: The data dictionary is organized into 11 categories; Events, Lacking Demographic, Socioeconomic, and Medications, Formal diagnoses, Triggers, Social determinants, Oral 373 Environmental Variables in Training Machine Immunotherapy (OIT), Reactions, Procedures, Therapeutic plan, Clinical Learning Algorithms Makes Generalizability trial, Unique external data identifier. Each concept has a hierarchical Flawed in Asthma Studies categorization into super classes and subclasses, and concept attributes have been defined to include 977 FA concepts. Although existing clinical Emily Chen1, Timothy Darby1, Sunit Jariwala, MD FAAAAI2; 1Albert vocabularies cover many of these, noticeable gaps are evident, and some Einstein College of Medicine, 2Albert Einstein/Montefiore Medical Cente. concepts are missing entirely, such as ‘‘baked eggs’’ or OIT phases. RATIONALE: Artificial intelligence has become an increasingly valu- CONCLUSION: The FA data dictionary provides a pivotal resource for able tool for analyzing large datasets. As algorithms are trained to understanding of complex, multi-institutional data to promote scientific supplement clinical diagnoses, utilizing representative populations is discovery in the field of FA. crucial to ensure that racially diverse communities would benefit to the same degree as the overall population. METHODS: Utilizing PRISMA guidelines, a literature search was conducted using the search terms ‘‘asthma’’ and ‘‘artificial intelligence.’’ PubMed, Web of Science, Medline, Embase, and Cochrane were utilized in this scoping review. Inclusion criteria consisted of articles published after 2015, written in English, and excluded review papers and abstracts. RESULTS: The search criteria resulted in a total of 390 articles. A preliminary review was conducted based on inclusion criteria, thereby resulting in 55 articles. Relevant articles were subcategorized based on diagnosis (23.6%), endotypes (32.7%), triage/risk assessment (14.5%), Natural Language Processing (NLP)/big data (12.7%), and wearables/ telemonitoring (16.5%). A secondary review was performed to identify the patient populations that were used to train AI software. Only ten articles (18.2%) included sociodemographic information of the patient population and considered this as a factor in determining training cohorts. Six (10.9%) articles used environmental factors such as weather and pollutants as risk factors. CONCLUSIONS: Existing literature on machine learning and asthma often fails to thoroughly characterize the participants in their training populations. Specifically, patients within our network at Montefiore face unique environmental and socioeconomic challenges that are not reflected J ALLERGY CLIN IMMUNOL Abstracts AB119 VOLUME 147, NUMBER 2

A Retrospective Study of Risk Factors for Systematic Food Allergy Educational Resource 375 Redocumentation of Penicillin Allergy 377 Evaluation by Caregivers of Children with Food Allergy Alexander Horbal1, Sunjay Modi, MD1, Alexandra Sitarik2, Bin Liu3, Haejin Kim, MD2, Edward Zoratti, MD FAAAAI1; 1Henry Ford Hospital, Stephanie Kubala1, Ashley Ramos, PhD2, Hemant Sharma, MD, MHS2, 2Henry Ford Health System, 3Henry Ford Health Systems. Linda Herbert, PhD2; 1NIH, 2Children’s National Hospital. RATIONALE: Electronic Medical Record (EMR) documentation of RATIONALE: Food allergy (FA) management impacts the daily life of allergies is critical for patient safety and efficacious for appropriate children and their caregivers. Parental FA knowledge is poor at diagnosis, treatment. Inaccuracies in documentation can cause serious problems and and current available educational resources have not been systematically lead to increase in mortality and morbidity. Studies have addressed the evaluated for quality amongst families. We assessed available FA detrimental effects of redocumentation of penicillin (PCN) though few educational resources in print form in order to formulate an efficient have expanded on risk factors. packet of materials for the newly diagnosed FA family. METHODS: Patients who underwent inpatient or outpatient PCN skin METHODS: Seven caregivers of children with FAwho served as mentors testing between 3/1/13 and 10/31/19 at Henry Ford Health System were in a tertiary pediatric allergy clinic evaluated a binder of 52 commonly used identified using EMR data. Existence and potential removal of PCN allergy FA resources via the Patient Education Materials Assessment Tool for in the EMR was extracted. Risk factors such as age, race, ethnicity, Printable Materials [PEMAT-P]. Resources fell into 9 categories, ranging language, testing location, insurance, deprivation index, and dementia from FA basics to managing allergic reactions to the psychosocial impact diagnosis were tested for association with PCN redocumentation using of FAs. The PEMAT-P is a 26-item measure that has two subscales: ANOVA, chi-squared tests, and Fisher’s exact tests. understandability and actionability. Items are rated as ‘yes51’ or ‘no50’; RESULTS: A total of 456 patients had a negative PCN skin test and had each subscale score is summed with higher scores indicating greater PCN allergy deleted from their EMR. Eleven of these patients were excluded understandability/actionability. because a reaction to PCN following skin testing was documented and PCN RESULTS: Understandability scores ranged from 62% to 100% was therefore added back to their chart. Of the remaining 445, 81 (18.2%) (M588%; SD510%). Actionability scores ranged from 0% to 100% had PCN redocumented without further explanation. Significant of reentry (M576%; SD519%). Five resources, including anaphylaxis emergency wasrecordedby17MDs,30RNs,18MAs,4CNPs.Nostatistically care, received perfect PEMAT-P scores. Four resources scored below 70% significant associations were identified with the examined risk factors, for understandability, and 14 scored below 70% for actionability. The though patients who had an inpatient PCN skin test were slightly more likely lowest ratings were given to resources about primary prevention of FA. to have PCN redocumentation (23.5% vs. 15.9%, p50.072). CONCLUSIONS: This study used parent mentors to evaluate currently CONCLUSION: None of the examined risk factors were significantly available FA resources and found inconsistent quality among resource associated with PCN redocumentation, though redocumentation was more topics. Resources in domains such as emergency anaphylactic care are well likely to occur after inpatient PCN skin testing, and was primarily recorded understood and can be acted upon, but understandable and actionable by non-physicians. resources regarding the primary prevention of FA need to be developed.

Quality Improvement: Enhancing Asthma Control Weekly and Seasonal Variation in Controller 376 Test Documentation via Smarter EMR Integration 378 Adherence by Age in Asthma

Omar Waqar, MD1, Mauli Desai, MD1; 1Icahn School of Medicine at Leanne Kayen, Rahul Gondalia, PhD1, Meredith Barrett, PhD1, Bruce Mount Sinai. Bender, PhD FAAAAI2, David Stempel, MD FAAAAI3; 1ResMed, 2Na- RATIONALE: Appropriate assessment of asthma control includes tional Jewish Health, 3Propeller Health. evaluation of five parameters: 1. daytime symptoms, 2. nighttime RATIONALE: Better understanding of the determinants of poor adher- awakenings, 3. interference with normal activity, 4. short-acting beta2- ence may aid in the development of targeted mitigation strategies. agonist (SABA) use and 5. number of asthma exacerbations requiring oral METHODS: Participants with asthma enrolled in a digital platform that steroids in the last year. To improve documentation of asthma control, an included an electronic medication monitor (EMM) and an accompanying electronic asthma control test (ACT) survey for seamless integration into smartphone application (app) to track controller inhaler use (Propeller the EMR was developed. Health). Participants were >_4 years old and had >_52 weeks of controller use METHODS: A retrospective chart review was performed to analyze data. Temporal trends of mean daily adherence by day of week and season asthma control documentation. A Plan-Do-Study-Act cycle was performed by age group (4-11, 12-17,18-39, 40-59, 60+) were quantified. Paired t- to assess barriers to documentation of asthma control. A digital ACT tests compared maximum vs. minimum difference in adherence by day of survey was developed with our EMR support team that provided dropdown week for each calendar week. Adherence was defined as the number of answer choices and directly embedded the survey into the physicians note. controller actuations recorded divided by the prescribed number of This intervention was launched to the clinical team via live demonstration actuations per day, capped at 100%. during grand rounds. RESULTS: 9130 participants were included (mean age: 35.4 (17.5)) with RESULTS: In the preintervention phase, 25 charts were reviewed. SABA 10.7% children (<12 years); mean adherence was 42 (33)%. Children use was most reliably documented in 88% (N525) of patients, whereas demonstrated larger differences in adherence by day of week, with Monday oral steroid usage was least documented, appearing in 32% (N58) of the - Thursday having the highest mean adherence (range: 42.4-43.0%) and charts reviewed. 12% (N53) of patients had all five parameters of asthma Saturday having the lowest (36.0%). Children had lowest adherence during control assessed. Chart review also revealed that only 40% (N510) of the summer (May – August) with lower, but persistent day of week patients had lung function testing performed in the past year, becoming a adherence differences. Day of week differences was observed in adults, but potential second target for quality improvement and digital interventions in was less pronounced than in children, respectively: 4.0% (95% CI: 3.8, 4.3, the future. p < 0.001) vs. 8.4% ( 95% CI: 7.6, 9.1, p < 0.001). CONCLUSION: Documentation of asthma control was suboptimal in our CONCLUSIONS: Differences in day of week adherence were greatest in clinic. A digital EMR solution was implemented that seamlessly integrates children and modified by season. Understanding medication-taking ACT flowsheets into providers’ notes. Anecdotally, physician feedback has behaviors can help inform the type and timing of clinical intervention. been positive, and a post intervention analysis is planned after the COVID- 19 pandemic. AB120 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Study on Allergy to Beta-lactams. Should all the Influenza Vaccination of High Risk Brooklyn 379 patients be delabeled? 381 Residents Questionnaire

Marıa Dolores Rodrıguez Bote1, Leticia Domınguez-Cereijo2, Amparo Venkatesh Sabhae Gangadharappa1, Rauno Joks, MD FAAAAI2; Conde-Alcaniz~ 2, Pedro Guardia-Martınez2; 1Virgen Macarena University 1SUNY Downstate Medical Center, 2SUNY-HSC. Hospital (HUVM), Seville, Spain, 2Virgen Macarena University Hospital RATIONALE: To learn more about inner-city high-risk patients’ (HUVM), Seville, Spain. knowledge and attitudes regarding influenza and influenza vaccine. RATIONALE: Beta-lactams are a kind of antibiotics frequently used to METHODS: We administered in person influenza vaccine questionnaire treat infections. Many people with negative allergy tests for these beta- to patients with asthma and other co-morbid conditions who attended the lactams are still labeled as allergic in their medical records. This research allergy and immunology clinic in inner-city Brooklyn. aims to estimate the actual allergy prevalence to these antibiotics. The rate After pre-survey, all patients received a flu vaccine education session and between the quantity of practiced tests and the number of people who have post-survey was given. been consequently delabeled as allergic is also to be studied. RESULTS: Patients (N 5 49) were between 19-92 yrs. (mean 48.2, SD METHODS: From January to June 2019, in the HUVM Department of 19.2) with 11/49 (22.4%) male and 38/49 (77.5% female). 17/49 (34.6 %) Allergy, 149 allergy tests were practiced (n5149) in patients ranging from were Caribbean born and 23/49 (46.9 %) Brooklyn/ NY born, 9/49 (18.3%) 1 to 86 years old, in order to discard beta-lactams allergy. These were skin other US born. tests (with PPL, MDM, penicillin G, amoxycillin/clavulanate, cefuroxime, 23/49 (46.9%) received flu vaccine last season, 6/49 (12.2 %) never and the beta-lactam involved), as well as controlled exposure trials. The received flu vaccination. 34/49 (69.3%) said to have received at least one outcome was afterwards compared with the allergy records database in or- dose for last 5 yrs., only 4/49 (8.1%) received flu vaccine consecutively for der to ponder the rate of patients who are still labeled as allergic to these last 5 yrs. antibiotics. 10/43 (23.2 %) who have previously received a flu vaccine said they will RESULTS: The prevalence of allergic patients to beta-lactams was of never take flu vaccine again. However, after education, 6/10 patients (60%) 12.75%. Allergy was discarded in 84.56% of the cases. After this research, in this group said they would either consider, most likely or definitely take 40.47% of the latter were still labeled as allergic to beta-lactams, whereas flu vaccine. 58.73% of them already had their medical record delabeled. There were no changes in attitudes after education session for patients who CONCLUSIONS: Nearly half of the patients discarded as beta-lactams had never received flu vaccine. allergic are still labeled as such in their medical records. These data prove Only 17/49 (34.6%) said they will consider COVID-19 vaccine, 3/49 (6 %) not only the convenience of practicing allergy tests on these patients, but were unsure and 29/49 (59.1%) indicated that they will not take vaccine also of delabeling their medical records according to the results obtained even if it’s available. from the tests. 2/6 (33.3 %) patients who never received flu vaccine said they will consider COVID-19 vaccine. Combatting Inappropriate Allergy Alert CONCLUSIONS: Health care professionals can target high-risk patients 380 Overrides in specialty clinics with focused education sessions to reinforce adherence for flu vaccine. Soombal Zahid1, Annette Piotrowski1; 1Lenox Hill Hospital-Northwell Health. Risk of Postmarket Black Box Warnings in FDA RATIONALE: Monitor and characterize drug allergy alert overrides at a 382 Approved Monoclonal Antibodies community hospital in NYC. We investigated whether overrides were justified and further, elicited responses from medicine residents to under- John Hagan1, Elizabeth Ender, MD2, Rohit Divekar, MBBSPhD1, Thanai stand the logic behind unjustified responses. Pongdee, MD FAAAAI1, Nilay Shah3, Matthew Rank, MD FAAAAI4; METHODS: Providers at our hospital have to provide a free text 1Mayo Clinic, 2Marshfield Medical Center, 3Mayo Clinic, Rochester, explanation when overriding an allergy alert. We conducted a retrospective 4Mayo Clinic and Foundation. review of 1377 drug allergy alert overrides over a five-month period. The RATIONALE: It is important for Allergists/Immunologists to understand responses were deemed as justified or unjustified based on whether they the risks and benefits of monoclonal antibodies (mAbs), which include mentioned clinical logic behind overriding the alert. We then conducted a unknown future risks especially for recently approved mAbs. We sought to 5-question survey of the housestaff to assess their knowledge about allergy estimate the potential risk of a future postmarket black box warning (BBW) alerts and barriers that exist in responding to them with clinical judgment. in FDA-approved mAbs. RESULTS: An average of 66% of the time, the responses were without METHODS: We searched FDALabel (https://nctr-crs.fda.gov/fdalabel/ clinical justification as to why the alert was being dismissed. Answers such ui/search) and reviewed the literature to determine current and previously as ‘‘ok’’ (38%) and random letters (34%) were the most frequent FDA approved mAbs as of March 2020. BBWs and initial FDA issued inappropriate responses. Survey results from 35 residents revealed that safety warnings were identified. BBWs were categorized as premarket or an excessive number of alerts makes it hard to focus on the importance of postmarket. For mAbs with specific postmarket BBWs, previous FDA la- any individual one (43%), followed by lack of time (22%), and inaccuracy bels were evaluated to identify the presence or absence of an initial, corre- of the recorded allergy (17%). sponding, specific FDA warning. CONCLUSIONS: This study provides insight into the causes behind high RESULTS: In March 2020 there were 83 FDA approved mAbs. Thirty- allergy override rates. Alert fatigue in this era of electronic healthcare is three had BBWs (27 premarket, 13 postmarket). Of the 33 mAbs with heightened and we need to develop ways of distinguishing alerts that have BBWs there were a total of 55 individual, specific BBWs (36 premarket the potential to affect patient safety. Our next steps are to implement and 19 postmarket specific warnings). On average, specific BBWs initiatives that focus on drug allergy documentation upon admission and occurred in the postmarket period at a rate of 3.4 percent per year. A workshops that modify alerting mechanisms with IT. majority (74 percent) of postmarket BBWs were preceded by an FDA warning by a median of 3.61 (IQR 1.36-5.78) years. Postmarket BBWs not preceded by a specific FDA product label warning occurred at an average rate of 0.89 percent per year. CONCLUSIONS: Postmarket BBWs occurred in FDA approved mAbs at a rate of 3.4 percent per year. Postmarket BBWs not preceded by a specific FDA product label warning occurred at a rate of 0.89 percent per year. J ALLERGY CLIN IMMUNOL Abstracts AB121 VOLUME 147, NUMBER 2

The Impact of Education on Health Literacy of Design of a Mast Cell Activation Syndrome 383 Asthmatics in the Bronx 385 Symptom Scorecard

Obumneme Njeze, BS1, Brian Hsia, MD2, Anjani Singh, MD1, Emine Claire Amelio, RN, BSN1, Mildred Kwan, MD PhD FAAAAI1, Onyinye Cosar1, Savneet Kaur1, Sunit Jariwala, MD FAAAAI1; 1Albert Einstein Iweala, MD PhD1; 1University of North Carolina. College of Medicine/Montefiore Medical Center, 2Mount Sinai Hospital. RATIONALE: Mast Cell Activation Syndrome (MCAS) results from RATIONALE: Poor health literacy contributes to worse patient outcomes dysregulated mast cell (MC) degranulation, often without triggers. No in asthma, while educational programs have been associated with standardized tools exist to assess MCAS-associated symptoms and impact improved clinical outcomes. ASTHMAXcel is a smartphone application on quality of life (QOL) or to monitor MCAS symptoms following designed to promote asthma education for patients. Our objective was to initiation of MCAS-directed therapy. We designed an MCAS Symptom evaluate participants’ education level and health literacy. Scorecard (MSSC) for use in patients with presumed or confirmed MCAS. METHODS: We included adult patients with persistent asthma, currently METHODS: We generated questions using symptoms from four organ taking a controller inhaler, and with smartphone access. During the systems deemed "of diagnostic value’’ (cutaneous, cardiovascular, gastro- baseline visit, we collected demographic information and used the Newest intestinal, respiratory) by the 2019 AAAAI Mast Cell Disorders Vital Sign tool to assess health literacy. Participants received an ice cream Committee Work Group and two patient-proposed organ systems, nutrition facts label and were asked five questions pertaining to the genitourinary and neuropsychiatric. Input from stakeholders shaped information on the label. Scoring of the Newest Vital Sign (0-6) indicated scorecard clarity and patient comprehension. different levels of literacy: 0-15high likelihood of limited literacy, 2- RESULTS: The 44-item questionnaire has 3 sections: 1) A 21-item 35possible limited literacy, 4-65adequate literacy. A Welch’s t-test was symptom section with 5 domains (cardiovascular; skin; respiratory; performed to compare means. gastrointestinal/urinary; neuropsychiatric) to track symptom frequency, RESULTS: 28 users participated in our study (Females 5 21, mean age severity, and QOL over 1 week. Three different symptom scores can be 45.5 +/- 15.2). Users with high school degrees (n59) were the reference calculated: "AAAAI score’’ incorporating points ONLY deemed "of point. Participants with some college or tech school education (n58) diagnostic value’’ by the 2019 AAAAI Work Group (range 45 to 180 scored higher than high school graduate/GED holders (4.37 vs 2.00, points), a "neuro/psych score’’ (range 12 to 48), and a total score (range 63 p50.001). College graduates (n58) also scored higher than high school to 252); 2) A 13-item medication section (11 listed, 2 free response) graduate/GED holders (4.75 vs 2.00, p50.0003). Participants with less tracking controller and rescue medication use and 3) A 10-item symptom than a high school degree (n53) scored similarly to those with a high trigger section (8 listed, 2 free response). school degree (1.67 vs 2.00, p50.751). CONCLUSIONS: We created an MCAS Symptom Scorecard to quantify CONCLUSIONS: A higher degree of education is associated with greater frequency and severity of MCAS-associated symptoms, triggers, controller health literacy. ASTHMAXcel may close the gap in health literacy between and rescue medication use in patients seeking evaluation and management less educated and more educated patients. of confirmed or presumed MCAS. Future plans include scorecard validation and determining if the MSSC distinguishes MCAS patients Applying a Symptom Scorecard to the from other atopic individuals. 384 Management of Presumed or Confirmed Mast Cell Activation Syndrome Practice improvement module variability among 386 care providers Onyinye Iweala, MD PhD1, Claire Amelio, RN, BSN1, Mildred Kwan, MD PhD FAAAAI1; 1University of North Carolinas. Aaron Case1, Thomas Casale, MD FAAAAI2, Sharmilee Nyenhuis, MD RATIONALE: Mast Cell Activation Syndrome (MCAS) results from FAAAAI1; 1University of Illinois at Chicago, 2University of South dysfunctional, spontaneous mast cell (MC) degranulation. No validated Florida. instruments exist to measure severity of MCAS-associated symptoms; RATIONALE: The Asthma IQ (Asthma Specialist Tool to Help Manage effects on quality of life; or course with MCAS-directed therapy. We Asthma and Improve Quality) is a Practice Improvement Module (PIM) incorporated an MCAS symptom scorecard (MSSC) in the management of offered to primary care physicians (PCPs) and asthma specialists to comply patients with presumed or confirmed MCAS. with the quality improvement (QI) component of their Maintenance of METHODS: Our MCSS tallied symptoms across six different organ Certification. This study aims to examine differences in provider systems (cardiovascular, dermatologic, respiratory, gastrointestinal, geni- preference of PIM asthma topics between PCP’s and asthma specialists. tourinary and neuropsychiatric). Patients also identified symptom triggers, METHODS: Data was obtained from 642 providers (226 PCPs, 416 daily controller and rescue medications for symptom exacerbation. We specialists) from March 2008 to March 2017 in the Asthma IQ database. distributed the MSSC to patients undergoing evaluation for presumed or Providers completed a self-assessment of PIM topics and then chose one confirmed MCAS in a single academic allergy/immunology practice to specific PIM to address for their practice QI. Chi-square analysis tests used complete at the index visit and 4-8 weeks later. to examine differences between provider groups. RESULTS: Patients used a 4-point scale (1: ‘‘not at all’’ to 4: ‘‘extreme’’) RESULTS: The PIMs identified as important by both PCPs and specialists to rate MCAS-associated symptoms over 1 week, indicating ‘‘how often,’’ included: assessment of smoking history, use of validated patient ‘‘how severe,’’ and ‘‘how bothersome.’’ We calculated a ‘‘AAAAI score’’, questionnaires (ACT/ATAQ), providing patients new/updated asthma including points only from organ systems deemed of ‘‘diagnosticvalue’’by action plan and assessment of inhaler technique. For PIM selection, the 2019 AAAAI Work Group (range 45-180), a ‘‘neuro/psych score’’ PCPs chose not to address patient education on allergens and triggers or (range 12-48), and a total score (range 63-252). Significant changes in smoking cessation for current smokers. Specialists were more likely to average AAAAI and total scores, but not the neuro/psych score, occurred choose performance of lung function tests (p<0.01) and providing new/ after therapeutic regimen adjustments. updated asthma action plans (p5.04). CONCLUSIONS: Our MCAS Symptom Scorecard allowed us to quantify CONCLUSIONS: Differences exist between PCPs and specialists in PIM frequency and severity of MCAS-associated symptoms in patients seeking topics chosen for MOC requirements. Further research is needed to identify evaluation and management of confirmed or presumed MCAS. Future provider barriers and facilitators to implementing PIMs for MOC and the plans include 1) scorecard validation, 2) assessing whether the MSSC impact of PIMs on asthma outcomes. distinguishes MCAS patients from those with other allergic conditions and 3) applying the MSSC in multiple centers to determine its utility in diverse clinical settings. AB122 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Creation of a Novel Shared Decision-Making Reducing Disparities in Asthma & Atopic 387 Tool in Pediatric High-Risk Asthma Clinic 389 Dermatitis – The Patient Experience

Christina Huddleston1, Kirsten Kloepfer, MD MS FAAAAI2, Nadia Tonya Winders1, Erica Gonzalez-Reyes1; 1Allergy & Asthma Network. Krupp, MD3, James Slaven, MS, MA2, Cindy Fiscus, RN4, Kathryn RATIONALE: Black and Hispanic patients with asthma and/or atopic Treadwell, RN4; 1Riley Children’s Hospital, Indiana University School dermatitis (AD) have more difficulties and issues because of their condition of Medicine, 2Indiana University, 3Indiana University School of Medicine, than the general population. They are medically challenged and bear a 4Riley Children. heavy emotional burden. Understanding these issues will allow providers RATIONALE: Best practices regarding communication using shared- to reduce disparities in their practice. decision making (SDM) strategies in pediatric high-risk asthma remain METHODS: 841 adults, ages 18 and older, who were diagnosed with unexplored. This project examines whether the addition of a written asthma and/or atopic dermatitis, were surveyed over a two-week period in communication tool based on principles of SDM facilitates improves early 2020. The objectives were to analyze data on the prevalence, severity communication between patient families and the care team in a pediatric and burden that these conditions have on communities of color. high-risk asthma clinic (HRA), when compared to established communi- RESULTS: 67% of low-income asthma patients report that their physician cation practices. always/often understands their needs (compared to 74% overall), and only METHODS: A novel shared decision-making form (SDMF) was two in five (42%) have an asthma action plan (compared to 52% overall). developed with the help of a clinical communications specialist. Patients At-risk asthma patients are more likely to have been to ER/Urgent Care for >_ 9 years of age and their families were given a HRA communication asthma in the past year – 50% of Blacks/Hispanics and 47% of low-income survey at the end of their baseline visit to assess satisfaction of patients compared to 39% overall. Emotionally, two in five AD patients communication with existing standard communication (SC). During the feel embarrassed (41%) and a third are embarrassed because of physical intervention period, the SDMF will be implemented in clinic, and the HRA limitations AD imposes upon them (35%). At-risk populations bear an communication survey will be repeated. The primary outcome will be the emotional burden with half of asthma sufferers changing their lifestyle family’s perception of success of communication with the care team, using (50% of both Blacks/Hispanics and low-income patients). a Likert scale. The two groups, SC and SDMF, will be compared by survey CONCLUSIONS: Asthma and atopic dermatitis disproportionately alter results using Wilcoxon. the lives of low-income communities of color. The practitioner that can RESULTS: Interim analysis of the baseline communication survey show address these issues can reduce health disparities for vulnerable that 95% (n579) of patients are completely satisfied with existing clinic populations. communication. Given the high baseline satisfaction with communication, direct comparison between SC (conversation) and SDMF (conversation School-Based Asthma Education Intervention is plus a written plan) questions were added to the survey. 390 Associated with Improved Asthma Knowledge CONCLUSIONS: Creation of a unique SDMF tool incorporating in Spanish bi-lingual children with asthma principles of SDM has not been previously evaluated in pediatric HRA Margee Louisias, MD MPH1, Wanda Phipatanakul, MD MS FAAAAI2; patients. Post-intervention surveys will allow for comparison of the SDMF 1 2 tool to SC and allow for estimation of whether this novel written form has Brigham and Women’s Hospital, Boston Children’s Hospital. incremental benefit over existing communication practices. RATIONALE: A multicomponent school-nurse led intervention consist- ing of asthma education and asthma preventive therapy supervision is an Evaluating Clinical Outcomes and Impact of a innovative way to reduce asthma disparities in students with asthma 388 Pharmacist-managed Asthma Clinic attending a Spanish dual-language elementary school METHODS: Recruited subjects from a dual-language Spanish elemen- Ikjae Chin tary school completed validated asthma surveys at baseline, after the RATIONALE: Pharmacists have increased their clinical role in providing education intervention and during followup at 2, 4, and 6 months. comprehensive care with advanced knowledge in medications therapy. Educational intervention consisted of subjects watching the Iggy and the Clinical pharmacists have the ability to provide the most appropriate InhalersTM video; school nurse review; and post-knowledge survey. During pharmacotherapy, education on self-management of asthma, and counseling followup, subjects (who opted-in) had daily supervised preventive therapy. on medication use and compliance. This study evaluated the clinical Repeated Measure Analysis of Variance was performed to analyze change outcomes and impact of pharmacist-managed asthma clinic in a federal of outcomes over time. Indian Health Service facility focusing on reduced Emergency Room (ER) RESULTS: Enrolled subjects (n510) were mean of 9 years old, 60% visits due to asthma and improvement of patient-reported asthma symptoms. female, 60% Latino. 60% of subjects’ guardians reported a household METHODS: The Pharmacy Asthma Clinic at the Lawton Indian Hospital income less than $45,000. 60% of participants were on asthma controller recruited 180 patients from age 5 to 70 with asthma diagnosis who were medications and 30% had an asthma specialist. 20% reported daily referred from their Primary Care Providers via Electronic Health Record secondhand smoke exposure. 90% reported seeing mice in the home. system. A retrospective chart review was conducted on all patients who Child asthma control, child and parent self-management efficacy did not completed pre-clinic screenings, initial visits, and at least one follow-up significantly change over the 6-month follow-up of participants. Child clinic visit. Data were collected on the number of patients who reported ER asthma knowledge score significantly changed over time (p50.0413), with visits primarily due to asthma prior to enrollment to the clinic and were a significant change observed from baseline post-education to month-2 compared to after completing their clinic visits. Also, initial Asthma (68% to 87%, p50.0060). Severity assessments and Asthma Control trends were collected according CONCLUSIONS: Baseline child asthma knowledge scores demonstrate to the guideline criteria. an asthma knowledge deficit, despite baseline self-management efficacy RESULTS: The number of ER visits primarily due to asthma after scores showing participants were confident in their ability to manage enrollment to the clinic decreased by 97.8% and 82.2% (n5111) of asthma. Future research is needed to explore asthma knowledge and self- enrolled patients achieved Well Controlled status after completing an management efficacy discordance and increasing access to asthma initial visit plus at least one follow-up visit. specialty care in minority children. CONCLUSIONS: Pharmacist-managed asthma clinic reduced ER visits and improved patients’ asthma symptoms by providing most appropriate medication therapy combined with thorough education and counseling on medication use and compliance. J ALLERGY CLIN IMMUNOL Abstracts AB123 VOLUME 147, NUMBER 2

Improving Influenza Immunization Rates Association of Chronic Diseases with Penicillin 391 393 Allergy Status– A Retrospective Study

Jun Mendoza, James Quinn, MD FAAAAI1; 1Wilford Hall. Paul Faybusovich, DO1, Maria Paula Henao, MD1, Taha Al-Shaikhly, RATIONALE: Influenza virus is an important cause of respiratory disease MBChB1; 1Penn State College of Medicine. during the winter months. This past flu season, our objective was to ensure RATIONALE: Chronic diseases such as emphysema and heart failure are 5>80% of eligible patients seen in our clinic were up to date for the associated with increased risk of infection and antibiotic use including influenza vaccine by 1Dec2019. penicillin; however, the relationship between chronic diseases and METHODS: Outcomes were measured between September and penicillin allergy is not well established. Such relationship may serve to November by gathering 20 surveys per month. Initial survey data showed guide penicillin allergy evaluation. a baseline immunization rate of 60% for September. Improvement Cycles 1 METHODS: We conducted a case-control study using the TriNetX, a and 2 were then planned for October and November, respectively. For global federated health research network providing access to EMRs from Improvement Cycle 1, a ‘‘strong physician recommendation’’ for the flu our organization. We identified two cohorts seen yearly in an ambulatory vaccine was made at the end of a visit, increasing our immunization rate to setting over the past 5 years. Penicillin allergic group had an ICD-10 code 80%. For Improvement Cycle 2, plans were made to ‘‘identifyand mitigate of either ‘allergy status to penicillin’ or ‘adverse effect to penicillin’ patient-level barriers’’ for those who refused the flu vaccine, but survey between 01/01/2019 and 04/30/2020. Non-penicillin allergic group data showed a 100% influenza immunization rate prior to the visit. consisted of patients without these ICD-10 codes. The two groups were RESULTS: By making a ‘‘strongphysician recommendation’’,we showed matched for age, sex, white race, asthma, allergic rhinitis and HIV a 20% increase in flu immunization rates. The 100% immunization rate for diagnoses using the propensity score matching. The two groups were Improvement Cycle 2 was attributed to many factors, to include: an compared for the presence of common chronic diseases. ongoing flu campaign at our hospital, an opportunity to obtain a flu shot in RESULTS: Penicillin allergic individuals (N52,150) were similar to our clinic prior to being seen, and a selection bias for patients already those without penicillin allergy (N52,150) in demographics, HIV immunized by their PCM prior to being referred diagnosis and atopic comorbidities. Compared to those without penicillin CONCLUSIONS: Studies have shown that patients trust their doctor’s allergy, penicillin allergic individuals had higher odds of GERD guidance, whether it is their PCM or specialty care physician. By making a (OR52.99; P<0.001), cirrhosis (OR52.04, P<0.001), heart failure ‘‘strongrecommendation’’for the flu vaccine, physicians can feel confident (OR53.44; P<0.001), emphysema (OR52.06; P<0.001), diabetes that this quick and simple intervention in their clinic can influence a (OR52.20, P<0.001), obesity (OR52.13; P<0.001) and chronic kidney patient’s decision to vaccinate. disease (OR 5 2.52; P<0.001). CONCLUSION: We established a significant association between Allergists Should Be Proficient In Providing penicillin allergy and several chronic diseases, notably with heart failure, 392 Comprehensive Care For Patients With Alpha-1 and GERD. Such association may serve to guide targeted penicillin allergy Antitrypsin Deficiency evaluation and warrant further investigation.

Anna Ptasinski1, Timothy Craig, DO FAAAAI1; 1Penn State University. Identifying and overcoming barriers to inpatient RATIONALE: Alpha-1 Antitrypsin Deficiency (AATD) is an inherited 394 Penicillin allergy de-labeling by non-allergists. protein deficiency that may cause emphysema and cirrhosis. The severe ZZ genotype initiates multi-organ disease and patients see various specialists; Cheryl Rozario1, Jessica Stern, MD1; 1University of Rochester Medical quality assurance ensures excellent care. Center. METHODS: The study is quality assurance, meeting exclusion criteria RATIONALE: Given the public health burden of a penicillin (PCN) from the Institutional Review Board. An EMR search provided patients allergy label, non-allergists have been called to evaluate and de-label low with coding for AATD. Then, each chart was reviewed for testing, risk patients. We discuss barriers identified in implementing a QI initiative vaccination, medication, and education from allergists, pulmonologists, aimed to train non-allergists to risk stratify and de-label low risk PCN and gastroenterologists. allergy patients. RESULTS: A total 329 patients were screened; 203 patients had a METHODS: A PCN allergy risk stratification tool and workflow were significant genotype. The ZZ genotype included 48 patients with average created to identify, risk stratify, and de-label low risk patients after oral age of 50.6 years with 26 males and 22 females. Allergists saw 25 patients; amoxicillin challenge. The initiative was presented to stakeholders of an pulmonologists and gastroenterologists saw 6 each. Testing was compared adult inpatient unit in a focus group. Participants completed a pre and post by specialist (allergist, pulmonologist, gastroenterologist) for spirometry survey. Comfort with managing anaphylaxis and priority of PCN allergy (56%, 83.3%, 0%) , liver function tests (48%, 50%, 33.3%), abdominal US/ de-labeling were assessed via ordinal scale from 0 (none) to 10 (high). CT (40%, 33.3%, 50%), and chest CT (68%, 83%, 16.7%). Additionally, Discussion and survey responses identified perceptions and barriers vaccination history was compared for Pneumovax (88%, 100%, 16.7%), regarding PCN allergy evaluation. Prevnar (88%, 83.3%, 33.3%), influenza (96%, 100%, 33.3%), and RESULTS: 10 participants completed pre and post survey. Barriers to hepatitis A/B (92%, 100%, 83.3%). Medications of augmentation, (48%, implementing a PCN de-labeling initiative were: lack of provider time, fear 16.7%, 0%) inhaled corticosteroid (68%, 50%, 33.3%), long-acting Beta of provoking anaphylaxis, poor recognition/management of anaphylaxis, agonists (56%, 66.7%, 0%), anticholinergics (52%, 83.3%, 0%), and and view of initiative as low priority. Only 50% could identify criteria for albuterol (64%,100%, 16.7%) was compared. Pulmonary rehabilitation anaphylaxis on pre survey (increased to 100% on post), and 60% could referral (36%, 66.7%, 0%) and patient education for alcohol (88%, 100%, identify treatment (increased to 90%). Median pre and post survey comfort 100%) and tobacco (88%, 100%, 83%) was analyzed. level with managing anaphylaxis was 5 and 7 respectively. Median pre & CONCLUSION: Continuous quality assurance ensures comprehensive post survey priority of PCN allergy de-labeling was 4.5 and 8 respectively. care in large healthcare systems. Allergists are proficient in treating CONCLUSIONS: Successful PCN allergy de-labeling by non-allergists obstructive lung disease and augmenting diseases. Allergists are equipped requires identification of clinical champions, ongoing education regarding to care for AATD patients; however, further education will lead to anaphylaxis, developing sample scripts/dialogue, and reducing time improved care. burden by integrating risk tools with decision support guidance and documentation templates into the EMR. AB124 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Development and Initial Validation of a Food group were higher than those of the reactive therapy group (Median 395 Allergy Associated Parental Anxiety Screening CDLQI of proactive 2 [n584] vs. reactive 1 [n578], p 5 0001; Median Tool: IMPAACT DFI of proactive 2 [n583] vs. reactive 0 [n576], p 5 0.000). CONCLUSIONS: Proactive therapy is performed for moderate to severe Sharon To1, Clara Westwell-Roper, MD, PhD2, Lianne Soller, PhD3, Ed- AD patients using intermittently TCS. Children who require proactive mond Chan, MD FAAAAI4, S. Evelyn Stewart, MD2; 1Department of Psy- therapy and their caregivers may have a worse QoL which warrants further chology, BC Children’s Hospital, Vancouver, BC, Canada, 2Department of attention and support. Psychiatry, Faculty of Medicine, UBC, 3Division of Allergy and Immu- nology, Department of Pediatrics, Faculty of Medicine, UBC, Vancouver, Quality of Life in Food Allergic Children and 4Division of Allergy and Immunology, Department of Pediatrics, Faculty 397 Adolescents at a Community Educational of Medicine, UBC, Vancouver, BC, Canada. Symposium RATIONALE: When faced with the uncertainty of potential allergen Diem-Tran Nguyen, MD1, Kathleen Pitts, PhD, APRN, PNP-BC, MPH1, exposure and anaphylaxis, anxiety about the management of a child’s food 1 1 1 allergy (FA) is adaptive. Parental FA-associated anxiety (PFAA) is Kristen Staggers, MS , Carla Davis, MD ; Baylor College of Medicine. prevalent and impacts parent, child and family functioning. RATIONALE: The purpose of this study was to determine whether Understanding normative PFAA has important implications for identifying quality of life (QoL) differed between food allergic (FA) adolescents and families who may benefit from psychosocial support for FA management. children who participated in an educational Food Allergy Symposium We developed and validated a screening tool (Impairment Measure for (FAS) from 2018-2019. Parental food Allergy-related Anxiety and Coping Tool, IMPAACT) to METHODS: Children and adolescents with a diagnosis of FA were assess impairment caused by PFAA. recruited at the FAS in September 2018 and 2019. FA adolescents, METHODS: The preliminary IMPAACT questionnaire was developed children, and their parents were invited to complete the Food Allergy using inductive and deductive approaches to item generation with clinician Quality of Life Questionnaire (FAQLQ) and the Food Allergy Independent and parent feedback. The screening tool and measures of parental burden Measure (FAIM), which reflects concerns about accidental food exposure (FAQL-PB) and generalized anxiety (STAI, GAD-7) were distributed and disease severity. Higher FAIM and FAQLQ scores reflect worse QoL. online through Canadian food allergy advocacy groups. Factor and Summary scores were compared using the Wilcoxon rank sum test, correlation analyses were used to examine the factor structure of Fisher’s exact test or Chi-square test. IMPAACT and its relationship with related constructs. RESULTS: Seventy-four surveys (82% children; 18% adolescents) were RESULTS: 296 parents completed the questionnaires. The 28-item included. Adolescents had fewer food allergies (0% vs 31.5% with >6 food 5 measure demonstrated high internal consistency (a5.96). Factor analysis allergies;p 0.042). The FAQLQ total score was higher among adolescents 5 revealed a four-factor structure, addressing 1) FA-associated worries than children (median 5.2 vs 4.2;p 0.045), and the FAIM was lower in 5 (cognitions), 2) behavioural avoidance and reassurance-seeking, 3) anxiety adolescents (median 2.2 vs 2.8;p 0.037). More adolescents reported 5 impact, and 4) child coping/anxiety, which together explained 67% of the previous anaphylaxis (91.7% vs 51.8%;p 0.011) and feeling reassured by 5 total variance. IMPAACT scores were strongly correlated with FAQL- having epinephrine (81.8% vs 45.8%;p 0.046). Adolescents had a higher 5 PB(r50.79, p<.001) and weaker associations with STAI(r5.42, p<.001) percentage of dysphagia (58.3% vs 22%;p 0.029). and GAD-7(r5.37, p<.001). CONCLUSIONS: Adolescents had significantly lower QoL, with more CONCLUSIONS: IMPAACT assesses the impact of FA-associated concern about their disease and more reassurance by epinephrine carriage parental worries, behavioural avoidance and reassurance-seeking, and than children, which may reflect their increased autonomy. The higher consequences for the family. Our psychometric evidence suggests that incidence of dysphagia in teenagers may indicate eosinophilic esophagitis IMPAACT provides a reliable and valid measure of PFAA. Further studies as an under-recognized cause of dysphagia among FA youth. This are needed to evaluate its use as a longitudinal outcome measure and its assessment of QoL and FA symptoms at a community event reveals a validity in other FA-populations. significant impact of FA in adolescent populations.

Quality Of Life Comparison Between Proactive 396 And Reactive Therapy In Children With Atopic Dermatitis

Yuri Endo1, Kenji Toyokuni1, Kiwako Yamamoto-Hanada, MD PhD1, Yukihiro Ohya, MD PhD2; 1National Center for Child Health and Devel- opment, 2National Center for Child Health and Dev. RATIONALE: Proactive therapy is selected for moderate to severe atopic dermatitis (AD). AD is known to affect the quality of life (QoL) of children and caregivers significantly. We investigated the difference of QoL between the proactive and the reactive therapy group. METHODS: A cross-sectional survey was conducted at the outpatient clinic of the Allergy Center at the National Center for Child Health and Development from November 2019 to December 2019. Inclusion criteria were patients aged 0 to 16 years with AD who use topical corticosteroids (TCS). The Infants’ Dermatitis Quality of Life Index (IDQOL), the Children’s Dermatology Life Quality Index (CDLQI) and the Dermatitis Family Impact (DFI) were examined. RESULTS: There were no significant differences in the IDQOL score or the DFI score of caregivers of children 0-3 years of age between the proactive and the reactive therapy group (Median IDQOL of proactive 2 [n563] vs. reactive 1 [n522], p 5 0.188; Median DFI of proactive 1 [n556] vs. reactive 0 [n520], p 5 0.090). The CDLQI score and the DFI scores of caregivers of children 4-16 years of age in the proactive therapy J ALLERGY CLIN IMMUNOL Abstracts AB125 VOLUME 147, NUMBER 2

The clinically important impact of preschool Mepolizumab Improves Health Related Quality 398 food oral immunotherapy on parental quality of 399 of Life for Patients with Chronic Rhinosinusitis life with Nasal Polyps: Data from the SYNAPSE study Rishma Chooniedass1, Lianne Soller, PhD1, Sandeep Kapur, MD2, Greg- ory Rex, MD2, Mary McHenry, MD2, Timothy Vander Leek, MD Stella Lee, MD1, Maggie Tabberer, MSc2, Andrew Trigg, MSc3, Joseph FAAAAI3, Raymond Mak, MD1, Tom Gerstner, MD4, Stuart Carr, MD Han, MD FAAAAI4, Wytske Fokkens, MD PhD5, Robert Naclerio, MD FAAAAI3, Edmond Chan, MD FAAAAI1; 1University of British FAAAAI6, Philippe Gevaert, MD7, Ana Sousa, PhD2, Peter Columbia, 2Dalhousie University, 3University of Alberta, 4University of Howarth, MD8, Bhabita Mayer, MSc2, Steven Yancey, MS MBA9, Robert Manitoba. Chan, MD10; 1University of Pittsburgh School of Medicine, Pittsburgh, RATIONALE: Our group previously showed the safety of peanut oral Pennsylvania, USA, 2GSK, Stockley Park, Uxbridge, Middlesex, UK, immunotherapy (OIT) in 270 preschool-aged children (0.4% had severe 3Adelphi Values Ltd, Manchester, UK, 4Eastern Virginia Medical School, reactions). The impact of preschool OIT on parental quality of life (QoL) Norfolk, VA, USA, 5Amsterdam University Medical Centres, Location has not been previously described. AMC Amsterdam, Amsterdam, The Netherlands, 6Pritzker School of METHODS: We enrolled preschool-aged children into OIT. The project Medicine, University of Chicago, Chicago, IL, USA, 7Ghent University was conducted in four clinics across Canada (Halifax, Winnipeg, Hospital, Ghent, Belgium, 8GSK, Brentford, London, UK, 9GSK, Respi- Edmonton, Vancouver). The OIT protocol used capsules and/or food, ratory Triangle Park, NC, USA, 10GSK, Stevenage, UK. and the maintenance dose was 300mg of protein daily. The 17-item Food RATIONALE: To report the efficacy of 4-weekly add-on mepolizumab Allergy Quality of Life– Parental Burden (FAQL-PB) questionnaire was 100 mg SC on health-related quality of life (HRQoL) in adults with administered to parents at baseline and end of build-up, and Wilcoxon Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) . signed-rank test was performed to compare the FAQL-PB scores between METHODS: SYNAPSE (NCT03085797), a randomised, double-blind, timepoints. placebo-controlled, multicentre, 52-week study, enrolled adult patients RESULTS: Between May/2019-August/2020, 29 patients aged 9–32.3 with highly symptomatic CRSwNP and prior surgery, treated with months (58.6% males) completed OIT (28 peanut, 1 sesame), and FAQL- intranasal corticosteroids. Co-primary endpoints: change from baseline PB questionnaires. There was a significant improvement in FAQL-PB from in endoscopic NP score (Week 52) and nasal obstruction visual analogue baseline to end of build-up with a median change in score of -14 ((IQR: scale (VAS) score (Weeks 49–52). HRQoL was measured every 4 weeks -33.5, -7.5); p<0.00001), representing a change of 0.82 in mean total score using the SinoNasal Outcome Test (SNOT-22), assessing symptoms and (>_0.5 is considered a minimal clinically important difference [MCID]). impact of CRSwNP. Blinded psychometric analysis of SYNAPSE data and CONCLUSIONS: Our real-world study found that preschool OIT prior qualitative research in patients with CRSwNP was conducted to improves parent QoL from baseline to end of build-up (exceeding the confirm domain structure and meaningful within-patient change MCID), even though families may be most fearful of potential reactions thresholds. during this period based on reaction risks described in older children. This RESULTS: Psychometric analyses support a six-domain solution: nasal reduction in parental burden is most likely associated with the superior symptoms, ear/facial symptoms, non-nasal symptoms, fatigue, impact on safety experienced by families of preschoolers. Future work will involve sleep, and emotional impact supporting the validity of a total score. A analyzing QoL at various timepoints during maintenance, to determine threshold of -28 points was defined using anchor-based methods and whether improvement in QoL holds over time. supported by distribution-based methods. Although substantially greater than previously published thresholds, this value is supported by qualitative patient research. LS mean change from baseline total score at week 52 was -29.5 (SE1.62) for mepolizumab and -15.6 (SE 1.65) for placebo, with 54% and 32% responders respectively (post-hoc analyses). Odds ratio of response was 2.66 95% CI (1.75, 4.04) favouring mepolizumab. Change from baseline in all domain scores was approximately twice as large for mepolizumab compared with placebo, with similar magnitude of improve- ment across all domains. CONCLUSIONS: Mepolizumab significantly and meaningfully im- proves HRQoL in CRSwNP. FUNDING: GSK [GSK ID:205687/NCT03085797] AB126 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Peer Relationships in Children with Food While additional in-person events have not occurred due to the COVID-19 400 Allergies crisis, engagement via virtual programming has been consistent. CONCLUSIONS: For youth managing food allergies, participation in a Christian Coletta1, Kisha Radliff2, Benjamin Prince, MD MCSI community mentorship program has the potential to increase interpersonal FAAAAI1, Rebecca Scherzer, MD FAAAAI3, Irene Mikhail, MD3; connections with same-age peers as well as mentors/mentees. 1Nationwide Children’s Hospital, 2The Ohio State University College of Mepolizumab reduces disease symptoms for Education and Human Ecology, 3Nationwide Children. Patients with Chronic Rhinosinusitis with RATIONALE: Previous studies show children with food allergies (FA) 402 Nasal Polyps: Data from the SYNAPSE study experience being bullied at higher rates than peers. It is unknown if bullying in kids with FA is related to school policies surrounding FA. Maggie Tabberer, MSc1, Andrew Trigg, MSc2, William Busse, MD METHODS: One hundred thirty-seven children were recruited from a FAAAAI3, Valerie Lund, MB BS, MS, FRCS, FRCSEd4, Jason tertiary pediatric allergy clinic. Children or their parents completed a Lee, MD FAAAAI5, Claus Bachert, MD PhD6, Brent Senior, MD7, survey and were separated based on provider diagnosed FA. Thirteen Kathleen Buchheit, MD8, Zuzana Diamant, MD PhD9, Ana surveys were excluded because of self-diagnosed FA. Chi square analysis Sousa, PhD10, Steven Smith, PhD MSc11, Bhabita Mayer, MSc1, Steven was used for comparisons. Yancey, MS MBA12, Robert Chan, MD13; 1GSK, Stockley Park, Ux- RESULTS: Fifty-six patients in the FA group and sixty-eight patients in bridge, Middlesex, UK, 2Adelphi Values Ltd, Manchester, UK, 3Univer- the control group completed the survey. The median age was nine years old sity of Wisconsin, Madison, Wisconsin, USA, 4University College and 56% were male. The most common food allergies reported were tree London, London, UK, 5Toronto Allergy and Asthma Clinic, Toronto, nuts (55%) and peanuts (50%). 42% reported being bullied. Rates of ON, Canada, 6Ghent University and Ghent University Hospital, Ghent, bullying and the types of bullying reported were similar in those with and Belgium, 7University of North Carolina, Chapel Hill, NC, USA, 8Brigham without a diagnosis of FA. Of those reporting bullying, most (83%) and Women’s Hospital, Boston, MA, USA, 9Skane University Hospital, reported incidents of bullying being rare and that bullying was not a current Lund University, Lund, Sweden, 10GSK, Stockley Park, Uxbridge, UK, issue. Children with FA who reported being bullied about their FA were 11GSK, Research Triangle Park, NC, USA, 12GSK, Respiratory Triangle similar to those who deny FA bullying. However, there was a higher rate of Park, NC, USA, 13GSK, Stevenage, UK. FA bullying among children with co-existing eczema (OR 11.9, p-<.005). RATIONALE: Assess efficacy of 4-weekly add-on mepolizumab 100 mg Different school policies for the management of FA did not influence the SC on patient reported symptoms of Chronic Rhinosinusitis with Nasal rates or types of FA bullying. Polyps (CRSwNP). Co-primary endpoints of change from baseline in CONCLUSIONS: Contrary to prior studies, we found no difference in endoscopic NP score and nasal obstruction visual analogue scale (VAS) rates of bullying among kids with FA and other atopic children without a score have been previously reported. physician diagnosis of FA. History of eczema could be a risk factor for FA METHODS: SYNAPSE (NCT03085797), a randomised, double-blind, related bullying. placebo-controlled, multicentre, 52-week study, enrolled 407 adult MassGeneral Hospital for Children Food Allergy patients with highly symptomatic CRSwNP uncontrolled by previous 401 Buddies Program: A Multidisciplinary surgery, treated with intranasal corticosteroids. Nasal Obstruction, Nasal Community Mentorship Program Discharge, Mucus in Throat, Loss of Smell, Facial Pain, Overall Symptoms VAS scores (0-100) were completed daily, reported as 4-weekly means on Maria Theodorakakis, PhD, Psychologist1, Mharlove Andre, BA1, 0-10 scale. Blinded psychometric analyses, informed by prior qualitative Michael Pistiner, MD MMSc2; 1Massachusetts General Hospital, 2Mass- research in CRSwNP patients, determined meaningful within-patient General Hospital for Children, Harvard Medical School. change for each VAS. RATIONALE: Food allergy has been shown to impact quality of life RESULTS: Thresholds for meaningful change: -3.0 for Nasal (QOL) for youth and their parents, as it can limit participation in Obstruction, Mucus in Throat, Loss of Smell and -2.5 for Nasal community activities. A program offering guided interactions with peers, Discharge, Facial Pain, Overall Symptoms. Median change from baseline mentors/mentees, and program staff may address unmet needs for families in VAS at weeks 49-52 and percentage responders (post-hoc analyses) for managing food allergies. mepolizumab and placebo were: Nasal Obstruction, -4.41(60%), METHODS: The MGHfC Food Allergy Buddies Program is a community -0.82(36%); Nasal Discharge, -4.51(64%), -0.85(40%); Mucus in Throat, mentorship initiative designed to bolster participants’ QOL by offering a -4.21(57%), -0.97(36%) ; Loss of Smell, -0.53 (36%), 0.00 (19%); Facial supportive community for youth managing food allergies. It was launched Pain, -3.63(58%), -0.68(40%) Overall Symptoms, -4.48(64%), in January 2020 in Boston, MA after 2 years of program development. -0.90(40%). Loss of Smell VAS showed greater improvement for patients Results of pre-program surveyss indicated a need for community with one prior surgery; median change from baseline for mepolizumab, connection.The team includes a multidisciplinary group of MGHfC staff -1.87, placebo -0.07. No difference vs. placebo in those with > 2 prior (pediatric allergist, pediatric psychologist, nurse, research assistants, surgeries. clinical trainees) and parent volunteers. Program curriculum emphasizes CONCLUSIONS: Clinically and statistically significant improvements in friendship, community, self-management, and safe choices while cele- symptoms were demonstrated with mepolizumab 100 mg SC compared to brating participants’ strengths/interests. Current participants include placebo. Improvement in sense of smell was related to prior history of NP approximately 100 local families – 30 high school students (‘‘Big surgery. Buddies’’) and 70 elementary/middle school students (‘‘Little Buddies’’). FUNDING: GSK [GSK ID:205687/NCT03085797] Big and Little Buddies are matched up in groups of 8-10 to participate in both in-person and virtual programming. Concurrent parent programming is also offered. RESULTS: Results of a post-orientation survey, completed by Big Buddies and parents of Little Buddies, suggested that strong interpersonal connections were fostered and desire to continue participation was high. J ALLERGY CLIN IMMUNOL Abstracts AB127 VOLUME 147, NUMBER 2

The Food Allergy Parent Mentoring Program: A Moving Forward In Health Disparities: Aqueous 403 novel intervention for parents of children with 405 Intradermal Immunotherapy newly diagnosed food allergies Arnaldo Capriles Hulett1, Cinthya Rondon, MD2; 1Hospital San Juan de Ashley Ramos, PhD1, Frances Cooke, BA1, Emily Miller, BS1, Linda Dios, 2HOSPITAL SAN JUAN DE DIOS , CARACAS, VENEZUELA. Herbert, PhD1; 1Children’s National Health System. RATIONALE: Mites (Dp/Df and Blomia tropicalis) are the major allergens RATIONALE: Parents of young children with newly diagnosed food in the tropics. Subcutaneous Immunotherapy (SCIT), hallmark of the allergy allergy (FA) are at risk for poor psychosocial outcomes due to FA’s life- specialty, is an expensive effective tool for house dust mite allergic rhinitis threatening nature and demanding management routines. Presently, there (AR). Intradermal administration of low-dose mite allergens provides a are no interventions to support FA parents during this adjustment phase. cost-effective alternative for the impoverished majorities in tropical settings. The current study explores the feasibility and acceptability of a novel, pilot METHODS: Forty-three AR children (ages 4-18) attending an allergy intervention using peer mentorship to improve psychosocial functioning in clinic were offered intradermal immunotherapy. Only 25 with a Total Nasal parents of young children with newly diagnosed FA. Symptom Score (TNSS) >100 points were recruited and 17 completed METHODS: Parent mentors were trained in mentorship and ethics and one-year treatment. Injections consisted of a non-incremental volume of then matched with a mentee for a 6-month intervention period. Mentees, 0.05ml containing 50ng of Dp/Df major allergens and 120ng of Blomia tro- parents of children diagnosed with FA within 1 year, completed baseline picalis allergens. Shots were given following a 3-month schedule: once and follow-up questionnaires to assess demographic and medical charac- weekly for the first 3 months, later bi-weekly, then every 3 weeks and teristics, FA knowledge, self-efficacy, social support, anxiety and depres- finally, monthly until a year’s completion. TNSS and fVAS were registered sion and a program evaluation. Follow up focus groups with mentors and throughout the treatment year. IgG4 and IL10 serum levels along with QoL individual interviews with mentees were conducted. questionnaire, were evaluated before and after treatment.

RESULTS: Participants were 8 mentors and 10 mentees (Mage 5 36.60 RESULTS: Qualitative scores TNSS, fVAS and QoL significantly years, 80% Caucasian) of children ages 0-3 years (Mage 5 16.15 months; improved (p<0.05): 8.5860.86 vs 4.763.0 points, 6.061.5 vs 3.261.4 60% male). Mentees reported high acceptability for the intervention in pro- points, 35.0611.4 vs 8.364.8 points, respectively. Quantitative results for gram evaluation and interviews, noting improvements in their social sup- IL-10, Dp/Df IgG4 and Blomia tropicalis IgG4 significantly increased port, FA-related stress, confidence in FA management, and positive (p<0.05): 3.6164.2 vs 18.5615.1 IU/ml, 2.0761.8 vs 16.2613.4 IU/ml, changes in FA parenting behaviors. 0.1160.11 vs 12.69613 IU/ml, respectively. Cost per shot was estimated CONCLUSIONS: The current study supports the use of a mentorship at less than USD 10 cents, making this approach a significant cost-saving program to support parents of children with newly diagnosed FA. Future strategy. Only mild local reactions were observed. research is needed to determine how to scale this intervention to meet the CONCLUSIONS: Clinical improvement/laboratory responses were attained needs of a large medical division. with this novel intradermal cost-effective technique. Health disparities concerning allergen immunotherapy might find, if reproduced, a step forward. Efficacy and Safety of Subcutaneous 404 Immunotherapy for Allergic Asthma with Novel dose-adjustment protocol for Summer and Autumn Pollen Mixed Allergen 406 subcutaneous immunotherapy interruption Extract Denise Sanchez Tejera1, David Rosenstreich, MD FAAAAI2, Golda Zhirong Du1, Jia Yin1, Lun Li1; 1Peking Union Medical College Hospital. Hudes, MD PhD3, Denisa Ferastraoaru, MD4,ElinaJerschow,MD RATIONALE: To evaluate the efficacy and safety of subcutaneous FAAAAI2, Merhunisa Karagic5, Sunit Jariwala, MD FAAAAI6,ManishRa- immunotherapy (SCIT) for allergic asthma with summer and autumn mesh, MD PhD3; 1Albert Einstein College of Medicine/ Montefiore Medi- pollen mixed allergen extracts. cal Center, 2Albert Einstein College of Medicine, 3Montefiore Medical METHODS: Clinical data of 25 allergic asthma patients were collected Center, 4Albert Einstein College of Medicine/Mont, 5Montefiore Medical and analyzed. Self-assessment of asthma control, asthma control test Center/Albert Einstei, 6Albert Einstein/Montefiore Medical Cente. (ACT), medication scores, and the percentage of forced expiratory volume RATIONALE: Though recommended by the practice parameters, to date, in the first second to predicted value (FEV1%) were evaluated pre- and there is no standardized protocol for dose adjustment following interrup- after SCIT. Adverse reactions were also recorded. tion of subcutaneous immunotherapy (SCIT). Following the COVID19 RESULTS: Among the 25 patients with allergic asthma, 13 were pandemic, immunotherapy was stopped for all our patients (n5664) for prescribed with single summer and autumn pollen allergen mixed extracts, nearly 3 months. In this study we describe the development and and 12 with pollen and dust mite allergen combined extracts. After SCIT, implementation of a novel dose adjustment protocol. asthma symptoms improved in all patients, of which 52% (13/25) patients’ METHODS: This protocol was developed based on the distancing asthma symptoms improved significantly. The asthma control rate requirements, access to the clinic, and a review of prior literature. increased from 52% to 92%, 36% (9/25) patients completely discontinued Distancing requirements limited the number of patients that could traffic asthma medication, and 32% (8/25) patients’ asthma medication dose was through a practice at one time. Consequently, an increased numbers of significantly reduced. The average effective time of SCIT was 20.569.6 visits were required for buildup back to prior dose. A novel regimen months. Compared with the baseline level, the ACT score of the two groups involving a test dose, followed by cluster buildup was devised. of patients increased significantly (P <0.05), FEV1% was increased RESULTS: The protocol involves administering a test dose followed by a significantly (P <0.05), and the total score of asthma medication was 50% of the previous dose after a 30-minute waiting period. This was then reduced significantly (P <0.01). Twelve patients had local adverse followed by a 2-dose cluster buildup in 0.05mL increments. If the last dose reactions caused by injection, and 4 patients had a total of 4 systemic was <0.2mL, the test dose was 0.01mL followed by 50% of the previous adverse reactions. All patients’ adverse reactions relieved within a short dose. If the last dose was >_0.2 mL, the test dose was 0.025mL followed by period. 50% of the previous dose. Immunotherapy was restarted from the CONCLUSIONS: The application of summer and autumn pollen allergen beginning for patients who had been on the lowest concentration vial of mixed allergen can treat summer and autumn pollen-induced allergic immunotherapy. Implementation of the protocol and outcomes will be asthma effectively and safely. described. CONCLUSION: This novel protocol reduces the number of visits that patients need to buildup back to their pre-interruption SCIT dose while maintaining social distancing needs. AB128 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

An Exploratory Field Study With A Prolonged Maintenance Interval Of Allergen 407 Subcutaneously Administered Tyrosine 409 Subcutaneous Immunotherapy during COVID19 Adsorbed Modified Grass Allergen + MPL pandemic

Pieter-Jan de Kam, PhD MBA1, Stefan Zielan2, Kemi Oluwayi, MD1, Jaspreet Dhami, MD1, Vivian Wang, MD1, Mohamed Eloustaz, MD2, Jo- Marion Seybold1, Murray Skinner3; 1Allergy Therapeutics, 2Goethe Uni- seph Yusin, MD FAAAAI1; 1VA Greater Los Angeles Healthcare System, versity, Frankfurt, Germany, 3Allergy Therapeutics, PLC. 2University of South California. RATIONALE: This exploratory field study explores the safety and RATIONALE: Prolonged immunotherapy maintenance interval has been efficacy of an optimized dose of a modified grass allergen subcutaneous studied in venom immunotherapy, however limited data exists on the safety immunotherapy (SCIT) product (1.0 ml) with microcrystalline tyrosine and efficacy of a maintenance interval extending beyond 1 month for (MCT) and monophosphoryl lipid A (MPL) adjuvant system for the environmental allergen immunotherapy. We hypothesize that patients treatment of allergic rhinoconjunctivitis (ARC) due to grass pollen. extending to a 6-8 week allergen immunotherapy maintenance interval will METHODS: This multi-center, randomised, double-blind, placebo- have no increase in adverse local or systemic reactions, as well as no controlled, parallel-group exploratory field study is conducted in approx- increase in allergic rhinitis symptoms. imately 150 subjects in Europe and the US. Subjects are randomized to six METHODS: 28 patients had their maintenance interval extended beyond pre-seasonal subcutaneous injections of active treatment or placebo in a 2:1 every 4 weeks, to every 6-8 weeks for allergen immunotherapy in order to ratio. The primary endpoint is the combined symptom and medications reduce unnecessary patient exposure to the healthcare system during the score (CSMS) during the peak grass pollen season. COVID19 pandemic. Patients were provided a survey, which assessed any RESULTS: The subject population included in this study will be presented increase in symptoms and whether they suffered any local or systemic by baseline characteristics (e.g. country, age and gender). The study design adverse reactions following their injection. The findings were compared to applies two frequently used primary endpoint scores: the CSMS and the a similar interval of time, one year prior. Total Combined Score (TCS). As this study also includes conjunctival RESULTS: Analysis of the first 6-8 week cycle, has demonstrated that out provocation testing (CPT), this study allows the evaluation of the of a total of 28 patients, 3 patients experienced an increase in symptoms, relationship between CPT, CSMS and TCS. In addition, the while 8 out of 28 patients noticed no increase in symptoms. 17 patients did Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) will be not complete a survey. 24/28 patients had no adverse local reaction, 3 evaluated and the extensive panel of biomarkers applied will be presented. patients had a wheal size of 3mm, while 1 patient had a wheal size of 7mm. CONCLUSIONS: This stepwise clinical development approach is novel CONCLUSIONS: Preliminary data suggests a 4 week maintenance in allergen immunotherapy. The results of this exploratory field study will interval may be safely extended, with no significant increase in adverse dictate the optimal design of the pivotal Phase III study. The completion of local or systemic reactions, or increase in symptoms. the recruitment of this exploratory field study is an important achievement in the development of an efficacious and safe state-of-the-art grass SCIT No Severe Anaphylaxis in Clinical Trials of product to be developed for the European and the US markets. 410 House Dust Mite Sublingual Immunotherapy Tablet Using a Standardized Identification Review of Anaphylaxis Associated with Algorithm 408 Subcutaneous Immunotherapy in a Single Allergy Center Veronica Hulstroem1, Ruta Gronskyte Juhl, PhD1, Hendrik Nolte, MD PhD2; 1ALK, Hørsholm, Denmark, 2ALK, Bedminster, NJ, USA. Nerissa D’Silva, MD1, Walaa Hamadi, MD1, Aurora Moberly1, Ashley RATIONALE: A standardized anaphylaxis definition is needed for Snyder, MPH1, Zach Ney1, Jeanna Ryan, PA-C1, Hannah Duffey, MD1; clinical trials of allergy immunotherapy products. An algorithm in the 1University of Utah. Standardized MedDRA Query (SMQ) was used to identify anaphylaxis in RATIONALE: Subcutaneous immunotherapy (SCIT) is a proven house dust mite (HDM) sublingual immunotherapy (SLIT)-tablet clinical effective modality to help reduce symptoms caused by allergic rhinitis trials. and improve quality of life, however it is not without risk. A thorough re- METHODS: Criteria 1 of the algorithm was the narrow term view of the literature demonstrated that risk of severe systemic reaction has ‘‘Anaphylactic reaction.’’ Criteria 2 was all treatment-emergent AEs with only been quantified with survey data, and rate of response to surveys broad terms from >_2 of 3 categories (respiratory, skin, and cardiovascular) changes from year to year. No formal study has been published to identify occurring on the same day. Narrow terms indicate high certainty of the the prevalence of severe systemic reactions. condition. Broad terms are less specific and require further evaluation and METHODS: A 5-year retrospective chart review was conducted to interpretation. The criteria were applied to a pooled dataset of all subjects identify patients who received SCIT at University of Utah Health between treated with HDM SLIT-tablet (12 SQ-HDM dose) in randomized clinical the years 2015-2020. Data was collected on number of injections received, trials and after treatment interruptions of 12 SQ-HDM of any duration for injection schedule, risk factors, prevalence and type of reaction. any reason. All identified events were reviewed by a medical professional. Descriptive statistics and statistical significance determined via Fisher’s RESULTS: In the 12 SQ-HDM pooled dataset (N52166), criteria 1 exact test were calculated. identified one event. This event occurred at first dose and was considered RESULTS: 175 patients met our inclusion criteria. Most (62.3%) were non-treatment-related (food allergy). Criteria 2 identified 101 potential female, and the average age was 38.3 (614.8), ranging from 9 to 80 years cases in 77 subjects. Most events were mild-to-moderate local allergic old. 10 patients (5.7%) had a reaction meeting NIAID criteria for reactions. Medical review identified 1 systemic allergic reaction (facial anaphylaxis and required epinephrine. Reactions were most common in flushing, itchy palms, swollen throat). This event occurred at first dose and the fall (44.4%) and spring (33.3%). No patients experienced anaphylaxis was assessed as moderate. while on maintenance dosing. The dose of immunotherapy received on the In the treatment interruption dataset (300 interruptions in 207 subjects), no day of anaphylaxis ranged from 0.1 to 0.5 and the concentrations of each events were identified by criteria 1. Criteria 2 identified 5 cases in 3 vial ranged from 1:1 to 1:1000. subjects. After medical review, none of the events met the criteria for CONCLUSIONS: In our patient population, 5.7% of patients developed anaphylaxis. anaphylaxis associated with SCIT. Prevalence of reactions was most CONCLUSIONS: In clinical trials, there was no severe anaphylaxis with common in the fall and spring and was not dose dependent. Once on the HDM SLIT-tablet using the SMQ algorithm. maintenance, patients were unlikely to experience anaphylaxis. J ALLERGY CLIN IMMUNOL Abstracts AB129 VOLUME 147, NUMBER 2

Impact of Age and Region on Immune Responses Review of Systemic Reactions to Subcutaneous 411 to Allergy Immunotherapy 413 Immunotherapy Based on Injection Schedule in a Single Allergy Practice Josephine Nolte Peterlin1, Vibeke Backer2, Thomas Stranzl3, Veronica Hulstroem3, Peter Sejer Andersen3, Hendrik Nolte, MD PhD4; 1Center Walaa Hamadi, MD1, Nerissa D’Silva, MD1, Aurora Moberly1, Ashley of Physical Activity Research (CFAS), Rigshospitalet, University of Co- Snyder, MPH1, Zach Ney1, Jeanna Ryan, PA-C1, Hannah Duffey, MD1; penhagen, Copenhagen, D, 2Center of Physical Activity Research 1University of Utah. (CFAS), Rigshospitalet, University of Copenhagen, Copenhagen, RATIONALE: Subcutaneous allergen immunotherapy (SCIT) is an Denmark, 3ALK, Hørsholm, Denmark, 4ALK, Bedminster, NJ, USA. effective treatment for allergic rhinitis, asthma, and venom hypersensitiv- RATIONALE: Allergy immunotherapy (AIT) can prevent allergic dis- ity. Although rare, severe, and potentially life-threatening systemic ease by modifying the adaptive immune system, similar to anti-pathogen reactions (SR) such as anaphylaxis can occur. However, our knowledge vaccines, supporting the concept of AITas an ‘‘allergy vaccination’’.Some of SR between SCIT buildup (standard and accelerated) is limited. This vaccines, e.g. influenza, pneumococcal pneumoniae, are administered study aimed to compare SCIT-related reactions between standard buildup globally with the same dose for all age groups. The aim of this study was to (18-shot or 30-shot) and accelerated buildup (cluster). determine if sublingual immunotherapy (SLIT) across regions and age METHODS: We conducted a retrospective chart review for SCIT-related groups induce similar immunologic changes in IgE and IgG4 with the goal reactions between 2015-2020 at the University of Utah. Statistical analysis of using the same dose and formulation worldwide. of descriptive statistics and significance determined via Fisher’s exact test METHODS: Immunologic data from 12 completed multi-national pivotal was conducted. trials of birch, timothy grass, ragweed, and house dust mite SLIT-tablet RESULTS: 175 patients met our inclusion criteria. The average age was (N55645) were analysed post-hoc by age and region. PubMed was 38.3 (614.8), ranging from 9 to 80 years old. Most patients were on the 18- searched for relevant human trials from 01/01/2000 to 04/01/2020 shot buildup schedule. Twenty-seven of 132 (20.45%) patients on the 18- evaluating age and regional factors related to dosage and immunologic shot buildup experienced a reaction (P50.04), and 3 of the 11 (27.25%) response to AIT or vaccine prevention of hepatitis A, influenza, and patients on the 30-shot buildup developed a reaction (P50.73). Thirteen of pneumococcal pneumoniae. the 32 (40.63%) patients on the cluster schedule developed a reaction RESULTS: The literature search did not reveal conclusive data supporting (P50.02). Ten of those 43 patients who had a reaction met NIAID criteria a universal AIT dosage. Published data indicated that age and other host for anaphylaxis and required epinephrine. Five were on the 18-shot factors can influence anti-pathogen vaccine immunogenicity. buildup, 2 were on the 30-shot buildup and 3 were on the cluster schedule. SLIT-tablets induced a significant immunologic response compared with CONCLUSIONS: Our data suggest that patients on the cluster schedule placebo shortly after initiation. The pattern and magnitude of the response had a significantly higher prevalence of reactions (40% of patients on this for both IgE and IgG4 were similar across species, regions, and age. schedule had a reaction). There does not appear to be a significantly CONCLUSIONS: The results support that the overall immunologic increased risk of SR with 18-shot or 30-shot buildup, and larger sample size responses to SLIT-tablet are insensitive to region and age. is required to make further conclusions.

Don't Rush to Judgement: Systemic Reactions Dosing Aeroallergen Immunotherapy from 412 During Rapid Desensitization to Multiple 414 Freshly Prepared Maintenance Vials: To Adjust Aeroallergens or Not?

Alegra Grieb1, Alexandra Chastant1, Evan Atkinson, MD MS1; 1Tulane Katherine Oberhelman, MD1, Aimee Sutherland, MD2, Evan Atkinson, University. MD MS2; 1St. Louis University, 2Tulane University. RATIONALE: Rush immunotherapy (RIT) expedites the buildup phase RATIONALE: Current guidelines suggest dose-adjustment when a of aeroallergen immunotherapy (AIT), yielding symptom relief in fewer patient starts freshly prepared vials of allergen immunotherapy (AIT) visits at the expense of a higher likelihood of systemic reaction (SR). With extracts. We hypothesize administering the first dose from a freshly this study, we aimed to determine if the number of aeroallergens in prepared vial in a cluster protocol, splitting it into two equal doses given 30 immunotherapy prescriptions increased the rate of SR during a 1-day RIT minutes apart, is safe. protocol. We hypothesized SRs would increase concomitant with the METHODS: We retrospectively reviewed AIT injection visits of patients number of allergens. in Tulane and VHA clinics from July 2016 through June 2020. Our primary METHODS: We retrospectively reviewed 49 RIT procedures performed measure was the rate of systemic reaction (SR) for patients receiving a in the TUMC Allergy Clinic from 01/01/2016 to 12/31/2019. We compared fresh-vial dose of AIT by the cluster protocol, e.g., RED 1:1 v/v 0.25 mL, SR rates stratified by the number of extract vials and total number of then an additional 0.25 mL after a 30-minute period. A secondary measure allergens in the prescription. We characterized the WAO grade and was SR severity, and we also sought to identify SR risk by age, sex, asthma treatment of each SR. AIT extracts were formulated according to JTF diagnosis, and number of aeroallergens in the extract prescription. practice parameters. RESULTS: For 174 fresh-vial cluster procedures (115 patients), there RESULTS: SR rates by number of allergens were: 1-5 allergens (31%), 6- were 6 SRs (3% of procedures). The WAO grades of SRs were 1 (n53), 2 10 allergens (44%), 11-15 allergens (56%), 16-20 allergens (30%), 21-25 (n52), and 3 (n51). All reactions were treated in clinic, no patients allergens (0%), and 26-30 allergens (0%). SR rates by number of vials discontinued AIT due to SR, and no patient had more than one SR. There were: one vial (37%), two vials (48%), and three vials (11%). The total SR was no significant correlation between SR and patient age, sex, asthma rate by WAO definition was 37% (18/49). For management of SR, 29% of diagnosis, number of aeroallergens extracts, type of aeroallergen included all patients required treatment (14% required epinephrine). All SRs were of (e.g., grass pollen), or time of year. WAO grade 1 or 2. CONCLUSIONS: Introduction of freshly mixed extract vials can be CONCLUSIONS: There was not a predictable increase in SR rate for safely done, without dose reduction, using a two-step cluster protocol. The patients undergoing RITwith a greater number of aeroallergens. While the risk of SR, while manageable, should be discussed with the patient. overall reaction rate was higher than expected based on prior chart review, no SRs were severe and almost all consisted of one or more mild grade-1 findings. AB130 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Autoserum Therapy as a Method of Non-specific Evaluating sensitization patterns on 415 Immunoprophylaxis of Pollen Allergy 417 ImmunoCAP-detected polysensitized patients with microarray-based multiplex assay (ISAC) Iryna Shchurok1, Dzmitry Novicov1, Iryna Semenova1, Aksana Ish- chenka1, Lawrence Dubuske, MD FAAAAI2; 1Vitebsk State Medical Uni- Sujoy Khan1, Harpal Singh, MBBS2, Ekansh Sharma3, Esben Eller, PhD versity, Vitebsk, Belarus, 2George Washington University School of MSc4, Anirban Maitra5; 1Hull University Teaching Hospitals NHS Trust, Medicine, Washington, DC, USA, Immunology Research Institute of 2AstraZeneca Pharma India Ltd., New Delhi, India, 3Thermo Fisher Sci- New England, Gardner, MA, USA. entific Immunodiagnostics Division, Uppsala, Sweden, 4ThermoFisher RATIONALE: Intracutaneous auto-serum therapy (AST) is a method of Scientific, Uppsala, Sweden, 5Manchester University Hospitals NHS nonspecific immunotherapy for the prevention of recurrence of hay fever. Foundation Trust, UK. This study assesses the clinical manifestations and dynamics of immuno- RATIONALE: Limited availability of validated allergy tests prevents logical parameters in serum of patients with pollen allergy after a course of assessment of the true extent of allergic problems in the Indian sub- AST. continent. We utilised Immuno-Solid phase Allergen Chip (ISAC) results METHODS: During 2 pollen seasons 56 grass sensitized patients were from polysensitized patients as revealed by the extensively validated studied including: Group 1 (n 5 34), patients receiving pre-seasonal AST ImmunoCAP to further develop accurate sensitization profiles. and standard pharmacotherapy (PT); and Group 2 (n 5 22) receiving only METHODS: Retrospective, observational and descriptive study on four PT. Blood sampling and preparation of auto-serum for AST occurred 2 polysensitized patients with disparate clinical symptoms weeks before the onset of the grass pollen season after provocation with RESULTS: Patient 1 (26years/Male) with possible food allergies and no grass pollen allergens. Assessments included Total Nasal Symptom Scores rhinitis symptoms was considered dust-mite/cockroach sensitized (TNSS) Asthma Control Tests (ACT), and serum levels of IgG, IgM, IgA, [ImmunoCAP d1(7.86), d2(7.28), i206(8.34), fx2(6.15)] but ISAC re- IgE, IL-10, and IL-4. vealed only Pen m2 reactivity (shrimp allergen) and non-reactive to mites RESULTS: Pre-seasonal AST in comparison with PT reduced TNSS (p (Dermatophagoides or Blomia/Blo t5). Similarly, dust mite and cockroach <0.001) and asthma symptoms -ACT (p < 0.002), with increases in levels allergy [d1(87.8), d2(>100), i206(>100)] in patient 2 (11-year-old girl) of IL-10 and decreases in IL-4 (p <0.05) but no significant changes with perennial rhinitis/asthma was revealed on ISAC as mite cross- between the Groups 1 and 2 in levels of IgG, IgM, IgA, or IgE (p> 0.05). reactivity than genuine cockroach sensitization [Bla g5 (1.3ISU-E)], CONCLUSIONS: Pre-seasonal AST in combination with PT during grass allowing accurate choice of allergen immunotherapy. Use of ISAC showed season symptom exacerbations is more effective than pharmacologic co-sensitization with Blo t5 and Dermatophagoides species was frequent in monotherapy. Availability and simplicity of AST may allow use of this Eastern India; and with known low IgE cross-reactivity, routine testing for method of treatment in patients who were unable to receive pre-seasonal Blomia species in patients with rhinitis appears reasonable. Patient 3 pollen- specific immunotherapy. (20years/female) with multiple allergic reactions negative on ImmunoCAP food panels but high dust mite IgE [d1(96.6), d2(72.4)] was positive to Efficacy of epinephrine rinse in allergen betv1(PR-10) and tri a19 on ISAC suggesting symptoms were probably 416 immunotherapy with aeroallergen and venom related to pollen-wheat-dependent anaphylaxis episodes. A middle-aged

1 2 farmer (patient 4) with chronic avian hypersensitivity pneumonitis (IgG Phuong Daniels, DPT, OMS-II , Reimus Valencia, DO , Robert Hos- pigeon antigens 72mgA/L) found positive to Aspergillus family mitogilin toffer, DO3; 1Lake Erie College of Osteopathic Medicine, 2University 3 (rAsp f1) on ISAC responded to dual steroid-itraconazole therapy. Hospitals, Cleveland Medical Center, Allergy/Immunology Associates. CONCLUSION: Multiplex allergen arrays such as ISAC in resource- RATIONALE: In a large suburban allergy outpatient office, epinephrine limited countries can prove extremely informative with ImmunoCAP when rinse of subcutaneous allergen immunotherapy (SCIT) syringes prior to used in clinically relevant settings. injection has been employed for over 30 years with documented favorable clinical outcomes. We conducted a retrospective study to explore the effectiveness of epinephrine rinse in managing local site reactions. METHODS: A chart review of patients currently receiving SCITs identified a total of 549 SCITs of which 140 cases were traced to employ the use of epinephrine rinse to improve local site reactions following SCITs. The data was separated into allergic rhinitis and venom immuno- therapy group and was recorded for build up and maintenance phases. RESULTS: Out of 140 total patients requiring epinephrine rinse, 88.6% patients were in the allergic rhinitis group, 11.4% patients were in the venom group. A total of 69.3% patients in the allergic rhinitis group and 87.5% patients in the venom group required epinephrine rinse during build up phase. In the allergic rhinitis group, 65.8% patients receiving SCIT injections at maintenance dose and 69.8% patients at build-up dose had resolution of local site reactions post epinephrine rinse. In the venom group, 64.3% patients receiving SCITs at build up dose improved local site reactions after epinephrine rinse. CONCLUSIONS: Epinephrine rinse technique showed favorable out- comes in over 60% of patients currently receiving treatment for allergen hypersensitivity. Epinephrine rinse is especially beneficial for the build-up phase of SCIT to manage local site reaction to effectively increase allergen dose. J ALLERGY CLIN IMMUNOL Abstracts AB131 VOLUME 147, NUMBER 2

ALLERGY TO DERMATOPHAGOIDES significantly decreased for the high target HDM-allergics for hours 2 418 PTERONYSSINUS. MOLECULAR RECOGNITION (p<0.05), 2.5 (p<0.05), and 3 (p<0.01). PATTERN ATTRIBUTED TO DIFFERENT CONCLUSIONS: The HDM-EEU can be used to elicit a measurable PATHOLOGIES dose-dependent symptomatic response from HDM-allergic participants.

Fernando Pineda de la Losa, PhD1, Ruperto Gonzalez-Perez2, Miriam A Single-Center, Randomized, 3-Way, Crossover Castillo3, Paloma Poza-Guedes, MD, PhD4, E. Mederos-Luis4,C. 420 Study to Evaluate the Effect of an Exhalation Alava-Cruz4, Victor Matheu, MD, PhD4, Inmaculada Sanchez-Machin4; Delivery System on Nasal Nitric Oxide 1DIATER Laboratorios, Madrid, Spain, 2Universitary Hospital of Canary Concentrations in Patients with Chronic Islands, Santa Cruz de Tenerife, Spain, 3DIATER Laboratories, Madrid, Sinusitis 4 Spain, Universitary Hospital of Canary Islands, Santa Cruz de Tenerife, 1 2 3 Spain. Miguel Lanz, MD FAAAAI , Per Djupesland , John McGinnis, MPH , Eric Zaccone, PhD3, John Messina, PharmD3; 1AAADRS Clinical RATIONALE: The profile of sensitization to house dust mites (HDM) 2 3 may differ depending on specific geographical areas and the allergic Research Center, OptiNose AS, OptiNose US, Inc. pathology of each patient. The present study aims to characterize the RATIONALE: Nasal nitric oxide (nNO) is thought to provide important immune pattern of a selected population, focusing on their sensitization to benefits for the sinuses and the upper airways. The inflammation associated house dust mites. with chronic rhinosinusitis (CRS) restricts the release of nNO. CRS with METHODS: We selected 36 non-consecutive patients sensitized to predominant eosinophilic inflammation is thought to be associated with Dermatophagoides pteronyssinus (DPT) with atopic dermatitis, rhinitis move severe nasal inflammation. The exhalation-delivery-system (EDS) and/or persistent, moderate or severe asthma, according to ARIA and/or provides improved drug deposition and creates positive pressure in the GINA guidelines. Skin test (SPT) with standardized extracts of DPT. nasal cavity. An inverse relationship between serum eosinophil counts Blood serum samples were obtained from all participating subjects. (EOS) and response with the EDS-placebo in subjects with nasal polyps Total IgE and sIgE were quantified including a custom-made panel of 9 al- has previously been shown. We report observed differences in nNO after lergens (MADx, Vienna). EDS use by EOS count. RESULTS: The 36 patients, divided into groups according to clinical METHODS: An ongoing, single-center, randomized, 3-way crossover, picture and severity, showed a positive skin test for PTD with different pilot study is evaluating nNO levels in patients with CRS without nasal sensitization patterns. Regarding the main allergens, a predominance of the polyps (CRSsNP) after use of empty EDS, EDS-placebo, and forceful nasal recognition of Der p 5, Der p 2 and Der p 23 was observed in patients with exhalation. Change in mean nNO (ppb) in subjects with >300 EOS versus severe vs. mild-moderate atopic dermatitis. Der p 1, Der p 2 and Der p 23 in those with <300 was examined. severe vs. mild-moderate rhinitis and Der p 2, Der p 23 and Der p 5 in RESULTS: Seven patients with CRSsNP have been enrolled (6 females, 3/ severe vs. mild-moderate asthma. 7 had prior sinus surgery, 3/7 anosmic, 7/7 atopic, 5/7 mild-moderate CONCLUSIONS: Both the main allergens and the so-called mid-tier asthma). Four subjects had a significantly lower mean baseline serum EOS 6 6 allergens presented a serodominant profile characteristic of each pathol- [103 32/uL versus 395 39/uL (p<0.001)], as well as significantly lower ogy. The endotype of each one of these allergens in the pathology of the Lund-Mackay CT scores (compared with those with higher baseline EOS; different phenotypes, as well as their relevance in the severity of the same, p<0.05). Increases of nNO levels were found in these 4 patients after each has yet to be determined. maneuver, with significant changes with EDS-empty use (mean +78ppb), EDS-placebo (mean +192 ppb), and nasal exhalation (mean +100ppb). Evaluation of House Dust Mite Dose Response in CONCLUSIONS: These data suggest that the EDS increases release of 419 the Environmental Exposure Unit nNO and that release is higher in patients with lower EOS levels.

Lubnaa Hossenbaccus, BScH1, Jenny Thiele, MSc1, Lisa Steacy, BSc, CCRP2, Terry Walker2, Crystal Malone2, Anne Ellis, MD FRCPC FAAAAI1; 1Queen’s University, 2Kingston Health Sciences Centre. RATIONALE: As a controlled allergen challenge facility, the Environmental Exposure Unit (EEU) is a valuable model to investigate allergic rhinitis (AR). While seasonal allergens have been previously studied in the EEU, here we sought to evaluate the clinical manifestations of house dust mite (HDM)-induced AR in the HDM-EEU. METHODS: HDM-allergic volunteers, deemed eligible to participate based on relevant clinical history and positive skin prick test (SPT) results, and healthy control participants were invited to one of two exposure sessions in the HDM-EEU. Following a baseline collection, symptomatic data including Total Nasal Symptom Score (TNSS) and Peak Nasal Inspiratory Flow (PNIF) were collected every half hour for the 3-hour HDM exposure, on an hourly basis until 12 hours post-exposure, and at 24 hours. RESULTS: Following the screening visit, 20 HDM-allergic and 4 non- allergic participants were exposed to a moderate target of HDM while 24 atopics and 6 non-atopics received a high HDM dose. Both groups of allergics had significantly greater (moderate target: p<0.01; high target: p<0.001) SPT wheal sizes against D. pteronyssinus and D. farinae compared to controls. Elevated TNSS responses were sustained for up to 5 hours for allergics exposed to either condition, however those in the high target session had significantly greater mean TNSS scores at hours 2.5 and 3 (p<0.05 and p<0.01, respectively). PNIF fall (%) was AB132 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

The Study of a Novel Triple Spray Combination A Responder Analysis To Demonstrate 421 of Corticosteroid, Antihistamine and 423 Dupilumab Treatment Effect Across Objective Decongestant Delivered in a Single Spray and Patient-Reported Subjective Endpoints For Patients with Severe Chronic Rhinosinusitis Reimus Valencia, DO1, Phuong Daniels, DPT, OMS-II2, Katheryn with Nasal Polyps (CRSwNP) Birch, DO3, Tina Abraham, DO4, John Murray, MD PhD5, Robert Hos- toffer, DO6; 1University Hospitals, Cleveland Medical Center, Cleveland, Claus Bachert, MD PhD1, Anju Peters, MD MSCI FAAAAI2, Enrico Ohio, 2Lake Erie College of Osteopathic Medicine, 3University Hospitals, Heffler3, Joseph Han, MD FAAAAI4, Heidi Olze5, Oliver Pfaar6, Chien- Cleveland Medical Center, Cleveland Ohio, 4Pulmonary Allergy Critical Chia Chuang7, Raj Rout8, Richa Attre9, Ledia Goga10, Juby Jacob- Care & Sleep Medicine Associates, Rochester Hills, Michigan, 5McLaren Nara7, Paul Rowe, MD11, Yamo Deniz9, Zhen Chen, PhD9, Siddhesh Ka- Macomb Hospital, Mount Clemens, Michigan, 6Allergy/Immunology mat9, Shahid Siddiqui9; 1Ghent University, Ghent, Belgium, 2Allergy- Associates. Immunology Division and the Sinus and Allergy Center, Feinberg School RATIONALE: Allergy rhinitis (AR) is a chronic condition that affects of Medicine, Northwestern University, Chicago, IL, USA, 3Personalized quality of life of many individuals. We hypothesized that a novel triple Medicine, Asthma & Allergy - Humanitas Clinical and Research Center spray combination would provide better symptom relief for patients with IRCCS, Rozzano, Milan, Italy, 4Eastern Virginia Medical School, Nor- AR compared to the use of a single nasal spray. folk, VA, USA, 5Charite-Universit€atsmedizin, Berlin, Germany, 6Univer- METHODS: Triple spray is a mixture of triamcinolone, azelastine, and sity Hospital Marburg, Philipps-Universit€at Marburg, Marburg, Germany, eight sprays of oxymetazoline combined in one bottle. We administered an 7Sanofi, Cambridge, MA, USA, 8Sanofi Genzyme, Reading, UK, 9Regen- institutional review board approved questionnaire to patients with AR age eron Pharmaceuticals, Inc., Tarrytown, NY, USA, 10Sanofi, Chilly-Ma- 18 and above currently on any types of nasal sprays. zarin, France, 11Sanofi, Bridgewater, NJ, USA. RESULTS: Out of 97 patients, 67 used a single nasal spray (either an RATIONALE: Dupilumab has demonstrated reduction in nasal polyp antihistamine or a corticosteroid spray), and 30 used the triple spray score (NPS) and individual symptom scores in patients with severe combination. There is no difference (p 5 0.134) in the total symptom relief CRSwNP; however, combined responder analyses using these endpoints score between the use of one nasal spray versus triple spray. However, the have not been conducted. This post hoc analysis explored the overall effect triple spray provided a statistically significant difference in the scores of dupilumab across both objective and patient-reported subjective rating sinus pressure relief (p 5 0.039) compared a single nasal spray. endpoints. There was no statistical difference (p 5 0.687) in the severity of symptoms METHODS: Endpoints were compared in patients with severe CRSwNP between the two groups. receiving dupilumab 300 mg or placebo every 2 weeks in the Phase 3 CONCLUSIONS: The triple spray decreases AR symptoms by SINUS-52 study (NCT02898454; intention-to-treat population). The decreasing inflammation and mast cell activities with an addition of the objective endpoint was NPS (range 0–8); subjective endpoints were vasoconstrictive property of oxymetazoline. Our preliminary data suggests patient-reported symptoms of nasal congestion (NC), loss of smell that the triple spray is an effective AR treatment that offers a statistically (LoS), anterior rhinorrhea, and posterior rhinorrhea scores (all 0–3); significant improvement in management of sinus pressure compared to a higher scores indicate worse disease burden. The proportion of patients single nasal spray. achieving >_1-point improvement from baseline in endpoints was assessed at Weeks 24 and 52: NPS OR any of NC/LoS/anterior/posterior rhinorrhea Eosinophil-derived neurotoxin as a biomarker in scores; NPS AND any of NC/LoS/anterior/posterior rhinorrhea scores. 422 children with allergic rhinitis RESULTS: A greater proportion of patients achieved >_1-point improve-

1 1 1 1 ment in NPS OR any of NC/LoS/anterior/posterior rhinorrhea scores with Kyunhoon Kim , Woori Bae , Hye Jin Lee , Eun Ae Yang , Hwan Soo 5 5 1 1 1 dupilumab (n 104/132, 78.8%; n 104/132, 78.8%) versus placebo Kim, MD , Yoon Hong Chun , Jong-seo Yoon, MD PhD , Hyun Hee 5 5 1 1 1 (n 51/137, 37.2%; n 42/137, 30.7%) at Weeks 24 and 52, respectively Kim, MD , Jin Tack Kim ; College of Medicine, The Catholic University (both P<0.0001). A greater proportion of patients also achieved the more of Korea, Seoul, Korea. stringent responder definition of >_1-point improvement in NPS AND any RATIONALE: Eosinophil-derived neurotoxin (EDN), an eosinophil of NC/LoS/anterior/posterior rhinorrhea scores with dupilumab (n562/ degranulation product, is considered as a biomarker for allergic diseases, 132, 47.0%; n586/132, 65.2%) versus placebo (n58/137, 5.8%; n513/ such as asthma. The purpose of our study was to investigate whether EDN 137, 9.5%) at Weeks 24 and 52, respectively (both P<0.0001). reflects eosinophilic inflammation in children with allergic rhinitis. CONCLUSIONS: Responder analyses show that dupilumab treatment led METHODS: Patients aged <18 years with rhinitis for >2 weeks or >2 to significant improvements versus placebo in objective and subjective episodes per year were enrolled. We examined nasal cytology and endpoints, both individually and combined, in patients with severe measured eosinophil-active cytokine and chemokine nasal levels. CRSwNP. RESULTS: Forty-four children with allergic rhinitis and thirty-two children with non-allergic rhinitis were enrolled. The age (8.0 years vs. 7.0 years; p50.05) and male to female sex ratio (63.6% vs. 46.9%; p50.22) were not significantly different between the two groups. EDN levels were significantly higher in allergic rhinitis than in non-allergic rhinitis (29.39 vs. 18.70, p<0.001) patients. EDN levels significantly corre- lated with nasal eosinophil counts (r50.45, p<0.001) and nasal eosinophil percentage (r50.46, p<0.001). EDN levels also significantly correlated with other cytokines, such as eosinophil peroxidase (p<0.001), eotaxin (p50.001), interleukin 10 (p<0.001), and eosinophil cationic protein (p<0.001). CONCLUSIONS: These findings suggest that elevated nasal EDN levels reflect eosinophilic inflammation in children with allergic rhinitis. J ALLERGY CLIN IMMUNOL Abstracts AB133 VOLUME 147, NUMBER 2

Prevalence of cat induced allergic rhinitis in inflammatory drug-exacerbated respiratory disease (NSAID-ERD). 424 children with chronic and frequent rhinitis Population norm scores (US) were 50 for SF-36 and ;72 for EQ-5D VAS. RESULTS: In the overall intention-to-treat population (n5276), mean Nichaporn Chalermpalanupap, MD1, Watcharoot baseline SF-36 Physical Component Score (PCS) and Mental Component Kanchongkittiphon, MD PhD2, Wiparat Manuyakorn, MD, PhD3, Wora- Score (MCS), and EQ-5D VAS score were below population norms (46.40, lak Sutiratanachai, MD1, Suwat Benjaponpitak, CME4, Cherapat Sasisa- 48.58, and 66.00, respectively). In each subgroup, based on baseline kulporn1, Potjanee Kiewngam1, Wanlapa Jotikasthira1; 1Mahidol comorbidity (asthma or NSAID-ERD) or previous treatment (surgery and/ University, 2Washington University School of Medicine, 3Ramathibodi or prior SCS use), mean baseline SF-36 PCS and EQ-5D VAS scores were Hospital, 4Faculty of Medicine Ramathibodi Hospital. also below population norms. Mean baseline SF-36 MCS scores were <50 RATIONALES: Cat allergy has been reported 10-20% of the population. except for patients without prior surgery (50.00) and with prior SCS use Here, we sought to study the current prevalence and risk factors of cat- without surgery (50.04). induced allergic rhinitis (AR) and local allergic rhinitis (LAR) in children. CONCLUSIONS: Patients with severe CRSwNP despite previous METHODS: Chronic and frequent rhinitis children aged 5-18 years old surgery/SCS use and surgery, or comorbid asthma/NSAID-ERD, had were enrolled. The demographic data, total nasal symptom scores (TNSS), worse HRQoL burden at baseline than general population norms. and visual analog scales (VAS) were recorded. Skin prick test, serum specific IgE to cat allergen, and cat allergen nasal provocation test (NPT) Dupilumab as an adjunct to surgery in patients were performed. 426 with aspirin-exacerbated respiratory disease: RESULTS: Sixty-one children were enrolled with the mean age a case series 6 9.07 3.93 years, 59% were male. The mean TNSS and VAS were 1 2 3 2.5461.89 and 3.5062.05, respectively. Of 48 (78.7%) children with Pooja Patel , Jillian Bensko, PA-C , Tanya Laidlaw, MD FAAAAI , Kathleen Buchheit, MD4; 1Beth Israel Deaconess Medical Center, 2Brig- positive SPT to any aeroallergens, 14 (29.2%) children were positive SPT 3 4 to cat. Of all children with positive SPT to cat, 13 (92.9%) children were ham and Women, Harvard Medical School, Brigham and Women’s positive specific IgE to cat. Children who were negative to SPT and serum Hospital. specific IgE to cat, 14 (29.8%) children were positive NPT to cat and were RATIONALE: Patients with aspirin-exacerbated respiratory disease diagnosed with LAR. The prevalence of cat-induced AR and LAR were (AERD) have severe chronic rhinosinusitis with nasal polyps (CRSwNP) 23%. No differences were obtained in SPT size, specific IgE level, and cat that is often refractory to standard therapies including intranasal cortico- NPT positivity between cat owners and non-owners. 64.3% of children steroids, endoscopic sinus surgery (ESS), and daily aspirin therapy. with cat-induced AR were positive to the lowest dose of cat NPT (500 Dupilumab is FDA approved for inadequately controlled CRSwNP, but BAU/ml), while the patients with LAR to cat allergen were almost positive the utility of dupilumab as an adjuvant to ESS in patients with AERD is to cat NPT at higher concentration. unknown. CONCLUSIONS: The prevalence of AR and LAR to cat have been METHODS: We performed a retrospective analysis of 7 patients with increasing compared with previous reports. Cat-induced AR patients seem AERD with rapid nasal polyp recurrence following initial ESS, who to have NPT positivity at lower concentration compared to LAR. underwent revision ESS with initiation of dupilumab in the perioperative setting. Health-Related Quality of Life Impairment RESULTS: Patients had a mean of 3.4 6 1.4 lifetime ESSs. All patients 425 Among Patients With Severe Chronic previously underwent aspirin desensitization/daily aspirin therapy: one did Rhinosinusitis With Nasal Polyps in the not tolerate desensitization, four had inadequate response, and two stopped SINUS-24 Trial aspirin due to GI side effects. Six of 7 patients reported historical regrowth of nasal polyps within <_ 6 months after initial ESS (mean time to polyp Jorge Maspero, MD FAAAAI1, Carl Philpott2, Peter Hellings, MD3, recurrence 3.4 6 2.5 months) compared to 0 of 7 patients treated with Claire Hopkins4, Martin Wagenmann, MD FAAAAI5, Shahid Siddiqui6, dupilumab perioperatively (P 5 0.04, McNemar’s test). With an extended Juby Jacob-Nara7, Jerome Msihid8, Chien-Chia Chuang7, Siddhesh Ka- follow-up time > 6 months, only 1 of 7 patients had recurrence of polyps mat6, Asif Khan8; 1Fundacion CIDEA, Buenos Aires, Argentina, 2Nor- (mean follow-up of 12.7 6 5.3 months). There was no significant change in wich Medical School, University of East Anglia, Norwich, UK, FEV1 or ACT score pre/post-dupilumab. There was significant improve- 3University Hospitals Leuven, Leuven, Belgium, 4ENT Department, ment in SNOT-22 post-dupilumab (mean change of -22.6 points, Guy’s and St Thomas’ Hospitals, King’s College London, UK, 5Depart- P50.02, paired t-test). ment of Otorhinolaryngology, Dusseldorf€ University Hospital (UKD), CONCLUSIONS: Dupilumab may be a useful adjunct to surgery to Dusseldorf,€ Germany, 6Regeneron Pharmaceuticals, Inc., Tarrytown, prevent polyp regrowth for patients with AERD who have insufficient NY, USA, 7Sanofi, Cambridge, MA, USA, 8Sanofi, Chilly-Mazarin, response to or cannot tolerate standard-of-care therapies including France. intranasal corticosteroids and daily aspirin therapy. RATIONALE: Chronic rhinosinusitis with nasal polyps (CRSwNP) is an inflammatory disease of the nasal cavity and paranasal sinuses, with a high symptom burden and significant impact on health-related quality of life (HRQoL). This analysis compared baseline generic physical and mental HRQoL, and overall health status, of patients with severe CRSwNP on background mometasone furoate from the SINUS-24 (NCT02912468) study, with general population norms. METHODS: Post hoc analyses described baseline HRQoL, measured using the 36-Item Short-Form (SF-36) questionnaire, and health status, measured using the EuroQol-5 Dimensions visual analogue scale (EQ-5D VAS),of patients enrolled in the Phase 3 SINUS-24 study, grouped by prior surgery, systemic corticosteroid (SCS) use (within the last 2 years and with/ without prior surgery), and comorbid asthma or non-steroidal anti- AB134 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Decrease in Antibiotic Use and Radiographic CI:0.001-0.460, p-value50.01, AOR(ageusia):0.10, 95%CI:0.010-0.970, 427 Sinus Severity after Functional Endoscopic p-value<0.05). Male gender was independently associated with a lower Sinus Surgery in Patients with Chronic probability of ageusia (AOR:0.56, 95%CI:0.380-0.820, p-value<0.01) Rhinosinusitis and Antibody and a better recovery from ageusia (AHR:1.44, 95%CI:1.05-1.98, p-val- Immunodeficiencies ue<0.05). Latinos too had better ageusia recovery than the whites (AHR:1.82, 95%CI:1.05-3.18, p-value<0.05). Matthew Perez, MD1; 1Northwestern University. CONCLUSIONS: COVID-19 patients with anosmia and ageusia are more RATIONALE: Antibody immunodeficiencies are common in patients likely to report greater presence of systemic, respiratory, and gastrointes- with chronic rhinosinusitis (CRS) and are associated with recurrent sino- tinal symptoms. Older patients and those with higher blood eosinophil pulmonary infections. The role of functional endoscopic sinus surgery counts are less likely to report anosmia and ageusia. Men have a lower (FESS) has not been established in the management of these infections and probability of reporting ageusia and men and Latinos recover faster from it. clinical guidelines suggest caution with surgery. This study evaluates number of antibiotic courses for sino-pulmonary infections and radio- Alcohol Hypersensitivity In CRSwNP And graphic sinus disease severity after FESS in patients with CRS and 429 Polyphenols antibody immunodeficiencies. 1 2 METHODS: Patients with CRS and antibody immunodeficiencies un- Will Eschenbacher , Larry Borish, MD FAAAAI , Monica Lawrence, MD FAAAAI3, Spencer Payne, MD1; 1University of Virginia, dergoing FESS at Northwestern Medicine between 2007-2017 were 2 3 identified using an automated review of electronic medical records. A University of Virginia Health System, University of Virginia Division of manual chart review of 35 randomly selected patients was performed. The Asthm. number of antibiotic courses prescribed annually for sino-pulmonary RATIONALE: Alcohol sensitivity is reported in up to 74-86.5% of infections was determined, 1 year before and up to 5 years after FESS. patients with chronic rhinosinusitis with nasal polyposis (CRSwNP) and Lund-Mackay scores were calculated in patients who had sinus CT scans especially in those with aspirin-exacerbated respiratory disease (AERD). available before and after FESS. These patients typically report sensitivity to beverages fermented in wood RESULTS: The 35 patients identified were 51.4% male, 82.9% white, and casks, with fruit skins, or with hops, but not to other alcohol-containing had an average age of 52.968 years. There was a reduction in the drinks. We speculated that alcohol sensitivity in AERD/CRSwNP could mean6SD number of antibiotics prescribed per year for sino-pulmonary result from activation of basophils by polyphenols derived from the aging infections after FESS (2.862.2 pre vs. 1.561.2 post, P50.001) in patients of fermented beverages. with CRS and antibody immunodeficiencies. There was a reduction in METHODS: We collected whole blood samples from controls and Lund-Mackay scores with FESS (N521, 10.265.3 pre vs. 7.563.2, alcohol sensitive subjects with AERD/CRSwNP. We exposed these cells P50.009). to red wine extract, various bioactive polyphenols known to be present in CONCLUSIONS: FESS is associated with a reduction in antibiotic red wine, and ethanol, as well as positive activation controls. We evaluated basophil activation via flow cytometry using CD63. Basophils were defined prescriptions for sino-pulmonary infections and improvement in radio- low high graphic sinus disease severity in patients with CRS and antibody in these whole blood samples as cells within a side scatter CCR3 flow immunodeficiencies. This suggests that FESS can be an effective strategy cytometry gate. for reducing sino-pulmonary infections and disease burden in these RESULTS: We demonstrated robust basophil activation in alcohol 6 patients. sensitive subjects (increased CD63 expression from 0.72% 0.21 to 25.97%65.35;n54; p<0.018) in response to components within red Risk Factors Associated With COVID-19 Related wine extract. No significant changes were observed in control subjects. 428 Anosmia And Ageusia No activation was observed with ethanol. However, we could not ascribe activation to known immune active polyphenols including either (+)-cate- Esha Sehanobish, PhD1, Mali Barbi1, Valerie Fong1, Meryl Kravitz1, chin or resveratrol. Cynthia Matsumura1, Denise Tejera1, Mohammad Asad, PhD1, Denisa CONCLUSIONS: Up to 74-86.5% of patients with AERD/CRSwNP Ferastraoaru, MD1, Meaghan O’Neill1, Merhunisa Karagic1, Nadeem report sensitivity to alcoholic beverages, primarily those associated with Akhbar1, Danielle Bottalico1, Viraj Patel1, Golda Hudes, MD PhD1, aging in wooden casks. We demonstrated that components in red wine – but Mimi Kim1, Ruth Eisenberg1, Avindra Nath2, Bryan Smith2, Thomas not alcohol itself – can directly activate basophils. We were not able to Ow1, Elina Jerschow, MD FAAAAI1; 1Albert Einstein college of Medi- define the specific bioactive substance(s) in these aged beverages that cine/Montefiore Medical Center, 2National Institute for Neurologic Disor- produce these hypersensitivity reactions. ders and Stroke, National Institutes of Health. RATIONALE: Anosmia and ageusia are associated with COVID-19 in addition to other symptoms. In this study we examined factors associated with anosmia and ageusia and their recovery in an ethnically diverse cohort in Bronx, NY, and assessed the overall rate of anosmia and ageusia and their associations with other COVID-19 related symptoms. METHODS: Individuals tested for SARS-CoV-2 at Montefiore Medical Center were included in the study. Those who consented from a randomly selected subsample and answered the questionnaire were included in the analysis. RESULTS: Overall, 33% and 50% of COVID-19 patients (N5486) reported anosmia and ageusia, respectively, and 58% reported both. Those with reported anosmia and ageusia more often had systemic symptoms (fever, body aches, fatigue), respiratory symptoms (cough, sore throat), and diarrhea, compared to those without anosmia or ageusia (p-value<0.01). Patient characteristics associated with lower probability of anosmia and ageusia included older age (AOR(anosmia):0.980, 95% CI:0.967-0.993, p-value<0.01, AOR(ageusia):0.98, 95%CI:0.970-0.990, p-value<0.01) and higher peripheral eosinophil count (AOR(anosmia):0.021, 95% J ALLERGY CLIN IMMUNOL Abstracts AB135 VOLUME 147, NUMBER 2

Mitochondrial Oxidative Stress and Damage Is The Prevalence of Hereditary Alpha-Tryptasemia 430 Associated with age-related Glandular 432 in Patients Diagnosed With POTS via Tilt Table Remodeling and Nasal Polyp Formation Testing

Ara Jo, PhD1, Jung Yeon Han1, Mark Tabor, MD1, Richard Lockey, MD Jenny Huang, MD1, Jose Criado Del Valle2, Andrew White, MD FAAAAI1, Seong Cho, MD FAAAAI1; 1University of South Florida. FAAAAI2; 1Scripps Clinic/Scripps Green Hospital, 2Scripps Clinic. RATIONALE: Our microarray data demonstrate significant reduction of RATIONALE: Autonomic disorders are reported at higher rates in submucosal gland-related genes in nasal polyps (NP) subjects and elderly patients with extra copies of the alpha-tryptase gene, known as hereditary controls. We hypothesized that mitochondrial damage is an underlying alpha-tryptasemia (HaT). Clinical features of HaT include skeletal mechanism of glandular remodeling in aging and NP formation. abnormalities, higher rates and severity of anaphylaxis, abdominal pain METHODS: Nasal tissues (non-elderly, age 18-49yr; elderly, >_65yr) were among others. HaT has not been reported in patients with basal serum obtained during sinus surgeries. Mitochondrial dysfunction markers were tryptase (bST) < 8ng/mL. The prevalence of HaT is estimated at 4-6% in investigated. Nasal tissues were cultured in a short-term explant model and the general population, likely explaining a majority of individuals with submucosal gland cell line calu-3 was cultured with or without ROS modest tryptase elevations. Given the reported increased rates of stimulants (hydrogen peroxide (H2O2) and lipopolysaccharide (LPS)) and autonomic disorders, we examined tryptase levels in patients with postural mitochondria-targeted antioxidants (MitoQ and NecroX-5). Mitochondrial orthostatic tachycardia syndrome (POTS). ROS (mtROS) and DNA (mtDNA) were examined. METHODS: Patients who underwent tilt table testing at Scripps Clinic in RESULTS: There was an age-related reduction of serous cells and San Diego, California from May 2015 – July 2020 were reviewed. Patients increase of mucous cells in submucosal glands in healthy controls. meeting POTS criteria (increase in heart rate > 30 beats per minute in Glandular remodeling was prominent in NP regardless of age. adults or 40 beats per minute in children without orthostatic hypotension) Transmission electron microscopy showed that serous cells were damaged were extracted. Patient records were reviewed for tryptase levels. more in elderly controls compared to the non-elderly. There were unique RESULTS: 493 patients met POTS criteria and 250 had available tryptase features of damaged mitochondria in elderly controls and NP such as levels. 232/250 (92.8%) had bST < 8ng/mL. 18/250 (7.2%) had tryptase > reduced mitochondria size, floating mitochondria, and cytoplasmic 8ng/mL, 9 were > 11.4ng/mL (3.6%). 4/250 patients had genetic testing vacuoles. Immunofluorescence showed reduced expression of mitochon- confirming HaT, all with tryptase > 11.4ng/mL. drial antioxidant (SOD2) and increased expression of mitochondrial fission CONCLUSIONS: Assuming 80% of patients with tryptase between 8- protein (DRP-1) in the submucosal glands of elderly controls and NP 11.4ng/mL and 100% with tryptase > 11.4ng/mL had HaT, the upper limit subjects. In explant tissues and calu-3 cells, mtROS was increased with of estimated prevalence is 16/250 (6.4%). Prevalence of those with ROS stimulants, and decreased with MitoQ and Necro-X5 treatment, but elevated tryptase and/or confirmed HaT was 9/250 (3.6%). The estimated mtDNA was significantly reduced with ROS stimulants and rescued by prevalence of HaT in patients with POTS does not appear to be significantly MitoQ and Necro-X5. higher than the general population. CONCLUSIONS: Increased mitochondrial oxidative stress and damage was prominent in NP subjects and elderly controls compared to non-elderly Hereditary Alpha-Tryptasemia: A Case Series controls, suggesting mitochondrial dysfunction in aging and NP formation. 433 with Various Clinical Presentations

A novel case of beta-tryptase/TPSB2 allele Navid Ziaie1, Shyam Joshi, MD1; 1Oregon Health and Science University. 431 duplication RATIONALE: Hereditary alpha-tryptasemia (HAT) is a recently described genetic trait caused by an increased copy number of the alpha- Madeleine Chollet1, Anna Kovalszki, MD1, Cem Akin, MD PhD tryptase gene, TPSAB1. While the clinical significance of the mutation has FAAAAI1; 1University of Michigan. not been fully determined, it has been associated with an increased risk of RATIONALE: Serum tryptase is the product of two genes – TPSAB1 and venom-related anaphylaxis, idiopathic anaphylaxis, and systemic TPSB2. While TPSB2 reliably contains the b2 and b3 alleles, TPSAB1 mastocytosis. contains either the a or b1 allele to produce three possible genotypes - METHODS: In this case series, eight patients with elevated basal tryptase aa:bb, ab:bb, and bb:bb. Hereditary alpha tryptasemia is a genetic trait levels and a wide range of multi-system complaints were identified. defined by one or more extra copies of the a-tryptase allele. This is the first Genetic copy number variation testing was performed via droplet digital report of an extra copy of the b-tryptase allele. PCR for evaluation of an increase in alpha-tryptase copy number. METHODS: DNA was analyzed by Gene-By-Gene using digital droplet RESULTS: The mean basal tryptase level in this cohort of patients (6 PCR. Tryptase was calculated as an average of two baseline levels in his female, 2 male) was 17.7 ug/L (range 10.9-47.0 ug/L, normal <10.9 ug/L). medical record. Of the eight patients tested, all were positive for an abnormal alpha- RESULTS: This patient presented with an elevated tryptase of 16.6 ng/mL tryptase genotype (n54 aa:bbb, n53 aaa:bb, n51 aaaa:b). Of the and a history of generalized urticaria after being stung by a hornet. He had presenting symptoms, the most common organ systems involved were no urticaria pigmentosa on physical exam. He denied a history of flushing, gastrointestinal (75%) manifested by bloating, abdominal discomfort, pruritus, dysautonomia, gastric reflux, chronic pain, sleep disturbance, nausea, diarrhea, constipation, followed by dermatologic (50%) mani- IBS, or joint hypermobility. He does have a history of retained primary fested by flushing and urticaria, and respiratory (38%) manifested by teeth. Genetic testing revealed two copies of the a-tryptase allele and four cough, hoarseness, and shortness of breath. 75% of the patients in this copies of the b-tryptase allele. This result indicates that he has both an a- cohort reported moderate improvement in symptoms following initiation tryptase duplication and a b-tryptase duplication (aabb:bb) or two extra of high-dose second-generation antihistamines. copies of the b-tryptase allele (aa:bbbb). CONCLUSIONS: HAT can present with various clinical phenotypes and CONCLUSIONS: We believe this is the first reported case of a b-tryptase suspicion should remain high in patients with multi-system allergic duplication. Currently, it is assumed, when a patient has an extra tryptase symptoms. Based on this case series, genetic testing should be considered allele, that it is an extra a-tryptase allele. However, this case report raises early in the workup of patients with typical histaminergic symptoms and the possibility that some patients may have a b-tryptase duplication, elevated baseline tryptase levels to help validate patients’ concerns and to complicating the diagnosis of hereditary alpha tryptasemia. appropriately tailor management. AB136 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Aberrant mature active mast cells in wasp p50.01).In these subgroup only one patient had been diagnosed with 434 venom anaphylaxis associated with clonal cutaneous mastocytosis. mast cell disorders CONCLUSIONS: In our pediatric population, BST levels vary with age, being the lowest values in older patients.BST is higher in patients with Leander De Puysseleyr1, Jessy Elst, MD1, Didier Ebo, MD PhD mastocytosis even when most are cutaneous mastocytosis. The children FAAAAI2, Margaretha Faber, MD PhD1, Athina Van Gasse1, Ine with a history of recurrent anaphylaxis have increased BST values. Decuyper, MD PhD1, Christel Mertens1, Michel Van Houdt, MLT1, Margo Hagendorens, MD PhD3, Katrien Vermeulen, PhD4, Zwi Berneman, MD, Ephedra Herb, Mao, Inhibits Antigen-Induced PhD4, Vito Sabato, MD1; 1University of Antwerp, 2University Antwerp, 436 Mast Cell Degranulation by the Induction of 3University of Antwerp - Belgium, 4Antwerp University Hospital. the Affinity Receptor for IgE Internalization

RATIONALE: Uncertainties remain about the molecular mechanisms 1 1 1 1 1 that lead to Hymenoptera venom anaphylaxis (HVA),especially in patients Yuka Nagata , Hirokazu Ando , Yohei Sasaki , Ryo Suzuki ; Kanazawa with an underlying clonal mast cell disorder (CMCD) who show a different University, Kanazawa, Japan. clinical presentation than patients without CMCD. This study aims to RATIONALE: Ephedra herb (Mao in Japanese) is traditionally used in compare the burden, phenotypical and behavioural profiles of mast cells Japanese herbal medicine (Kampo) for treatment of allergic diseases. Mao (MC) and basophils in patients with wasp venom anaphylaxis with CMCD exerts potent anti-allergic effects, however the underlying mechanisms (WVA/CMCD) vs. wasp venom anaphylaxis without CMCD (WVA). remain elusive. In this study, we investigated the mechanisms of Mao on METHODS: This study included 15 patients with WVA/CMCD and 14 allergic inflammation using in vitro cultured mast cell (MC) and in vivo with WVA. In patients with WVA/CMCD and WVA we performed mouse model of allergy. immunophenotyping studies of MC and basophils. We also compared METHODS: Mao water extracts were applied on bone marrow-derived baseline serum tryptase (bST) and total and venom specific IgE (v-sIgE) in mast cells (BMMCs). The BMMCs were pre-sensitized with anti-DNP IgE the two patient groups. For basophil studies additionally 13 healthy and challenged by antigen (DNP-HSA). Degranulation responses and ε controls (HC) were included. localization of IgE receptor (Fc RI) in BMMCs were observed with/ RESULTS: Patients with WVA/CMCD had a higher bST and lower titers without Mao treatment. Passive systemic anaphylaxis (PSA)-treated mice of total and v-sIgE. MC of patients with WVA/CMCD had lower were subjected to Mao administration and the pathophysiological re- expression of CD117 and higher expression of CD203c, CD63, CD300a sponses were evaluated. and FcεRI. Expression of MRGPRX2 on MC did not differ between RESULTS: Mao inhibited the antigen-induced BMMCs degranulation. patients with WVA/CMCD and WVA. Coincubations of basophils with Mao-treated BMMCs exhibited significant reduction for the levels of IgE ε SCF did not alter their responsiveness to anti-IgE, nor to fMLP in any of the and its receptor Fc RI expressions on cell surface. Analysis of their ε study populations. subcellular localization of Fc RI by confocal laser scanning microscopy ε CONCLUSIONS: Patients with WVA/CMCD show an increased burden revealed that Mao treatment induced IgE-Fc RI internalization in ε of aberrant mature activated MC with a significantly higher expression of BMMCs. Additionally, Fc RI-induced tyrosine phosphorylation and cal- FcεRI. From a quantitative point of view, MRGPRX2 expression does not cium mobilization in the antigen-stimulated BMMCs were attenuated by contribute to the distinct phenotype and behaviour profiles observed in Mao treatment, indicating that Mao-treated BMMCs failed to respond to WVA/CMCD. the antigen. Further, Mao administration to the PSA models resulted in the prevention of antigen-induced hypothermia. Peritoneal mast cells (PMCs) Baseline serum tryptase levels in a pediatric in the PSA mice showed significant reduction of surface FcεRI by Mao 435 population administration, indicating Mao-induced FcεRI internalization in the PMCs. Alba Juarez1, Alicia Dominguez1, Joaquın Navarro1, Maria Luisa CONCLUSIONS: Mao induced IgE-FcεRI internalization in MCs, and Baeza1, Alberto Alvarez-Perea1; 1Gregorio Maranon~ University General may thereby inhibit the antigen-induced IgE-dependent degranulation. Hospital, Madrid, Spain. These findings provide novel mechanism of Mao on MC functions and RATIONALE: The values of basal serum tryptase in pediatric population allergic responses. are not well defined. Our aim was to describe the values of Baseline serum tryptase (BST) in a cohort of children attended in a pediatric hospital. METHODS: We led an observational, retrospective study, including all the determinations of BST in children under 18 years of age performed in the laboratory of Hospital Materno Infantil Gregorio Maran~on, Madrid, Spain(March 2010 to December 2019) RESULTS: Determinations of BST of 600 patients were included. 42% girls. Age (mean6SD)10.0265.03 years.(9 infant, 62 toddler, 170 child and 323 adolescents). Three hundred seventeen atopic. BST (mean6SD, mcg/ml) 4.7163.08. Infant (BST 5.5763.15), toddler (5.4363.17), child (5.2163.56), adolescent (4.2762.37).BST was higher among boys (5.0763.30 vs 4.2262.66, p50<0.001). Negative correlation between BST and age (R5-0.46, p5<0.0001). Nineteen (11%) had been diagnosed with mastocytosis (96.97% cutaneous mastocytosis, 3.03% systemic mastocytosis). Children with mastocytosis had higher levels of BST (6.8965.35mcg/ml) than those without mastocytosis (4.4462.55mcg/ml) (p<0.001).BST was higher in systemic 9.2563.66 vs 6.8165.33 (p50.0004). In the subgroup of patients with anaphylaxis (n5213). BST 4.5562.84. Sixty (28.17%) had a history of, at least, an additional episode of anaphylaxis. BST was higher among the later (5.3163.41 vs 4.2562.54, J ALLERGY CLIN IMMUNOL Abstracts AB137 VOLUME 147, NUMBER 2

Mast cells cultured from human peripheral Absolute bioavailability after SC administration was 49.7%. Garadacimab 437 blood and bone marrow: a phenotypic and (IV and SC) exhibited dose-dependent inhibition of FXIIa-mediated kalli- functional comparison krein activity with no or minimal residual activity at higher doses. CONCLUSIONS: Garadacimab (single-dose IV and SC) was well Jessy Elst, MD1, Didier Ebo, MD PhD FAAAAI2, Margaretha Faber, MD tolerated in healthy male subjects. Dose-dependent increases in plasma PhD1, Athina Van Gasse1, Ine Decuyper, MD PhD1, Chris Bridts, MLT1, concentration and pharmacodynamic effects in the kallikrein-kinin Leander De Puysseleyr1, Marie-Line Van Der Poorten, MD1, Christel pathway were observed. These results informed the design of further Mertens1, Margo Hagendorens, MD PhD3, Anke Verlinden4, Vito Sabato, investigations, including a phase 2 study in HAE. MD1; 1University of Antwerp, 2University Antwerp, 3University of Ant- werp - Belgium, 4Antwerp University Hospital. Cognitive Dysfunction and Co-morbid RATIONALE: Studies on the mechanisms that govern mast cell (MC) 439 Psychiatric Disturbances in Chronic Allergic functions are hindered by the difficulties in isolating sufficient numbers of Conditions these tissue-resident cells. Therefore, many research groups culture human Daniel Rosenberg1, Sameer Mathur, MD PhD FAAAAI2, Ravi Viswana- MC out of progenitor cells. However, as these culture methods significantly 2 1 2 differ regarding primary source material, culture durations and conditions, than, MD ; University of Wisconsin Hospital and Clinics, University of it is likely the finally obtained cells to exhibit morphological, phenotypical Wisconsin School of Medicine and Public Health. or functional heterogeneity. Therefore, the aim of this study is to compare RATIONALE: Patients with mast cell activation syndrome (MCAS) often the phenotype and functionality of primary MC cultured from peripheral report having ‘‘brain fog,’’ which has been noted in other chronic illnesses. blood (PBCMC) and bone marrow (BMCMC) progenitor cells from We previously identified evidence of cognitive dysfunction in a small patients with suspected clonal MC disease. number of MCAS patients via cognitive testing, though depression and METHODS: Twenty-one pairwise MC cultures starting from CD34+ pro- anxiety are potentially confounders. We sought to compare the presence of genitor cells from peripheral blood and bone marrow were compared. MC cognitive dysfunction in chronic rhinitis (CR) and chronic spontaneous were cultured for 4 weeks. Phenotyping included Giemsa and CD117 stain- urticaria (CSU) to that in MCAS. We hypothesize that similar degrees of ing and flow cytometric staining for CD117, CD203c, FcεRI, MRGPRX2, cognitive dysfunction, depression, and anxiety as observed in MCAS may CD300a, CD32, CD63 and CD25. Functional assessment included mea- be found in CSU rather than CR given more significant symptom burden in surement of the upregulation of CD63 after cross-linking of FcεRI with the former group. anti-FcεRI and ligation of MRGPRX2 with substance P. METHODS: Patients referred to a University of Wisconsin Allergy clinic RESULTS: At 4 weeks, PBCMC and BMCMC are phenotypically for evaluation of MCAS, CR, and CSU were identified. We enrolled female comparable. Functionally, after activation though an IgE-dependent patients between the ages of 18 and 50 with CR and CSU based on the mechanism or occupation of the MRGPRX2, both, PBCMC and demographics of our MCAS population in the University of Wisconsin BMCMC show similar CD63 upregulation. However, peripheral blood IRB-approved protocol. Executive cognitive function was assessed via a yields more MC and purer cultures than bone marrow. previously validated computer battery (CogState). PHQ-9 and GAD-7 CONCLUSIONS: PBCMC are an attractive alternative to BMCMC for questionnaires were administered to assess for co-morbid psychiatric the exploration of the complex mechanisms behind MC activation and disorders. degranulation. Unlike BMCMC, PBCMC are easily accessible and enable RESULTS: Preliminary analyses suggests four of twelve MCAS patients repetitive analyses. had evidence of cognitive dysfunction (33%). Ten had evidence of depression (83%) while six had evidence of anxiety (50%). Similar A Phase 1, Single-Center, Randomized, Double- analyses are forthcoming for CSU and CR. 438 Blind, Placebo-Controlled, Single Ascending CONCLUSIONS: We have identified cognitive dysfunction, depression, Dose Study to Investigate the Safety, and anxiety in the MCAS population. Upon completion of recruitment of Tolerability, and Pharmacokinetics of CR and CSU patients, we will be able to establish whether these are Intravenous and Subcutaneous Garadacimab features of other allergic diseases or unique to MCAS. (CSL312) in Healthy Subjects

Andrew McKenzie1, Anthony Roberts1, Sourabh Malandkar1, Henrike Feuersenger2, Con Panousis3, Dipti Pawaskar4; 1CSL Limited, Parkville, Victoria, Australia, 2CSL Behring GmbH, Marburg, Germany, 3CSL Limited, Parkville, Victoria, Australia, 4CSL Behring, King of Prussia, PA, USA. RATIONALE: Garadacimab is a fully human IgG4 monoclonal antibody against activated factor XII (FXIIa). A phase 1 study assessed the safety, tolerability, and PK/PD profile of single ascending doses of garadacimab in healthy volunteers. METHODS: Five IV cohorts (0.1, 0.3, 1, 3, or 10 mg/kg doses) and 3 SC cohorts (1, 3, or 10 mg/kg doses) were included, with matching placebo administered within each cohort. Safety follow-up lasted 85 days after administration. Blood samples were collected throughout for PK/PD analysis. RESULTS: Forty-eight male subjects, mean (SD) age 27.4 (6.4) years, were included. No deaths, serious TEAEs, or TEAEs leading to discontinuation were reported. The frequency and severity of TEAEs were not dose-dependent and no anti-drug antibodies were detected. Mean

Cmax and AUC0–t increased in a dose-dependent manner (IV and SC). Median tmax was 1.0 hour (end of infusion) for IV cohorts (except the 0.1 mg/kg dose [3.5 hours]) and 5.6–7.0 days for SC cohorts. Mean t½ was 14.3–20.4 days and 18.2–19.6 days for IVand SC doses, respectively. AB138 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Low Immunoglobulin Levels In Patients With Fibroblasts Regulate Mast Cell Activation in 440 Mastocytosis And Associated Clinical 442 Nasal Polyps Manifestations Tahereh Derakhshan1, Chunli Feng, MD1, Kathleen Buchheit, MD1, Kimberley Cousins1, Dean Metcalfe, MD FAAAAI2, Hirsh Nora Barrett, MD1, Tanya Laidlaw, MD FAAAAI1, Joshua Boyce, MD Komarow, MD3, Melody Carter, MD FAAAAI4; 1Mount Sinai Hospital, FAAAAI1, Daniel Dwyer, PhD1; 1Jeff and Penny Vinik Center for Allergic 2Laboratory of Allergic Diseases/NIAID/NI, 3NIAID/NIH, 4National In- Disease Research, Division of Allergy and Clinical Immunology, Brigham stitutes of Health/NIAID/LAD. and Women’s Hospital. Department of Medicine, Harvard Medical RATIONALE: Patients with low IgG alone or in combination with low School, Boston, MA, USA. IgA or IgM have been reported to be susceptible to respiratory tract RATIONALE: Chronic rhinosinusitis with nasal polyps (CRSwNP) is an infections and recurrent sinusitis. Patients with CVID also have a higher inflammatory sinus disease associated with mast cell (MC) expansion and prevalence of autoimmune diseases and lymphoid malignancies. activation. We find that MCs in the subepithelium of nasal polyps exhibit Mastocytosis is a myeloproliferative disease that is not typically associated elevated CD69 expression, a known leukocyte activation marker. However, with autoimmune disease or frequent infections. We determined the it is unclear which factors within the polyp drive this activation. As prevalence of infectious and autoimmune disorders in patients with subepithelial MCs colocalize with fibroblasts, cells known to influence MC mastocytosis with low IgG alone or in combination with low IgM and/or development and mediator release, we hypothesized that nasal polyp IgA to ascertain if there was clinical relevance. fibroblasts could directly drive MC activation. METHODS: We performed a 10 year retrospective analysis on 320 adult METHODS: Human umbilical cord blood-derived MCs (CBMCs) were and pediatric patients with all variants of mastocytosis using an electronic cultured in three-dimensional matrices or two-dimensional liquid culture with medical query. We identified 26 adults and 9 children with one or more low fibroblasts from CRSwNP and CRS without nasal polyps (CRSsNP) to mimic immunoglobulins levels. These patient records were then examined for a the subepithelial microenvironment. Cells and supernatants were collected for history of infections and autoimmune disorders. mediator measurement, flow cytometric evaluation, and RNA sequencing. RESULTS: Overall, among these 35 patients, 17% of patients had a RESULTS: Sinus fibroblasts profoundly altered the CBMC transcriptome, history of infections and 11% had an autoimmune disorder. The most eliciting CD69 upregulation as part of a broader set of transcripts, common infectious condition was recurrent otitis media (OM). No patients including IL-6 family cytokines (IL6, LIF, OSM), cytokine receptors required hospitalization for infection, two patients met criteria for CVID (IL2RA, IL4R, IL1RL1), and adhesion molecule-encoding genes (ICAM1, but did not require replacement therapy. Only one pediatric patient with ITGA2, ITGB2). CBMC surface expression of CD69 was significantly up- low IgG received IgG replacement therapy for OM and mastoiditis. regulated in fibroblast co-culture (p<0.0001) with further upregulation CONCLUSIONS: The routine determination of immunoglobulin levels in observed during co-culture with polyp fibroblasts (p<0.05). Surface upre- mastocytosis is thus not required and should be reserved for those with a gulation of CD69 was largely dependent on direct contact with fibroblasts, clinical condition which might relate to a low immunoglobulin levels. suggesting adhesion molecules or extracellular matrix components play a major role in MC activation. Demographic Features of Children with CONCLUSIONS: CD69 is a novel marker of human MC activation that is 441 Cutaneous Mastocytosis: One Institution's upregulated by sinus fibroblasts as part of an IgE-independent activation Experience program. Intrinsic fibroblast properties may contribute to the persistent MC activation typical of CRSwNP. Arjola Cosper1, Denisa Ferastraoaru, MD2; 1Albert Einstein College of Medicine/Montefiore Medical Center, 2Albert Einstein College of Medi- Clinical significance of mast cell counts in cine/Mont. 443 patients presenting with mast cell disorders RATIONALE: We sought to investigate whether there is a relationship between race, gender, and systemic manifestations of pediatric cutaneous Simin Zhang1, Umesh Singh, MD PhD1, Nives Zimmermann, MD mastocytosis (PCM) in our diverse patient population. FAAAAI2, Jonathan Bernstein, MD FAAAAI3; 1University of Cincinnati, METHODS: We retrospectively identified children (age<18) with 2Cincinnati Children, 3Bernstein Allergy Group, Inc. diagnosis of PCM (maculopapular CM (MPCM), solitary mastocytoma RATIONALE: Patients with chronic unexplained GI symptoms often (SoM), multiple mastocytoma (MuM) and diffuse cutaneous mastocytosis present for evaluation of a mast cell (MC) disorder. Current criteria suggest (DCM)) seen at Montefiore Medical Center in Bronx, NY, between 2014- MC counts >20 /high power field (hpf) in colon biopsies differentiate MC 2019. Chart reviews were performed in all cases. enterocolitis from non-MC gastrointestinal disorders. We hypothesize RESULTS: Overall, 51 children had PCM. Majority of patients were male using clinical and laboratory characteristics will identify a more accurate (34/51,66.66%), of Hispanic origin (21/51, 41.1%), with mean age of 3 MC cut-point for MC enterocolitis diagnosis. years 63.08. SoM was the most common diagnosis (24/51, 47%), followed METHODS: A retrospective chart review of 68 patients with a MC disorder by MPCM (18/51, 35.3%) and MuM (9/51, 17.7%). A similar distribution diagnosis that included a colonoscopy and biopsy was performed. A patient of PCM types was found in Hispanic versus non-Hispanic children, and in subgroup with presumed MC enterocolitis was identified using the clinical boys versus girls. No DCM diagnoses were recorded. Gastrointestinal and laboratory criteria of chronic diarrhea, no flushing, tryptase <3ng/ml, symptoms were more frequent in Hispanic children (4/21,19%), while and 24-hour urine 5-HIAA<9mg. Logistic regression analysis was used to none of the non-Hispanic patients had documented gastrointestinal determine diagnostic criteria for MC enterocolitis based on colonic mucosal manifestations (0/30, 0%, p50.024). All children with gastrointestinal MC counts using distance to (0, 1) on the ROC curve as the cut-point. symptoms were of male gender. Similarly, other systemic manifestations RESULTS: The entire cohort was 100% Caucasian, 84% female and were present only in Hispanic children with PCM (2 had associated strongly associated with POTS (p<0.004). The patient subgroup with the hematologic malignancy, 1 had anaphylaxis and 1 child had organomegaly specified criteria for MC enterocolitis compared to those without had on abdominal ultrasound). Flushing was present in 2 children, but their race increased colonic MC/hpf counts (mean 40.2 vs 26.8, p<0.02). An ROC was not documented in the chart. curve for the data indicates a colonic cut-point of 35 MC/hpf discriminates CONCLUSIONS: In this small PCM cohort, male was the predominant MC enterocolitis from non-mast cell-mediated GI disorders (sensitivity gender and systemic manifestations were most common in Hispanic 67%; specificity 79%). children. While this might reflect our large Bronx Hispanic population, CONCLUSIONS: Clinical and laboratory criteria correlate with colonic further expansive studies are needed to ascertain if race is a prognostic biopsy findings of increased MC counts, with a 35 MC/hpf cut-point showing factor in the systemic manifestations of PCM. a reasonable sensitivity and specificity for identifying MC enterocolitis. J ALLERGY CLIN IMMUNOL Abstracts AB139 VOLUME 147, NUMBER 2

Impact of Baseline Blood Eosinophil Count on Israel, 11MD Anderson Cancer Center, Houston, TX, 12National Jewish 444 Flare Reduction in Mepolizumab-Treated Health, Denver, CO, 13National Institutes of Health, Bethesda MD. Patients With Hypereosinophilic Syndrome RATIONALE: The goal of this study was to examine real world practice data to determine the safety and efficacy of various biologics that either Marc Rothenberg, MD PhD FAAAAI1, Florence Roufosse2, Stanislas directly or indirectly reduce eosinophils for the treatment of HES. Faguer3, Gerald Gleich, MD FAAAAI4, Jean-Emmanuel Kahn5, Jonathan METHODS: Retrospective data collection from 13 sites (3 international, Steinfeld, MD6, Namhee Kwon, MD PhD7, Jane Bentley, MSc8, Steve 10 US) via an online RedCap data repository is ongoing. Inclusion criteria Yancey9; 1Cincinnati Children’s Hospital Medical Center, University of include 1) peripheral eosinophil count >_1500/mm3 without a secondary Cincinnati, Cincinnati, OH, USA, 2Hopital^ Erasme, Universite Libre de cause, 2) clinical manifestations attributable to the eosinophilia, and 3) Bruxelles, Brussels, Belgium, 3Centre de Reference des Maladies Renales having received mepolizumab, benralizumab, omalizumab, alemtuzumab, Rares, Hopital^ Rangueil, CHU de Toulouse, Toulouse, France, 4School of dupilumab, or reslizumab outside of a clinical trial. Medicine, University of Utah, Salt Lake City, UT, USA, 5Hopital^ RESULTS: In an interim analysis of 111 patients (41% male; median age Ambroise Pare, Universite Versailles-Saint Quentin-en-Yvelines, Bou- 54 [range 17 to 96]; 82% Caucasian), 68% of patients received mepolizu- logne-Billancourt, France, 6GSK, Collegeville, PA, USA, 7GSK, Brent- mab, 10% benralizumab, 6% omalizumab, 6% alemtuzumab, 5% dupilu- ford, London, UK, 8GSK, Stockley Park, Uxbridge, Middlesex, UK, mab, and 4% reslizumab ; 21% of patients received more than 1 biologic. 9GSK, Research Triangle Park, NC, USA. Prescription indications varied: 38% asthma, 26% HES, 25% eosinophilic RATIONALE: Mepolizumab, an anti-interleukin-5 monoclonal antibody, granulomatosis with polyangiitis, 5% atopic dermatitis, 3% eosinophilic reduces disease flares and blood eosinophil counts (BEC) in patients with gastrointestinal disease, 1% urticaria. Overall, 74% had a complete or partial hypereosinophilic syndrome (HES). We assessed the impact of baseline clinical response, and 58% were able to taper or stop other HES therapies BEC on mepolizumab-associated flare reduction. while on the biologic (e.g., 69% were on systemic glucocorticoids before METHODS: This placebo-controlled, double-blind, parallel-group, biologic [median dose 15 mg prednisone/day] and tapered to a median dose Phase III trial enrolled patients >_12 years old with HES for >_6 months, of 0 mg/day while on biologic therapy). 14% of patients had no response to >_2 flares in the previous 12 months, and BEC >_1000cells/mL at screening. one or more biologic therapies. Nine biologic-related adverse reactions Patients maintained >_4 weeks stable HES therapy before randomization (none life-threatening) resulted in 3 discontinuations. (1:1) to 4-weekly subcutaneous mepolizumab (300mg) or placebo, plus CONCLUSIONS: In this preliminary analysis of the largest study of its baseline HES therapy, for 32 weeks. Primary outcome: proportion of kind, biologics appear to offer a safe and effective alternative treatment patients experiencing >_1 flare during the study; annualized flare rate was modality for patients with HES. also assessed. Treatment effects were assessed by baseline BEC, modeled as a continuous covariate. Outcomes were also assessed in baseline BEC Impact of mepolizumab on symptom severity in subgroups. Annualized flare rate by baseline BEC was assessed post hoc. 446 patients with hypereosinophilic syndrome 5 RESULTS: Among the 108 patients enrolled (mepolizumab[n 54]/placebo 1 2 [n554]), the proportion of patients with >_1 flare or who withdrew from the Florence Roufosse , Joseph Butterfield, MD FAAAAI , Robyn von Maltzahn, MSc3,LindaNelsen,MHS4, Jane Bentley, MSc5,Namhee study was reduced with mepolizumab versus placebo (odds ratio[OR; 95% CI]: 6 4 1 5 Kwon, MD PhD , Jonathan Steinfeld, MD ; Hopital^ Erasme, UniversiteLi- 0.28[0.12,0.64], p 0.003); ORs were similar irrespective of baseline BEC 2 5 bredeBruxelles,Brussels,Belgium, Mayo Clinic, 200 1st St SW, Rochester, (treatment-by-baseline BEC interaction: p 0.762; OR[95% CI]: <900cells/ 3 4 5 5 5 MN 55905, USA, GSK, London, UK, GSK, Collegeville, PA, USA, GSK, mL: 0.11[0.01,1.01],n 26; 900–<1500cells/mL: 0.89[0.18,4.42],n 30; 6 1500–<2200cells/mL: 0.13[0.02,0.91],n525; >_2200cells/mL: 0.16[0.03, Stockley Park, Uxbridge, Middlesex, UK, GSK, Brentford, London, UK. 0.98], n527). The annualized flare rate was reduced with mepolizumab versus RATIONALE: Mepolizumab reduces blood eosinophil counts (BEC), placebo (rate ratio[RR; 95% CI]:0.34[0.19,0.63], p5<0.001). The annualized oral corticosteroid use, and disease flares in patients with hypereosino- flare rate was similar between subgroups (treatment-by-baseline BEC interac- philic syndrome (HES). We assessed the impact of mepolizumab on HES- tion: p50.897; RR[95% CI]: <900cells/mL: 0.43[0.17,1.12],n526; 900– related symptom severity. <1500cells/mL: 0.48[0.13,1.80],n530; 1500–<2200cells/mL: 0.22 METHODS: This placebo-controlled, double-blind, parallel-group, multi- _ _ _ [0.05,1.02],n525; >_2200cells/mL: 0.24[0.06,0.95],n527). center, Phase III trial enrolled patients >12 years with HES >6months,>2 _ CONCLUSIONS: In HES, mepolizumab reduced the proportion of flares in the previous 12 months and a screening BEC >1000cells/mL. _ patients experiencing flares and the annualized flare rate versus placebo, Patients had >4 weeks stable HES therapy before randomization (1:1) to 4- irrespective of baseline BEC. weekly subcutaneous mepolizumab (300 mg) or placebo, plus existing HES FUNDING: GSK(200622/NCT02836496). therapy, for 32 weeks. At randomization, patients identified up to three most bothersome HES daily symptoms (HES-DS) of six pre-defined in the HES- An International, Retrospective Study of Off- DS questionnaire (abdominal pain/bloating; breathing symptoms; chills/ 445 Label Biologic Use in the Treatment of sweats; muscle/joint pain; nasal/sinus symptoms; skin symptoms). Each Hypereosinophilic Syndromes (HES) evening, patients rated the severity of all six symptoms over the previous 24hrs using an eDiary (05not present; 105worst imaginable). Baseline and Michael Chen1,PraveenAkuthota,MD2, Timothy Lax3,Sameer Week 32 most bothersome HES-DS scores for each patient were defined as Mathur, MD PhD FAAAAI4, Princess Ogbogu, MD FAAAAI5,Thanai the median scores for most bothersome symptoms in the 7 days before Pongdee, MD FAAAAI6, Marc Rothenberg, MD PhD FAAAAI7, Florence randomization and the Week 32 visit, respectively. Roufosse8, Dagmar Simon9, Miguel Stein10, Sa Wang11, Michael RESULTS: At Baseline, most bothersome symptoms (proportion of Wechsler, MD12, Amy Klion, MD13, Bruce Bochner, MD FAAAAI1; patients) were breathing symptoms (56%), skin symptoms (49%), mus- 1Northwestern University Feinberg School of Medicine, Chicago, IL, 2Uni- cle/joint pain (41%), nasal/sinus symptoms (38%), abdominal pain/ versity of California San Diego, La Jolla, CA, 3Beth Israel Deaconess Med- bloating (37%), and chills/sweats (14%). Median most bothersome HES- ical Center, Boston, MA, 4University of Wisconsin, Madison, WI, 5The DS scores were similar for patients receiving mepolizumab (4.18) and Ohio State University Wexner Medical Center, Columbus, OH, 6Mayo placebo (4.37). Mepolizumab was associated with a statistically significant Clinic, Rochester, MN, 7Cincinnati Children’s Hospital Medical Center, improvement from baseline to Week 32 in HES-DS score (median change: Cincinnati, OH, 8Hopital^ Erasme, Universite libre de Bruxelles, Brussels, -1.19 vs -0.13, p50.001) versus placebo. Belgium, 9Inselspital, Bern University Hospital, University of Bern, Bern, CONCLUSIONS: Severity of the most bothersome symptoms in patients Switzerland, 10Edith Wolfson Medical Center, Tel Aviv University, Holon, with HES was improved with mepolizumab versus placebo. FUNDING: GSK(200622/NCT02836496). AB140 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Effect of Dupilumab Treatment on Blood individual case reports (152 I-HES; 121 M-HES; 62 L-HES; and 12 447 Eosinophil Levels in Patients With Asthma, CEL) was reviewed. Chronic Rhinosinusitis With Nasal Polyps RESULTS: The mean age for all types was 44.3 years. Male predomi- (CRSwNP), Eosinophilic Esophagitis (EoE), or nance (;90% vs ;60%) and median eosinophil count (;10,700 vs Atopic Dermatitis (AD) ;6,000 cells/mL) were higher among M-HES/CEL than among I-/L-HES. The organs most affected were different aside from bone marrow (33% to Michael Wechsler, MD1, Amy Klion, MD2, Pierluigi Paggiaro3, Para- 42%). For I-HES: Heart (35%), lungs (34%), skin (30%), gastrointestinal meswaran Nair, MD PhD4, Delphine Staumont-Salle5, Amr Radwan6, (18%); L-HES: Skin (79%), lymph nodes (34%), joints (21%), lungs Robert Johnson7, Upender Kapoor7, Faisal A. Khokhar6, Nadia Daiza- (19%); M-HES: Spleen (65%), heart (30%), lungs (24%), liver (30%); deh7, Zhen Chen, PhD6, Elizabeth Laws7, Juby Jacob-Nara7, Leda CEL: Spleen (70%), liver (50%), heart (33%), skin (25%). Mortality rate Mannent, MD7, Marcella Ruddy, MD6, Paul Rowe, MD7, Yamo Deniz6; was ; 8-10% for all but CEL (33%). Corticosteroids were the most used 1National Jewish Health, 2Laboratory of Parasitic Diseases, National Insti- treatment except for M-HES and CEL where imatinib was used in 81% and tute of Allergy and Infectious Diseases, National Institutes of Health, 58% respectively. Other therapies included hydroxyurea in ;40% of I/M- 3University of Pisa, 4Firestone Institute of Respiratory Health, McMaster HES/CEL, anti-IL5 or methotrexate in 13-15% of L-HES, and interferon University & St. Joseph’s Healthcare Hospital, 5Service de Dermatologie, alpha used in 42% of CEL patients. Hopital^ Claude Huriez – CHRU, 6Regeneron Pharmaceuticals, Inc., CONCLUSIONS: Differences between subtypes were observed. For 7Sanofi. optimal management of HES patients it is important to differentiate the RATIONALE: Dupilumab blocks the shared receptor component of IL-4/ sub-types. IL-13, key and central drivers of type 2 inflammation. In patients with FUNDING: GSK (213566) asthma or CRSwNP, a transient increase in eosinophils was observed with dupilumab treatment which declined over time and was rarely of clinical Hypereosinophilic Syndrome (HES) Presenting consequence. The effect of dupilumab on blood eosinophils was assessed 449 as Coagulopathy across indications. Kestutis Aukstuolis, DO1, Katherine Altman1, Andrew Ayars2, Anna METHODS: Median (95% CI) percent change from baseline in blood 1 2 1 2 eosinophils was measured in dupilumab-treated uncontrolled moderate-to- Lang , Clinton Dunn, MD ; University of Washington, University of severe asthma (QUEST [NCT02414854]: N51,902; TRAVERSE Washington School of Medic. [NCT02134028] dupilumab/dupilumab-arm: N51,013), severe RATIONALE: While coagulopathy is not typically associated with CRSwNP (SINUS-52 [NCT02898454]: N5303; EoE [NCT02379052]: hypereosinophilic syndromes (HES), this can be a manifestation. Here N547), and moderate-to-severe AD (CHRONOS [NCT02260986]: we present a case of HES initially presenting with mesenteric vein N5425) patients. thrombosis with ischemic colitis resulting in hemicolectomy who was RESULTS: In asthma, blood eosinophils increased from baseline by 9.2% ultimately found to have HES. ([4.3–14.3]; P50.001) at Week 4, returned to baseline by Week 24, and fell METHODS: 33-year-old previously healthy male with no history of below baseline by Week 52 (212.3% [215.9 to 27.7]; P50.03). This atopic disease who presented with abdominal pain, hematochezia and was trend was sustained to Week 96 for dupilumab treated patients who found to have a significant peripheral eosinophilia (10,000) and mesenteric continued to open-label TRAVERSE. In CRSwNP, a 16.2% ([–5.9 to vein thromboses with ischemic colitis which resulted in hemicolectomy. 34.0]; P50.26) rise was seen at Week 16 which resolved by Week 24. The patient had upper and lower endoscopies showing eosinophilic No rise was observed over the treatment period in EoE or AD. infiltrates. Bone marrow biopsy showed normocellular marrow with no Hypereosinophilia (>3,000cells/mL) was rare, few patients discontinued morphologic or flow cytometry evidence of malignancy or a clonal dupilumab due to eosinophilia (QUEST: 7 discontinued/52 eosinophilia disorder. Despite an extensive workup for other potential etiologies by cases, TRAVERSE: 2/3, SINUS-52: 1/2), and the majority did not require hematology/oncology, infectious disease, rheumatology and allergy and corrective treatment. Rare cases of EGPA and eosinophilic pneumonia immunology, no other clear causes were identified, and the patient has been were reported; a causal association with dupilumab has not been diagnosed with HES. The patient improved on high-dose oral corticoste- established. roids (OCS) and subsequently was started on anti-IL5 therapy with CONCLUSIONS: Transient early elevation of blood eosinophils in benralizumab. asthma or CRSwNP patients on dupilumab treatment generally declined RESULTS: After starting benralizumab the patient has been weaned off to below baseline levels over time. Eosinophils did not rise in EoE or AD OCS therapy and has done extremely well from a clinical standpoint and patients. has not had a recurrence of peripheral eosinophilia. CONCLUSIONS: In patients with an unexplained coagulopathy and Description of Hypereosinophilic syndrome eosinophilia, eosinophilic disorders such as HES should be considered. 448 (HES) and subtypes in the literature This patient has been able to wean off OCS therapy with anti-IL5 treatment with benralizumab. Praveen Akuthota, MD1, Gema Requena, PhD2, Judith van den Bosch, PhD3, Jonathan Steinfeld, MD4, Namhee Kwon, MD PhD2, Anna Kovalszki, MD5, Melissa van Dyke, PhD4; 1University of Califor- nia, San Diego, La Jolla, CA, USA, 2GSK, Brentford, London, UK, 3Pallas Health Research and Consultancy, Rotterdam, the Netherlands, 4GSK, Collegeville, PA, USA, 5University of Michigan, Ann Arbor, MI, USA. RATIONALE: Hypereosinophilic syndrome (HES) is a group of rare hematologic disorders in which eosinophils are overproduced for pro- longed periods of time resulting in organ damage. Different subtypes of HES have been identified but little is known about their similarities or differences. This review aimed to describe clinical characteristics of HES types based on reported cases in the literature. METHODS: A literature search focused on different types of HES was performed in Pubmed from 2000 onwards. Information from 347 J ALLERGY CLIN IMMUNOL Abstracts AB141 VOLUME 147, NUMBER 2

Variability in Total IgE Levels in Patients patients, and the importance of vitellogenin in the pathobiology of German 450 Receiving Monoclonal Biologics for Allergic cockroach allergy. Conditions Proteomic evaluation of Alternaria alternata Moshe Beiser1, Deborah Schwartz1, Denisa Ferastraoaru, MD2; 1Albert 452 spores, hyphae, and commercial allergen Einstein College of Medicine, 2Albert Einstein College of Medicine/ extracts Mont. 1 1 1 RATIONALE: Omalizumab and dupilumab affect serum immunoglob- Michael Strader , Ramiz Ahmad , Aishwarya Saha , Brett Green, PhD 2 3 3 ulin E (IgE) levels. We sought to investigate in a real allergy clinical FAAAAI , Angela Lemons, MS , Donald Beezhold, PhD FAAAAI , Rob- 4 5 setting: 1) the trend of IgE levels in patients receiving biologics for ert Hamilton, PhD DABMLI FAAAAI , Samuel Mindaye, PhD , Jay 6 1 2 different allergic conditions; 2) if patients become IgE deficient (IgE<2.5 Slater, MD ; US Food and Drug Administration, Centers for Disease 3 4 kU/L). Control and Preventi, NIOSH, Johns Hopkins University School of 5 6 METHODS: We compared changes between IgE levels before and after Medic, FDA, FDA/CBER/OVRR/DBPAP. biologics initiation in patients who received dupilumab (Group 1), RATIONALE: Alternaria alternata is associated with allergic respiratory omalizumab (Group 2), and mepolizumab, benralizumab or reslizumab disease which has led to the need for allergen extract-based immunother- (Group 3) at our institution between 2014-2019. apies and diagnostics. Available commercial Alternaria allergen extracts RESULTS: Overall, 78/361 (21.6%) patients had IgE levels checked are neither standardized nor well-characterized with regard to allergen con- before and after biologics initiation. In the dupilumab group (n522), tent. Immunotherapy and diagnosis with existing products, while safe and median IgE decreased by 40% (from 157 kU/L, IQR:245.3 to 94 kU/L, effective, could be improved with better characterization and IQR:149.2, p50.001), after a mean treatment of 132 days698. Compared manufacturing consistency. The goal of this study is to apply analytical with baseline, median IgE levels decreased by 14% before 16 weeks (from methods, including quantitative mass spectrometry, for comparative and 105 kU/L, IQR:192.2 to 90 kU/L, IQR:156.3, p50.028), and by 59% after comprehensive characterization of Alternaria allergen extracts from 16 weeks (261 kU/L, IQR:221 to 108 kU/L, IQR:139, p50.005). In various source materials. contrast, in the omalizumab group (n539), median IgE increased by 22% METHODS: Spore and hyphae preparations of A. alternata and A. bras- (from 337 kU/L, IQR:629.5 to 411 kU/L IQR:1051, p50.035) after a mean sica were prepared in various growth media, and extracted under a variety treatment of 715 days6419. In patients receiving biologics which affect of conditions. Extracts were then subjected to SDS-PAGE (one- and two- eosinophils (Group 3) (n517), IgE levels remained stable. Overall, IgE did dimensional), and IgE-immunoblotting using human allergic sera. Using not decrease <11 kU/L. No patients became IgE deficient. these approaches, our laboratory has optimized extraction methods that CONCLUSION: In this real clinical setting, only few patients had IgE are amenable to downstream comparative proteomics, which includes levels checked before and after biologics initiation. While dupilumab commercial A. alternata extracts. decreased IgE levels significantly, no patients became IgE deficient. RESULTS: Extracts prepared from spores and hyphae had higher protein Longer, prospective studies are necessary to assess the long-term effect of abundance, greater complexity and more IgE-reactivity than commercial biologics on IgE levels and its clinical significance. extracts. CONCLUSION: The preliminary results from our optimization studies Purification and initial studies on vitellogenin, lay the groundwork to perform in-depth comparative proteomic analyses 451 an allergen in German cockroach using data independent acquisition liquid chromatography tandem mass spectrometry strategies. Our goal from these future studies will be to Joshua Somers1, Benjamin Rosen1, Coby Schal, PhD2, Taruna elucidate quantitative and qualitative differences between known and Khurana, PhD3, Samuel Mindaye, PhD4, Jay Slater, MD5; 1US Food candidate allergens from spore and hyphae proteomes. We will then apply and Drug Administration, 2North Carolina State University, 3CBER/ this information toward developing multiple reaction monitoring assays (a FDA, 4FDA, 5FDA/CBER/OVRR/DBPAP. mass spectrometry-based assay) for absolute quantification of allergen RATIONALE: German cockroach (Blattella germanica) is a source of content and standardization of Alternaria extracts. important urban indoor aeroallergens, associated with allergic rhinitis and asthma. Vitellogenin, a high molecular mass and abundant protein in B. germanica eggs and egg cases (oothecae), was purified and assessed for its allergenicity. METHODS: To identify vitellogenin, extracts made from whole body acetone-defatted German cockroach were purified by ammonium sulfate precipitation followed by size exclusion chromatography, and extracts from cockroach egg cases were purified by size exclusion chromatography alone. SDS-PAGE (one- and two-dimensional) and bottom-up liquid chromatography high-resolution mass spectrometry (LC-HRMS) analyses were performed to determine the presence of vitellogenin. IgE-ELISA and immunoblots, using sera from individuals with confirmed allergy to German cockroach, were used to assess allergenicity. RESULTS: Vitellogenin was successfully identified in German cockroach whole body samples by LC-HRMS and was reactive to cockroach-allergic patient sera in ELISA and immunoblot experiments. Fragments of vitellogenin were identified in many of the bands and spots present on the SDS-PAGE gels, in addition to the 100 kDa band where one fragment had been previously identified. We partially purified vitellogenin from both whole bodies and egg cases. About one-third of patient sera had IgE binding to vitellogenin from egg case samples. CONCLUSION: Vitellogenin is an abundant German cockroach protein that is a candidate allergen. Further work is needed to determine the percentage of IgE that specifically binds vitellogenin in cockroach-allergic AB142 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Genetic Deficiency of ß-Arrestin-1 Has No Effect LPS pretreated WT mice loss less weight than PBS pretreated WT mice 453 on Airway Hyperresponsiveness or Lung (LPS: lowest weight was 85.6761.66% of starting weight; PBS: Histopathology in a Mouse Model of Allergic 77.6861.97% mean6SEM, p50.0059, n>3/group). Occupational Asthma CONCLUSIONS: Protection from increased mortality to a SeV infection appears to depend in part upon an innate immune response to LPS. Further Richard Johnston1, Albert Pilkington, IV,1 Lori Battelli1, Michael Ka- studies will determine the cellular phenotypes and cytokine milieu shon1, Jeffrey Reynolds1; 1National Institute for Occupational Safety influenced by LPS in the WT and Rag1–/– mice. and Health. RATIONALE: b-arrestin-1 (b-AR-1) and b-AR-2 are ubiquitous cyto- Food antigen sensitization in genetically- solic proteins that desensitize G-protein coupled receptors. Allergen 455 susceptible mice is influenced by fecal IgA, (ovalbumin; OVA)-induced airway hyperresponsiveness (AHR) is non- antigen absorption, and gut microbiome existent and lung inflammation is reduced in b-AR-2-deficient mice. composition

Because b-AR-1 and b-AR-2 have overlapping functions, we hypothe- 1 2 3 sized that allergen-induced AHR and lung inflammation would be Johanna Smeekens, PhD , Brandi Johnson-Weaver , Andrew Hinton , M. Andrea Azcarate-Peril3, Timothy Moran, MD PhD4, Robert diminished in b-AR-1-deficient mice. 5 3 6 METHODS: Wild-type and b-AR-1-deficient mice were sensitized to Immormino, PhD , Janelle Kesselring , Erin Steinbach, MD PhD , Kelly Orgel3, Herman Staats7, A. Wesley Burks, MD FAAAAI3, Peter Mucha3, OVA and subsequently challenged with aerosols of either phosphate- 3 3 1 buffered saline (PBS) containing OVA or PBS alone. Afterward, responses Martin Ferris, PhD , Mike Kulis ; University of North Carolina at Chapel Hill, 2Duke University, 3University of North Carolina, 4University of to methacholine for respiratory system resistance (RRS) were measured us- North Carolina School of Medicine, 5UNC Chapel Hill, 6University of ing the forced oscillation technique while lung inflammation was semi- 7 quantitatively assessed in hematoxylin- and eosin-stained histological sec- North Carolina at Chapel H, Duke University Medical Center. tions obtained from formalin-fixed and paraffin-embedded lungs. RATIONALE: Despite the prevalence and severe nature of food allergy, RESULTS: In PBS-challenged animals, responses to methacholine for mechanisms underlying sensitization remain to be elucidated. Previously, we demonstrated CC027/GeniUnc mice, but not C3H/HeJ mice, develop RRS at 100 mg/ml were lower in b-AR-1-deficient as compared to wild- type mice. No genotype-related differences existed at any other dose of peanut allergy after oral exposure to peanut in the absence of a Th2- methacholine. OVA challenge significantly increased responses to metha- skewing adjuvant. Here we investigated factors contributing to sensitiza- choline in mice of both genotypes. Nevertheless, similar to PBS-chal- tion following oral exposure to peanut, walnut, milk, or egg. lenged mice, responses to methacholine were significantly lower in METHODS: Female CC027/GeniUnc and C3H/HeJ mice aged 4-6 weeks OVA-challenged b-AR-1-deficient as compared to wild-type mice only were sensitized weekly to peanut, walnut, milk, or egg via oral gavage for following administration of 100 mg/ml of methacholine. OVA challenge four weeks. The following week, mice were challenged to the correspond- caused significant peribronchiolar and lung perivascular inflammation in ing food vial oral gavage, and body temperatures were measured to monitor wild-type and b-AR-1-deficient mice. However, neither the degree of peri- anaphylaxis. Serum was collected to measure allergen-specific immuno- bronchiolar nor lung perivascular inflammation were different among the globulins, and fecal pellets were collected to quantify fecal IgA and genotypes. analyze the gut microbiome. € CONCLUSIONS: In contrast to b-AR-2, b-AR-1 has no effect on RESULTS: Naıve CC027/GeniUnc mice had markedly lower fecal IgA allergen-induced AHR or histopathological lung inflammation in mice. compared to C3H/HeJ, which was accompanied by stark differences in gut Thus, despite a number of overlapping functions, the contributions of b- microbiome composition. CC027/GeniUnc mice mounted antigen-specific AR-1 and b-AR-2 to the pathophysiology of allergic occupational asthma IgE responses to peanut, walnut and egg, but not milk, while C3H/HeJ mice must be independently considered. were not sensitized to any antigen. After oral challenge, peanut- and walnut-sensitized CC027/GeniUnc mice experienced anaphylaxis, Lipopolysaccharide (LPS) protects from severe whereas milk- and egg-sensitized mice did not. Major allergens were 454 respiratory paramyxoviral viral infection detected in serum collected post-challenge from peanut-sensitized mice, through an innate immune response but not milk- and egg-sensitized mice. Machine learning on the change in gut microbiome composition after sensitization identified a unique Jenny Resiliac1, Michelle Rohlfing2, Jennifer Santoro2, Syed-Rehan signature in CC027/GeniUnc mice that experienced anaphylaxis, Hussain, PhD2, Mitchell Grayson, MD1; 1Abigail Wexner Research Insti- including the depletion of Akkermansia. tute at Nationwide Children’s and The Ohio State University, 2Abigail CONCLUSIONS: Overall, these results demonstrate the factors contrib- Wexner Research Institute at Nationwide Children’s. uting to enteral sensitization in CC027/GeniUnc mice, including dimin- RATIONALE: Respiratory diseases are among the leading causes of ished fecal IgA, increased allergen absorption and altered gut microbiome death and disability in the world. Understanding the anti-viral immune composition. response is critical to relieve the morbidity and mortality burden of respiratory infections. Previous data using Sendai virus (SeV, murine parainfluenza virus type 1) suggested that pretreatment of C57BL6 wild- type (WT) mice with 0.1mg of lipopolysaccharide (LPS) prevented mortality from a normally lethal SeV infection. It is unknown if the protective effects of LPS are dependent on activation of innate immunity during the infection. While T cells are required to survive SeV infection, we hypothesized that Rag1–/– mice (lack an adaptive immune system) would survive longer when pretreated with LPS, if the survival effect required at least a component of the innate immune response. METHODS: WT and Rag1–/– mice were intranasally (i.n.) inoculated with 30 mL of 0.1 mg LPS or phosphate buffered saline (PBS) 24 hours before SeV (2x105pfu) i.n., and survival determined. RESULTS: Rag1–/– mice receiving LPS survived longer than those receiving PBS (p50004, Mantel-Cox); however, ultimately all Rag1-/- mice succumbed to the viral infection. All WT mice survived; however, J ALLERGY CLIN IMMUNOL Abstracts AB143 VOLUME 147, NUMBER 2

Human IgE Monoclonal Antibodies to Inhaled Staphylococcus aureus Carriage and 456 and Food Allergens: Unique Probes for Clinical 458 Differential Cell Counts in Nasal Lavages of Investigation. Ragweed-Induced Allergic Rhinitis Using Nasal Allergen Challenge Martin Chapman, PhD FAAAAI1, Crystal Richardson, PhD1, Bryan Smith2, Kristina Reid Black2, Jill Glesner1, Scott Smith, MD PhD3, Sophia Linton1, Rashi Ramchandani1, Alyssa Burrows2, Jenny Anna Pomes, PhD FAAAAI2; 1Indoor Biotechnologies, Inc., 2INDOOR Thiele, MSc1, Lisa Steacy, BSc, CCRP3, Prameet Sheth, PhD1, Anne Ellis, Biotechnologies, 3Vanderbilt University Medical Center. MD FRCPC FAAAAI1; 1Queen’s University, 2Kingston Allergy Research RATIONALE: Investigation of immediate hypersensitivity has been Unit, 3Kingston Health Sciences Centre - KGH Site. hampered by the limitations of using polyclonal IgE ab, present at low RATIONALE: The impact of Staphylococcus aureus nasal carriage on concentrations in allergic sera. Our goal was to isolate human monoclonal allergic rhinitis(AR) is essentially unknown. The current study sought to IgE antibodies (mAb) to specific allergens as they occur in vivo, to evaluate compare the differential cell counts in nasal lavage(NL) between (1) their allergen specificity, potency and binding activity. Ragweed(RW)-allergic and non-allergic participants and (2) S. aureus car- METHODS: Human IgE mAb (n520) were obtained by electrical riers and non-carriers using the nasal allergen challenge(NAC) model. cytofusion of cultured human B cells from peripheral blood of allergic METHODS: Nasal carriage was assessed using culture-based screening patients. IgE mAb were quantified by ImmunoCAP and analyzed by SDS- of nasal swabs in 20 RW-allergic and 11 non-allergic participants for S. PAGE. IgE mAb dose response curves to major inhalant and food allergens aureus. Subsequently, participants received cumulative intranasal doses (e.g. Der p 1, Fel d 1, Ara h 2, Gal d 2) were compared by ELISA. of RW until the participant achieved the qualifying criteria for a positive RESULTS: IgE mAb were produced in mg amounts (1mg IgE is NAC (Total Nasal Symptom Score(TNSS) >_8 and %Peak Nasal ;416,000 IU) and targeted major inhaled allergens (e.g. mite, dog, and Inspiratory Flow(PNIF) fall >_50%). 15 RW-allergic and 9 non-allergic par- cat) and foods (peanut, cashew, walnut, milk, and egg). IgE mAb directed ticipants qualified for the NAC. The NLs were collected at B, 6H and 24H against different epitopes were obtained (e.g. to Der p 2). ELISA dose post-NAC, differentially stained, and counted. All statistical analyses were response curves were sigmoidal with limits of detection of <1ng/ml, performed on GraphPad Prism 8.0. indicating the IgE mAb had high affinity. RESULTS: Nasal eosinophil counts were significantly elevated in RW- CONCLUSIONS: Natural human IgE mAb to a diverse panel of clinically allergics at 6H (p50.0465) and 24H (p50.0249) post-NAC compared to important allergens are unique probes for allergen identification, quanti- non-allergics. In RW-allergic participants, the proportion of eosinophils fication of IgE antibody responses, epitope analysis and mast cell and was significantly increased from baseline at 6H (p50.0001) and 24H basophil activation assays. Human IgE mAb used as calibrators will (p50.0061). However, no significant differences were observed between improve in vitro allergy molecular diagnostics and reduce dependence on and within RW-allergics compared to non-allergic participants for other allergic sera. They will also enable mechanistic studies of IgE mediated leukocytes at any time point. RW-allergic patients colonized with S. aureus allergic reactions. (n54), had significantly decreased nasal eosinophils compared to non-car- riers (n511) at 24H (p50.0385). Inflammatory response of ethanol and its CONCLUSIONS: NAC with RW induces local eosinophilia in allergic 457 metabolites in human primary bronchial individuals and to a lesser extent in S. aureus carriers. Differential counts in epithelial cells pre-stimulated with LPS nasal lavage suggest S. aureus carriage may impact the biological response to NAC, prompting future investigations with a larger sample size. Dustin Fowler, DO1, Lata Kaphalia, MS, MED, PhD2, William Calhoun, MD FAAAAI2; 1UTMB, 2University of Texas Medical Branch. Cytokines of Ejaculate from Men with Chronic RATIONALE: Previous in vitro studies have shown that ethanol metabo- 459 Prostatitis/chronic Pelvic Pain Syndromes lites directly causes toxicity to the respiratory tract including alveolar mac- Treated by Extracorporeal Shockwave Therapy rophages and primary airway smooth muscle cells. We hypothesize that oxidative and non-oxidative metabolites of ethanol would influence cyto- I. Gorpynchenko1, K. Nurimanov1, T. Poroshina1, V. Savchenko1,G. kine secretion and cellular metabolism to a greater degree than would Drannik1, Lawrence Dubuske, MD FAAAAI2; 1Institute of Urology of EtOH alone in human bronchial epithelial cells (hBEC). NAMS of Ukraine, Kyiv, Ukraine, 2George Washington University School METHODS: hBECs were pre-stimulated with LPS (10 mg/ml) and of Medicine, Washington, DC, USA, Immunology Research Institute of incubated with ethanol (1, 3, 6 mg/ml), or its major oxidative metabolite New England, Gardner, MA, USA. (acetaldehyde (ACE); 2.5, 5 mg/ml) or fatty acid ethyl esters (FAEEs) RATIONALE: Extracorporeal shockwave therapy (SWT) is non-phar- formed by nonoxidative metabolism [50, 100 mg/ml] over 24 hours. macological intervention for treating chronic prostatitis/chronic pelvic Inflammatory cytokines were measured in cells incubated with ethanol pain syndrome (CP/CPPS). Dynamics of cytokines were assessed during along with inhibitors of alcohol dehydrogenase (ADH) and cytochrome treatment. P450 (Cyp2E1) to determine the role of oxidative metabolism in ethanol- METHODS: The study included 30 patients aged 18-45 years with CP/ induced inflammatory response. The inflammatory response was assessed CPPS who received SWT to the prostate and the seminal vesicles. by Multiplex ELISA. Prostatitis symptoms were assessed by NIH-CPSI scale and cytokines of RESULTS: Increased ethanol concentrations led to suppression of pro- ejaculate assessed by ELISA before and after treatment. inflammatory cytokines and chemokines (IL-8, IL-6, GM-CSF, GCSF, RESULTS: After treatment 17 (57%) patients had significantly (p<0.05) VEGF, TNF, and IL-1ß) in hBECs. In comparison, ACE and FAEE decreased prostatitis symptoms. The content of pro-inflammatory cytokine incubation led to statistically significant (p < 0.05) increases in IL-8, IL-6, (IL-1) in the seminal significantly (p<0.05) increased only for patients with GM-CSF, GCSF, and VEGF. Cyp2E1 inhibition led to increased TNF and clinical improvement. There were no differences in the anti-inflammatory IL-1ß expression alone, while ADH inhibition sharply increased all cytokine IL-10. There was significant correlation between the symptoms of cytokine expression by several folds. prostatitis and the concentration of IL-1 in the seminal plasma seen only in CONCLUSIONS: Although ethanol reduced inflammatory response in patients with clinical improvement. pre-stimulated human primary bronchial epithelial cells, both metabolites CONCLUSIONS: Extracorporeal shockwave therapy provides signifi- were found to be proinflammatory. Therefore, a real time analysis of cantly decrease in prostatitis symptoms by inducing only minimal damage ethanol metabolites in cells treated with ethanol should explain the and inflammation of the prostate and seminal vesicles associated with differential inflammatory response of ethanol and its metabolites. increases in IL-1. AB144 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Production of Recombinant Cannabis Sativa MCP-1, MIP-1 alpha, and MIP-1 beta consistent with an impact of 460 Allergen, Can s 3, and Development of a Two- endurance training on chemokine production. site Immunoassay CONCLUSIONS: Chemokine production assessed by PBMC supernatant assays may be a useful tool for assessing immune changes developing Bryan Smith1, Kristina Reid Black1, Cathy Thorpe1, Sayeh Agah1, Ste- during endurance training of boxers. phanie Filep1, Sabina Wuenschmann, PhD1, Martin Chapman, PhD FAAAAI1; 1Indoor Biotechnologies. Dupilumab Improves Signs And Symptoms RATIONALE: As cultivation of Cannabis sativa and production of 461A Of Severe Atopic Dermatitis In Children related products increases throughout the world, exposure to Cannabis al- Aged 6–11 Years With And Without lergens is also likely to increase. Our goal was to produce recombinant Can Comorbid Allergic Rhinitis s 3 allergen (rCan s 3) and develop an immunoassay for Can s 3 Lisa Beck, MD FAAAAI1, Andreas Wollenberg, MD FAAAAI2, Amy quantification. 3 4 5 METHODS: Recombinant Can s 3 was expressed in E. coli and purified Paller, MD , Elaine Siegfried, MD , Zhen Chen, PhD , Alvina Abramova, PharmD, RPh5, Randy Prescilla, MD6; 1University of Roches- using multi-step HPLC chromatography. Protein concentration was deter- 2 mined by amino acid analysis (AAA) and purity assessed by SDS-PAGE ter Medical Center, Rochester, NY, USA, Ludwig-Maximillian Univer- sity, Munich, Germany, 3Northwestern University Feinberg School of and LC-MS/MS. Biological activity was confirmed by IgE binding 4 ELISA using serum samples from Cannabis sativa allergic patients. Medicine, Chicago, IL, USA, Saint Louis University and Cardinal Glen- non Children’s Hospital, St. Louis, MO, USA, 5Regeneron Pharmaceuti- Purified rCan s 3 was used to immunize rabbits for polyclonal antibody 6 production. Affinity purified polyclonal antibody was paired with biotin- cals, Inc., Tarrytown, NY, USA, Sanofi Genzyme, Cambridge, MA, USA. conjugated purified polyclonal antibody in a two-site ELISA using rCan RATIONALE: Atopic dermatitis (AD) is a chronic inflammatory skin s 3 as the assay standard. Immunoassay performance characteristics disease that frequently occurs with atopic comorbidities, including allergic were determined by method validation and testing a variety of Cannabis rhinitis (AR). Dupilumab inhibits signaling of interleukin (IL)-4 and IL-13 sativa extracts and commercial products. – key drivers of type 2-mediated inflammation in multiple diseases, RESULTS: Can s 3 had a relative abundance of >99% assessed by LC- including AD and AR. This subgroup analysis evaluated the efficacy of MS/MS. Sixty-six percent of Cannabis sativa allergic patient sera (21/32) dupilumab with concomitant topical corticosteroids (TCS) for severe AD tested positive for IgE using a chimeric IgE ELISA. The two-site Can s 3 in children with and without comorbid AR. ELISA was highly sensitive with a standard curve from 125-0.24ng/mL METHODS: In this double-blind, 16-week, phase 3 trial and a limit of quantification of 0.49ng/mL. (NCT03345914), 367 children aged 6–11 years were randomized 1:1:1 CONCLUSIONS: Highly purified rCan s 3 was used to develop a to 300mg dupilumab every 4 weeks (q4w), weight-based 100/200mg sensitive and specific ELISA for Can s 3 quantification. The assay has dupilumab every 2 weeks (q2w), or placebo, with concomitant medium- applications for measuring Can s 3 in diagnostic and therapeutic allergenic potency TCS. AR history was ascertained by caregiver report. products and for monitoring environmental and occupational exposure to RESULTS: At baseline, 75/75/77 patients in the q4w/q2w/placebo groups Cannabis. reported a history of AR; 47/47/46 patients had no AR history. Baseline disease severity was comparable in both subgroups. At Week 16, more Boxing Changes Chemokine Production by patients receiving dupilumab q4w/q2w vs placebo achieved Investigator’s 461 PBMC Global Assessment (IGA) score 0/1 (with AR:32.0%/30.7% vs 9.1%; without AR:34.0%/27.7% vs 15.2%), >_75% improvement in Eczema Area Roman Khanferyan1, N. Riger2, M. Korosteleva3, Lawrence Dubuske, and Severity Index (with AR:68.0%/69.3% vs 20.8%; without AR:72.3%/ MD FAAAAI4; 1Peoples’ Friendship University of Russia, Moscow, 63.8% vs 37.0%), and >_4-point reduction from baseline in Peak Pruritus Russia, 2Federal Scientific-research Center on Nutrition and Bio- Numerical Rating Scale (with AR:50.0%/56.2% vs 13.2%; without thechnology, Moscow, Russia, 3All-Russian Research Institute of Dairy AR:52.2%/61.7% vs 10.9%); P<0.05 for all comparisons except q2w vs Industry, Moscow, Russia, 4George Washington University School of placebo for IGA in patients without AR (not statistically significant). Medicine, Washington, DC, USA, Immunology Research Institute of Safety in the overall population was consistent with the known dupilumab New England, Gardner, MA, USA. safety profile in adults and adolescents. RATIONALE: Boxing is a sport requiring significant endurance training. CONCLUSIONS: Dupilumab with concomitant TCS improved signs and Such training may influence production of both cytokines and chemokines symptoms of severe AD in children aged 6–11 years with and without leading to persistent inflammation. This investigation uses peripheral comorbid AR. blood mononuclear cells (PBMC) to assess production of chemokines in boxers during training. METHODS: Professional boxers in intensive training period and healthy controls were assessed for chemokine production by PBMC after 72 hours culture by assaying the culture supernatants using "ProcartaPlexTMH. Cyto- / Chemokine/Growth Factor Panel 1"(eBioscience, Austria) and Luminex 200 equipment (Luminex Corporation, USA). RESULTS: Boxers were shown to have greater amounts of select chemokines in the PBMC supernatants including MIP-1 beta, GRO-alpha, RANTES, SDF-1-alpha and IL-8 (P<0.05). Healthy controls however had greater supernatants levels of MCP-1, Eotaxin, and MIP-1 alpha. PBMC of the control group stimulated by Con-A had supernatants with lower amounts of and SDF-1-alpha GRO-alpha, and IL-8, and increased MIP-1 beta whereas boxers showed decreases in RANTES but significant (p<0.05) increases in SDF-1alpha, Eotaxin, IL-8, GRO-alpha, IL-8 J ALLERGY CLIN IMMUNOL Abstracts AB145 VOLUME 147, NUMBER 2

Efficacy of Lanadelumab in Hereditary 2006-2017. This post hoc analysis evaluated perinatal outcomes of 30 462 Angioedema Patients With and Without Prior patients enrolled in EXPECT who received omalizumab for CSU during Use of Long-Term Prophylaxis: Final Results their pregnancy. From the HELP Open-Label Extension Study RESULTS: All patients were exposed to omalizumab in the first trimester of pregnancy, with a mean duration of 11.8 months before enrollment; Kim Paes, Clinical Scientist1, Jonathan Bernstein, MD FAAAAI2, Hilary 70.0% (21/30) received omalizumab 300mg, and 86.7% (26/30) received Longhurst, PhD MBBS MRCP FRCP3, Emel Aygoren-Pursun, MD4, monthly dosing. All pregnancies >20 weeks were live births. One Hong Ren, MS5, Timothy Craig, DO FAAAAI6; 1Takeda Pharmaceutical spontaneous abortion (<20 weeks) occurred, and premature birth (<37 Company Limited, Lexington, MA, USA, 2Department of Internal Medi- weeks) occurred in 13.3% (4/30) of pregnancies. Median (IQR) gestational cine, Division of Immunology, University of Cincinnati College of Med- age at delivery was 39.3 (39.0-40.3) weeks (mean 38.2 [SD 6]) for live icine, Bernstein Allergy Group and Bernstein Clinical Research Center, births. Small for gestational age was not observed; 1 preterm infant had low Cincinnati, OH, USA, 3Addenbrooke’s Hospital, Cambridge University birth weight. Two infants had major congenital anomalies: plagiocephaly Hospitals NHS Foundation Trust, Cambridge, and University College resolved after 3 months of orthotic helmet use; mild pyelocaliectasis was London Hospitals, London, UK, 4Department for Children and Adoles- resolved at 6-month follow-up. cents, Angioedema Centre, University Hospital Frankfurt, Goethe Univer- CONCLUSIONS: Overall, the results of the present analysis were sity, Frankfurt, Germany, 5Cytel Inc., Cambridge, MA, USA, 6Department comparable to studies of patients with asthma in EXPECT where no of Medicine, Pediatrics and Graduate Studies, Penn State University Her- increased risk was observed. Given the observational nature and low shey Medical Center, Hershey, PA, USA. patient number in EXPECT, absence of increased risk with omalizumab in RATIONALE: Efficacy of lanadelumab in preventing HAE attacks was patients with CSU cannot be definitively concluded. demonstrated in the phase 3 HELP Study (NCT02586805). Previous use of long-term prophylaxis (LTP) may indicate greater HAE disease severity. Skin Macrophages Drive Immune Dysregulation Herein, we report monthly HAE attack rates in patients treated with 464 in Atopic Dermatitis lanadelumab in the completed HELP open-label extension (OLE) study Sabina Islam1, Ellinor Tai, BS1, Julianna Tengku, B A2, Akiba Sato, MS1; (NCT02741596), based on prior LTP use. 1 2 METHODS: Patients >_12 years old with HAE-1/2 received lanadelumab Massachusetts General Hospital, Massachuestts General Hospital. 300 mg every 2 weeks (q2wks) for 132 weeks, including HELP rollover RATIONALE: The causes of immune dysregulation in atopic dermatitis patients (n5109), and newly-enrolled nonrollover patients (n5103) who (AD) remain poorly understood. Distinct clinical endotypes of AD are could continue receiving existing LTP for <_3 weeks. Monthly (attacks/ known, but an in vivo model of the Th2-dominant AD endotype is not well 4wks) HAE attack rates were compared with baseline (ie, the 4-week run- established. Macrophages have long been described in AD skin, and in period of the HELP Study for rollover patients or the monthly rate for the CCL18, a highly induced biomarker that correlates with disease activity, 12 weeks preceding OLE enrollment for nonrollover patients). is derived from IL-4-differentiated macrophages, M(IL-4)s. However, RESULTS: Overall, 106/212 patients (50.0%) received prior C1-INH– the role of macrophages in AD remains unknown. only LTP (53 rollovers, 53 nonrollovers), 20 (9.4%) received other LTP, METHODS: Itching is a cardinal feature of AD, and scratching results in and 86 (40.6%) had no prior LTP (47 rollovers, 39 nonrollovers). Patients epidermal wounding. We developed a model of AD in which engaging the with prior C1-INH–only LTP had mean(SD) attack rates/4wks of hair follicle stem cell regulated epidermal barrier repair response during 0.28(0.57) with lanadelumab versus 3.32(2.97) baseline (82% mean repeated epicutaneous allergen sensitization and epidermal wounding reduction from baseline). Patients without prior LTP use had mean(SD) results in sustained eosinophilic Th2-type inflammation that replicates attack rates/4wks of 0.21(0.57) with lanadelumab versus 2.89(2.39) features of the Th2-dominant human AD endotype. We used depletion baseline (93% mean reduction from baseline). Patients who switched studies, adoptive transfer, genetically modified mice, macrophage specific from other LTP also experienced attack rate reductions with lanadelumab. gene deletion, transcriptional analysis, histology and immune cell Attack rate reductions were similar between rollover and nonrollover phenotyping to define the importance of macrophages. patients in all subgroups. RESULTS: Induction of chronic eosinophilic inflammation coincides CONCLUSIONS: Long-term treatment with lanadelumab 300mg q2wks with the generation of unique pro-inflammatory skin M(IL-4)s which are significantly reduces monthly HAE attack rates compared with baseline in essential for inflammation, persist long-term in skin, and whose induction patients with and without prior LTP use. coincides with increased bone marrow stem and progenitor myelopoiesis. Macrophage-derived mouse CCL8 (mCCL8), the functional analog of Pregnancy and infant outcomes among pregnant CCL18, IL-4Ra on macrophages, and signaling through the CCL18/ 463 women with Chronic Spontaneous Urticaria mCCL8 receptor CCR8 are crucial for the generation of pro-inflammatory (CSU) treated with omalizumab: a descriptive macrophages and inflammation. analysis from the EXPECT pregnancy registry CONCLUSIONS: Cross talk between the epidermis and the immune system during repeated topical allergen sensitization and epidermal repair Jennifer Namazy, MD FAAAAI1, Angela Scheuerle, MD2,Vic facilitates the Th2-high endotype of AD in which skin pro-inflammatory Spain, PhD DVM3, Pranathi Janampally3, Ayesha Ahmed, PharmD3, Sa- M(IL-4)s drive local and systemic immune dysregulation. chin Gupta, MD3, Cecile Holweg3, Nayla Mumneh4, Cristine Radojicic, MD5; 1Scripps Clinic, 2University of Texas Southwestern Medical Center, 3Genentech, Inc., 4Novartis Pharmaceuticals Corp., 5Duke Asthma, Al- lergy, and Aiway Center. RATIONALE: Treatment options for pregnant women with CSU are limited in patients who do not respond to high-dose antihistamine treatment as immunosuppressants are contraindicated during pregnancy. Omalizumab received FDA approval for antihistamine-resistant CSU, providing an alternative. Understanding pregnancy outcomes in women receiving omalizumab is important to guide continued treatment during pregnancy. METHODS: EXPECT was a prospective observational registry evalu- ating pregnancy outcomes in women receiving omalizumab (n5309) from AB146 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Berotralstat Reduces Use of On-demand Penicillin was used in 43% of deliveries. Two patients subsequently had 465 Medication in Hereditary Angioedema (HAE) drug reactions. Patients Previously Treated with Prophylactic CONCLUSIONS: Penicillin allergy evaluation, including drug challenge, Therapies can be safely conducted in pregnant women. Similar to the general population, most pregnant women with penicillin allergy have negative Richard Gower, MD FAAAAI1, Paula Busse, MD FAAAAI2, Jessica testing, and can receive penicillin intrapartum. Best, DHSc, PA3, Sharon Murray, PhD3, Heather Iocca, PhD4, Tamar Kin- aciyan, MD5; 1Marycliff Clinical Research, 2Mount Sinai School of Med- Efficacy and Safety of Abrocitinib in Adolescent icine, 3BioCryst Pharmaceuticals, 4BioCryst Pharmaceuticals, Inc., 467 Patients With Moderate-to-Severe Atopic 5Medical University of Vienna, Dept. Of D. Dermatitis (AD): Results From the Phase 3 RATIONALE: The goal of HAE prophylaxis is to minimize the number of JADE TEEN study

HAE attacks and the associated disease burden, including treatment with 1 2 3 on-demand medications. Berotralstat is an oral once-daily selective plasma Lawrence Eichenfield , Carsten Flohr , Robert Sidbury , Zsuzsanna Sza- 4 5 6 7 kallikrein inhibitor that has been shown to reduce attack frequency in a lai , Ryszard Galus , Zhirong Yao , Hidetoshi Takahashi ,Sebastien Bar- barot8, Claire Feeney9, Fan Zhang10, Marco DiBonaventura10, Ricardo Phase 3 study (NCT03485911). This analysis evaluates reduction in on- 10 10 10 1 2 demand medication in patients with prior prophylaxis. Rojo , Hernan Valdez , Gary Chan ; UC San Diego, St John’s Insti- tute of Dermatology, Guy’s and St Thomas’ NHS Foundation Trust, METHODS: A double-blind, placebo-controlled study (APeX-2) ran- 3 4 5 5 King’s College London, Seattle Children’s Hospital, Heim Pal Chil- domized patients to berotralstat 110 mg (n 41):150 mg (n 40):placebo 5 6 5 dren’s Hospital, Medical University of Warsaw, Xinhua Hospital, (n 40) daily for 24 weeks in Part 1. For this post hoc analysis, patients 7 were grouped according to their prior prophylaxis: prior C1 esterase Shanghai Jiaotong University School of Medicine, Takagi Dermatolog- 8 ^ 9 10 inhibitor (C1-INH), prior androgen, or no prior prophylactic medication. ical Clinic, CHU Hotel-Dieu, Pfizer Ltd., Pfizer Inc. Prior C1-INH and prior androgen categories are not mutually exclusive. RATIONALE: Abrocitinib, an oral, once-daily Janus kinase 1 selective RESULTS: In patients with prior C1-INH prophylaxis (berotralstat 150 inhibitor, significantly improves the signs and symptoms of AD in mg n521; placebo n516), the rate of use of on-demand treatment was adolescent and adult patients with moderate-to-severe AD. We investigated significantly reduced vs placebo (-59.2%, p50.002). Similar reductions the efficacy and safety of abrocitinib versus placebo in adolescent patients were noted for patients with prior androgen use (berotralstat 150 mg n522; with AD in JADE TEEN (NCT03796676). placebo n525) (-51.8%; p50.004) and in patients without prior prophy- METHODS: Adolescent patients (aged 12-17 years) with moderate-to- laxis (berotralstat 150 mg n510; placebo n510) (-71.2%; p50.019). The severe AD were randomly assigned (1:1:1) to receive abrocitinib 200 mg, rate reduction corresponds to approximately 2.2 fewer doses of on-demand abrocitinib 100 mg, or placebo with standardized medicated topical medication per month compared to placebo in patients with prior C1-INH therapy for 12 weeks. Coprimary endpoints were Investigator’s Global _ use, 1.6 for those with prior androgen use, and 1.4 for those with no prior Assessment (IGA) response (clear [0] or almost clear [1] with >2-grade _ prophylaxis. improvement) and Eczema Area and Severity Index >75% improvement CONCLUSIONS: Prophylactic treatment with oral berotralstat 150 mg (EASI-75) at week 12. Multiplicity-controlled secondary endpoints _ resulted in significant reductions in on-demand medication compared to included Peak Pruritus Numerical Rating Scale (PP-NRS) response (>4- placebo irrespective of prior prophylactic treatment. point improvement) at week 12. Adverse events (AEs) were assessed. RESULTS: Overall, 285 patients were treated (mean age, 14.9 years; Safety and Outcomes for Penicillin Skin Testing 50.9% male; 56.1% white). At week 12, more patients treated with 466 in Pregnancy abrocitinib (200 mg, 100 mg) versus placebo achieved IGA (46.2%, 41.6% vs 24.5%; P<0.05 for both), EASI-75 (72.0%, 68.5% vs 41.5%; P<0.01 for Vima Patel1, Olajumoke Fadugba, MD1, Steven Ralston, MD, MPH1, Ka- both), and PP-NRS (55.4%, 52.6% vs 29.8%; P<0.01 for 200 mg vs pla- thryn Delaney, MD1, Scott Feldman, MD PhD1; 1University of cebo) responses. Larger mean percentage reductions in PP-NRS scores Pennsylvania. were observed with abrocitinib versus placebo within 2 days of treatment RATIONALE: Penicillin allergy in pregnant women is associated with initiation. Treatment-emergent AEs occurred in 62.8%, 56.8%, and 52.1% increased morbidity and use of less effective antibiotics to treat group B of patients in the 200-mg, 100-mg, and placebo groups, respectively, and streptococcus infections. Although the American College of Obstetrics and led to discontinuation in 2.1%, 1.1%, and 2.1% of patients. Gynecology recommends evaluation of women with penicillin allergy CONCLUSIONS: Abrocitinib combined with medicated topical therapy prior to delivery, testing in pregnancy remains infrequent. We studied the was efficacious and well tolerated in adolescent patients with moderate-to- largest known cohort to date of pregnant women who underwent penicillin severe AD. allergy evaluation to assess the effectiveness and safety of penicillin skin test and oral drug challenge in pregnancy. METHODS: A retrospective review was conducted of pregnant women with penicillin allergy referred by obstetrics/gynecology to the University of Pennsylvania allergy clinic. We evaluated the index drug reaction, penicillin skin prick and intradermal testing, oral challenge outcomes, and antibiotic use after testing. RESULTS: Eighty-three pregnant women were identified with average gestational age of twenty-six weeks. The culprit drugs included penicillin (33%), amoxicillin (40%), and unknown (36%). Index reaction occurred greater than five years ago in 91% of women. 95% of index reactions were cutaneous or unknown. Skin testing was negative in seventy-six (92%) patients, positive in one (1%) patient, and inadequate or equivocal in six (7%) patients. Eighty women underwent graded challenge to penicillin V or amoxicillin. Seventy-nine tolerated the challenge. One developed isolated itching. Thirty-five patients used intrapartum antibiotics. J ALLERGY CLIN IMMUNOL Abstracts AB147 VOLUME 147, NUMBER 2

Application of a Physiologically Based Further, these reductions have been maintained for at least 15 months in 468 Modeling to Increase the Knowledge on an ongoing monkey study. Epinephrine Absorption from A Novel Nasal CONCLUSIONS: A single administration of NTLA-2002 resulted in Spray (ARS-1) In Healthy Adults robust, durable reduction of kallikrein protein and activity, supporting further development as a potential one-time treatment option for patients Jeff Barrett1; 1Critical Path Institute. with HAE. RATIONALE: ARS-1 is an intranasal (IN) epinephrine spray for the treatment of severe allergic reactions. Advantages as compared with the Safety and Outcomes of 2-step Non-steroidal current standard intramuscular auto-injector include the availability of an 470 Anti-inflammatory Drug Provocation Tests in easy-to-use device, convenient, and a more reliable treatment. We the Outpatient Setting developed a physiologically based absorption model (PBAM) to better 1 1 1 understand the absorption of this novel IN formulation in healthy adults Lily Li, MD , Kathleen Buchheit, MD , Jillian Bensko, PA-C , Rebecca Saff, MD PhD FAAAAI2, Tanya Laidlaw, MD FAAAAI1; 1Brigham and (HA). 2 METHODS: Studies EPI-03 (N570 HA) and EPI-07 (N536 HA) were Women’s Hospital, Massachusetts General Hospital. used for model development and verification, respectively. The model was RATIONALE: Adverse drug reactions to non-steroidal anti-inflammatory developed using GastroPlus 9.7 and R 3.6.0 using information of the drug-, drugs (NSAIDs) are commonly reported, but evaluation of these reactions formulation- (particle size, injection volume and concentration), and by drug provocation tests (DPTs) is not standardized. We characterized the physiological properties. One compartment systemic PK parameters safety and outcomes of a 2-step protocol for NSAID DPTs in the outpatient (CL: 5.493L/h/kg, Vd: 0.59L/kg) were estimated from historical published setting. data and applied into the PBAM model. The model was informed and METHODS: Patients evaluated for reported NSAID allergy between 10/ refined based on the EPI-03 PK data. 2018-7/2020 at two academic medical centers in Boston, MA, were RESULTS: A model with two deposition compartments (deposition-ratio: included. Demographic, reaction history, and drug challenge data were 80%:20%) in the nasal cavity representing the anterior (pre-turbinates) and obtained from the medical record. middle (turbinates- absorption compartment) cavities appropriately RESULTS: A total of 67 subjects underwent 73 2-step DPTs with aspirin (41), ibuprofen (28), or naproxen (4). Subjects had a mean age of 51.1 (SD described the absorption of ARS-1. Cmax,Tmax and AUC(0->last) were adequately predicted (prediction error <17 %). 15.7) years, with 41 (61%) female and 60 (90%) white. 62/73 (85%) of CONCLUSIONS: A PBAM that accounted for formulation and physio- DPTs were negative. Eight DPTs (6 aspirin, 2 ibuprofen) were positive for logical dependencies was successfully developed for ARS-1. Epinephrine an immediate reaction; 5 patients were treated with oral antihistamines is deposited in the anterior and middle cavities (ratio 80:20%) and is alone (2) or in conjunction with leukotriene antagonists (2) or albuterol and absorbed mainly from the turbinates with a transit time accounting for the oral prednisone (1). Three DPTs (1 aspirin, 1 ibuprofen, 1 naproxen) movement from the first to the second compartment. The model is being induced delayed reactions with hives and/or angioedema and were further applied to investigate the absorption and guide the dose selection in managed with antihistamines. No patients required emergency care or adult and pediatric patients by incorporating differences in physiology in intramuscular epinephrine. Notably, 8/11 (73%) of patients with positive the populations. DPTs reported recent reactions within the past five years, compared to 22/ 56 (39%) patients with negative DPTs (p50.053). In all, 44/67 patients NTLA-2002: CRISPR/Cas9-mediated gene were de-labeled for NSAID allergy. 469 knockout of KLKB1 to treat hereditary CONCLUSIONS: 2-step oral NSAID DPTs are safe to perform in the angioedema outpatient setting, and 85% of challenges were negative for any reaction. There was a trend toward association of shorter time since last NSAID Jessica Seitzer1; 1Intellia Therapeutics. reaction with continued NSAID hypersensitivity. RATIONALE: Hereditary angioedema (HAE) is a rare genetic disorder characterized by recurrent episodes of debilitating and potentially fatal swelling in various parts of the body including face, hand and airways. Prophylactic treatment options for HAE patients have dramatically improved in recent years, significantly reducing the frequency of attacks and overall disease burden but all require chronic, potentially life-long administration. The emergence of genome editing technologies as a new therapeutic modality offers the promise of curing many genetic diseases. To this end, Intellia Therapeutics is developing NTLA-2002, an investi- gational CRISPR/Cas9-based therapy targeting KLKB1 for the treatment of HAE. METHODS: Guide RNA targeting human- and cynomolgus monkey- specific KLKB1 were identified and formulated using Intellia’s modular CRISPR/Cas9 lipid nanoparticle (LNP) platform technology. These formulations were evaluated in a humanized KLKB1 mouse model (huKLKB1) and the cynomolgus monkey. KLKB1 gene editing, plasma kallikrein concentration and activity, and vascular leakage were evaluated. RESULTS: In the huKLKB1 mouse, a single administration of NTLA- 2002 resulted in robust KLKB1 gene editing (;70%), subsequent reduc- tions in total plasma kallikrein (>90%) and abrogation of captopril- induced vascular leakage. In the monkey, a single administration of cyno-specific LNP formulation resulted in robust gene editing (;70%) and reductions in both total kallikrein protein and activity (>95%). AB148 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Association of step count with PROMIS health- analysis was performed by calculating the coefficient of variation (CV) in 471 related quality of life measures in children and duplicate and replicate samples. adolescents with persistent asthma RESULTS: QA/QC analysis of relative mtDNA content demonstrated a CV of 1% for replicate and 4% for duplicate samples. Relative mtDNA Allison Burbank, MD1, Michelle Hernandez, MD FAAAAI1, Nicole Lu- copy number averaged 0.69 at baseline and 0.67 six months later, with an cas2, Courtney Mann2, Li Lin2, Wanda Phipatanakul, MD MS FAAAAI3, absolute difference of 0.025 (Wilcoxon p50.019). Jessica Brown4, Misha Sims4, Sally Ivins, BA4, Antonia Bennett5, Ampar- CONCLUSIONS: In this pilot work, changes in mtDNA copy number ito Cunningham, MD MPH6, Michelle Maciag, MD3, Nicole Akar- over time supports the feasibility that variation may be impacted by Ghibril, MD3, Bryce Reeve7; 1University of North Carolina, Chapel environmental exposures and/or disease activity. Future analyses will Hill, 2Department of Population Health Sciences, Duke University School examine the relationship between environmental exposures with changes of Medicine, Durham, NC, 3Boston Children’s Hospital, 4University of in mitochondrial biomarkers and changes in mitochondrial biomarkers North Carolina at Chapel Hill, 5Department of Health Policy and Manage- with asthma symptoms, to assess whether mitochondrial biomarkers may ment, University of North Carolina at Chapel Hill, 6Harvard University, reflect response to environmental exposures. 7Department of Pediatrics, Duke University School of Medicine, Durham, NC. Gene-expression Patterns of Inflammation in RATIONALE: Patient-reported outcomes (PROs) better capture the 473 Asthma Associated with Brain Activation impact of disease on quality of life, allowing providers and researchers Melissa Rosenkranz1, Kimberly Dill-McFarland, PhD2, Stephane Es- to more fully gauge response to treatment, but are subjective and are 3 3 3 impacted by language barriers, cognition, and literacy level. Integrating nault , Nizar Jarjour, MD , William Busse, MD FAAAAI , Matthew Alt- man, MD2; 1University of Wisconsin-Madison, 2University of PRO measures with objective data, such as pedometry, can guide under- 3 standing of how disease and interventions impact patient health outcomes. Washington, University of Wisconsin School of Medicine. METHODS: Children ages 8-17 with partly or uncontrolled asthma wore RATIONALE: Asthma influences brain health both functionally (emo- pedometers to track step counts for 4 weeks. Each week, volunteers tions) and structurally (neurodegeneration). Although airway inflamma- completed PROMIS Pediatric measures addressing health-related quality tion is proposed to initiate afferent communications with the brain, the of life domains: Asthma Impact, Depressive Symptoms, Anxiety, Peer associated patterns of airway inflammation and gene-expression profiles Relationships, and Mobility. Bivariate analyses and linear mixed regres- are not established. sion modeling were performed to examine the association between average METHODS: Segmental allergen bronchial provocation (SABP) was used daily step count and PROs. to provoke airway inflammation and retrieve airway cells to characterize RESULTS: 105 children were enrolled from 2 sites. Younger children cellular responses by RNA-sequencing to determine gene-expression (ages 8-11) took more average daily steps than older children (ages 12-17). profiles. Differential gene-expression was assessed by cell deconvolution During weeks 1-2, lower daily step count was associated with higher self- modular analysis coupled with linear modeling. Functional magnetic reported asthma impact (wk 1: r5 -0.30, p50.01; wk 2: r5-0.28, p50.01) resonance imaging (fMRI) assessed brain function; data were acquired at and lower self-reported mobility (wk 1: r50.30, p50.01; wk 2: r50.35, baseline and 48h following SABP. Activation in brain regions of interest p50.002), with no significant relationships to other PROs studied. This (amygdala, insula and anterior cingulate cortex) was correlated with association remained significant after controlling for asthma severity and inflammatory patterns of airway cell gene-expression. other demographic factors. Average daily step count dropped significantly RESULTS: Allergen challenge increased BAL eosinophils and multiple during weeks 3-4, along with reduced adherence to wearing the pedometer. molecularly distinct eosinophil gene-expression modules. An eosinophil- CONCLUSIONS: Wearable technology to track activity shows promise associated module containing 416 genes was enriched for genes upregu- to complement but not replace PROs in asthma care, though strategies that lated in corticosteroid-resistant type 2 myeloid cell populations in the lung promote consistent use of these devices are crucial. (FDR<0.001). This module showed a variable magnitude of change with allergen challenge (average FC51.63; FDR<0.001) and was significantly Childhood Asthma and Mitochondrial positively associated with the magnitudes of change in activation in brain 472 Biomarkers for Exposure-Related Outcomes regions of interest. Interestingly, genes functionally central in this module (CAMERO) study: Time-related Changes in include multiple pathways with overlapping roles in neuronal (e.g. Mitochondrial DNA Copy Number NOTCH1, SYN1, NTRK1), vascular, and lung (e.g. VEGFA, LIF, SFTPD) development. Jessica Oh, MD1, Janelle Rivera1, Jacqueline Jezioro, MS1, Lydia Lich- CONCLUSIONS: Allergen provoked airways in asthma caused striking tiger1, Kyung Jung2, Matthew Perzanowski, PhD2, Elizabeth increases in eosinophils and patterns of type 2 cytokines, along with a Matsui, MD MHS FAAAAI3, Rachel Miller, MD FAAAAI1; 1Icahn gene-expression profile that significantly associated with brain activation. School of Medicine at Mount Sinai, 2Columbia University, 3Dell Medical Collectively, we conclude that these markers of inflammation are School at the University of. mechanistic factors involved in lung-brain emotion-related afferent RATIONAL: Air pollution and allergen exposure leads to reactive oxygen communication. species production, causing DNA damage and mitochondrial metabolic activity changes. The Childhood Asthma and Mitochondrial Biomarkers for Exposure Related Outcomes (CAMERO) study hypothesizes that mitochondrial DNA (mtDNA) copy number and methylation patterns change in response to environmental exposures. We hypothesize that changes in biomarkers are associated with disease activity among asthmatic children. METHODS: Buccal epithelial samples were obtained from two separate but comparable pediatric urban cohorts (n523) at two time points six months apart. mtDNA amplification was performed and relative mtDNA content was assessed by qPCR as a ratio of mitochondrial cytochrome c oxidase I (CO1) gene copy number to single gene copy 36B4. QA/QC J ALLERGY CLIN IMMUNOL Abstracts AB149 VOLUME 147, NUMBER 2

Asthma Exacerbations and Intimate Partner Comorbid Asthma Within a Prospective 474 Violence 476 Household Study of Respiratory Viral Infections

Eileen Wang, MD1, Bryan Simmons1, Kristen Holm1, Frederick Wam- Alastair Murray1, Janet Englund, MD1, Naomi Wilcox, MPH2, Jessica boldt1; 1National Jewish Health. Heimonen, MPH2, Anne Emanuels, MPH2, Helen Chu, MD, MPH2; 1Uni- RATIONALE: The etiologies for difficult-to-control asthma are complex versity of Washington, Seattle Children’s Hospital, 2University of and incompletely understood. Intimate partner violence (IPV) is a Washington. pervasive issue and may be an important determinant of difficult-to- RATIONALE: Viral upper respiratory infection is a common trigger of control asthma. IPV is associated with increased prevalence of asthma. asthma exacerbations. We hypothesized that households with asthmatic There are no studies evaluating IPV’s impact on adult asthma control and members would have an overall higher burden of viral respiratory disease morbidity. This study hypothesized that IPV exposure is associated with with longer duration of illness, more severe symptoms and greater asthma exacerbations among adults. transmission between household members in comparison to households METHODS: Analyses are based on 1934 adults who participated in the 2005 without asthmatic members. Behavioral Risk Factor Surveillance System survey, reported active asthma, METHODS: 1171 subjects (119 with asthma) were enrolled by household and completed the IPV questions. We used multivariate logistic regression to (n5303) in a prospective longitudinal study of respiratory viral infections examine the association of IPV with asthma exacerbations within the last year in Seattle, WA, USA from November 2019 through April 2020. Subjects while controlling for the following potential confounders: sex, race, education, self-reported sociodemographic data, symptoms, severity, and underlying smoking status, age, and self-assessment of health status. comorbidities. At the onset of respiratory symptoms, individuals self- RESULTS: The overall prevalence of IPV among asthmatics was 37.4%. collected a mid-nasal swab and completed a symptom log. Swabs 42.3% of women reported a history of IPVas compared to 22.6% of men. All underwent RT-PCR testing for eight common respiratory viruses including of the potential confounders had a statistically significant association with RSV, rhinovirus, influenza and SARS-CoV-2. IPV (i.e., all p-values were below .05). IPV was associated with increased RESULTS: 592 respiratory illness episodes (77 complicated by asthma) odds of an asthma exacerbation in the last year (OR 5 1.66, 95% CI: 1.35 – were reported with 40 secondary detections of virus in 33 of 207 households 2.04, p < .0001) while controlling for these potential confounders. with illness. No significant difference was observed in secondary viral CONCLUSIONS: IPV is a prevalent and under-recognized determinant detection within household by asthma status, adjusted by household size (t- of exacerbations among adults with asthma, even after adjusting for key test). Individuals with asthma were more likely to report shortness of breath confounders. Further research is needed to more fully understand the (p50.001), without significantly increased overall illness duration or self- effects of IPV on asthma. reported severity. Individuals with asthma had a lower rate of viral detection for symptomatic illness (34% versus 50%, p50.01, x2 test). Five-month Outcomes for Asthmatics with CONCLUSIONS: No significant difference in viral spread or duration of 475 COVID-19 and Associations with Atopy and illness within households by asthma status was noted. Household members Inhaled Corticosteroids Use with asthma were more likely to have a symptomatic illness without an isolated viral pathogen, suggesting a different cause of acute illnesses. Katharine Foster1, Donyea Moore, BSc2, Emilio Jauregui, MD3, Aame Andy-Nweye1, Mahboobeh Mahdavinia, MD PhD FAAAAI1; 1Rush Uni- Nociceptor Neurons Control Pollution- versity Medical Center, 2Rush University Medical Center, Chicago, IL, 477 exacerbated Asthma 3Los Angeles County+University of Southern California Medical Center. RATIONALE: COVID-19 viral infection has been associated with Jo-Chiao Wang1, Theo Crosson1, Tuany Eichwald2, Katiane Roversi1, respiratory tract inflammation. Asthma exacerbations are frequently Maryam Ahmadi1, Mohammad Balood1, Sebastien Talbot, PhD3; 1Uni- triggered by viral respiratory infections, which subsequently cause poor versite de Montreal, 2Universidade Federal de Santa Catarina, 3University asthma control. However, the effect of COVID-19 on asthma exacerbations of Montreal. and outcomes beyond the initial COVID-19 infection is not well studied. RATIONALE: Half of the severe asthma patients suffer from uncontrolled METHODS: Adult COVID-19-positive patients with history of asthma exacerbations. Our work in neuro-immunology has shown that, in the evaluated at a university medical center between February and April,2020 context of asthma, vagal nociceptor neurons drive a feed-forward inflam- were entered in the study at the time of COVID-19 infection and followed matory loop with lung immune cells, and that silencing these neurons for 4-6 months. reverses allergic airway inflammation (AAI). Here, we aim to expand these RESULTS: Seventy-six patients with asthma were followed for a 151- findings to a clinically relevant model of pollution exacerbated asthma. day-average after COVID-19 infection. At COVID-19 infection onset, METHODS: Experimental allergen Ovalbumin (OVA) was co-exposed 55.2% of subjects presented with symptoms suggestive of an asthma with fine particulate matter (FPM) to OVA-sensitized wild type or sensory exacerbation. These patients experienced an average of 2.6-weeks of neuron-ablated TRPV1-DTA mice. Cells in bronchoalveolar lavage fluid uncontrolled asthma and sought medical care for asthma symptoms at 1.9 (BALF) and lung were immunophenotyped by flow cytometry. Gene mean provider visits. 9.2% of patients required step-up therapy; 23.6% expression in isolated alveolar macrophages and whole lung tissue was received oral steroids post-COVID-19 infection. Stratified by asthma assessed by RT-qPCR. severity, 66.6% of subjects with intermittent, 50.0% with mild persistent RESULTS: We found that mice co-exposed to FPM and OVA show an and 68.4% with moderate/severe persistent asthma experienced exacer- aberrant bronchoalveolar lavage fluid immune profile characterized by a bations(p50.78). The asthma exacerbation rate in patients who took mixed infiltration of neutrophil and eosinophil as well as the expansion of inhaled corticosteroids (ICS+LABA) (n525, 53.3%) or ICS alone(n513, lung gd T cells. Along with these changes, we found that the neurotrophic 55.2%) did not differ from those who were not taking ICS (n538, 52.6%), factor artemin was increased in whole lung tissue as well as by FPM- (p50.82). 42.3% of asthma patients with a history of allergic rhinitis versus stimulated alveolar macrophage. In addition, to these changes, we 64.5% of nonallergic patients experienced an exacerbation(p50.086). discovered that the genetic ablation of sensory neurons prevents the CONCLUSIONS: Our data showed no effect of asthma severity nor development of the pollution exacerbation of asthma. ICS+/-LABA therapy on the rate of asthma exacerbations after COVID-19 CONCLUSIONS: In terms of inflammatory cell infiltration in BALF and infection in five-month follow up. Atopic patients had a trend towards lung gd T cell expansion, co-exposure of FPM exacerbates OVA-induced protection against COVID-19-associated asthma exacerbations, which AAI in a TRPV1+ sensory neuron-dependent fashion. In parallel, artemin is needs confirmation in larger studies. induced by the exposure of FPM, which implies an artemin-related neuro- immune network in such pollution exacerbation of AAI. AB150 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

QCT-based Measures Of Airway Narrowing And (p5.001) during the early COVID19 pandemic, despite no significant 478 Shape Changes Associated With Endobronchial change in weather from the two previous years. Biopsy Tissue Measures of Airway Remodeling CONCLUSION: The drop in pediatric asthma ER visits during COVID19 And Clinical Outcomes In Asthma school closure is consistent with previous observations that school attendence correlates with a spike in children’s asthma. This observation Jiwoong Choi1, Jonathan Boomer2, In Kyu Lee3, Fred Shi4, Stephanie strongly emphasizes the need for more data as school reopens in order to Christenson5, Jenna Nguyen6, Leonard Bacharier, MD FAAAAI7, Prescott verify increased asthma with school attendance and to elucidate specific Woodruff, MD, MPH6, Michael Peters, MD6, Sanghun Choi8, Ching- triggers. Long Lin9, Mario Castro, MD MPH2; 1University of Kansas School of Medicine, Kansas City, KS, University of Kansas, Lawrence, KS, 2Univer- Quantitative Measurement of IgG to SARS-CoV-2 sity of Kansas School of Medicine, Kansas City, KS, Washington Univer- 480 Proteins Using the Phadia ImmunoCAP 250 3 sity School of Medicine, St. Louis, MO, University of Kansas, Lawrence, 1 2 4 Behnam Keshavarz, PhD , Joseph Wiencek, PhD , Lindsay KS, University of Kansas School of Medicine, Kansas City, KS, Univer- 1 3 1 5 Bazydlo, PhD , Matthew Straesser, MD , Lisa Workman, BA , Thomas sity of Kansas School of Medicine, Kansas City, KS, University of Cal- 1 1 1 6 Platts-Mills, MD PhD FAAAAI , Jeffrey Wilson, MD PhD ; University ifornia School of Medicine, San Francisco, CA, University of California, 2 3 San Francisco, CA, 7Washington University School of Medicine, St. of Virginia, Vanderbilt University, Central Pennsylvania Asthma and Louis, MO, 8KyungPook National University, Daegu, Korea, 9University Allergy. of Iowa, Iowa City, IA. RATIONALE: Measurement of IgG to SARS-CoV-2, the cause of RATIONALE: We hypothesized quantitative CT (QCT) features corre- coronavirus disease 2019 (COVID-19), has an important role to play in lates to airway remodeling and clinical outcomes of patients with asthma. understanding the epidemiology and immune response to the novel METHODS: Asthmatic patients (N520) from Severe Asthma Research coronavirus. To date, most commercial antibody assays have not had a Program (SARP) III underwent bronchoscopy and CT at baseline. QCT quantitative read-out. Measures (N557), endobronchial biopsy tissue measures: Epithelial Area, METHODS: SARS-CoV-2 spike-receptor-binding-domain (RBD) and mucin (Muc5AC), Cilia (Foxj1) and Proliferation (Ki67); brush RNA-seq nucleocapsid proteins were biotinylated and used on the solid-phase of the data of mucin (Muc5B, Muc5AC) and cilia-related genes (SPAG6, TEK2 ImmunoCAP using the biotin-streptavidin technique. The assay was and RFX3) and clinical outcomes. Statistical significance was determined developed using plasma from 15 patients hospitalized with COVID-19 by p<0.05 for Spearman correlation and denoted by **. and serum from 86 subjects recruited prior to the emergence of SARS- CoV-2. Assay quantitation was validated using a commercially available RESULTS: Normalized hydraulic diameters (Dh*) at the right main bron- chus (RMB), the left lower lobe bronchus (LLB), and the right upper lobe monoclonal anti-SARS-CoV-2 Spike-RBD antibody (CR3022). Specific segmental branches (sRUL) were associated with SPAG6 (r50.46**, IgG was subsequently measured in 17 patients hospitalized with COVID- 0.49**, 0.58**), RFX3 (r50.34, 0.24, 0.64**), and FOXJ1 (r50.23, 19 in which serum was available at day 0 and 7 post-admission. 6 0.39, 0.12). Superior-inferior to anterior-posterior size ratios (SI/AP) RESULTS: The cut-off limit for the assays (mean 2SD) was determined inversely correlated to Muc5B and TEKT2 at expiration (r5-0.55**, using pre-COVID-19 samples as 4.9 mg/mL for spike-RBD and 4.6 mg/mL -0.74**). End-tracheal angle inversely correlated to Epithelial Area (r5- for nucleocapsid. Based on these cut-offs, the assay performance 0.71**) and Ki67 (r5-0.5**). Percent predicted pre-bronchodilator characteristics were: 100% sensitivity and 97.7% specificity for spike- RBD and 100% sensitivity and 97.6% specificity for nucleocapsid. FEV1 correlated with Dh* at RMB and LLB (r50.50**, 0.45**) and inversely with tissue Muc5AC (r5-0.51**). Exacerbations in the past 12 Experiments using known concentrations of CR3022 correlated strongly 25 months correlated positively to expiratory SI/AP (0.50**) and inversely with the assay results (R 0.998). Among the 17 patients there was a wide to Muc5B and RFX3 (r5-0.49**, -0.57**). ACQ was associated inversely variation in the magnitude of IgG responses. At day 7 of admission median with end-tracheal angle (r5-0.45**), yet positively with Epithelial Area values were 86.4 mg/mL [range 3.2-158.0] and 38.6 mg/mL [range 0.6- (r50.87**) and TEKT2 (r5-0.66**). FEV1/FVC inversely correlated to 191.0] for spike-RBD and nucleocapsid, respectively. SI/AP at inspiration and expiration (r5-0.45**, -0.36) and MUC5AC tis- CONCLUSIONS: We have described a quantitative assay to measure IgG sue and gene expression (r5-0.47**, -0.38). to SARS-CoV-2. The assay has a read-out in standardized units (mg/mL) CONCLUSIONS: Airway narrowing and lung shape change measures by and could be adopted for use in clinical laboratories. QCT correlated to tissue measurements for airway remodeling and clinical variables including lung function, asthma control, and exacerbations.

Pediatric Emergency Visits for Asthma Drop 479 Significantly with COVID19 School Closure

Elizabeth Secord1, Pavadee Poowuttikul, MD FAAAAI2, Milind Pan- sare2, Divya Seth2, Shweta Saini, MD3; 1Wayne State University, 2Central Michigan University, 3Children’s Hospital of Michigan. RATIONALE: Asthma exacerbations in children leading to emergency room (ER) visits are often cited as increasing in the autumn and may be associated with weather change or pollen. Some studies reference school stress or school opening as a factor in this autumn peak of asthma ER visits. We are reporting a significant decrease in ER visits for asthma in a hospital in Detroit, Michigan correlating with the Corona virus disease 2019 (COVID19) school closure from March 15th to May 31st 2020. METHODS: Total ER visits for pediatric astha were collected by ICD9 code from March 15th 2020 to May 31st 2020 and from the same time period in 2019 from a children’s hospital in Detroit, MI. Weather data was compared for both years on an online website (Weather Underground). RESULTS: Asthma ED visits for children significantly decreased:1304 vs 260 or an average of 17+5.0 to 3.5+4.2 daily in the 2.5-month period J ALLERGY CLIN IMMUNOL Abstracts AB151 VOLUME 147, NUMBER 2

Enhanced BAFF expression is negatively patients. SIgAD patients lack IgA bound microbes and have higher 481 correlated with a suppressed isotype-switched frequency of IgG bound microbes. memory B cell pool in CVID patients with CONCLUSIONS: SIgAD has significant impacts on immune phenotype complications (B cell differentiation, inflammatory cytokine profile and T cell activation) and the access of commensal gut microbes to the systemic immune Charlotte Cunningham-Rundles, MD PhD FAAAAI1, Lin compartment. We are currently linking these alterations to the diverse Radigan, MD2, Haoli Jin, MD PhD3; 1Mt. Sinai Medical Center, 2Icahn phenotypes of IgA deficiency in humans and mice. School of Medicine at Mount Sinai, 3Mount Sinai Health Network. RATIONALE: Common variable immunodeficiency (CVID) is a primary Alterations in STAT Signaling Dysregulate CD8 T immunodeficiency due to selected genetic defects. This syndrome is 483 Cell Activation frequently associated with non-infectious complications such as interstitial 1 2 3 lung disease, enteropathy, autoimmunity and malignancies, with lack of Jose Campos , Peyton Conrey , Samir Sayed , Tiphanie Vogel, MD/ PhD4, Jennifer Leiding, MD FAAAAI5, Lisa Forbes Satter, MD isotype-switched B cells. B cell–activating factor (BAFF) is one of the TNF 6 7 7 1 family members important for IgA class switching and plasma cell FAAAAI , Steven Holland, MD , Alexandra Freeman, MD ; University of Pennsylvania, 2Children, 3The Children, 4Texas Children’s Hospital, survival. Excessive levels of BAFF are found in CVID patients. In this 5 6 7 study, we investigated the correlation of BAFF levels with isotype- University of South Florida, Texas Children, NIH. switched memory B cells. RATIONALE: Dysregulated cytokine signaling due to alterations in METHODS: Serum BAFF levels in 70 CVID patients and 15 healthy STAT1 and STAT3 signaling may be perceived by T cells as amplified or controls were measured by ELISA. The percentages of isotype switched- skewed inflammation, impairing tolerance to self and our protective memory B cells were measured by flow cytometry. The correlation responses to pathogens and malignancy. STAT1 and STAT3 GOF between BAFF and isotype-switched memory B cells in CVID patients mutations impersonate unchecked Type I and II Interferon signaling and with and without complications were analyzed by Pearson’s correlation. chronic IL-6 signaling, respectively, yielding immune dysregulation RESULTS: The serum BAFF levels in all CVID patients were signifi- whereas LOF mutations yield pathogen susceptibility. Here, we focus on cantly higher than healthy controls (p<0.0001), whereas BAFF levels are quantifying the immunometabolic mechanisms underlying T cell dysre- higher in the group with non-infectious complications than the group gulation as a result of altered STAT signaling. without complications (p <0.005). In contrast, isotype-switched memory B METHODS: Patient and age-matched healthy control PBMCs were cells were significantly lower in CVID patients than healthy controls (p profiled via 43-parameter mass cytometry (CyTOF). Intracellular cytokine <0.001). Furthermore, BAFF levels in all CVID patients and the group expression was measured by flow cytometry following PMA/Ionomycin stimulation. Cell energy metabolic flux was assessed by Seahorse. with complications were negatively correlated to isotype-switched mem- + 5 Analysis of altered transcriptional networks in non-na€ıve CD4 and ory B cells (p 0.012). + CONCLUSION: Our data suggests that excessive BAFF expression in CD8 T cells is ongoing. CVID patients with non-infectious complications may cause suppression RESULTS: Immune profiling of a cohort of STAT1 and STAT3 GOF and of memory B cell switching. Alternatively exhaustive switching memory B LOF patients demonstrates imbalances in the CD4 T helper cell subsets and cell pools in CVID patient may drive upregulation of BAFF, promoting the exhaustion-like dysregulation of activation markers (e.g. Ki67 and non-infectious complications. Future study to reveal the underlying Granzyme B) and inhibitory receptors (e.g. CD39, PD-1, CTLA-4, mechanism is needed. TIGIT) in non-naive CD8 T cells. In addition, both CD4 and CD8 non- naive T cells had altered cytokine production (e.g. IL-2, IFN-gamma). Selective IgA deficiency alters systemic CONCLUSIONS: Immunometabolic dysregulation as a result of altered 482 immune response to commensal gut microbiome STAT signaling affects both T cell phenotype and function, yielding potential novel therapeutic targets for our rare patients as well as deeper Peyton Conrey1, Lidiya Denu2, Kaitlin O3, Jean-Bernard Lubin, PhD4, understanding of these fundamental cytokine signaling pathways. We will Tereza Duranova5, Laura Vella, MD/PhD2, E. John Wherry, PhD3, Jona- pursue these hypotheses in mouse models and in vitro human cellular than Spergel, MD, PhD6, Michael Silverman, MD/PhD2; 1Children, 2Chil- studies. dren’s Hospital of Philadelphia, 3University of Pennsylvania, 4Childrens Hospital of Philadelphia, 5CHOP, 6Children Hospital of Philadelphia. RATIONALE: Immunoglobulin A (IgA) is a fundamental component of mucosal immunity, but only ;1/3 of patients with selective IgA deficiency (SIgAD) are symptomatic with increased rates of allergy, infection and/or autoimmunity. We cannot yet explain or predict the variability in the clinical phenotype so we sought to investigate whether IgA impacts access of gut microbes to the systemic immune compartment and immune function. METHODS: We recruited a cohort of pediatric SIgAD patients, with unaffected sibling controls and collected blood and stool. We performed immune profiling (flow cytometry and CyTOF) and microbial flow cytometry (mFlow) and metagenomic sequencing. In mFlow, patient’s serum is added to their stool microbes and Ig binding to these microbes is measured by flow cytometry (to measure anti-commensal responses). Stool microbes can then be sorted based on whether bound IgA, IgM and/or IgG and sequenced (in addition to bulk stool metagenomic sequencing). RESULTS: Patients who were deficient in both serum and stool IgA had fewer IgA+ memory B cells and IgG+ B cells. Serum cytokine analysis demonstrated a broad increase in inflammatory cytokines in SIgAD AB152 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

SARS-CoV-2 full length spike protein for COVID- managed at home without requiring supplemental oxygen, hospitalization 484 19 vaccine development and diagnostic testing or residual complications. CONCLUSIONS: Despite concern for worse outcomes for patients with Crystal Richardson, PhD1, Mayuresh Abhyankar2, Jillian Bracaglia1, immunodeficiency including HyperIgE syndromes, our patients exhibited Sayeh Agah1, Zachary Schuhmacher, BS1, Bryan Smith1, Sabina favorable outcomes with relatively mild COVID-19 clinical course. This Wuenschmann, PhD1, William Petri, Jr, MD, PhD2, Martin may underscore the absence of excessive immune response to SARS-CoV2 Chapman, PhD FAAAAI1, Anna Pomes, PhD FAAAAI1; 1Indoor Biotech- in this patient population; however, number of patients was limited, and nologies, Inc., 2University of Virginia. more research is required to understand significance of these underlying RATIONALE: As of August 2020, the Centers for Disease Control and diseases. Prevention have reported >5.6 million cases and >175,000 deaths due to COVID-19 in the US. Our goal was to produce high quality SARS-CoV-2 Immunodeficiency during COVID-19 pandemic: proteins for vaccine development and diagnostic testing. 486 analysis of a 243 patients' cohort followed at a METHODS: Recombinant full-length spike protein was genetically Brazilian tertiary hospital engineered to have enhanced stability, expressed in CHO cells, and Laıs Cunha1, Priscila Franco, MD1, Bruna Gehlen, MD1, Mariana purified by affinity chromatography. Expression was validated by western 1 1 2 1 blot. An ELISA was performed to evaluate binding of a commercially Fernandes, MD , Alex Prado, MD , Grazielly Pereira , Pereira GF , Ana Karolina Marinho, DO1, Otavio Grecco1, Myrthes Barros, MD, available anti-spike antibody to the recombinant spike protein. Purity was 1 1 1 1 assessed by silver-stained SDS-PAGE and by relative peptide abundance PhD , Jorge Kalil, MD, PhD , Cristina Kokron, MD, PhD ; University ~ 2 ~ using LC-MS/MS. COVID-19 positive patients’ sera were tested for IgG of Sao Paulo, Hospital das Clı´nicas, FMUSP, Sao Paulo, Brazil. reactivity to the spike protein. Mice were immunized with SARS-CoV-2 RATIONALE: COVID-19 pandemic raised doubts about susceptibility proteins. and disease prognosis of immunodeficient patients compared to general RESULTS: The recombinant spike protein was found to be >95% pure by population. Our objective was to evaluate these patients’ profile and their LC-MS/MS (peptide signal abundance) and silver-stained SDS-PAGE. evolution during pandemic. Expression of the full-length spike was confirmed by western blot which METHODS: Retrospective analysis of 243 immunodeficientpatients’ showed a single band at ;140 kD, which was recognized by an anti-spike medical records from March-July 2020. We evaluated socioeconomic antibody. Ten COVID-19 positive patients’ sera, but not negative controls, conditions, adherence to social distancing, symptoms and type of immu- had high IgG reactivity to the spike protein (titers >1/10,000). Mice nodeficiency and comorbidities. Diagnosis was established through immunized with the spike S1 subunit had IgG reactivity to the full spike. symptoms and positive SARS-CoV-2 PCR. CONCLUSIONS: High quality SARS-CoV-2 spike protein was produced RESULTS: Most were women (58%), mean age 42.3y. The majority and used to develop an IgG antibody immunoassay. The purified spike presented CVID (48.2%), followed by IgA deficiency (14.8%), agamma- protein did not react with COVID-19 negative patient sera and had high globulinemia (4.1%). Some presented secondary immunodeficiency reactivity to COVID-19 positive patients. The pure and immunoreactive (14.4%). Comorbidities: bronchiectasis (22.6%), asthma (20.2%), COPD spike protein has applications in antibody testing and vaccine (9.5%), SAH (17.7%), obesity (14%), diabetes (7.8%) and cardiovascular development. diseases (5%). COVID-19 was confirmed in 10(4.1%) patients, of which 55.6% had positive IgG. About housing, 94.2% lived in the city, 72% in Outcomes of SARS-CoV2 infection in STAT3 and houses, with an average of 6.3 rooms and 3.1 residents/household. During 485 PGM3 Deficiency pandemic, patients left home on average 7 times/month and 93.4% usedmask, 63.4% used their own car, 23.9% used public transport. Those Muhammad Khalid, MD1, Amanda Urban, CRNP2, Dirk Darnell, RN1, infected with SARS-CoV-2 had a higher mean of visitors compared to total Alexandra Freeman, MD1; 1NIAID, National Institute of Health, 2Clinical cohort(2.4x1.4), lived more in apartments (50%x27.6%),left home more Research Directorate, Frederick National Laboratory for Cancer often (8.8x7,0 times/month) and were more obese (60% x14%) Research. CONCLUSIONS: Lower percentage of immunodeficient patients in- RATIONALE: While SARS-CoV2 continues to spread globally, our fected with COVID-19 (4.1%) was observed compared to that in general understanding of the disease continues to be limited in patients with population of the city of S~ao Paulo (11%), possibly due to greater isolation underlying immune dysregulation. and fear of being contaminated. Those infected were less adherent to METHODS: Four subjects with known monogenic immunodeficiency preventive measures and had higher incidence of comorbidities (obesity) with HyperIgE phenotype and confirmed or clinically suspected SARS- related to worse prognosis of COVID-19. CoV2 infection were tele-interviewed to assess for symptoms, duration, severity and complications of illness. RESULTS: Three patients had STAT3 deficient HyperIgE syndrome and one had PGM3 deficiency. All were on antimicrobial prophylaxis during SARS-CoV2 infection. 8-year-old male with PGM3 deficiency related lymphopenia, neutropenia, and reactive airway disease tested positive for SARS-CoV2 and experienced 2 days of low-grade fever and cough. 26- year-old male with STAT3 deficiency working in a high-exposure environment tested positive and experienced symptoms for 2 weeks including headache, myalgias, low-grade fever and dyspnea on exertion. He received additional antibiotics around day 7 of illness when his course worsened briefly. 45-year-old male with STAT3 deficiency, with exposure to confirmed positive family member, developed intermittent low-grade fever, chills, myalgias, severe fatigue, and dyspnea on exertion, lasting for 20 days. His 14-year-old daughter with STAT3 deficiency experienced 14 days of fatigue, low-grade fever, anosmia and ageusia. All 4 patients were J ALLERGY CLIN IMMUNOL Abstracts AB153 VOLUME 147, NUMBER 2

Impact of the COVID-19 pandemic on physical (p<_0.0277; p<_0.0198),and IV (p<_0.0024; p<_0.0033), resulting in decrease 487 and mental health among individuals with in expression of Foxp3 + gene mRNA and an increase in Rorgt+, primary immunodeficiency: results of a respectively. Administration of B.fragilis to animals caused a decrease in nationwide survey SFB (p<_0.0001; p<_0.0001) and Rorgt + mRNA, and, conversely, increased the number of Bacteroides and Prevotela group (p<_0.0001; p<_0.0001), and Deepti Deshpande, MD1, Christopher Scalchunes, MPA2, Jordan Clostridium spp. clusters XIV (p<_0.0151; p<_0.0021), IV (p<_0.0019; Orange, MD PhD FAAAAI3, Joshua Milner, MD FAAAAI3; 1Columbia p<_0.0005) and the expression of Foxp3+ genes. University, 2Immune Deficiency Foundation (IDF), 3Columbia University CONCLUSIONS: Manipulation of the gut microbiome may lead to Irving Medical Center/ Presbysterian Hospital. restoration of correct immune balances in GALT which has undergone RATIONALE: The swiftly spreading COVID-19 pandemic may differ- bacterial inflammation entially affect individuals with primary immunodeficiencies (PIDs), who have variable infection risk, immune-dysregulation and report worse CARD14 is Required for FLG Homeostasis in health-related quality of life (HRQoL) than the general population. Our 489 Human Skin, and the CARD14 Variant objective was to assess the impact of COVID-19 on healthcare access, Rs11652075 Regulates the Expression of FLG in physical and mental health among adults with PIDs. a Genotype-Dependent Fashion METHODS: Using data from the ongoing Immune Deficiency Stanley DeVore1, Mariana Stevens, PhD2, Hua He, MS2, Jocelyn Biagini Foundation longitudinal surveys [April-June 2020 (IRB exempt)] on 2 2 2 individuals with PIDs that opted-in [;9% response-rate (2086/ 22,341 Myers, PhD , John Kroner, MS , Lisa Martin, PhD , Gurjit Khurana Her- shey, MD PhD FAAAAI2; 1University of Cincinnati College of Medicine, emails)], we included adults with available PROMIS global health/ 2 HRQoL questions. New healthcare access problems during COVID-19 Cincinnati Children’s Hospital and Medical Center. (immunoglobulin replacement (IgRT) delays, location/ product changes, RATIONALE: Low epidermal filaggrin (FLG) is a major risk factor for medication issues or missed appointments) and resulting negative impact the development and progression of atopic dermatitis (AD) and atopic on physical/ mental health were analyzed using Chi-square (Fisher’s march sequelae. We recently found that low non-lesional, but not lesional, exact)/ t-tests/ Mann-Whitney tests. FLG levels are associated with the development of co-sensitization and RESULTS: Of the 565 adults included (;30% of adults that opted-in), food allergy. We hypothesized that variance in genetic loci other than majority were females [86% (485/561)] and antibody defects were the FLG contribute to low epidermal FLG expression in non-lesional skin. most common diagnosis [96% (543/565)]; 90% (507/565) on IgRT. While METHODS: We conducted a genome-wide association study in the 63% (359/565) reported healthcare access problems, IgRT issues were Mechanisms of Progression from ADtoAsthma in Children (MPAACH) infrequent [4% (23/565)]. Mean PROMIS global physical (39.6) and cohort using log-transformed non-lesional skin FLG mRNA levels as a mental health scores (43.5) were below the national average (p <0.001) continuous outcome (eQTL) adjusted for age, sex and race. CpG percent (longitudinal follow-up ongoing). Individuals with healthcare access methylation was measured using bisulfite-converted pyrosequencing, and problems more often reported a moderate-severe negative impact on their the magnitude of allelic expression was measured by allele-specific physical and mental health vs. those without access issues [84% (103/123) qPCR. Functional experiments examining CARD14-mediated FLG vs 58% (250/428), p< 0.01 and 70% (204/291) vs 57% (149/260), p< 0.01 expression were performed in HaCat and primary human keratinocytes us- respectively]. ing chemical and/or genetic manipulation (e.g. CRISPR-Cas9) approaches. CONCLUSIONS: Healthcare access issues are common during COVID- RESULTS: The CARD14 variant rs11652075, a C>T transition mutation, 19 and negatively impact physical and mental health among individuals is associated with low non-lesional epidermal FLG expression 5 -7 5 with PIDs providing insight into potentially modifiable factors. (p 4.02*10 ; b -0.77) in children with AD. Presence of the T-allele re- duces methylation of the CpG at the wild-type rs11652075 locus in Relationship of Gut-Associated Lymphoid Tissue MPAACH skin and primary keratinocytes in a copy-number-dependent 488 and the Gut Microbiome in Experimental fashion, and CARD14 expression from the T-allele is consistently higher Salmonella-induced Intestinal Inflammation than from the C-allele in heterozygous keratinocytes. CARD14-deficient keratinocytes exhibit elevated baseline FLG expression, and the effect of Halyna Koval1, Aleksandr Kamyshnyi2, Yulia Bukina2, Iryna Bilous1, IL17A-induced CARD14 signaling on FLG expression is dependent on Lawrence Dubuske, MD FAAAAI3; 1Bukovinian State Medical Univer- rs11652075 genotype. sity, Chernivtsi, Ukraine, 2Zaporozhye State Medical University, Zaporoz- CONCLUSIONS: The CARD14 variant rs11652075 influences the hye, Ukraine, 3George Washington University School of Medicine, methylation and allelic expression of CARD14 in human keratinocytes, Washington, DC, USA, Immunology Research Institute of New England, and CARD14 regulates the expression of FLG in a genotype-dependent Gardner, MA, USA. fashion. RATIONALE: Segmental filamentous bacteria (SFB) induce differenti- ation of Th17-cells in the intestinal-associated lymphoid tissue (GALT), while Clostridium (cluster IV and XIVa) and Bacteroides fragilis (poly- saccharide A (PSA)) stimulate formation of T-regulatory cells (Treg) and suppressor IL-10 production. Short-chain fatty acids (SCFAs) are impor- tant B.fragilis metabolites which activate GALT cells. Decreased SCFA concentration reduces Treg in the intestine and disrupts Th17/Treg balance. METHODS: Assessment of levels of immunoregulatory bacteria in GALT, with RT-PCR used to identify them by 16S rDNA genes. RESULTS: During the experiment with introduction to animals of vancomycin and Salmonella there was an increase in levels of SFB (p<_0.0001) and decreases in A.muciniphila (p<_0.0001), and F.prausnitzii (p<_0.0017). When S.enteritidis and S.typhimurium were infected, there was increased numbers of SFBs (p<_0.0001; p<_0.0001) against the background of a pronounced decrease in the Bacteroides and Prevotela groups (p<_0.0189; p <_0.0017), and Clostridium spp. clusters XIV AB154 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Natural Human IgE Monoclonal Antibody Proteomic analysis of Food Protein Induced 490 Defines a Unique Epitope on Der p 2 492 Enterocolitis Syndrome (FPIES) reactions reveals Th17 immune signature Anna Pomes, PhD FAAAAI1, Jill Glesner1, Anyway Kapingidza2, Crys- tal Richardson, PhD1, Lisa Vailes1, Sabina Wuenschmann, PhD1, Martin Cecilia Berin, PhD1, Charuta Agashe1, Mary Grace Baker, MD2, Chapman, PhD FAAAAI1, Scott Smith, MD PhD3, Maksymilian J. Andrew Bird, MD FAAAAI3, Anna Nowak-Wegrzyn, MD, PhD4; Chruszcz, PhD2; 1Indoor Biotechnologies, Inc., 2University of South Car- 1Mount Sinai School of Medicine, 2Icahn School of Medicine at Mount olina, 3Vanderbilt University Medical Center. Sinai, 3UT Southwestern Medical Center, 4NYU Langone Health. RATIONALE: There is limited knowledge of the epitopes associated with RATIONALE: The immune mechanisms responsible for adverse re- the human IgE repertoire. Our aim is to identify and analyze epitopes actions to foods in FPIES are poorly understood beyond a lack of recognized by human IgE monoclonal antibodies (mAbs) as they occur in involvement of IgE-mediated hypersensitivity. Previous studies have vivo. revealed a strong innate immune activation signature during reactions, METHODS: A Der p 2-specific human IgE mAb, 2F10, was isolated by but the initiating events are unclear. hybridoma technology after electrical cytofusion of cultured human B cells METHODS: Children with a history of FPIES underwent a supervised from the peripheral blood of a mite-allergic patient and a non-secreting food challenge. Serum samples were obtained at baseline, at time of human myeloma cell line. Relative 2F10 epitope mapping was assessed by symptoms (if any) and 4 h after challenge or symptom onset. A 92-marker immunoassays. Recombinant 2F10-Fab was expressed in mammalian cells proximity ligation assay (O-link) was used to quantify inflammatory and Der p 2.0103 in Pichia pastoris. The X-ray crystal structure of Der p biomarkers. 2.0103 in complex with 2F10-Fab was determined by molecular replace- RESULTS: Pre/post serum samples were tested on 22 children, 10 who ment using crystals obtained using vapor diffusion. A site-directed muta- reacted and 12 who tolerated the challenge. When examining the change genesis analysis of the 2F10 epitope was performed. from baseline, 12 biomarkers were significantly elevated only in those who RESULTS: The first X-ray crystal structure of an allergen (Der p 2) in reacted to the food challenge (multiple T-test with FDR correction). complex with a human IgE mAb-Fab with the correct pairing of the heavy Upregulated biomarkers could be grouped into those that were epithelial and light chains was determined at 2.2 A resolution. The unique ;740 A2 derived (IL-17C, IL-8, CCL20, CCL25), monocyte/macrophage derived epitope was recognized by 2F10 (70% by the heavy chain) through hydro- (IL-6, IL-10, TNF), and lymphocyte derived (IL-2, IL-17A). The top three phobic interactions and hydrogen bonds. A double and a quadruple mutant upregulated biomarkers were related to the Th17 pathway (IL-17A, of epitope residues close to the C-terminus of the allergen led to loss of CCL20, and IL-17C). 2F10 binding (almost 50% or 100%, respectively). CONCLUSIONS: We demonstrate that FPIES reactions are associated CONCLUSIONS: We report the first X-ray crystal structure of an allergen with a Th17 inflammatory signature. The source of IL-17 (conventional in complex with a human IgE mAb that has the natural pairing of heavy and Th17 cells, gd T cells, ILC3) needs to be identified to understand the light chains. Epitope analysis will facilitate the design of hypoallergens for mechanism of initiation of symptoms. immunotherapy and contribute to understand the IgE antibody repertoire. CysLT1R antagonists block early P2Y6 receptor- Effects of Androgen Receptor (AR) Signaling on 493 dependent signaling that prevents type 2 491 Airway inflammation in an Obesity-Associated allergic sensitization Asthma Model Jun Nagai, PhD1, Junrui Lin2, Barbara Balestrieri, MD1, Laura Nowrin Chowdhury1, Jacqueline Cephus, MS2, Vivek Gandhi, PhD2, Fanning, MD1, Timothy Kyin, MD1, Haley Cirka2, Patrick Stokes Peebles, MD FAAAAI3, Jeffrey Rathmell2, Dawn Newcomb, Brennan, MD PhD1, Joshua Boyce, MD FAAAAI1; 1Harvard Medical PhD2; 1Vanderbilt University, 2Vanderbilt University Medical Center, School/Brigham and Women’s Hospital, 2Brigham and Women’s 3Vanderbilt Univ School of Medicine. Hospital.

RATIONALE: Obese women are disproportionately affected by severe RATIONALE: The therapeutic efficacy of CysLT1R antagonists for the asthma. Androgen receptor signaling attenuated neutrophilic and eosino- treatment of asthma and allergic rhinitis varies, with 24-78% of patients philic airway inflammation in asthma, and administration of dehydroepi- failing to show symptomatic improvement. Several in vitro studies re- androsterone (DHEA-S), an androgen upstream of testosterone and vealed that current clinical CysLT1R antagonists block type 6 purinergic estrogen that is increased in males, decreased asthma symptom scores (P2Y6). However, the potential off-target effects of CysLT1R antagonists and increased lung function in women with moderate to severe asthma. in allergic inflammation are not known.

However, it remains unknown how AR signaling affects airway inflam- METHODS: We examined the off-target effect of CysLT1 antagonists us- mation during an obese state. We hypothesized that AR signaling decreases ing P2Y6 transfectants, bone marrow (BM)-derived macrophages, and a eosinophilic and neutrophilic airway inflammation by decreasing T cell mouse model of Dermatophagoides farinae (Df)-induced airway disease metabolism and differentiation of Th2 and Th17 cells. with wild type and P2Y6 gene deleted mice. METHODS: High-fat diet (HFD) or regular chow was introduced for 12 RESULTS: CysLT1R antagonists blocked UDP (an endogenous agonist weeks in female C57BL/6 mice. Mice were then pre-treated with DHEA or for P2Y6 receptor)-induced calcium flux in P2Y6 transfectants. UDP eli- vehicle intraperitoneal treatment followed by administration of Alternaria cited potentiation of Df-induced protective IL-12 production in BM- alternata extract for 9 days. Lungs and BAL were harvested for flow cy- derived macrophages, and this potentiation was inhibited by CysLT1R an- tometry and infiltration of eosinophils and neutrophils. Additionally, tagonists. Intraperitoneal injection of CysLT1R antagonists during sensiti- splenic naive CD4+ T cells from male, female, and ARtfm (a nonfunctional zation blocked the Df-induced IL-12 production in vivo and suppressed

AR mutation) mice were differentiated into Th2 and Th17 in vitro and T exacerbated type 2 inflammation observed in P2Y6 deficient mice, but cell metabolism was determined by Seahorse. not in wild type controls.

RESULTS: DHEA treatment decreased the eosinophils and lymphocytes CONCLUSIONS: CysLT1R antagonists inhibit P2Y6 receptor-dependent in the BAL as well as the Th2 and Th17 cells in the lung of HFD female signaling that counterbalances CysLT1R-induced type 2 allergic priming mice. Furthermore, AR signaling decreased Th2 and Th17 metabolism and during sensitization. Controlling P2Y6 signaling might prove to be a poten- spare respiratory capacity in vitro. tial additional treatment strategy for allergy. CONCLUSIONS: DHEA and AR signaling decreased airway inflamma- tion and reduced Th2 and Th17 metabolism, providing a potential mechanism for the increased prevalence of severe asthma in women. J ALLERGY CLIN IMMUNOL Abstracts AB155 VOLUME 147, NUMBER 2

Basal Cell Adhesion Molecule Marks an Early A Transcription Factor Blimp1 in CD4+ T cells 494 Progenitor Epithelial Cell in the Murine Trachea 496 Promotes Type 2 Immune Responses in the Lungs While it Suppresses IgE Antibody Xin Wang1, Nora Barrett, MD2; 1Brigham and Women’s Hospital, Har- Production in Mice vard Medical School, 2Brigham and Women. RATIONALE: Recent studies in the human sinonasal and bronchial Koji Matsumoto, MD1, Takao Kobayashi, PhD1, Koji Iijima, PhD2, Hir- mucosa have identified novel airway epithelial cell (EpC) populations in ohito Kita, MD1; 1Mayo Clinic Arizona, 2Mayo Clinic. type 2 inflammation (T2I), including two subsets of airway basal cells RATIONALE: Allergic immune responses generally involve generation (BCs), but functional studies are lacking in part because of lack of of antigen-specific type 2 CD4+ T cells and production of IgE antibodies. A validated flow cytometric panels to distinguish EpC subtypes. transcription factor B lymphocyte-induced maturation protein-1 (Blimp1) METHODS: We developed a protocol for the isolation and flow regulates plasma cell development and effector functions of T cells. cytometric characterization of murine tracheal EpCs in C57BL/6 WT However, little information is available regarding the roles of Blimp1 in and choline acetyl transferase (ChAT) reporter mice. A murine model of allergic immune responses. airway BC differentiation in T2I was established using repetitive METHODS: We crossed Prdm1 (encoding Blimp1)-floxed mice with Cd4 inhalation of Alternaria alternata (ALT). Fate mapping was performed us- Cre mice to delete Blimp1 specifically in the CD4+ T cell compartment ing tamoxifen-treated, ALT-challenged KRT5CreERT2R26tdTomatomice. (Blimp1 cKO mice). Mice were exposed intranasally (i.n.) to ovalbumin RESULTS: We identify two distinct BC subsets by flow cytometry, (OVA) antigen with extract of fungus Alternaria as an adjuvant. distinguished by variable expression of BC adhesion molecule (BCAM). RESULTS: When exposed i.n. to OVA plus Alternaria, Blimp1 cKO mice Both BCAMhi and BCAMlow BCs express KRT5 and CD49f, indicating showed higher numbers of T follicular helper T cells and germinal center B they are BCs. As compared to BCAMlow BCs, BCAMhi BCs express higher cells in draining lymph nodes as compared to wild-type (WT) mice. levels of tumor protein p63 (p63), nerve growth factor receptor (NGFR), Accordingly, serum levels of OVA-specific IgE were higher in Blimp1 podoplanin and Ki67, indicating an earlier progenitor stage. After tamox- cKO mice. In contrast, when challenged i.n. with OVA antigen, Blimp1 ifen-induced labelling of KRT5+ BCs and ALT challenge, BCAMhi BCs cKO mice showed marked reduction in type 2 immune responses in the retained their label, while increasing numbers of BCAMlow BCs and differ- lungs, including production of type 2 cytokines, airway eosinophilia, entiated EpCs were labeled, indicating a differentiation trajectory from mucus production and airway hyperreactivity. The number of memory- BCAMhi BCs a BCAMlow BCs a differentiated EpCs. Furthermore, after type CD69+ Th2 cells was significantly lower in the lungs of Blimp1 ALT challenge, we detected labelled uteroglobin+ club cells. cKO mice. Furthermore, expression of genes associated with effector func- CONCLUSIONS: BCAMhi BCs are an early airway progenitor cell in the tion and tissue localization was modulated in Th2 cells from Blimp1 cKO murine trachea. Future studies using the flow cytometric panel developed mice. here will be helpful to understand the role of this BC population in airway CONCLUSIONS: Type 2 immune responses in the lungs and IgE repair, remodeling, and disease. antibody production can be regulated reciprocally at the CD4+ T cell level. Blimp1 likely plays critical roles in type 2 airway inflammation during Dysfunctional Mucosal Immune Defense in CRS allergic immune responses. 495 Increase Susceptibility to Staphylococcus Aureus

Sun Mi Choi1, Sandra Christiansen, MD2, Adam DeConde3, Taylor Doherty, MD FAAAAI4, Victor Nizet5; 1University of California, San Diego, 2UCSD, 3University of California San Diego, 4UC San Diego, 5University CA San Diego School Medicine. RATIONALE: Sinusitis affects 10% of adults, chronic rhinosinusitis (CRS) is varied in etiology and clinical presentation. Staphylococcus aureus (SA) colonization is increased from 30% to 60-90% in those with symptoms of CRS. Airway epithelial cells are first line of defense and has important role in differentiating pathogenic bacteria from commensal bacteria. Increased permeability of epithelium, decreased antimicrobial production, and dysregulated mucin secretion are features of CRS. METHODS: To elucidate the mechanism of mucosal dysfunction in CRS to SA, we have developed air liquid interphase (ALI) culture model of airway epithelial cells. Using this model, we exposed SA to airway epithelial cells from different clinical patients. Epithelial barrier integrity was evaluated by FITC-Dextran assay in ALI and immunohistochemistry of dapi, occludin, and zo-1 in culture. Antimicrobial peptide, Reg3g production was measured by RT-qPCR and western. RESULTS: Airway epithelium of CRS patients show impaired barrier integrity compared to normal epithelium when exposed to SA with faster transfer of FITC-dextran to basolateral media. In addition, CRS cells were more likely to lose attachment properties in presence of SA shown by immunohistochemistry. Furthermore, growth of SA increased with expo- sure to CRS airway epithelial cells. Lastly, CRS cells show deficiency of Reg3g induction upon infection with SA, which shows impaired innate mucosal immunity in CRS. CONCLUSIONS: Airway epithelium of CRS patients are susceptible to SA due to innate immune defects in barrier integrity and impaired production of antimicrobial, Reg3g. AB156 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Circulating fetal mast cell progenitors are Patient-Reported Outcomes (PROs) With 497 phenotypically distinct from adult progenitors 498 Abrocitinib Treatment in Adolescent Patients With Moderate-to-Severe Atopic Dermatitis Hannah Martin1, Joshua Boyce, MD FAAAAI2, Daniel Dwyer, PhD3; (AD): Results From the Phase 3 JADE TEEN Study 1Brigham and Women’s Hospital, 2Brigham and Women, 3Harvard Med- ical School. Amy McMichael1, Michael Cork2, Joyce Teng3, Ricardo Rojo4, Hernan RATIONALE: Mast cells (MCs) in peripheral tissues arise from Valdez4, Fan Zhang4, Daniela Myers4, Gary Chan4, Marco DiBonaven- circulating progenitors, and recent mouse studies suggest distinctions tura4; 1Wake Forest School of Medicine, 2Sheffield Dermatology between the origins of neonatal MCs and adult MCs. However, little is Research, University of Sheffield, 3Stanford University, 4Pfizer Inc. known about human neonatal MC progenitors and how they differ from RATIONALE: AD is characterized by pruritic, scaly, and inflammatory adults. Therefore, we wanted to use a novel approach to identify the cord patches/plaques that impact the quality of life (QoL) of patients and blood (CB) MC progenitor that gives rise to the mature MC using a caregivers. Here, we describe the patient-reported changes in disease signs/ validated culture system. symptoms and QoL in adolescents with moderate-to-severe AD treated METHODS: Human umbilical CB was collected, and mononuclear cells with abrocitinib or placebo in JADE TEEN (NCT03796676). were iteratively fractionated based on cell surface markers, including METHODS: Adolescent patients (aged 12-17 years) with moderate-to- CD34, CD117, FCER1a, and CD38. The sorted cells were cultured with severe AD were randomly assigned (1:1:1) to receive once-daily abroci- SCF, IL6 and IL10, and the development of mature MCs assessed through tinib 200 mg, abrocitinib 100 mg, or placebo with standardized medicated toluidine blue staining and flow cytometry. topical therapy for 12 weeks. PRO assessments included Patient Global RESULTS: MC differentiation potential was restricted to a subset of CB Assessment (PtGA; disease severity), Patient-Oriented Eczema Measure cells expressing the receptors CD34+CD117+CD38+ while lacking (POEM; AD signs/symptom severity), Children’s Dermatology Life FCER1a. These cells rapidly matured, with metachromatic granules Quality Index (CDLQI; dermatology-specific QoL of patients), and observed by week 2. These mature CBMCs expressed FCER1a, in contrast Dermatitis Family Impact (DFI; dermatology-specific QoL of caregivers). to the CBMCs grown in bulk. Cells from the same samples matching RESULTS: In total, 285 patients were treated in the study (mean age, 14.9 previously defined FCER1a+ and CD117+ adult MC progenitors also years; 50.9% male; 56.1% white). At week 12, more adolescents treated developed metachromatic granules but had limited expansion capacity and with abrocitinib (200 mg, 100 mg) versus placebo achieved PtGA response died by week 3. Mononuclear cells isolated from adult peripheral blood did of ‘‘clear’’ or ‘‘almost clear’’ with >_2-grade improvement from baseline not expand in this same culture system. (36.6%, 30.0% vs 10.6%), >_4-point improvement from baseline in POEM CONCLUSIONS: The mature CBMC grown from the (83.9%, 77.0% vs 60.2%), and >_2.5-point improvement from baseline in CD34+CD117+CD38+ compartment is distinct from the adult peripheral CDLQI (78.5%, 80.9% vs 67.7%). Least-squares mean reductions in DFI blood MC. The CBMC progenitor lacks FCER1a in contrast to the defined scores (95% CI) reported by caregivers at week 12 were 27.3 (28.6 to adult MC progenitor. The expansion potential of CD34+CD117+CD38+ 26.0), 26.7 (27.9 to 25.4) and 25.2 (26.5 to 23.9) in the 200-mg, progenitors exceeds that of adult-type MC progenitors, potentially 100-mg, and placebo groups, respectively. ensuring seeding of tissues with MCs during embryonic life. CONCLUSIONS: Abrocitinib combined with medicated topical therapy substantially improved the signs/symptoms of AD and QoL of adolescents with moderate-to-severe AD and the QoL of their caregivers. J ALLERGY CLIN IMMUNOL Abstracts AB157 VOLUME 147, NUMBER 2

Tezepelumab Efficacy in Patients with Allergic LAR. Benralizumab also depleted eosinophils in blood, bone marrow and 499 and Non-Allergic Asthma: A Post Hoc Analysis sputum before and 24h post-AIC (p<0.05). Benralizumab significantly of the PATHWAY Phase 2b Study reduced, but did not completely deplete, basophils in blood and bone marrow before and 24h post-AIC. There was no effect of benralizumab on Jonathan Corren, MD1, Gene Colice, MD2, Kinga Salapa, Msc3, Karin sputum basophil levels. Bowen2, Jean-Pierre Llanos-Ackert, MD4; 1University of California, Los CONCLUSIONS: These data demonstrating depletion of eosinophils by Angeles (UCLA), CA, USA, 2AstraZeneca, Gaithersburg, MD, USA, 3As- benralizumab throughout the AIC suggest that eosinophils do not traZeneca, Warsaw, Poland, 4Amgen, Thousand Oaks, CA, USA. contribute to the allergen-induced LAR. Although basophil levels were RATIONALE: Tezepelumab is a human monoclonal antibody that targets significantly reduced systemically, the data suggest that benralizumab did thymic stromal lymphopoietin. In the PATHWAY phase 2b study not completely deplete basophils in bone marrow or blood, and had no (NCT02054130), tezepelumab significantly reduced annualized asthma effect on basophils in the airways (sputum) at any time point. The exacerbation rates (AAERs) and improved lung function in adults with possibility that basophils contribute to the LAR and that this effect is driven severe, uncontrolled asthma. This post hoc analysis evaluated the efficacy by factors other than IL-5 cannot be excluded. of tezepelumab in patients with allergic and non-allergic asthma grouped according to eligibility for omalizumab (OMA) based on US prescribing Biologic Pathways Involved In Chronic information (USPI). 501 Spontaneous Urticaria And Response To METHODS: Patients (18-75 years old) with severe, uncontrolled asthma Benralizumab Treatment were randomized to receive subcutaneous tezepelumab 70mg every 4 1 2 weeks (Q4W), 210mg Q4W or 280mg every 2 weeks, or placebo, for 52 Debayoti Ghosh, PhD , Umesh Singh, MD PhD , Jonathan Bernstein, 3 1 2 weeks. OMA-eligible patients (defined as having allergic asthma) had a MD FAAAAI ; University of Cincinnati College of Medicine, Univer- _ sity of Cincinnati, 3Bernstein Allergy Group, Inc. positive (>0.35 kUA/L) fluorescence enzyme immunoassay test for any common perennial aeroallergen, a baseline total serum IgE level >_30 to RATIONALE: Chronic spontaneous urticaria (CSU) is a debilitating skin <_700 IU/mL and an IgE-body weight combination within the dosing range condition with complex pathomechanisms still poorly elucidated. We on the OMA USPI. AAER and forced expiratory volume in 1 second reported the efficacy of Benralizumab (anti-IL5 mAb) in the treatment of CSU (Bernstein et al NEJM; in press). (FEV1) were determined in OMA-eligible and OMA-ineligible patients. RESULTS: Of 550 randomized patients, 147 and 390 were OMA-eligible METHODS: In a single-blind, single-center, repeated-measures, 24-week 5 and OMA-ineligible, respectively (13 unknown). Tezepelumab 210mg study, antihistamine-unresponsive CSU subjects (N 12, F:M-9:3, 6 reduced AAER by 83% (95% CI: 51-94) and 64% (95% CI: 32-81) versus 47.3 1.3 years) were initially treated with a single dose placebo placebo in OMA-eligible and OMA-ineligible patients, respectively. For subcutaneously (SQ) followed by three SQ doses of benralizumab 30mg pooled tezepelumab doses, AAER was reduced by 65% (95% CI: 28-83) every 4-weeks and 2-monthly off-medication follow-up visits. Lesional and uninvolved skin biopsy samples collected post-placebo and and 69% (95% CI: 51-81), respectively. Tezepelumab improved FEV1 in both eligibility subgroups. post-benralizumab were analyzed by RNAseq. Molecular pathways were CONCLUSIONS: Tezepelumab reduced exacerbations and improved elucidated by Ingenuity Pathway Analysis (IPA, Qiagen). RESULTS: CSU lesions were associated with upregulation of multiple FEV1 versus placebo in patients with allergic and non-allergic asthma, sup- porting its potential benefits in a broad population of patients with severe epidermal olfactory receptors including OR2AT4, OR56A5, OR2J2 (log2 asthma. fold-changes 5.525, 4.727, 4.174 respectively). In addition, significant upregulation of genes coding CC and CXC chemokines (CCL8, CCL2, The Effect of Benralizumab On Allergen-Induced CCL3, CXCL2, CXCL6, C CXCL8) and interleukins (IL6, IL10, IL20, 500 Responses In Subjects With Mild Allergic IL13, IL5R) with downregulation of keratin-transcripts were observed, Asthma which were ameliorated by benralizumab treatment. Granulocyte adhesion/diapedesis (p55.04 x 10-14) and neuroimmune inflammation (p Gail Gauvreau1, Roma Sehmi, PhD1, J. FitzGerald, MD2, Richard 5 4.48 x 10-9) were two significant canonical pathways associated with Leigh, MD PhD3, Donald Cockcroft, MD FAAAAI4, Beth Davis, PhD4, CSU while glucocorticoid receptor signaling (p58.1 x 10-9) and cytokine- Irvin Mayers, MD5, Louis-Philippe Boulet, MD FRCPC6, Brittany mediated immune cell signaling (p54.06 x 10-5) were potentially relevant Salter, MD, PhD1, Ruth Cusack, MD1, Imran Satia, MD, PhD1, Kieran for benralizumab treatment. Killian, MD1, Patrick Mitchell, MB BCh3, Viktoria Werkstrom, MD, CONCLUSIONS: The results of this study suggest involvement of PhD7, Tomasz Durzynski, MD, PhD8, Kathryn Shoemaker, MS9, Rohit multiple cytokines and chemokines important for epidermal infiltration Katial, MD FAAAAI9, Maria Jison9, Paul Newbold, PhD9, Paul O’Byrne, of inflammatory cells along with enhanced chemosensory responses MD1; 1McMaster University, 2University of BC, 3University of Calgary, caused by upregulated ectopic odorant receptors might play critical roles 4University of Saskatoon, 5University of Alberta, 6Laval University, 7As- in CSU pathogenesis. In addition to eosinophil-specific function, beneficial traZeneca, Sweden, 8AstraZeneca, Poland, 9AstraZeneca, USA. disease-modifying molecular pathways of benralizumab might warrant RATIONALE: Eosinophils and basophils have been hypothesized to further investigation. contribute to the allergen-induced late asthmatic response (LAR). Treatment with benralizumab, an anti-IL-5Ra, afucosylated, monoclonal antibody, results in near complete depletion of blood, sputum and tissue eosinophils and a reduction in blood basophils. We hypothesized that depletion of eosinophils and basophils with benralizumab would attenuate the allergen-induced LAR. METHODS: 46 mild allergic asthma subjects demonstrating early and late asthmatic responses and increased sputum eosinophils following allergen inhalation challenge (AIC) were randomized to benralizumab 30 mg sc. Q4W or placebo for 3 doses. AIC was conducted again at week 9. Eosinophils and basophils were measured in blood and bone marrow (pre/24h post-AIC) and sputum (pre/7h/24h post-AIC). RESULTS: Benralizumab significantly inhibited allergen-induced sputum eosinophils 7h post-challenge (p<0.05) but it did not inhibit AB158 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Ligelizumab is more effective in patients with frequency of exacerbations. Asthma morbidity and mortality reduction 502 chronic spontaneous urticaria previously with biologic therapies through medication assistance programs may ease treated with omalizumab disease burden and health disparities in high risk urban populations.

Karl Sitz, MD FAAAAI1, Gordon Sussman, MD FAAAAI2, Martin A Single-Dose of REGN1908-1909 Reduced Metz3, Michihiro Hide, MD PhD4, Marcus Maurer, MD5, Nathalie Bar- 504 Bronchoconstriction in Cat-Allergic Subjects bierStatitiscian6, Eva Hua6, Reinhold Janocha, PhD7, Thomas Severin7; with Mild Asthma for up to 3 months following 1Little Rock Allergy and Asthma Clinic, P, 2University of Toronto, 3Char- a controlled cat allergen challenge: A Phase 2, ite Campus Mitte, 4Hiroshima University, 5Charite-Universitatsmedizin Randomized, Double-Blind, Placebo-Controlled Berlin, 6Novartis, 7Novartis Pharma AG. Study

RATIONALE: sIn the core Phase 2b study (NCT02477332), ligelizumab 1 1 72 mg and 240 mg every four weeks [q4w] exhibited earlier and greater Frederic De Blay De Gaix, MD , Alina Gherasim, MD , Nathalie Do- mis1, Pretty Meier2, Furat Shawki2, Michelle DeVeaux2, Divya Ramesh2, improvements in urticaria disease activity through Week 20 compared with 3 2 2 omalizumab 300 mg q4w and placebo. Here, we explore the effect of Lorah Perlee, PhD , Gary Herman, MD , David Weinreich , George Yan- copoulos2, Meagan OBrien2; 1ALYATEC Environmental Exposure Cham- ligelizumab on urticaria disease activity in CSU patients who were 2 3 previously treated with omalizumab. ber, Regeneron Pharmaceuticals, Inc., Regeneron Pharmaceuticals Inc. METHODS: We analyzed the effect of treatment on disease activity RATIONALE: To evaluate the efficacy of a novel anti-Fel d 1 monoclonal (using the weekly urticaria activity scores [UAS7]) in patients who were antibody cocktail (REGN1908-1909) in reducing acute bronchoconstric- treated with omalizumab 300 mg in the 20-week phase 2b core study, tion, defined as early asthmatic response (EAR), in cat-allergic subjects followed by up to 24 weeks of treatment-free washout period, and then with mild asthma (NCT03838731). switched to ligelizumab 240 mg q4w in the single-arm, 52-week Phase 2b METHODS: Cat-allergic subjects with asthma were randomized to 5 5 open label extension study. single-dose REGN1908-1909 600 mg SC (n 29) or placebo (n 27) prior RESULTS: Baseline mean6SD UAS7 of the 53 patients who switched to cat-allergen exposure in a controlled environmental exposure unit from omalizumab to ligelizumab were similar for the core (29.768.0) and (EEU). FEV1 was measured every 10 minutes up to 4 hours during cat- extension (27.868.9) studies. Post-treatment UAS7 values were lower, and allergen exposures at baseline and on days 8 (primary endpoint), 29, 57, _ change from baseline (CFB) in UAS7 was larger with ligelizumab versus and 85, where time to EAR is defined as >20% reduction from baseline omalizumab treatment at week 12 (ligelizumab: 6.969.3 and -20.9613.1 FEV1. Between-group differences in time to EAR, change from baseline in 6 6 FEV1 AUC(0–2 hours) and cat allergen quantity tolerated (Fel d 1 versus omalizumab: 11.8 13.3 and -17.7 13.1) and week 20 (ligelizu- 3 mab: 6.269.4 and -21.7612.3 versus omalizumab: 12.4613.0 and concentration [ng/m ] x minute ventilation x time in EEU) were assessed, -17.1612.6). The decrease in UAS7 was sustained with ligelizumab adjusted for baseline values and Fel d 1 allergen concentration. treatment throughout the 52-week extension study (week 28 5 4.669.2, RESULTS: Compared with placebo, REGN1908-1909 significantly week 36 5 3.868.3, week 44 5 4.469.2, and week 52 5 4.769.1). increased the median time to EAR from 51 minutes (baseline) to >4 hours 5 CONCLUSIONS: For patients with CSU previously treated with (maximum exposure) on days 8 (HR 0.36; P<0.0083), 29 (0.24; 5 omalizumab, ligelizumab may provide added benefit of further decreasing P<0.0001), 85 (0.27; P 0.0003) and to 232 mins on 57 (0.45; 5 urticaria activity. P 0.0222). As compared to baseline, REGN1908-1909 improved FEV1 AUC(0–2 hours) at day 8 (+15.2%) versus placebo (+1.6%, P<0.001). A Clinical Outcomes of Biologic Therapy on 3-fold higher allergen quantity was tolerated on day 8, relative to baseline, 503 Asthma in a Medically Underserved Urban after single-dose REGN1908-1909 (versus placebo P50.003). Population CONCLUSIONS: Single-dose REGN1908-1909 significantly reduced acute bronchoconstriction and increased the time to EAR in cat-allergic Sylwia Nowak1, Liseth Burbano1, James Moy1, Byung Yu, MD mild asthmatic subjects upon EEU exposure to cat allergen at 8 days and up FAAAAI1, Dipika Patel1; 1Cook County Health, Chicago, IL. to 3-months post dose. RATIONALE: Asthma is a heterogeneous disease that disproportionately affects urban populations. Uncontrolled and severe asthma necessitates frequent healthcare utilization. Biologic therapies are clinically efficacious in asthma control, but there is still an unmet need. This study evaluated the clinical outcomes of biologic therapy in moderate-to-severe persistent asthma in a population with restricted medical care access. METHODS: We evaluated 65 patients with moderate-to-severe persistent asthma that were on mepolizumab (n533), omalizumab (n518), dupilumab (n55), or benralizumab (n53). We collected demographic information, evaluated symptom control and healthcare utilization for 12 months prior to and for 12 months after initiating biologic therapy. Independent t-test was used to assess statistical significance. RESULTS: Our cohort was predominantly African American (49%) and Hispanic (27%). Forty-nine percent lived in impoverished communities without insurance (41%), and among those with insurance, 69% had managed Medicaid. Patients on biologic therapy had significantly less acute care visits (2 vs 0.6 visits, p<0.001), hospitalizations (1.1 vs 0.3 admissions, p50.001), routine provider visits (9.8 vs 8 visits, p50.03) and prednisone courses (4.2 vs 1.8, p<0.001) as well as higher peak flow values (288 vs 347, p50.01) and asthma control test (ACT) scores (10.8 vs 17.3, p<0.001). Side effect profile was favorable. CONCLUSIONS: Our study found and confirmed that biologic therapies for moderate-to-severe persistent asthma decreased medical utilization, systemic corticosteroid reliance, and showed a marked reduction in J ALLERGY CLIN IMMUNOL Abstracts AB159 VOLUME 147, NUMBER 2

A Comparison of Lysine Acetylsalicylate to Anti- >5(6%), none (37%). 57% have EpiPen with them always. 61% attested to 505 IL4/13 and Anti-IL5 Agents in the Management of knowing how to use an epi-pen. However, only 24% selected the correct Type 2 Asthma method, 63% didn’t know. 53% of the participants responded ‘‘Yes’’ to have had a WAP revised with them, 45% of participants had never revised Meghan E. Robbins, BS1, Gloria Hwang, MD2, Jaqueline R. one with their providers. It should be acknowledged that the 53% that Hwang, BS3, Timothy Craig, DO4; 1The Pennsylvania State University responded ‘‘Yes’’does not reflect with the poor knowledge base on EpiPen College of Medicine, Hershey, PA, 2Department of Surgery, Penn State use or that this was a novel intervention in our institution. Health Milton S. Hershey Medical Center, PA, 3The University of Mary- CONCLUSIONS: Simple tools like a WAP can help reduce the incidence land School of Medicine, Baltimore, MD, 4Department of Allergy, of mortalities. However, many community hospitals are yet to adopt this as Asthma & Immunology, Penn State Health Milton S. Hershey Medical standard care. This PrIP mirrors the importance of having a standardized Center, PA. educational tool for patients and caregivers with food allergies. RATIONALE: This systematic and literature review directly compares the various outcomes including pharmacokinetics, asthma forced expira- Bridging Knowledge Gaps in Anaphylaxis tory volume in one second (FEV1), quality of life, sinusitis exacerbations, 507 Management Through a Video-Based and required polyp surgery for three potential asthma medications: lysine Educational Tool acetylsalicylate (L-ASA), dupilumab (anti-IL-4/13), and mepolizumab 1 2 3 (anti-IL-5). Jumanah Karim , Sofianne Gabrielli, MSc , Bahar Torabi , Adam 4 5 5 METHODS: Analysis of L-ASA was performed using the Preferred Byrne, MD , Sarah De Schryver , Vanessa Gadoury-Levesque , Reza Ali- zadehfar6, Christine McCusker, MD MSc3, Matthieu Vincent5, Judy Mor- Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 7 8 5 protocol. Due to their ongoing clinical trials, the biologic agents dupilumab ris , Jennifer Gerdts , Xun Zhang, PhD , Moshe Ben-Shoshan, MD FAAAAI3; 1McGill, 2McGill University Health Centre, 3Montreal Chil- and mepolizumab were studied through comprehensive literature reviews. 4 5 RESULTS: The 6 studies in the systematic review found significant dren, Children Hospital of Eastern Ontario, Montreal Children Hospital, 6MCGill University, 7HA~f E€ pital du SacrA~f A^Ó-Coeur de MontrA~f A,^ protective effects of inhaled L-ASA (nebulized solution of 90 mg/ml) 8 against the fall in FEV1 produced by various bronchoconstrictive Food Allergy Canada. stimulants, which included adenosine 5’-monophosphate, histamine, RATIONALE: To develop and test the effectiveness of an education tool neurokinin A, bradykinin, and methacholine. Four out of the 6 studies to help pediatric patients and their families better understand anaphylaxis found increased provocative concentration causing a 20% fall in FEV1 and its management, and to improve current knowledge and treatment from baseline (PC20) after L-ASA administration. The optimum dose of guidelines adherence. dupilumab (subcutaneous injection 200-300 mg) every 2 weeks signifi- METHODS: From June 2019 to July 2020, 111 pediatric patients with cantly decreased exacerbations and the severity of symptoms, while history of food-triggered anaphylaxis who presented to our center were increasing FEV1 and fractional nitric oxide concentration (FeNO) values. recruited. Consenting families were asked to complete 6 questions related Subcutaneous injection of mepolizumab (100 mg) every 4 weeks reduced to the triggers, recognition and management of anaphylaxis at the time of exacerbations in patients with severe eosinophilic asthma. FEV1 and presentation to the clinic. Participants were then shown a 5-minute Asthma Control Questionnaire-5 (ACQ-5) scores showed improvement animated video addressing the main knowledge gaps related to the causes, and reduction in daily symptoms. presentation and management of anaphylaxis. At the end of the video, CONCLUSIONS: From this systematic and comprehensive literature participants were redirected to the same 6 questions to respond again. The review, we conclude, from this model, that the airway response from scores were recorded in percentage of correct answers (minimum 0.0; selective bronchoconstrictive stimulants and can be targeted through the maximum 1.0). 6 use of anti-inflammatory agents. It appears that inhaled L-ASA can provide RESULTS: The mean age of the patients was 5.7 4.5 years (range: 0.5- similar benefit to monoclonal antibodies directed against the T-helper-2- 17.9 years). The majority were males (61 patients; 55.0%). The mean 6 cell cytokines-induced inflammation. baseline pre-video education score was 0.77 0.16 (range: 0.3-1.0), while the mean follow-up score was 0.81 6 0.17 (range: 0.3-1.0). This score IMPLEMENTATION OF A FOOD ALLERGY difference of 0.04 was statistically significant (p50.001). There were no 506 WRITTEN ACTION PLAN IN A COMMUNITY- significant associations between change in scores and age or sex of the BASED HOSPITAL TO REDUCE THE INCIDENCE participants. OF FOOD-INDUCED ANAPHYLAXIS IN CONCLUSIONS: Our video teaching method was successful in PEDIATRIC POPULATION 12 MONTHS TO educating patients and their families to better understand anaphylaxis 18YEARS OLD and its management at the moment of the clinical encounter. The test will be repeated at a 1-year interval to determine their retention of knowledge. Data Don-Pedro1, Bamzai Rashi1, Chioma Osemwegie1, Mayela Duque Blanco1, Vivian Vega1, Olayinka Odetola1, Juhishree Adhikari1; 1WOODHULL. RATIONALE: Food allergies are the most common triggers of life- threatening anaphylaxis in children less than 18years. The purpose of this study was to commence the routine use of a written action plan (WAP) and to determine its effectiveness in reducing incidence of food-induced anaphylaxis in a community hospital. METHODS: This is a cross-sectional, Knowledge, attitude and preva- lence study amongst pediatric population aged 12months-18years with self or physician- diagnosed food allergies in a community-based Hospital. Total of 51, sixteen-question based voluntary surveys filled in the pre- intervention phase (PrIP); lasted 4 months. Statistical analysis was by Microsoft excel. RESULTS: 90% of participants selected ‘‘yes’’; 8% ‘‘not sure’’ to having food allergies. As regards frequency of allergic episodes in the pediatric population/ year (a risk factor for severe anaphylaxis); once (39%), AB160 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Fractional exhale nitric oxide in children with Management of a Immunotherapy Unit During 508 moderate persistent chronic rhinitis 510 the COVID-19 Outbreak: Building a Resilient Health Care System. Woralak Sutiratanachai, MD1, Wiparat Manuyakorn, MD, PhD2, Watcharoot Kanchongkittiphon, MD PhD3, Nichaporn Inmaculada Sanchez-Machin, MD PhD1, Ruperto Gonzalez Perez, MD Chalermpalanupap, MD1, Cherapat Sasisakulporn1, Potjanee Kiewngam1, PhD1, Paloma Poza Guedes, MD PhD2, Cristina Alava Cruz, MD1, Elena Wanlapa Jotikasthira1; 1Mahidol University, 2Ramathibodi Hospital, Mederos Luis1, Victor Matheu, MD, PhD1; 1Hospital Universitario de 3Washington University School of Medicine. Canarias, 2Hospital Universitario de Canarias, Tene. RATIONALE: To evaluate fractional exhale nitric oxide (FeNo) in RATIONALE: Immunotherapy Units (IU) went through an unexpected moderate to severe persistent chronic rhinitis transformation in order to get re-organized during the COVID pandemic. METHODS: Children age 5-15 years with moderate to severe chronic The aim of the present work is to share our experience in the IU through this rhinitis were enrolled in a cross-sectional study. Skin prick test (SPT) to rapid conversion during the outbreak. common aeroallergens, fractional exhaled nitric oxide (FeNO), and blood METHODS: The current investigation was carried out at the IU located test for specific IgE (sIgE) to house dust mite (HDM) were performed. serving the Allergy Department in a public Tertiary-care referral Hospital, RESULTS: Fifty-four children were enrolled. The mean age of patients regularly managing an average of 320 in-patients/month. Standard was 9.4 6 2.4 years, 59.3% were male. SPT was positive in 47 children scheduled regimes included hymenoptera venom subcutaneous immuno- (87%): 32 children showed positive result to only HDM, 14 children were therapy (SCIT), cluster or specific SCIT schedules for respiratory positive to HDM and other aeroallergens, 1 child had positive SPT to other conditions and subjects with documented previous SCITadverse reactions. aeroallergens. sIgE to HDM showed positive result in 45 children. Four RESULTS: During the enforced COVID-19 confinement, only hymenop- children had the discordance result between sIgE and SPT to HDM. FeNo tera SCIT was maintained in the IU, while all SCIT-associated respiratory levels were significantly correlated with the level of sIgE and mean wheal disease was postponed. Telehealth, including telephone e-mail consulta- diameter (MWD) to HDM (Pearson 0.433; P50.001 and 0.535; P< 0.001). tions and previously developed electronic consultations, enabled the The level of FeNO in children with HDM sensitization (positive to sIgE virtual management of the IU. The number of re-scheduled SCIT was and/or SPT) was significantly higher than those without HDM sensitization over 100 subjects per month. During confinement, a total of 65 starting and (28.7 6 21.4 VS 7.8 6 4.4 ppb; P <0.001). Children who had sIgE to HDM 176 maintenance SCIT doses were re-scheduled reaching 494 starts and 0.35-50 KUA/L had significantly higher FeNO than those with sIgE to 332 maintenance SCIT doses, with a median of 23 telephone and 16 mail HDM >50.01 KUA/L (23.7 6 19.1 VS 37.3 6 22.8 ppb; P5 0.04). resolved user’s questions per week. A full re-allocation of human CONCLUSIONS: Moderate to severe persistent chronic rhinitis children resources, spaces and operation hours have been achieved, regardless of with allergic sensitization have evidence of elevated fractional exhaled the increase in the absolute number of SCIT adverse reactions during this nitric oxide. This results would emphasize the significant of lower airways period. allergic inflammation in rhinitis children especially allergen those CONCLUSIONS: In our experience, telemedicine greatly aided in the sensitization transition to the re-organization of the IU, favoring further work in this direction. The unexpected COVID-19 outbreak resulted in no increase of Cost Assessment Of Allergy Procedures To AIT-associated adverse reactions in the IU despite the associated greater 509 Improve High Value Care Implementation work pressure related to this period.

Catherine Popadiuk1, Maria Paula Henao, MD2, Jennifer Kraschenewski, MD3, Edeanya Agbese, MPH3, Doug Leslie, PhD3; 1Penn State Milton S. Hershey Medical Center, 2Penn State Hershey Med- ical Center, 3Penn State Milton S Hershey Medical Center. RATIONALE: High value care aims to improve outcomes and eliminate wasteful practice. While oral challenges and desensitizations are per- formed routinely in Allergy & Immunology Clinics, our review of the literature does not identify studies evaluating their cost effectiveness. We aim to analyze the cost of these procedures by clinicians in the outpatient setting. METHODS: Using MarketScan, a commercial database of deidentified medical encounters, a retrospective review identified patients who received outpatient oral challenges and desensitizations in 2017. The clinician performing the procedure was identified and placed into one of 3 categories: allergist, nurse practitioner/physician assistant (CRNP/PA) and other physician. Statistical analysis was performed using analysis of variance (ANOVA). RESULTS: 23,181 oral challenges were performed. Allergist 74.3%, CRNP/PA 2.3% and other physician 23.4%. Total mean $189; but cost of other physician ($280) was significantly higher than other clinician types. 16,263 desensitzations were performed. Allergist 85%, CRNP/PA 4% and other physician 11%. Mean cost of desensitization was $341; other physician cost ($410), significantly more than all other clinician types while, allergist cost significantly more than CRNP/PA. CONCLUSIONS: An understanding of cost and risk are critical steps in providing high value care. Allergist and CRNP/PA provided the lowest cost for oral challenges and CRNP/PA for desensitizations. However, this needs to be weighted with the risks of the procedure to provide the best value. J ALLERGY CLIN IMMUNOL Abstracts AB161 VOLUME 147, NUMBER 2

Intensive Infection Control at a Canadian chrysogenum, and Rhodotorula mucilaginosa were significantly increased 511 Tertiary Allergy and Clinical Immunology Clinic in springtime. during COVID-19 to Provide Crucial Services CONCLUSIONS: Over 75% of fungal species identified in NAAS cohort were most abundant in the springtime. Further, concentrations of 5 Jodi Valois, RPN1, Hoang Pham, MD2, Derek Lanoue, MD3,Tim established allergenic species were significantly higher in the spring Olynych, MD PhD4, William Yang, MD FAAAAI4; 1Ottawa Allergy when compared to other seasons. These findings demonstrate seasonal Research Corporation, Ottawa, ON, Canada, 2McGill University Health variation of allergic fungal species implicated in asthma control, and better Centre, Montreal, QC, Canada, 3University of Ottawa, 4University of characterize patterns of indoor microbial exposures in New York City Ottawa & Ottawa Allergy Research Corporation, Ottawa, ON, Canada. overall. RATIONALE: Several groups have made recommendations for adjust- ments during COVID-19 to facilitate the care of urgent/high-risk patients. Effect modification of the association between Here we describe our Canadian multi-allergist tertiary allergy & clinical 513 domestic mold report and wheeze by age and immunology clinic’s observational data with intensive infection control seroatopic predisposition among children measures to provide crucial services. living in lower-income New York City METHODS: After instituting an intensive infection control protocol, we neighborhoods measured the daily number of patients seen (virtually and in-person), skin 1 2 1 tests, target biologic therapy (TBT), venom (VIT) and allergy immuno- Adnan Divjan , Karen Dannemiller, PhD , Luis Acosta, MD , Lori Hoepner3, Andrew Rundle, DrPH4, Julie Herbstman, PhD1, Frederica therapy (AIT) administered as well as adverse safety events (allergy related 5 6 and viral transmission related). Perera, PhD , Rachel Miller, MD FAAAAI , Matthew Perzanowski, PhD1; 1Columbia University, 2Ohio State University, 3SUNY Downstate, RESULTS: Our protocol consisted of scheduling in-person visits by 4 5 6 appointment-only, health screening during the reminder call (ensuring no Mailman School of Public Health, Columbia Center for Children, Icahn COVID-19 symptoms, exposures, and recent high-risk travel history) and School of Medicine at Mount Sinai. before clinic entry, providing obligatory hand sanitizer and mask at the RATIONALE: Report of domestic mold is a well-established risk for door, scanning body temperature, disinfecting rooms in-between patients, wheeze. However, how age, sex and allergic sensitization modify daily deep cleaning after-hours, donning full personal protective equip- susceptibility is less well-characterized. We hypothesized that report of ment for any direct patient care, and performing spirometry in outdoor mold would be associated with wheeze among children living in lower- tents with plexiglass. AIT patients waited in their own vehicle, if possible, income New York City (NYC) neighborhoods and that this association to be directly monitored by staff for 30 minutes to maximize physical would be modified by age, sex, and seroatopic predisposition. distancing. For any concerns, patients immediately called over front door METHODS: Current domestic mold exposure and wheeze in the previous staff or honked their car horn. Since the pandemic, we provided virtual care year were reported at multiple ages between 1 and 11 years in the Columbia and accommodated over 18,000 patients. On average per day, there were 25 Center for Children’s Environmental Health birth cohort study. Seroatopic new teleconsults, 12 skin tests, 40 TBT, 30 VIT, and 80 AIT patients. There predisposition at all ages was defined as IgE against common aeroallergens have been no adverse safety events. measured between 5-9 years. Prevalence Ratios (PR) were calculated in CONCLUSIONS: By adopting intensive infection control measures, we repeated measures models adjusting for age, sex, race/ethnicity, maternal can optimize reduction of viral transmission and maintain crucial allergy asthma, environmental tobacco smoke and material hardship. Effect services to keep high-risk allergic conditions under control. modification was tested with multiplicative interaction terms. RESULTS: Data were available on n5644 children at an average of 5.5- Springtime is associated with increases in total time points. Children in homes with reported mold (17.4%) were more 512 indoor fungi and allergenic species likely to have wheezed (PR51.22, P50.002). This association did not concentrations in a pediatric asthma cohort in differ by sex (Pinteraction>0.99) and was observed among children at ages 3, New York City 5, and 7 (all P<0.005), but not among children at ages 1-2 or 9-11 (all P>0.4). Among children with IgE data (n5414), the association was Samuel Cochran, BS1, Adnan Divjan2, Luis Acosta, MD2, Angela observed among children with (PR51.4, P<0.001), but not among children Lemons, MS3, Brett Green, PhD FAAAAI3, Matthew without seroatopic predisposition adjusting for IgE measurement age. Perzanowski, PhD2, Karen Dannemiller, PhD1; 1Ohio State University, CONCLUSIONS: Among children living in lower-income NYC neigh- 2Mailman School of Public Health, Columbia University, 3NIOSH, Cen- borhoods, report of domestic mold was associated with wheeze among ters for Disease Control and Prevention. boys and girls between the ages of 3-7 years and among those predisposed RATIONALE: Allergy and asthma severity commonly vary by season, to seroatopy. due to a confluence of factors including fluctuating outdoor and indoor allergen levels. Seasonal variation in indoor microbial communities may also play a role. We hypothesized that total fungal concentration and concentrations of select allergenic species in house dust vary by season in this pediatric asthma cohort. METHODS: The Neighborhood Asthma and Allergy Study (NAAS) recruited 349 participants from higher (HAPN) and lower (LAPN) asthma prevalence neighborhoods in New York City. We extracted DNA from bedroom floor dust samples collected throughout the year and combined next-generation sequencing with quantitative polymerase chain reaction (qPCR) to obtain absolute concentration of fungal species. RESULTS: Total fungal concentration in spring was significantly higher than all other seasons (p<_0.005). A total of 291 fungal species were identified in at least 20% of homes. Mean concentrations of 227 of these species were elevated in the spring, and of these, 77 were significantly higher (p<0.05) than all other seasons. We identified 10 allergenic fungal species significantly associated (p<0.05) with seasonal variation. Aspergillus niger, Candida albicans, Epicoccum nigrum, Penicillium AB162 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Seasonal changes of mite allergen (Der 1) levels the larger NEC room presents a valuable new tool for the study of cat 514 in houses with different architectural styles and allergies. ventilation systems Association Of Dog Exposure and Early-Life IgE Hideharu Shirai1, Hiromichi Yamaguchi2, Kohara Yudai3, Makoto Yosh- 516 Production In The Microbes, Asthma, Allergy ida3, Junko Ishihara4, Jumpei Uchiyama4, Masahiho Sakaguchi4; 1Envi- and Pets (MAAP) Birth Cohort 2 ronmental Allergens Info and Care, Yamaguchi Respiratory and 1 1 1 Dermatology Clinic, 3Ichijo Co., Ltd., 4Azabu University. Ahmed Elisa , Abigail Chatfield , Suzanne Havstad, MA , Alexandra Si- tarik1, Haejin Kim, MD1, Kyra Jones2, Ganesa Wegienka, PhD FAAAAI1, RATIONALE: Research on the influence of different architectural styles 1 3 1 and ventilation systems on mite allergen levels is crucial to decrease mite Christine Joseph, PhD , Nicholas Lukacs, PhD , Christine Johnson , Den- nis Ownby, MD FAAAAI4, Susan Lynch, PhD5, Edward Zoratti, MD allergen exposures in houses. The purpose of this study was to examine the 6 1 2 seasonal changes in mite allergen (Der 1) levels on the floors and FAAAAI ; Henry Ford Health System, Henry Ford Health Systems, 3University of Michigan Medical School, 4Augusta University, 5Asthma, mattresses of houses with different architectural styles and ventilation 6 systems. Immunology & Allergy Assoc., Henry Ford Hospital. METHODS: Thirty-one families, without considering the families’ RATIONALE: Early-life dog exposure has been associated with histories of allergies, participated in this study. Written consent was decreased IgE levels. 5 obtained from all the families. All 31 families lived in Hamamatsu-city, METHODS: Pregnant women living with indoor dog(s) (n 81) and those 5 Japan. Dust samples were monthly collected from the floors of the living with no pets (n 60) were recruited. Total IgE trajectories were constructed rooms and mattresses in the bedrooms from March 2019 to February 2020. using serum samples collected at cord, 6 months and 18 months of age. Mite allergen Der 1 (Der f 1 and Der p 1) levels were measured using Using mixed effects models, the trajectories were compared between sandwich ELISA. The air temperature and relative humidity in each house infants from pet-free and dog-keeping households, and between dog-free, 1 were measured using hygrothermography. dog only, and 2 or more dog households. Demographic variables were RESULTS: Ten families lived in detached houses with balanced assessed as potential effect modifiers. ventilation (group A), 10 families lived in detached houses with exhaust- RESULTS: Prenatal indoor dog exposure and the number of dogs was not 5 only ventilation (group B), and 11 families lived in concrete apartment associated with early life IgE (p 0.12 and 0.71, respectively). Infant sex buildings with exhaust-only ventilation (group C). All groups showed was a significant modifier for both the binary dog and number of dogs 5 5 significant seasonal changes in mean monthly temperature and relative outcomes (p 0.013 and p 0.024, respectively). humidity. Group A showed significantly lower mean monthly relative For males, total IgE trajectory was 44.3% lower with prenatal indoor dog 5 5 humidity than other groups. Group A showed significantly lower levels of exposure (p 0.013), versus 39.3% higher for females (p 0.206). Der 1 in mattress dust than other groups. Compared to males without prenatal indoor dog exposure, total IgE 5 CONCLUSIONS: Different architectural styles and ventilation systems trajectory was 34.7% lower when exposed to one dog (p 0.084), and 5 may have some influence on mite allergen levels and could possibly be 60.6% lower when exposed to 2 or more dogs (p 0.003). This effect was 5 modified to decrease mite allergen exposure in houses. not observed in females (p 0.205). CONCLUSIONS: Infant sex was a significant modifier in the relationship Commissioning of a Larger Naturalistic between prenatal dog exposure and early life IgE. Specifically, males with 515 Exposure Chamber for Cat Dander prenatal indoor dog exposure have lower early life total IgE trajectories than males without indoor pet exposure. Laura Haya, PhD1, Shawn Somers-Neal2, Rym Mehri2, Zachary Huff- man2, Stefan Van de Mosselaer1, Suzanne Kelly, PhD3, Bryan Santone1, Edgar Matida, PhD2, William Yang, MD FAAAAI1; 1Red Maple Trials, 2Carleton University, 3Red Maple Trials Inc. RATIONALE: We previously developed a 2-person capacity (14.4 m3) Naturalistic Exposure Chamber (NEC) providing naturalistic and controlled exposure to cat allergen. We scaled this model to a larger 8-per- son capacity room (36.7 m3). Fel-d-1 was measured throughout the room and over time for 2-hour aerosolization tests. Target Fel-d-1 was 40-100 ng/m3 to mimic home environments. METHODS: Robot vacuum cleaners were modified to bypass the filter and have variable suction control. Two carpets in the NEC naturally accumulated dander shed by 2 resident cats. Carpet allergen levels were monitored and supplemented by shaking cat bedding ahead of testing and by evenly distributing 10 or 20g of milled cat hair (Stallergenes, Greer). Throughout the tests, a vacuum moved about each carpet aerosolizing the aspirated dander, which was circulated by fans. Air samples (5L/min for 30-min) were collected by sampling pumps (Gilian 5000) at 4 locations across the room and 4 time-intervals. Collected Fel-d-1 was quantified by ELISA to determine air concentration in ng/m3. Repeatability was demon- strated on separate days under optimized settings (N55). RESULTS: Mean Fel-d-1 (N55) under optimized settings was 79 (612 SD) ng/m3. Excellent temporal stability and spatial homogeneity were observed with 19% and 11% maximum deviations from the mean, respectively. CONCLUSIONS: The NEC method of cat allergen exposure has demonstrated superior control and repeatability of allergen levels compared to standard bedding shaking methods, while maintaining the naturalistic advantages of a field exposure-type setting. The validation of J ALLERGY CLIN IMMUNOL Abstracts AB163 VOLUME 147, NUMBER 2

Inhaled Nicotine Salt Counteranions Induce subjects were unable to detect the smells of lime, pickle, lemon, orange, 517 Airway Inflammation and Promote a soap, and banana respectively at baseline. Neutrophilic Asthma Phenotype CONCLUSIONS: SARS-CoV2 infection results in complete or partial anosmia associated with inability to smell ‘‘sour’’ items, banana, and soap. Robert Immormino, PhD1, Bridger Scoggins2, Timothy Moran, MD More than a third of COVID-19 patient did not recover their sense of smell PhD1; 1University of North Carolina School of Medicine, 2University of at ;6weeks. Objective evaluation of the sense of smells in COVID-19 North Carolina-Chapel Hill. patients may be used as marker of disease and for monitoring sense of smell RATIONALE: The popularity of electronic cigarettes (e-cigs) that utilize recovery. nicotine salts has rapidly increased since the introduction of JUUL pods in 2015. The immunotoxicology of nicotine salts in the respiratory tract is Integrative Proteomics and Phosphoproteomics understudied. We hypothesized that nicotine salt counteranions induce 519 of Asthmatic Airways following RV Infection airway inflammation and alter immune responses to inhaled allergens Joshua Kennedy, MD FAAAAI1, Katherine Caid1, Suzanne House, BS1, independent of nicotine. 2 1 1 METHODS: The nicotine salt counteranions lactate, levulinate, salicylate Claire Putt , Nathan Avaritt, PhD , Stephanie Byrum, PhD , Alan Tackett, PhD1, Richard Kurten, PhD1; 1University of Arkansas for Medi- or benzoate (5% solution) were administered to C57BL/6J mice by 2 oropharyngeal aspiration daily for three days (acute exposure model) or cal Sciences, University of Arkansas for Medical Scien. three times weekly for three weeks (persistent exposure model). In some RATIONALE: Rhinovirus (RV) infection is associated with 60-80% of studies, mice were also exposed to house dust mite (HDM) allergen alone childhood asthma exacerbations in the emergency department. Global or in combination with benzoate three times weekly for three weeks. proteomics and phosphoproteomics were performed using human preci- Airway inflammation was assessed by enumeration of inflammatory cells sion cut lung slice (PCLS) airways from deceased asthma and non-asthma in bronchoalveolar lavage fluid and lung histology. donors with and without infection with RV in order to confirm previously RESULTS: Acute exposure to nicotine salt counteranions induced an identified dysregulated pathways and identify new areas of investigation. influx of neutrophils into the airways. Persistent exposure to nicotine salt METHODS: PCLS were prepared from 5 asthma and 4 non-asthma donor counteranions resulted in a mixed neutrophilic and lymphocytic airway lungs for phosphoproteomic analyses. PCLS were infected with RV39 or inflammatory response. Neither acute nor persistent exposure to nicotine treated with vehicle for 48 hours. Carbachol induced airway bronchocon- salt counteranions caused airway eosinophilia. In a HDM-mediated striction was measured pre-/post-infection. PCLS were collected and allergic airway inflammation model, co-exposure to benzoate and HDM airways were microdissected for LC-MS/MS. Proteins and enriched increased the percentage of airway neutrophils but decreased the percent- phosphopeptides from each sample were labeled with TMT10plex isobaric age of eosinophils compared to HDM alone. tags and peptides were identified on an Orbitrap Eclipse Tribrid mass CONCLUSIONS: Both acute and persistent exposure to nicotine salt spectrometer. counteranions induces airway inflammation in mice independent of RESULTS: Asthma donors showed airway hyper-responsiveness to nicotine. Benzoate also induced neutrophilic inflammation in a HDM- carbachol after RV infection (Control uninfected -0.6207, infected 5 mediated allergic airway inflammation model, suggesting that exposure to -0.4877; p NS; Asthma uninfected -0.7113, infected 1.099; p<0.001). e-cigs containing nicotine salts may promote a neutrophilic asthma Global comparison between asthma and non-asthma airways identified 412 phenotype. proteins and 1049 phosphopeptides differentially expressed using a p- value < 0.05 and an absolute fold change > 2 threshold. Comparison of Loss of sense of smells associated with sour asthma + RV to non-asthma + RV identified 381 significant proteins and 518 taste is a possible diagnostic marker for 763 phosphopeptides. Pathologic pathways were identified with integrative COVID-19 bioinformatics and human protein-protein interactome network analyses. Dysregulated pathways in asthma infected compared to non-asthma Mohammad Asad, PhD1, Esha Sehanobish, PhD1, Valerie Fong1, Mea- infected involved inflammatory responses, TNF-a signaling, Interferon-g ghan O’Neill1, Viraj Patel1, Danielle Bottalico1, Merhunisa Karagic1, De- response, and IL-6/STAT3. nisa Ferastraoaru, MD1, Inessa Gendlina1, Mali Barbi1, Meryl Kravitz1, CONCLUSIONS: Asthma donor airways were hyper-responsive after Cynthia Matsumura1, Denise Tejera1, Golda Hudes, MD PhD1, Nadeem infection with RV, and this finding was associated with dysregulated Akbar1, Avindra Nath2, Bryan Smith2, Thomas Ow1, Elina Jerschow, pathways in the inflammatory response compared to similar non-asthma MD FAAAAI3; 1Albert Einstein College of Medicine/Montefiore Medical donors. Center, Bronx, NY, 2National Institute for Neurologic Disorders and Stroke, National Institutes of Health, Bethesda, MD, 3Albert Einstein Col- lege of Medicine. RATIONALE: SARS-CoV2 infection causes loss of sense of smell. We hypothesized that specific smell loss is associated with COVID-19. METHODS: Patients recruited for the study within 48 hours of COVID- 19 test at Montefiore Medical Center, Bronx, NY were evaluated for sense of smell by UPSIT (University of Pennsylvania Smell Identification TestÒ). A follow-up UPSIT score was recorded after ;6weeks of the first visit. Paired t-test was used for statistical analysis. RESULTS: Patients with similar distribution of age, gender, race, and disease severity were included into the study. At baseline, there was no significant difference in smell recognition between COVID-19+ (N514) and COVID-19-negative patients (N56) (54 (IQR 43-70) and 71 (IQR 39- 80), p50.5). Among COVID-19+, eight patients (57%) recovered their sense of smell with the UPSIT score increasing from 49%-correct (IQR 40- 63) to 69%-correct (IQR 61-85), p50.01. Five patients (36%) had no recovery of the sense of smell, and there was a significant worsening in the score from 60%-correct (IQR 48-78) to 55%-correct (IQR 45-68), p50.04. Among COVID-19+ patients, 79%, 71.4, 64.3, 64.3%, 79% and 64.3% AB164 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Recent Common Cold Does Not Reliably Protect T Test, and sensitivity and specificity for predicting milk-triggered EoE 520 from Re-Infection and Fails to Cross-Protect was calculated. Fifteen Weeks Later, Despite Involvement of RESULTS: Endotoxin removal from milk peptides reduced non-specific Cross-Reactive T Cells proliferation, while normalization to patient-specific tetanus response reduced inter-sample variability. With these modifications, there was a Lyndsey Muehling, PhD1, Ronald Turner, MD1, Alberta Paul, PhD2, significant difference in the proliferation of peripheral memory CD4+ T Cheree Denby-Taylor1, William Kwok, PhD3, Judith Woodfolk, MBChB cells from milk-triggered EoE patients compared with those from non- PhD FAAAAI1; 1University of Virginia, 2University of Virginia (Former), allergic controls (P 5 0.0005). A positive test threshold of 0.8 (% milk 3Benaroya Research Institute. expanded T cells/% tetanus expanded T cells) resulted in an assay RATIONALE: Despite pre-existing immunological memory to cold sensitivity of 91%, and specificity of 78%. viruses, little is known about how exposure to one cold virus strain CONCLUSIONS: Milk-specific T cells circulate in the blood of milk- influences re-infection with another related strain. Here, we evaluated the triggered EoE patients, and proliferate in response to stimulation with milk response to two rhinovirus strains using sequential challenge designed to peptides. Tolerance or sensitivity to milk can be determined by this method mimic repeated natural exposures. with high sensitivity, high specificity, and minimal risk to the patient. METHODS: Screening of 664 healthy adults (ages 18–40 years) yielded Expansion to other EoE-causal foods as well as prospective study of this 94 who were seronegative for both RV-A16 and RV-A39; 46 were assay are needed to better define its predictive value and clinical utility. challenged with RV-A16, and randomized for re-challenge with either RV-A16 or RV-A39 after 15 weeks. Infection was assessed by viral Effect on age on clinical and immunologic shedding and seroconversion. Numbers of circulating RV-A16-specific 522 efficacy of peanut sublingual immunotherapy

CD4+ T cells were tracked for 30 weeks using peptide/MHCII tetramers. 1 1 2 RESULTS: After first RV-A16 challenge, 82.5% of subjects became Olivia Francis , Michael Kulis, PhD , Ping Ye , Edwin Kim, MD MS FAAAAI3; 1UNC Chapel Hill, 2University of North Carolin at Chapel infected, and 24% of these remained asymptomatic. Higher viral load in 3 the nose was associated with higher antibody titers. RV-A16 re-challenge Hi, University of North Carolina School of Medicine. resulted in reduced rates of infection and viral shedding compared with RV- RATIONALE: Peanut immunotherapy studies suggest benefit of initia- A39 re-challenge (46.2% vs. 88.2% and 38.5% vs. 82.4%; p<0.001). At re- tion at younger ages, but direct age comparisons are lacking. challenge with RV-A16, elevated pre-existing antibody titers to RV-A16 METHODS: Children ages 1-11 years underwent peanut sublingual did not correlate with viral load (p50.54), whereas upon heterologous re- immunotherapy (SLIT) in a previously published study. The cohort was challenge with RV-A39, higher pre-existing antibody titers to RV-A16 subdivided into ages 1-5 and 6-11 years for post-hoc analysis. Subjects related to higher viral load and a higher rate of viral shedding (p50.03). with clinical history of peanut allergy and elevated peanut-specific IgE (ps- Cross-reactive T cells responded in those who were infected during re- IgE) were treated with 2 mg peanut SLIT and double-blind placebo- challenge with RV-A39. controlled food challenges (DBPCFC) were performed after 3-5 years. Ps- CONCLUSIONS: These findings highlight the capricious nature of the IgE was followed throughout treatment, while peanut-specific IgG4 (ps- immune response to common cold virus. Given the high seropositivity rate IgG4) and peanut skin prick test (SPT) wheal sizes were recorded at for cold viruses in adults, the ability for pre-existing antibodies to confound baseline and after 3-5 years of SLIT. protection to a related cold virus could have broader implications for RESULTS: Median peanut protein successfully consumed at DBPCFC 5 respiratory viruses. was 2750mg for the younger group and 1750mg in the older group (p 0.3). Mean SPT wheal size decreased from 12.7 to 9 mm in the younger group, Development of an Antigen-Specific T Cell and 11.3 to 10.4 mm in the older group, however between group differences 521 Assay to Identify Food Triggers in Eosinophilic were not significant at baseline or DBPCFC. Baseline mean ps-IgE and ps- Esophagitis IgG4 levels were not significantly different between groups, nor were there significant differences at DBPCFC. Julianna Dilollo1, Elizabeth Martin1, David Hill, MD, PhD1, Jonathan CONCLUSIONS: Post-hoc analysis of children treated with SLIT did not Spergel, MD, PhD2; 1The Children’s Hospital of Philadelphia, 2Children show significant age-related differences in amount of peanut protein Hospital of Philadelphia. consumed at DBPCFC, nor in immunologic makers of peanut allergy at RATIONALE: Eosinophilic esophagitis (EoE) is a chronic, T cell baseline or DBPCFC, suggesting age at which SLIT begins may be less mediated disease that is triggered by specific foods and results in important in predicting treatment response. Prospective studies are needed odynophagia and progressive esophageal dysfunction. Due to the absence to determine the effects of peanut immunotherapy among children of of food-specific IgE antibodies in some EoE patients, skin prick testing is different ages. not reliably helpful when attempting to identify EoE-causal foods. As such, the current standard of care involves empiric food elimination diets or swallowed steroids with repeated endoscopies. There is significant need for a quick, non-invasive laboratory test which can accurately predict tolerated and trigger foods in EoE patients. METHODS: Blood samples were obtained from milk-triggered EoE patients or non-food allergic controls, and PBMCs were isolated by Ficoll gradient. PBMCs were cultured at 1 million cells/mL in OpTimizer SFM for 6 days in vitro in the absence or presence of a cocktail of 5 endotoxin- depleted milk peptides (a/b/k-casein, a-lactalbumin, and b-lactoglobulin at 6.25 mg each per 200k cells), or tetanus toxoid (0.625 mg per 200k cells). CD4/CD45RO+ T cell proliferation was assessed by CFSE dilution, and measured by flow cytometry. Proliferation in response to milk peptides was normalized to proliferation in response to tetanus toxoid. Statistically significant differences in T cell proliferation were determined by Student’s J ALLERGY CLIN IMMUNOL Abstracts AB165 VOLUME 147, NUMBER 2

The Influence of Early and Continuous Exposure for discontinuation overall (65%), followed by suspected reaction in the 523 of Infants to Cow's Milk Formula on The child (18%) and fear of the child reacting (12%). Occurance of Milk Allergy CONCLUSIONS: Discontinuation of peanut after introduction was relatively common in high-risk infants, particularly those with a family Idit Lachover-Roth1, Anat Cohen - Engler2, Yossi Rosman, MD1, Keren history of PA, while new diagnosis of PA, though rare, occurred almost Meir-Shafrir2, Yael Furman3, Tal Biron-Shental4, Ronit Confino-Cohen4; exclusively among those with AD. Families with another PA child may 1Meir Medical Center, Kfar Saba, Israel. Sackler School of Medicine, Tel need support with peanut introduction. Aviv University, Israel, 2Meir Medical Center, Kfar-Saba, Israel, 3Meir Medical Center, Kfar-Saba, Israel. Sackler School of Medicine, Tel Transcriptomic and Gene Set Enrichment Aviv University, Israel, 4Meir Medical Center, Kfar-Saba, Israel. Sackler 525 Analysis of Peanut stimulated CD4+ T cells School of Medicine, Tel Aviv University, Israel. during Peanut Oral Immunotherapy RATIONALE: Cow’s milk protein (CMP) allergy is a common food Yamini Virkud, MD FAAAAI1, Bert Ruiter, PhD1, Neal Smith2, David allergy in infants. Information regarding the best timing to first introduce 1 1 CMP is controversial. There are data suggesting that avoidance of CMP for Pyle, MD PhD , Sarita Patil, MD FAAAAI , Wayne Shreffler, MD PhD FAAAAI3; 1Massachusetts General Hospital, 2Center for Immunology at least the first three days of life has a protective effect for CMP allergy 3 (CMA). Others suggest that introduction of CMP after the first 15-30 days & Inflammatory Dis, Massachusetts General Hospital / Harvard. of life, raises the risk for CMA. RATIONALE: Early studies suggest that oral immunotherapy (OIT) The current ongoing study assesses the effect of early and continuous decreases Th2 cytokine production, a possible mechanism for desensiti- exposure to cow’s milk formula (CMF) on the development of CMA. zation. However, data remains limited on the differences between in- METHODS: Newborns were prospectively recruited shortly before birth dividuals who develop transient desensitization (TD) versus sustained and divided to groups according to parents’ preference: exclusive unresponsiveness (SU), a longer-lasting protection after OIT. breastfeeding; breastfeeding with at least one daily meal of CMF, and METHODS: We performed bulk RNA-sequencing on peanut-stimulated feeding with CMF only. Infants were followed monthly until the age of 12 CD154+ CD4+ T cells from longitudinal samples of 22 participants over months. the course of a peanut OIT trial (5 SU, 6 TD, 6 treatment failures, and 5 on RESULTS: To date 1,560 infants were recruited: 1,160 (74.35%) were placebo). We conducted differential expression analysis comparing end of followed for six months or more, and 635 (40.7%) completed 12 months of maintenance to baseline timepoints and analyzed the results using gene set follow up. Five hundred and seven infants (51.4%) were exclusively enrichment analysis (GSEA) with an FDR of q<0.05. breastfed untill 2 months of age, 318 (32.2%) combined breastfeeding and RESULTS: GSEA revealed differential enrichment of 18 Th1, 7 Th2, and CMF, and 162 (16.4%) ate only CMF. Immediate reaction proven by skin 13 Th17 gene sets among OIT-treated participants, as compared to placebo. test developed in 9 infants (0.91%), all were exclusivly breastfed. Within All Th2 and Th17 gene sets and 13/18 Th1 gene sets demonstrated this group, the prevalence of CMAwas 1.77% compared to zero in the other enhancement at baseline compared to maintenance, and examination of groups (RR51.96, CI 95% 1.23-1.96, p50.004). these signatures demonstrated that these Th1, Th17, and Th2 signatures CONCLUSIONS: It appears that early and contineous exposure to CMF were more predominantly enhanced in the TD and treatment failure since birth has a protective effect against the development of IgE mediated groups, as compared to the SU group. CMA. A larger cohort is needed in order to validate these results. CONCLUSIONS: These data support the hypothesis that OIT shifts T helper cell phenotypes away from Th1, Th2, and Th17 signatures, and that Rates of Peanut Discontinuation After these shifts occur predominantly in TD and treatment failures, but not in 524 Introduction Among High-Risk Infants SU participants. These early differences may prove useful in predicting responses to OIT and discovering mechanisms to improve the efficacy of Abhilasha Banerjee1, Michael Pistiner, MD MMSc2, Wayne OIT. Shreffler, MD PhD FAAAAI3, Robert Wood, MD4, Joan Dunlop, MD5, Jennifer Dantzer, MD6, Mihaela Plesa6, Daria Szelag, PNP7, Roger Peng6, Alkis Togias, MD FAAAAI8, Corinne Keet, MD MS PhD9; 1Johns Hopkins Department of Allergy and Immunology, 2MassGeneral Hospital for Children, Harva, 3Massachusetts General Hospital / Harvard, 4Johns Hopkins University School Medicine, 5Johns Hopkins Hospital, 6Johns Hopkins, 7Johns Hopkins University, 8NIAID/NIH, 9John Hopkins Hospital. RATIONALE: Current guidelines recommend that high-risk infants consume at least 2 grams of peanut protein three times a week. It is not clear how well families will be able to comply with these guidelines. METHODS: Participants aged 4-11 months with no prior peanut exposure and (i) diagnosis of non- peanut food allergy, (ii) moderate-severe atopic dermatitis (AD), or (iii) first degree relative with peanut allergy (PA) were enrolled at Johns Hopkins (n5311) and Massachusetts General Hospital (n514). After PA was excluded, participants were advised to consume 2 grams of peanut protein three times per week and were followed to 18 months with questionnaires and office visits. RESULTS: Of 247 participants thus far, 30 (12%) were diagnosed with PA (n55) or discontinued peanut (n525). PAwas more common among those with AD (4/140 [2.8%] vs 1/107 [ 0.9%], p50.288), while discontinuation without diagnosed allergy was less common (10/136 [7%] vs 15/106 [14%], p50.085), although these differences were not statistically signif- icant. Discontinuation without diagnosis of allergy was higher among those with family history of PA (22/161 [14%] vs 3/81 [4%], p50.016), with fear of another household member reacting the most common reason AB166 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Basophil activation tests identify a peanut OIT production and downregulation of hsa04622 RIG-I-like receptor signaling 526 subgroup with improved safety and outcomes pathway at week 104 post-OIT. CONCLUSIONS: To our knowledge, this unique assessment using Sharon Chinthrajah, MD1, Shu Cao1, Mindy Tsai2, Kaori Mukai, PhD3, biopsies from OIT participants for the first time provides insights into Robert Tibshirani, PhD4, Sayantani Sindher, MD1, Kari Nadeau, MD PhD the transcript-level changes at the local GI tissue. We anticipate FAAAAI5, Stephen Galli, MD6; 1Stanford University - Sean N. Parker discovering further novel molecular biomarkers in conjunction with Center for Allergy and Asthma Research, 2Stanford University - Pathol- blood-derived data from these participants. ogy Sponsored Projects, 3Stanford University - Department of Pathology, 4Stanford University - Biomedical Data Science and of Statistics, 5Stan- Presence of Ara h 2, the major peanut allergen, ford Univ School Medicine, 6Stanford University - Department of Pathol- 528 in human milk ogy, Stanford University, Stanford. 1 2 2 RATIONALE: Oral immunotherapy (OIT) treatment for peanut allergy is Amy Burris , Nichole Diaz, BA , Antti Seppo, PhD , Kirsi Jarvinen- Seppo, MD PhD FAAAAI3; 1Univeristy of Rochester Medical Center, now FDA approved for treatment of peanut allergic patients. The need for 2 3 accurate and robust prognostic biomarkers to aid in patient selection is University of Rochester Medical Center, University of Rochester Med- critical. We investigated the long-term safety of peanut OIT from our ical Center. POISED study, and the potential role of BATs in predicting adverse events RATIONALE: Dietary antigens can be secreted in human milk, including during long-term OIT and double-blind-placebo-controlled-food chal- Ara h 2, which is detected in about one-third of mothers after peanut lenges (DBPCFCs). consumption. Studies examining the role of diet during lactation in METHODS: 120 participants were enrolled and underwent peanut OIT development of atopic disease use diet history as the measure of exposure build-up and maintenance followed by daily peanut avoidance (n560), low of the breastfed infant; however, there is significant inter-individual dose of 300 mg peanut (n535), or placebo (n525). DBPCFCs were variation in the secretion of dietary proteins in milk. completed every 13 weeks following 2 years of OIT. Blood was obtained METHODS: In this pilot study, 15 lactating mothers were recruited from for BAT during OIT therapy and at each DBPCFC time point. the pediatric allergy clinic and medical center. Mothers avoided peanut for RESULTS: Participants with lower baseline basophil responsiveness as 24 hours then consumed either 2 tablespoons of peanut butter or a handful determined by BATs experienced fewer dose-related adverse events and of peanuts. Human milk samples were collected 1 hour after peanut less severe symptoms both during OIT and in follow-up food challenges. ingestion. Ara h 2 was measured by sandwich ELISA, as described before Importantly, the rate and severity of OIT-induced adverse events and use [1]. of epinephrine diminished with continued OIT, suggesting that OIT is a RESULTS: The Ara h 2 ELISA had a quantification range at 0.032-20 ng/ long-term treatment option for food allergy. Furthermore, we explored ml. Eight of the 15 mothers had detectable Ara h 2 in their milk with levels the predictive utility, in clinical outcomes, of changes in basophil respon- ranging from 0.056 to >20 ng/ml. Recovery of Ara h 2 protein spiked into siveness within the first two years of OIT. We found that sequential use of control milk was 42%. BATs aided in distinguishing those who were successful versus those who CONCLUSIONS: This highly sensitive assay detected Ara h 2 in 53% of failed. women 1 hour after peanut protein consumption. Detection of dietary CONCLUSIONS: Our findings underscore the importance of BATs as antigens in human milk lays the groundwork for investigations into how biomarkers for predicting long-term efficacy, and safety, of peanut OIT. dietary antigen secretion in human milk promotes induction of tolerance vs. sensitization or allergic symptoms in breastfed infants. Transcriptomics Of Gastrointestinal Biopsies 1. Schocker, F., et al., Detection of the Peanut Allergens Ara h 2 and Ara h 6 527 During Oral Immunotherapy Reveals Changes in Human Breast Milk: Development of 2 Sensitive and Specific Sandwich In IgA Pathway ELISA Assays. Int Arch Allergy Immunol,2017.174(1): p.17-25.

Gopal Krishna Dhondalay, PhD1, Wenming Zhang, PhD2, Ramona Hoh, PhD3, Neeraja Kambham2, Scott Boyd, MD, PhD2, Sandra Andorf, PhD4, Monali Manohar, PhD5, Sharon Chinthrajah, MD3, Kari Nadeau, MD PhD FAAAAI6; 1Sean N Parker Centre for Allergy & Asthma R, 2Stanford University, 3Stanford, 4University of Cincinnati Col- lege of Medicine, 5Stanford Univesity, 6Stanford Univ School Medicine. RATIONALE: Oral immunotherapy (OIT) has shown promising results in successfully desensitizing peanut allergic patients under research settings. We aimed to understand transcriptional changes in the biopsied gastrointestinal (GI) tissue during OIT using transcriptomic profiling. METHODS: Biopsies were collected from 5 sites of the upper GI tracts of six participants undergoing a randomized, placebo-controlled, phase II peanut OIT trial (NCT02103270), at baseline, week 52, and week 104. cDNA libraries were constructed with TakaraBio SMARTer kits from pooled-RNA from GI sites and sequenced on Illumina Hiseq4000. The raw files were quality-checked with FastQC, aligned to human genome (GRCh38) with STAR, and quantified for gene-level counts using RSEM method. DESeq2 and generalized linear mixed effect modelling was used for differential expression analysis (log2FoldChange > 2; FDR < 0.01). RESULTS: Transcriptomic results from participants undergoing active peanut OIT (N56) showed 33 differentially expressed genes across time- points baseline, week 52 and week 104. Notably, we observed significant up-regulation of TRIM21, TFAM, IGFL1 and down-regulation of COQ10B, HDAC11 across OIT treatment. KEGG pathway enrichment analysis of differentially expressed gene set revealed upregulations of pathways including hsa04672 Intestinal immune network for IgA J ALLERGY CLIN IMMUNOL Abstracts AB167 VOLUME 147, NUMBER 2

Differential Contribution Of TNFSF14/LIGHT- rating telemedicine noninferior to in-person visits. Predictably, telemed- 529 Receptor Mediated Pathways To Inflammatory icine compared least favorably to traditional clinical encounters for Fibroblast Phenotypes In Eosinophilic teaching or learning about physical exam findings. Esophagitis CONCLUSIONS: This survey recorded attitudes about several aspects of telemedicine, including implementation and perceived educational value Mario Cabrero Manresa1, Elaine Pham2, Loan Duong3, Haruka Miki4, compared to traditional clinical care. As telemedicine is now a fixture in Michael Croft5, Seema Aceves, MD PhD FAAAAI6; 1University of Cali- clinical medicine, research must continue to identify strengths and fornia San Diego, 2UNIVERSITY CALIFORNIA SAN DIEGO, 3UCSD, weaknesses of telemedicine in delivering educational objectives in 4La Jolla Institute for Immunology, 5La Jolla Institute, 6University of Cal- academic settings. ifornia, San Diego. RATIONALE: Fibroblasts (FBL) mediate tissue remodeling in eosino- Identifying Baseline Differences in Autonomy in philic esophagitis (EoE), a chronic allergen driven inflammatory pathol- 531 Patients with Moderate-Severe Asthma ogy. We recently defined a putative role of the cytokine TNFSF14/LIGHT Timothy Buckey, MD, MBE1, Knashawn Morales, ScD2, Andrea Apter, as a promoter of an inflammatory esophageal FBL subtype. LIGHT can 2 1 2 signal through two receptors, herpes virus entry mediator (HVEM) and MD MA MSc FAAAAI ; Temple University Hospital, University of lymphotoxin-beta receptor (LTßR). We investigated the relative contribu- Pennsylvania. tions of each receptor to LIGHT-mediated inflammatory FBL RATIONALE: The specialty of Allergy and Immunology is unique in that differentiation. its providers are tasked with caring for patients of all ages, sexes, and METHODS: Esophageal FBL were isolated from healthy donors and backgrounds. With diverse populations, medical ethics, especially auton- pediatric active and inactive EoE patients. siRNAs and expression vectors omy, play an important role in healthcare delivery. Autonomy is the ability were used to manipulate HVEM and LTßR. RNA sequencing (RNAseq), of patients to make informed medical decisions. This ethical value is rooted qRT-PCR, flow cytometry, immunofluorescence and immunoblots were in disease state understanding. We sought to identify patient characteristics used to investigate molecular pathways activated by LIGHT and the that influence autonomy. contribution of each receptor to the LIGHT transcriptome. METHODS: 295 adults with moderate-severe asthma from practices RESULTS: Active EoE FBL demonstrated higher frequency of HVEM+ serving low-income neighborhoods completed two surveys at the begin- and ICAM-1+ cells under basal conditions compared to inactive EoE FBL, ning of a one year randomized clinical trial. The Navigating Ability and while LTbR levels were similar. We have previously shown that HVEM is ICS Knowledge questionnaires were combined to create a 21-question induced by TGF-ß1 in healthy and active EoE FBL. TGF-ß1 increased assessment of autonomy with possible scores ranging from 18-103. Linear HVEM in inactive EoE FBL to a level similar to that found at baseline in regression was performed on the derived autonomy score predicted by active EoE FBL. siRNA and over-expression studies demonstrated that patient baseline characteristics. HVEM regulates a defined subset of LIGHT targets including ICAM-1 and RESULTS: Comparison revealed lower baseline autonomy in patients 5 IL-32, whereas LTßR had a more general regulatory effect on the LIGHT reporting Spanish as their primary language (p 0.01) and those with 5 transcriptome. LIGHT activated the canonical and alternative NF-kB diabetes (p<0.01) or depression (p 0.03) at 11.4, 4.7, and 3.1 points lower pathways and inhibition of the alternative pathway had a potent silencing respectively. 8.2 points higher autonomy was observed in non-Hispanic effect on the LIGHT transcriptome. whites (p<0.01) and individuals with higher functional health literacy CONCLUSIONS: Our studies reveal differential functions of the LIGHT (measured by S-TOFHLA, p<0.01). No other associations were observed. receptors and NF-kB signaling on FBL differentiation and identify CONCLUSIONS: This study demonstrated associations of autonomy potential therapeutic targets in EoE. with co-morbidities, demographics, and literacy. These results may reflect differences in social, educational, and economic opportunities. Further Attitudes Among Faculty Members and Trainees investigation is needed to assess and understand how socioeconomic and 530 About the Effects of Telemedicine on Clinical educational factors influence autonomy. By identifying baseline differ- Education During COVID-19 ences in autonomy based on patient characteristics, this project provides an initial step in the process of developing interventions to improve patient Patrick Gleeson1, Di Sun, MD MPH2, Jennifer Heimall, MD FAAAAI3, autonomy. Olajumoke Fadugba, MD1; 1Hospital of the University of Pennsylvania, 2Children’s Hospital of Philadelphia, 3CHOP. RATIONALE: Telemedicine utilization has increased during the COVID- 19 pandemic. However, telemedicine’s impact on the clinical learning environment is not well-studied. METHODS: A survey was developed to assess attitudes about tele- medicine’s effect on clinical education. The survey was distributed to faculty and trainees in clinical training programs at the Children’s Hospital of Philadelphia (CHOP) and the Hospital of the University of Pennsylvania (HUP), and to Allergy & Immunology (A&I) training programs nationwide. RESULTS: 127 responses were recorded. Nearly all respondents indicated that they were participating in telemedicine. Overall, a majority (76%) of respondents reported experiencing logistical or technical difficulties with the implementation of telemedicine within their departments, which was frequently identified as either delays in setting up the telemedicine software or with patients having difficulty using the software. In comparing telemedicine to in-person visits for educational purposes, responses were mixed, with overall 37/112 (33%) respondents reporting that telemedicine was as effective as, or more effective than, in-person visits. Interestingly, on this question, A&I fellows and faculty members had discordant responses, with 9/17 (53%) of fellows and 11/34 (32%) of faculty members AB168 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Improving Drug Allergy Education Among technology and found these visits acceptable to complete their clinical 532 Internal Medicine Residents encounter. Additional work is needed to determine how to incorporate allergy telehealth within and beyond the COVID-19 pandemic. Darya Koenig1, Santiago Alvarez-Arango, MD1, N. Franklin Adkinson, MD FAAAAI2; 1Johns Hopkins University, 2Johns Hopkins Asthma and Methods for Identifying and Reconciling Allergy Allergy Center. 534 Information in the Electronic Health Record

RATIONALE: Up to 35% of patients have a drug allergy listed in their 1 2 3 electronic medical record reducing prescribing options and increasing the Carlos Ortega , Ying-Chih Lo, MD, PhD , Suzanne Blackley, MA , Sa- chin Vallamkonda4, Frank Chang3, Oliver James3, Sharmitha Yerneni1, use of less-effective, more expensive drugs. Internal medicine residents are 3 2 often the first to provide care but their drug- allergy knowledge is limited. Diane Seger, RPh , Liqin Wang, PhD , Kimberly Blumenthal, MD MSc FAAAAI5, Foster Goss, DO, MMSc6, Paige Wickner, MD FAAAAI2,Li METHODS: Internal medicine residents from Johns Hopkins were tested 2 1 2 on drug allergy knowledge (using nine clinical vignettes) and knowledge Zhou, MD, PhD ; Brigham and Women’s Hospital, Boston, MA, Brig- ham and Women’s Hospital, Harvard Medical School, Boston, MA, 3Mass confidence (scale 1-10). After completion of the pre-test, residents were 4 presented with an educational session on drug allergy scenarios commonly General Brigham, Boston, MA, Brigham and Women’s Hospital, Boston, MA, 5Massachusetts General Hospital, Harvard Medical School, Boston, encountered in clinical practice. Following this educational intervention, 6 residents were re-tested on the same day and three months after. MA, University of Colorado Hospital, University of Colorado School of RESULTS: A total of 45 internal medicine residents participated (18 Medicine, Aurora, CO. PGY-1, 10 PGY-2, 13 PGY-3, 4 PGY-4). The median number of correct RATIONALE: Patient allergies are documented in multiple areas of the responses among all 45 participants in the pre-test was 4/9, which doubled electronic health records (EHRs) including areas beyond the allergy list to 8/9 following the educational session. The mean difference of correct (e.g., notes, laboratory tests, and flowsheets). Systematically reconciling responses post-intervention compared to pre-intervention on the same day allergy information is critical to improve the accuracy of the EHR allergy was 3.5 (95% CI 2.8, 4.1). Only 13 residents completed the test three- list and facilitate clinical decision support to maintain patient safety. months post-intervention with the median number correct of 6/9. There METHODS: Our retrospective study included all patients who visited was no significant difference in pre-test correct responses based on the Mass General Brigham (MGB) in 2018. We examined patient allergy participants’ training level. The mean difference of knowledge confidence information documented in five EHR areas (i.e., allergy list, clinical notes, score post-intervention compared to pre-intervention was 2.8 (95% CI 2.3, laboratory tests, flowsheets, and drug-allergy alerts) and proposed 3.4). approaches to reconciling discrepancies between these EHR areas. We CONCLUSION: We observed drug allergy knowledge deficits in internal used natural language processing to identify free-text reactions in allergy medicine residents at all training levels. We observed a significant increase lists. We consolidated duplicate allergens in allergy lists by mapping in knowledge about important drug allergy concepts after a brief previous entries with the same name/ingredients into a preferred allergen. educational intervention which we believe should be incorporated into We manually reviewed amoxicillin challenge tests performed where the the standard residency education curriculum. allergy was deleted, but then later re-added. We reviewed drug-allergy interaction alerts and identified active allergies with >_3 allergy alert COVID-19 Pandemic and Telehealth: allergy overrides by a clinician to identify active allergies unlikely to be clinically 533 patient perspectives in an urban, academic relevant. medical center RESULTS: Of 1,588,979 patients studied, 266,275 (16.8%) had allergy lists indicating need for review and reconciliation. Allergy issues detected Darshil Patel1, Andrea Pappalardo, MD FAAAAI1, Vanessa Harmon2, included free-text reactions (n5428,770), >_3 allergy alert overrides Mary Pasquinelli1, Julia Trosman3, Christine Weldon4, Sharmilee Nyen- (n510,896), duplicate allergies listed (n521,051), penicillin allergy active huis, MD FAAAAI1; 1University of Illinois at Chicago, 2University of Il- despite negative challenge test (n536). linois Hospital and Health Sciences System, 3center for business models, CONCLUSIONS: Incomplete and inaccurate EHR allergy lists are 4Center for Business Models in Healthcare. common. Reconciliation methods may allow for allergy information RATIONALE: The COVID-19 pandemic created an unprecedented need identification and reconciliation. Further work is needed to develop for telehealth. Studies exploring patient’s perspective and access to automated reconciliation methods to ensure the accuracy of patient allergy telehealth technology are lacking. This study aims to assess the patient lists and provide safe patient care. perspective on telehealth technology during the COVID pandemic. METHODS: A survey was created by a multi-disciplinary team at an urban academic center which includes questions addressing patients’ access and satisfaction with telehealth visits (phone and/or video). Survey was distributed to 346 patients in a mixed allergy/pulmonary outpatient clinic via email, text message, phone, or in-person. Data was analyzed using Fisher’s exact test. RESULTS: Survey response rate was 22.5% (n578). Respondents were middle-aged (mean551.6 years), minority (68%) women (82%). All patients reported having phone access to complete telehealth visits; however, only 83% report access to a smartphone and 82% had access to a computer/tablet. Over half of patients previously used a video conferencing application (62%). Telehealth visits during the pandemic were deemed ‘‘acceptable’’ by over two-thirds of respondents, with 15% finding telehealth ‘‘unacceptable’’. Almost two-thirds of respondents had no concerns/barriers related to telehealth visits (63%), while only 27% had no concerns/barriers for in-person visits (p<0.01). This finding remained significant when COVID-19 was eliminated as concern (p5 0.02). CONCLUSIONS: In our study of urban, minority allergy patients, a majority of patients had access to at least one device to complete a telehealth visit. Patients encountered minimal barriers to telehealth J ALLERGY CLIN IMMUNOL Abstracts AB169 VOLUME 147, NUMBER 2

Test-dose as a De-labeling Tool in Patients with Allergist satisfaction score was 93.11%, with 100% of allergists willing to 535 Self-reported Sulfonamide Allergy: A Quality offer virtually-supported food introduction even when in-person visits are Improvement Project fully available. CONCLUSIONS: Virtually-supported food introduction is a reasonable Gabriel Motoa Cardona1, Ismael Carrillo-Martin, MD1, Jared option for food introduction in high-risk infants during COVID-19. Both Nelson, DO1, Wendelyn Bosch, MD1, Justin Oring1, Miguel Park, MD1, caregivers and allergists reported positive experiences with virtual care Alexei Gonzalez-Estrada, MD1; 1Mayo Clinic. which can be a feasible option even when in-person visits resume. RATIONALE: We aimed to assess an intervention implemented in our Allergy Clinic to de-label non-HIV patients with self-reported sulfonamide An Institutional Survey of Patient Satisfaction allergy utilizing a previously published test-dose challenge of trimetho- 537 with Telemedicine Services in Pediatric prim-sulfamethoxazole (TMP-SMX). Allergy During the COVID-19 Pandemic METHODS: A pre-/post-intervention, quality improvement design in Kasey Lanier1, Merin Kuruvilla, MD1, Jennifer Shih, MD FAAAAI1; patients with self-reported non-severe delayed, immediate or unknown 1 reaction to TMP-SMX. We compared the effectiveness of a one-to-two step Emory University School of Medicine. test-dose versus a 6-step desensitization of TMP-SMX. The main outcome RATIONALE: This study investigates parent satisfaction with telemed- measure was the rate of success for desensitization versus test-dose. icine services offered at a pediatric allergy clinic during the SARS-CoV2 Patients were contacted in the test-dose group via phone to evaluate safety pandemic. of further TMP-SMX administration. Cost for each procedure was METHODS: Our study measured parent satisfaction using a cloud-based estimated based on current Medicare standards. platform at an academic institution-based pediatric allergy clinic during RESULTS: A total of 52 patients underwent sulfonamide desensitization the SARS-CoV2 pandemic. All consenting parents of pediatric patients in the two-year (2017-2018) pre-intervention period and were compared seen in the first two months of the pilot telemedicine program were with 53 patients who underwent test-dose administration of TMP-SMX in surveyed using a questionnaire-based satisfaction survey. the two-year (2019-2020) post-intervention period. In both periods, most RESULTS: 135 parents of 191 encounters (70.6%) completed the patients were female (87% versus 75%), white (85% versus 96%), and over questionnaire. The most common primary diagnoses were food allergy 60 years of age (60% versus 58%). In the test-dose group, 51% underwent a (31%), asthma (24%), rhinitis (24%), immune deficiency (12%), dermatitis two-step test-dose. The success rates of desensitization and test-dose were (7%) and urticaria/angioedema (3%). 89% of parents rated their comfort similar (94% versus 90%; P 5 .72). In the test-dose group, none of the 37 seeing a doctor via telemedicine as 10, and 93% felt their doctor explained patients who received a course TMP-SMX post de-labeling reported an their condition in an easily understandable manner. 67% strongly agreed adverse drug reaction. The estimated post-intervention cost reduction was that connecting their appointments was easy. 56% were likely to choose $13,217. telemedicine over in-person care while 73% would strongly recommend CONCLUSIONS: The implementation of a validated protocol for graded telemedicine services to others. However, only 36% percent strongly administration of TMP-SMX revealed similar success rates than desensi- agreed that seeing a doctor using telemedicine was just as good as in- tization, with a decrease cost, and without an increase of adverse events. person visits, and this was especially endorsed by parents of parents with government insurance (odds ratio 2.9). Interestingly, parents of established Web-based Infant Food Introduction (WIFI): patients were significantly less likely to feel comfortable seeing the doctor 536 Improving Access to Allergist-supervised using telemedicine. Also, parents of patients with government insurance Infant Food Introduction were 2.45 more likely to elect telemedicine. CONCLUSIONS: This study underscored parent perceptions and Meriem Latrous1, Rongbo Zhu, MD2, Samira Jeimy, MD PhD2, Douglas perceived deficiencies in telemedicine services offered by pediatric Mack, MD3, Lianne Soller, PhD1, Edmond Chan, MD FAAAAI1, Jennifer allergists possibly influenced by demographic factors. Future studies Protudjer, PhD4, Mariam Hanna, MD3, Elissa Abrams, MD FRCPC4, Vic- should investigate mechanisms to enhance the telemedicine experience in toria Cook, MD1, Scott Cameron, MD PhD1, Stephanie Erdle, MD1, pediatric allergy so it more closely resembles in-person experiences. Tiffany Wong, MD1; 1University of British Columbia, 2Western Univer- sity, 3McMaster University, 4University of Manitoba. RATIONALE: The COVID-19 pandemic has resulted in the modification and postponement of many allergy clinic services, including observed introductions of allergenic foods in high-risk infants. Delays may increase the risk of developing preventable food allergies. We performed a multi- centred quality improvement (QI) study to assess the feasibility of virtually-supported food introduction in high-risk infants. METHODS: A multi-centred QI study was conducted across Canada. Infants aged 24-months or younger deemed ‘‘high-risk’’ for development of food allergy underwent virtually-supported oral introduction to highly allergenic foods. Surveys were given to allergists and caregivers to assess their experience and perception of virtually-supported food introduction. RESULTS: Preliminary results of 17 allergist encounters demonstrated that the most common virtually-supported food introduction were peanuts (41.7%), and tree nuts (35.3%). The median age of the patients was 9 months. 94.1% successfully tolerated the introduction with only 1 patient having a mild reaction (urticaria). Pre/post surveys of caregivers showed increased confidence in introducing allergenic foods, recognizing signs and symptoms of allergic reactions, and treating allergies following the virtual encounter. The average satisfaction of virtually-supported food introduction was 94.4%, with 92% of caregivers choosing this method in the future if it meant shorter wait times. AB170 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Clinical Documentation of Peanut Allergy difference 20.4 (95% CI 3.89-37.3), and higher number of patients with 538 Prevention in an Academic Learning Health IGA 0/1 (14/35 SLIT and 5/31 placebo, RR 2.63, 95% CI 1.09-6.39), were System observed at 18 months. No sinificant at changes were found for EASI, DLQI and VAS. Edward Iglesia, MD1, Hunter Smith, MPH1, Edwin Kim, MD MS CONCLUSIONS: Results of this proof-of-concept clinical trial warrant FAAAAI1, Michelle Hernandez, MD FAAAAI1; 1University of North further investigation on the efficacy of SLIT with HDM as an adjuvant Carolina School of Medicine. treatment for AD. RATIONALE: Consensus guidelines recommend early peanut introduc- tion (EPI) as an effective strategy for preventing peanut allergy. Real-world Safe Subcutaneous Immunotherapy Dosing practice patterns of EPI guidance are poorly understood. We aimed to 540 Adjustments Following Prolonged Interruptions described EPI practice patterns within an academic learning health system. In Therapy Due To Covid-19 Pandemic METHODS: We queried the health system’s central data repository to Lois Kang, Maya Goldman1, Anny Uyehara, NP1, Michael Goldman, MD identify individuals eligible to receive EPI guidance from 1/6/2017 - 03/30/ 2 1 2 2020: persons less than 12 months of age at the time of a clinical encounter FAAAAI ; Allergy & Asthma Center of Central Maryland, Allergy & for either a health supervision visit or a problem-based visit related to Asthma Center of Central Maryl. eczema. We used the Electronic Medical Record Search Engine RATIONALE: Subcutaneous allergen immunotherapy is a well-estab- (EMERSE) to search clinical notes for the word ‘‘peanut.’’ These were lished treatment for allergic respiratory diseases. Once at maintenance manually reviewed for EPI documentation and other practice pattern doses, injections are typically given every 2 to 4 weeks and doses adjusted characteristics. due to missed injections. During the Covid-19 pandemic our practice RESULTS: Of a total of 18,149 individuals, 152 (0.8%, mean age 6.4 suspended immunotherapy injections from March 17, 2020 through May 5, months) had clinical documentation of EPI guidance (72% clinical note, 2020. Upon resumption, doses were adjusted with an emphasis on trying to 20% patient instructions, 5% both, 3% telephone note). EPI guidance was keep patients in the same concentration vial as their previous injection. We performed by 61 providers among 6 specialties (43% pediatrics, 40% sought to characterize reactions to restarting injections after prolonged family medicine, 15% allergy/immunology, 2% other) in 24 unique disruption. practices. Of those who received EPI guidance, the following comorbid METHODS: 187 patients were contacted after resuming immunotherapy diagnoses and/or characteristics were documented: 35% eczema, 11% egg following a 7- to 23-week interruption. All patients waited in the office 20 allergy, 21% family history of food allergy, 31% topical corticosteroid use. minutes after injections. Patients were surveyed 1-3 days after their first Twenty percent were referred to an allergist for peanut allergy risk injection regarding reactions. Local reactions were defined as a 1-5cm assessment and 12% had a peanut IgE obtained. wheal and/or erythema. CONCLUSIONS: Clinical documentation of EPI counseling is low. RESULTS: Of the 187 patients contacted, 167 patients (90%) reached the Further dissemination and implementation efforts are needed to encourage maintenance vial and 157 patients (84%) reached their maintenance dose providers to prioritize EPI and increase standard utilization of consensus prior to the treatment interruption. 170 patients (90%) stayed in the same guidelines. concentration vial as before the break. Among the 187 patients surveyed, 138 patients (73.8%) reported no local reactions to the initial injections, 48 Effect of house dust mite sublingual patients (25.7%) reported a local reaction similar to those experienced 539 immunotherapy in patients with Atopic prior to the break, and 2 patients (0.5%) reported experiencing a local Dermatitis: a randomized, double-blind, reaction for the first time. No patients reported reactions larger than 5cm. placebo-controlled clinical trial No systemic reactions occurred. CONCLUSIONS: Patients returning to immunotherapy following a 7-23- Sarah Langer1, Janaina Melo, PhD, MD1, Renata Cardili, PhD, MD1, week interruption may safely resume at a lowered dose within the same Roberto Bueno, PhD, MD2, Mariana Ferriani, PhD, MD1, Adriana concentration vial. This pertains mostly to patients who have previously Moreno, PhD3, Fabio Carmona, PhD, MD2, Jorgete Silva, PhD, MD1, Per- reached maintenance injections. sio Roxo, PhD, MD2, Davi Aragon, PhD2, Luisa Karla Arruda, MD PhD FAAAAI2; 1Ribeir~ao Preto Medical School Clinical Hospital, University of S~ao Paulo, Ribeir~ao Preto, SP, Brazil, 2Ribeir~ao Preto Medical School, University of S~ao Paulo, Ribeir~ao Preto, SP, Brazil, 3University of Sao Paulo, Ribeir~ao Preto, SP, Brazil. RATIONALE: House dust mites (HDM) sensitization is often found in patients with atopic dermatitis (AD). We aimed to investigate the role of sublingual immunotherapy (SLIT) as adjuvant treatment for patients with AD allergic to HDM. METHODS: We enrolled 91 AD patients 3 years of age and older, with SCORAD >_15 and positive skin prick tests and/or IgE to Dermatophagoides pteronyssinus (Dpt) in this randomized, double-blind, placebo-controlled trial. Patients were stratified by age (<12 and >_12 years) to receive SLIT with Dpt extract (6.7 mcg/mL Der p1, 0.9 mcg/ mL Der p2) or placebo for 18 months. Background therapy was main- tained. Primary outcome was a 15-point decrease in SCORAD in at least 40% of SLIT and 15% of placebo groups. Secondary outcomes were de- creases in SCORAD, EASI and VAS; IGA 0/1; and decrease >_4 points in DLQI. Relative risks were calculated by adjusting a log-binomial regres- sion model. RESULTS: 66 patients completed the study (35 SLIT, 31 placebo). After 18 months, 74.2% patients in SLITand 58% in placebo groups reached 15- point decrease in SCORAD (RR 1.28, 95% CI 0.89-1.83). Significant SCORAD decreases from baseline, 55.6% SLIT and 34.5% placebo, mean J ALLERGY CLIN IMMUNOL Abstracts AB171 VOLUME 147, NUMBER 2

Role of Acid-sensing Ion Channel 1 in sensing North America. Additional ongoing studies are being performed to refine 541 acidification and triggering inflammation in the diagnostic approaches for defining cannabis sensitization. Nasal Polyps with Asthma Temporal Trends of Skin Prick Tests Hai Lin1, Guang-Yi Ba1, Ru Tang1, Ming-Xian Li2, Wei-Tian Zhang1; 543 1Shanghai Sixth People’s Hospital, 2Shanghai Sixth People’s Hospital. Pasquale Mule1, Bruce Mazer, MD FAAAAI1, Danbing Ke, PhD1, Dun- RATIONALE: A variety of inflammatory cells are infiltrated histologi- 1 1 2 cally in sinonasal mucosa of chronic rhinosinusitis with nasal polyps can Lejtenyi, MSc , Liane Beaudette, RN , Julia Upton, MD , Edmond Chan, MD FAAAAI3, Ann Clarke4, Sofianne Gabrielli, MSc1, Moshe (CRSwNP), especially CRSwNP with asthma. Acid-sensing ion channel 1 1 1 (ASIC1) are essential in the process of sensing acidification and triggering Ben-Shoshan, MD FAAAAI ; Division of Allergy and Clinical Immu- nology, Department of Pediatrics, Montreal Children’s Hospital, McGill inflammation. The present study aimed to explore the roles and mechanism 2 of ASIC1 in the pathogenesis of CRSwNP. University Health Centre, Montreal, QC, Canada, Division of Immu- METHODS: Nasal secretions from control subjects, patients with nology and Allergy, Department of Pediatrics, The Hospital for Sick Chil- dren, Department of Paediatrics, University of Toronto, Toronto, ON, CRSwNP with or without asthma were collected for measuring PH values. 3 Western blotting, real-time PCR and immunohistochemistry (IHC) were Canada, Division of Allergy and Immunology, Department of Pediatrics, BC Children’s Hospital, University of British Columbia, Vancouver, employed to assess ASIC1 expression in nasal tissue samples from 4 included subjects. The co-localization of ASIC1 with inflammatory cells British Columbia, Canada, Division of Rheumatology, Department of was evaluated by immunofluorescence staining. Then, dispersed nasal Medicine, Cumming School of Medicine, University of Calgary, Calgary, polyp cells (DNPCs) were cultured under acidified condition (pH6.0), with Alberta, Canada. or without ASIC1 inhibitor amiloride. Western blotting, real-time PCR, RATIONALE: Although clinical practice recommends performing skin LDH activity kit and ELISA were performed to assess the effects and prick tests (SPTs) at least four weeks following an allergic reaction/ mechanisms of stimulators on the cells. anaphylaxis, it is not established if SPTs done earlier are useful in detecting RESULTS: PH values were significantly lower in the nasal secretions the culprit allergen. We aimed to assess SPTs for the culprit allergen as a from patients with CRSwNP with asthma. Significant upregulation of function of time after an allergic reaction/ anaphylaxis. ASIC1 protein, mRNA levels and positive cells was found in CRSwNP METHODS: SPTs were assessed at baseline, 30 minutes, 1-2 weeks, and with asthma. ASIC1 was detected in a variety of inflammatory cells. In one month after allergic reactions to food allergens through recruitment of cultured DNPCs, significant alterations of ASIC1 levels, LDH activity, 10 patients who underwent a food challenge at the Montreal Children’s HIF-1a levels and inflammatory cytokines were found under acidified Hospital. Given the small sample size, a non parametric test (Wilcoxon condition (pH6.0), but were prevented by amiloride. signed rank test) was used to determine statistically significant changes in CONCLUSIONS: Upregulation of ASIC1 might be essential in the SPT results between the given time intervals. process of sensing acidification and triggering inflammatory response via RESULTS: Patient ages ranged from 2 to 19 years old (mean 10.3, 70% enhancing HIF-1a expression and LDH activity to activate inflammatory male). Allergens used included eggs (30%), milk (20%), hazelnuts (10%), cells in pathogenesis of CRSwNP, especially in CRSwNP with asthma. and peanuts (40%). All patients developed objective allergic symptoms during the food challenges, and five cases of anaphylaxis were observed. Non-specific Lipid Transfer Protein (Can s 3) Is a SPTs were false-negative 30 minutes after an allergic reaction; with a 542 Relevant Cannabis Allergen in North America decrease in mean wheal diameter from 4.3 mm (SD 2.15) at baseline to 2.4 mm (SD 1.51) at 30 minutes. There was a clinical and statistically Henry Morelli1, Cathy Thorpe2, Ine Decuyper, MD PhD3, Cali Lo- significant (p<0.05) increase 1-2 weeks after the reaction (mean 6.4 mm, blundo1, Khaldon AbbasPremedical Student4, Didier Ebo, MD PhD SD 5.41), and no significant difference in SPT results between 1-2 weeks FAAAAI5, Gordon Sussman, MD FAAAAI6, Martin Chapman, PhD and one month after a reaction. FAAAAI7, Ajay Nayak, PhD1; 1Thomas Jefferson University, 2INDOOR CONCLUSION: SPTs performed 1-2 weeks after a food induced allergic Biotechnologies Inc., 3University of Antwerp, 4University of British reaction are a reliable measure, challenging the traditionally held Columbia, 5University Antwerp, 6University of Toronto, 7Indoor Biotech- viewpoint regarding the timing of SPTs. nologies, Inc. RATIONALE: Non-specific lipid transfer protein (nsLTP) of cannabis (Can s 3) has been reported as a major allergen for cannabis sensitization and a potential driver of cannabis-plant/food cross-reactive allergies in Europe. Here, we report for the first time that Can s 3 is a relevant allergen in patients presenting allergic sensitization to cannabis in North America. METHODS: Following skin prick testing (SPT) with cannabis extract, various environmental and plant food allergens, serum was collected for detection of specific IgE (sIgE) to recombinant Can s 3. Qualitative binding of sIgE to Can s 3 was examined by western blot analysis. Further, sIgE to recombinant Can s 3 was also quantified using a novel polyclonal antibody- based chimeric enzyme-linked immunoassay (ELISA). RESULTS: Western blot analysis revealed positive IgE reactivity to Can s 3 in (4/10) Canadian and (16/30) Belgian cannabis symptomatic patients. The chimeric ELISA standard curve was established using a polyclonal antibody. When patient sera were applied in this novel chimeric ELISA, multiple patients demonstrated positive sIgE reactivity to recombinant Can s 3 (19/30). There was a strong correlation between western blot and ELISA data sets, with patients demonstrating strong immunoreactivity in western blot showing O.D. values >1.0 in ELISA. CONCLUSIONS: Our studies demonstrate that Can s 3 (nsLTP of cannabis) is a relevant allergen among cannabis sensitized individuals in AB172 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Intranasal Ketorolac, Diagnosis and EDS-FLU (Exhalation Delivery System With 544 Desensitization for Aspirin Exacerbated 546 Fluticasone) is Associated With Improved Respiratory Disease (AERD) Sleep in Patients With Nasal Polyposis

Amie Nguyen1, Bruce Zuraw, MD2, Christina Wu, MD3, Alexander Anuja Kapil, MD1, Harry Sacks, MD2, John Messina, PharmD2, Mah- Kim, MD2, Sandra Christiansen, MD2; 1Kaiser Permanente Los Angeles boobeh Mahdavinia, MD PhD FAAAAI1; 1Rush Medical College, Rush Medical Center, 2UCSD, 3USCD. University, Chicago, IL, 2OptiNose US, Inc. Yardley, PA. RATIONALE: Intranasal ketorolac has been proposed as a diagnostic test RATIONALE: Patients with CRSwNP frequently suffer from poor for AERD as well as a faster, safer and reliable addition to facilitate ASA quality of sleep, significantly lower quality-of-life scores, and chronic desensitization. We conducted the first prospective study to dissect the depression. EDS-FLU has been shown to significantly improve symptoms impact of intranasal ketorolac incorporation during ASA desensitization of CRSwNP. This post-hoc analysis reports the effects on sleep from EDS- versus standard oral ASA protocols in concert with evaluating its FLU pivotal trials. diagnostic utility for AERD. METHODS: NAVIGATE I/II were similarly designed, prospective, METHODS: AERD subjects were enrolled in a prospective open-label randomized, 24-week [16 double-blind (DB) + 8 open-label (OL)], observational study between 11/2006 and 8/2013. Participants selected one placebo-controlled studies. Patients (N5482) with moderate-severe of the following desensitization protocols: Intranasal ketorolac one day CRSwNP received EDS-FLU 186mg(n5160), EDS-FLU 372mg prior to oral ASA (Group 1, combined) or ketorolac challenge with greater (n5161), or EDS-placebo (n5161) twice-daily. Data were pooled for than two weeks elapsing until oral ASA (Group 2, washout). All patients this post-hoc analysis. Outcomes were assessed with the MOS Sleep-R were on a leukotriene modifying drug (Montelukast) for at least 1 week Problems Index, Sinonasal Outcome Test (SNOT-22) sleep function prior to challenge. subscale, and Patient Global Impression of Change (PGIC). RESULTS: Twenty subjects were enrolled: 13 in Group 1; 7 in Group 2. RESULTS: Baseline demographics were similar across treatments. By

No significant differences were seen for baseline symptom scores or FEV1. week-16, greater improvements in the MOS Sleep-R Problems Index were Group 1 demonstrated significant increases for the threshold dose of ASA observed with EDS-FLU 186ug and 372ug compared with EDS-placebo (p50.009), likelihood of having a ’silent ASA desensitization’ (p50.0147) [least squares (LS) mean change: 214.90 and 212.4 vs 29.1; P<.001 and and decreased reaction severity to oral ASA (p50.036). There were no sig- P<.05, respectively]. EDS-FLU also improved MOS-Sleep-R subscales. nificant differences in reaction FEV1, incidence of extra-pulmonary symp- Patients receiving EDS-FLU showed improvements in the SNOT-22 toms, limited naso-ocular reactions, rescue treatment requirements or time Sleep Function subscale that were consistent with the MOS-Sleep to symptom resolution. There was 100% concordance between reactions to Problems Index. At week-16, LS mean changes from baseline were intranasal ketorolac and oral ASA for Group 2, supporting its utility as a 23.86 and 24.13 with EDS-FLU 186ug and 372ug, respectively, vs diagnostic test for AERD. 22.23 with EDS-placebo (P<.001, both comparisons). At week-24 (OL: CONCLUSIONS: Intranasal ketorolac is a useful diagnostic test and all patients received EDS-FLU 372ug), patients reported continued adjunct within the combined ketorolac/ASA protocol to achieve effective, improvement (24.05, 24.29, 23.66, respectively). At week-16, z66% efficient and perhaps safer desensitization to ASA for AERD patients. receiving EDS-FLU reported being ‘‘much/very much’’ improved as as- sessed by PGIC versus 33% with EDS-placebo. At 24-weeks, 72% to Systemic Reaction Rates in Subcutaneous 81% reported ‘‘much/very much’’ improvement. 545 Immunotherapy Patients Monitored Outside of CONCLUSIONS: In patients with moderate-severe CRSwNP, EDS-FLU Clinic treatment is associated with improved sleep scores and satisfaction

Alyssa Osheim1, Julia Smith1; 1Greater Austin Allergy, Asthma and Immunology. RATIONALE: Subcutaneous immunotherapy (SCIT) has been well proven in the literature to successfully treat multiple allergic conditions. A concern of SCIT is the risk of developing a systemic reaction following injections. Under standard care, patients typically receive SCIT inside the clinic and are required to wait 20-30 minutes post-injection before leaving. However, due to social distancing guidelines set forth by the CDC in regards to COVID-19, the clinic chose to provide patients with three options for receiving their injections: in-clinic, curbside, or wait in their vehicle after receiving injections in-clinic. We hypothesized that there is no difference in risk of systemic reaction between being monitored in the clinic versus outside of clinic. METHODS: GAAAI collected 98,220 injection records from six clinics within the Austin, TX area from January 1, 2020 through August 1, 2020. The number of systemic reactions following SCIT were recorded in our electronic shot records system. Medical Assistants were required to record and describe every systemic reaction to SCIT and indicate the method by which patients received their injections (in-clinic, curbside, or clinic injection-car wait). Chi-square analysis was used to calculate p-values for in-clinic observation versus pooled curbside/clinic injection-car wait. This study will continue with ongoing data collection. RESULTS: Allowing patients to wait in their vehicles post-injection was associated with a significantly greater incidence of systemic reaction (x25185.19; P<0.01). CONCLUSIONS: There is a significantly higher risk of systemic reactions associated with receiving immunotherapy injections outside of the clinic or waiting in the patient’s vehicle post-injection. J ALLERGY CLIN IMMUNOL Abstracts AB173 VOLUME 147, NUMBER 2

The 12-SQ HDM SLIT-Tablet Shows Similar alone and 10.4% for S. aureus alone to 74% for the combination of S. 547 Safety and Efficacy Across Geographies, aureus and RV (P50.003; Kruskal-Wallis test). Ethnic and Age Groups CONCLUSIONS: Staphylococcus aureus promotes RV replication, which leads to increased cell death in differentiated airway epithelial cells. Hendrik Nolte, MD PhD1, Tomokazu Matsuoka2, David Bernstein, MD These in vitro findings suggest that S. aureus colonization of the upper air- FAAAAI3, Veronica Hulstroem4; 1ALK, Bedminster, NJ, USA, 2Faculty ways could increase susceptibility to RV infection and associated damage of Medicine, Graduate Faculty of Interdisciplinary Research, University to the airway epithelium. of Yamanashi, Yamana, 3Bernstein Clinical Research Center and Division of Immunology, Allergy and Rheumatology, University of Cincinnati, Cyclic-Di-GMP promotes STING-dependent ILC2 Cincinnati, OH, USA, 4ALK, Hørsholm, Denmark. 549 to ILC1 shift and abrogates eosinophilia in ILC2- RATIONALE: House dust mite (HDM) sublingual immunotherapy driven lung inflammation

(SLIT)-tablets have been evaluated in large clinical trials of adolescents 1 1 1 1 and adults in North America and Japan. Now, it is possible to assess safety Kellen Cavagnero , Jana Badrani , Luay Naji , Michael Amadeo , An- thea Leng1, Lee Lacasa1, Alyssa Strohm1, Taylor Doherty, MD FAAAAI1; and efficacy across age groups and world regions. 1 METHODS: Efficacy and safety data from 2 randomized, double-blind, University of California, San Diego. placebo-controlled phase III clinical trials (NCT01700192 and JapicCTI- RATIONALES: Asthma has been associated with viral infection, bacte- 121848) with 12-SQ HDM were analysed by age (12-17 years/18-64 years) rial colonization, and host cell death. These processes drive the accumu- and ethnicity/region (Japan/North America [NA]). Trials were designed lation of intracellular cyclic-di-nucleotides such as cyclic-di-GMP (CDG). similarly with respect to medical practice, target population, eligibility Group 2 innate lymphoid cells (ILC2s) are critical drivers of experimental criteria, efficacy and safety monitoring. models of asthma; however, it is unclear how CDG regulates innate type 2 RESULTS: The treatment effect on the primary endpoint of total inflammation. In this study, we sought to determine whether CDG combined rhinitis score (TCRS) in Japanese (N5633) and NA modulates ILC2-driven allergic responses. (N51482) subjects were comparable both for the overall trial populations METHODS: WT and genetically modified mice were challenged and the adolescent and adult subgroups, ranging between 17%-22% intranasally with the clinically relevant fungal allergen Alternaria alter- relative to placebo. HDM SLIT-tablet was well tolerated, and in general, nata, with and without CDG, daily for 3 days. One day following the final the safety profile was similar in Japanese and NA populations. The challenge, lungs and brochoalveolar lavage fluid were harvested for flow placebo-subtracted treatment-related adverse event (AE) rate in NA cytometric analysis and ELISA. ILCs were identified by flow cytometry 2 adolescents/adults was 45%/44% and in Japanese adolescents/adults was as CD45+Lineage Thy1.2+ lymphocyte-sized cells and were further 2 2 47%/46%. There was no epinephrine use due to treatment-related events in separated into ST2+CD127+ ILC2s and ST2 CD127 ILC1s. Finally, adolescent subjects in either trial. Only 4 events of epinephrine use due to intracellular staining for ILC cytokine and transcription factors was treatment-related events were reported among NA adult subjects. The performed. RESULTS: CDG induced STING-dependent early type 1 and 3 interferon HDM IgE and IgG4 responses were comparable between Japanese and NA subjects and between age groups. (IFN) production and significantly suppressed lung ILC2s and airway CONCLUSIONS: In conclusion, the results show that SQ HDM SLIT- eosinophilia. Further, CDG administration led to the expansion of tablet is insensitive to ethnic, age or regional differences with a similar Tbet+IFNg+ ILC1s and airway neutrophil accumulation, through IL-18-, safety, efficacy, and immunologic profile. IL-12-, and STAT6-independent mechanisms. CONCLUSIONS: CDG is a strong immunomodulator of innate type 2 Staphylococcus aureus Increases Rhinovirus airway inflammation and activity through STING could potentially be used 548 Replication and Synergistically Enhances as a strategy to reduce ILC2-driven inflammation. Cytotoxicity During Co-infection of the Airway Epithelium

Eishika Dissanayake1, Rebecca Brockman-Schneider2, Reed Stubben- dieck2, Cameron Currie2, James Gern, MD2; 1University of Wisconsin - Madison, 2University of Wisconsin-Madison. RATIONALE: Early-life colonization patterns of the airway epithelium by bacteria and the co-detection of specific bacterial species with rhinovirus (RV) has been shown to increase the risk of childhood asthma. Staphylococcus aureus is a common nasal symbiont that has implicated in the development of childhood asthma and chronic sinusitis. In this study we tested how S. aureus and RV co-infection affected the bronchial epithelium. METHODS: We developed a co-culture system by differentiating bronchial epithelial cells from a healthy donor at air-liquid interface. We then incubated the apical surface of the mature epithelium for 24 hours with 33105 colony-forming units of three different S. aureus isolates ob- tained from the nasal secretions of children. Subsequently, we introduced of 105 plaque-forming units (PFUs) of RV-A16 for 48 hours. We analyzed cell lysates for RV replication by quantitative PCR and assessed cell viability by testing culture medium for lactate dehydrogenase. RESULTS: The three isolates of S. aureus significantly increased RV replication compared to controls without bacteria (7.21 vs 6.41 log PFU equivalents/sample; P50.03, Mann-Whitney test). The mean cellular cyto- toxicity increased from 6.3% for the no-treatment control, 10.1% for RV AB174 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

CD69+ Th2-type CD4+ T Cells are Responsible Air pollutant exposure induces peanut allergy in 550 for Long-term Memory Responses to Allergens 552 an animal model in the Lungs Timothy Moran, MD PhD1, Johanna Smeekens, PhD1, Robert Takao Kobayashi, PhD1, Koji Iijima, PhD1, Jyoti Lama1, Hirohito Kita, Immormino, PhD1, Zach Allen2, Andrew Ghio, MD3, Michael Kulis, MD1; 1Mayo Clinic Arizona. PhD1; 1University of North Carolina School of Medicine, 2University of RATIONALE: Persistent and recurrent inflammation in airway mucosa North Carolina-Chapel Hill, 3US Environmental Protection Agency. plays a central role in allergic airway diseases. However, our knowledge is RATIONALE: Birth cohort studies suggest that exposure to traffic-related air limited regarding the mechanisms that explain development and mainte- pollutants (TRAP) is associated with sensitization to foods, but whether this nance of immunologic memory in the lungs. The goal of this project was to results in food allergy is unclear. Here, we investigated if airway exposure to fill this gap by using mouse models. TRAP and other air pollutant particles induces peanut allergy in a mouse model. METHODS: BALB/c mice were exposed intranasally to ovalbumin METHODS: C57BL/6J mice were exposed to peanut antigen alone or in (OVA) antigen with fungus Alternaria extract as an adjuvant. An in vivo combination with either diesel exhaust particles (DEP), urban particulate antibody labeling strategy was used to identify T cells within the lung matter (PM), oil fly ash particles (OFAP) or wood smoke particles (WSP) tissues. by oropharyngeal aspiration twice weekly for two weeks. One week later, RESULTS: Single airway exposure of na€ıve BALB/c mice to OVA plus mice were challenged with peanut by intraperitoneal injection, and body Alternaria promoted accumulation of ST2+CD4+ T cells in the lung tissues temperatures were measured to monitor anaphylaxis. Levels of serum within 3 days, followed by their expression of Il4 and GATA-3 by day 7. peanut-specific (PNs) immunoglobulins and lung innate cytokines were Within these ST2+CD4+ T cells, CD69+ subpopulation expressed genes measured by enzyme-linked immunosorbent assay. related to effector functions including Il4, Il5, Il13 and Tnfsf11 more highly RESULTS: Airway co-exposure to peanut and DEP or PM induced than the CD69– counterpart. The CD69+ST2+CD4+ T cells remained in the PNsIgE and PNsIgG1 and resulted in anaphylaxis following peanut lung tissues for more than 2 months, responded within 6 hours to secondary challenge. Co-exposure to PN and OFAP induced PNsIgE but not exposure to OVAantigen, and expressed Il5. FTY720 that inhibits lympho- PNsIgG1 and mice did not develop anaphylaxis following peanut cyte egress from lymph nodes reduced circulating CD4 T cells by >93%, challenge. Co-exposure to PN and WSP did not induce sensitization to but did not affect the number of Il5-positive CD69+ST2+CD4+ T cells, lung peanut or anaphylaxis. Acute exposure to DEP increased lung levels of IL- levels of type 2 cytokines or eosinophilic airway inflammation. 1 and IL-33, but not thymic stromal lymphopoietin. CONCLUSIONS: Tissue-resident CD69+ Th2 cells that are generated CONCLUSIONS: Co-exposure to peanut and either DEP or PM induces during initial allergen exposure likely responsible for long-term Th2- allergic sensitization to peanut, resulting in anaphylaxis upon peanut type memory in the lungs. The immune responses in peripheral tissues challenge. DEP triggers the release of epithelial alarmins in the lungs, which and secondary lymphoid organs (e.g. lymph nodes) can be regulated by was associated with allergic sensitization to peanut. These findings suggest distinct mechanisms. that innate immune responses to inhaled TRAP may facilitate sensitization to environmental food antigens, thereby leading to food allergy development. Human IgE monoclonal antibodies define the 551 molecular basis of red meat allergy Intestinal Barrier Dysfunction Accompanies 553 Peanut Allergy in CC027/GeniUnc Mice Scott Smith, MD PhD1, Azadeh Hadadianpour2, Joshua Dolye1, Kelly Boyd1, Ryan McBride3, James Paulson, PhD3; 1Vanderbilt University Erin Steinbach, MD PhD1, Johanna Smeekens, PhD1, Layna Perini1, Sa- Medical Center, 2Vanderbilt University, 3The Scripps Research Institute. tyaki Roy, PhD1, Ana Berglind1, Michael Kulis, PhD1, Martin RATIONALE: Due to the very low concentration and polyclonal nature of Ferris, PhD1, Terrence Furey, PhD1, A. Wesley Burks, MD FAAAAI1, IgE in peripheral blood, the molecular detail underlying allergy to red meat Shehzad Sheikh, MD, PhD1; 1University of North Carolina at Chapel Hill. has eluded study. Human monoclonal antibodies (mAbs) from subjects RATIONALE: Peanut is the #1 cause of fatal food-induced anaphylaxis. with red meat allergy will now allow comprehensive characterization of Intestinal barrier dysfunction is a feature of peanut allergic patients and both the antibodies and allergens involved in this response. correlates with anaphylaxis severity; its relationship to pathogenesis is METHODS: We employ a human B cell hybridoma method to unknown. We investigated intestinal barrier dysfunction in the CC027/ immortalize IgE encoding B cells from peripheral blood mononuclear GeniUnc mouse, which develops peanut allergy by the oral route without cells (PBMCs) of subjects with red meat allergy, generating naturally- adjuvant. occurring human IgE mAbs. B cell cultures were screened in an unbiased METHODS: CC027/GeniUnc female mice were sensitized to peanut, manner for IgE production without regard to specificity. Isolated IgE mAbs egg, milk, or walnut by oral gavage once weekly for 4 weeks. In week 5, were tested for binding to alpha-gal using ImmunoCAP, bovine thyro- mice were orally challenged with respective allergens and FITC-dextran 4 globulin, and cetuximab, and their epitopes mapped using a 600 glycan kDa (FD4) for intestinal barrier analysis, and rectal temperature was microarray developed by the Consortium for Functional Glycomics. recorded to monitor the reaction. Murine small intestinal epithelial cells RESULTS: We isolated two IgE mAbs specific to the alpha-gal allergen (IECs) were isolated for RNA-seq and ex vivo monolayer cultures. from a subject with red meat allergy. The frequency of alpha-gal specific RESULTS: Peanut- and walnut-sensitized, but not egg- or milk-, mice during IgE-encoding B cells was exceedingly low at approximately 4.0 cells/108 challenge had elevated plasma FD4 levels. IEC from peanut-sensitized mice in PBMCs. The two antibody sequences exhibit a significant degree of so- ex vivo culture demonstrated peanut-induced barrier dysfunction. RNA-seq matic hypermutation, bind to alpha-gal allergens, and exhibit different analysis showed minimal differentially expressed genes (DEG) in IEC after fine specificity for glycan epitopes involving both classical alpha-gal peanut sensitization. During challenge, up-regulated DEG in IEC from sensi- (Gala1-3Gal) and non-alpha-gal moieties. tized/challenged, compared to sensitized/baseline, mice were enriched in cell CONCLUSIONS: We have generated the first human hybridomas stress, cell-cell junctions, and cell cycle pathways. secreting naturally-occurring alpha-gal specific IgE mAbs from a subject CONCLUSIONS: Intestinal barrier dysfunction is associated with peanut, with red meat allergy. The goal of our work is to improve upon our and to a lesser extent walnut, challenge of sensitized CC027/GeniUnc mice. Ex molecular understanding of the human IgE antibody response, which will vivo IEC monolayer cultures recapitulate in vivo barrier dysfunction and allow provide insights needed for the design of better immunotherapies and for mechanistic studies of barrier integrity. RNA-seq analysis of IEC after pea- allergy vaccines. nut challenge showed an enrichment of DEG associated with stress pathways and cell-cell junctions. The CC027/GeniUnc mouse is a unique animal model for studying mechanisms of intestinal barrier dysfunction in peanut allergy. J ALLERGY CLIN IMMUNOL Abstracts AB175 VOLUME 147, NUMBER 2

The Major Cat Allergen, Fel d 1, Is a Viable training of monocytes provoked a hyperinflammatory response character- 554 Target for CRISPR Gene Editing. ized by the upregulation of proinflammatory mediators. CONCLUSIONS: Specific alterations of monocytes associated with 1 1 Nicole Brackett , Anna Pomes, PhD FAAAAI , Martin Chapman, PhD PM2.5 exposure suggest an immune signature for the prognosis of asthma 1 1 FAAAAI ; Indoor Biotechnologies, Inc. in children living in areas with high PM2.5. Immune pathways underlying RATIONALE: Allergy to domestic cat (Felis domesticus) affects >10% pollution-induced trained immunity may provide novel therapeutic targets. of the population. Fel d 1, the major cat allergen, causes IgE sensitization in >90% of cat allergic subjects and accounts for 60-90% of anti-cat IgE. Activation of TLR3 Inhibits Innate Type 2 Immune Our goal was to identify and target conserved regions of Fel d 1 using 556 Responses through the Interferon-beta Pathway CRISPR gene editing, as an approach for ultimately generating allergen- Rinna Tei, MD1, Koji Iijima, PhD1, Takao Kobayashi, PhD1, Hirohito free cats. 1 1 METHODS: The genes encoding Fel d 1 chains 1 and 2 were sequenced Kita, MD ; Mayo Clinic Arizona. from >50 cats, and conserved gene regions were selected as targets for RATIONALE: Group 2 innate lymphoid cells (ILC2s) play a major role in CRISPR guide RNAs (sgRNAs). CRISPR sgRNAs and Cas9 nuclease allergic immune responses in the airways. However, cellular mechanisms were delivered to immortalized cat cells using lipid-based transfection. to regulate ILC2s remain unclear. TLR3 recognizes viral double-stranded CRISPR editing of Fel d 1 was evaluated by T7E1 mismatch detection and RNA, and polycytidylic acid (Poly(I:C)) serves a specific TLR3 agonist. DNA sequence decomposition. The goal of this project was to investigate the effects of TLR3 activation on RESULTS: Sequence analysis of Fel d 1 chains 1 and 2 from >50 cats ILC2-mediated innate type 2 response and the mechanisms involved. € identified 30 unique amino acid substitutions including 16 novel natural METHODS: Naıve BALB/c mice and Ifnar1- and Ifngr1-knockout (KO) variants, resulting in Fel d 1 polymorphisms with 92-99% identity. mice were pretreated with Poly(I:C) intranasally (i.n.) for 24 hours and Multiple conserved regions in the Fel d 1 genes suitable for CRISPR then exposed i.n. to Alternaria extract for up to 5 days. IL-33 release, innate editing were revealed. Sequence decomposition and T7E1 mismatch type 2 cytokine responses, and airway inflammation were analyzed. To € detection found CRISPR editing efficiencies of 5-55% and 5-45%, address the mechanisms, lung ILC2s were sorted from naıve mice and respectively, for 10 Fel d 1-specific sgRNAs evaluated. T7E1 analyses of cultured in vitro with cytokines. predicted off-target CRISPR cut sites found no evidence of off-target RESULTS: Intranasal exposure to Alternaria increased the lung levels of editing. IL-5 and IL-13 that are produced by ILC2s. Pretreatment with Poly(I:C) CONCLUSIONS: Sequencing data from >50 cats found novel structural significantly inhibited Alternaria-induced production of IL-5 and IL-13 polymorphisms of Fel d 1 and revealed high Fel d 1 sequence identity and subsequent eosinophilic airway inflammation. Poly(I:C) did not inhibit among cats. The results suggest that CRISPR/Cas9 is a viable approach for Alternaria-induced IL-33 release into the BAL fluids, but promoted IFN-a, editing Fel d 1 in cats, which may benefit cat allergic patients by alleviating IFN-b, IFN-g production in the lungs. Ifnar1 KO mice, but not Ifngr1 KO their symptoms. mice, were protected from the inhibitory effects of poly(I:C). IFN-b induced apoptosis within 48 hours and suppressed type 2 cytokine produc- Dysregulation of Circulating Monocytes is tions by lung ILC2s stimulated with IL-33 plus IL-7 in vitro. 555 Associated with Exposure to Air Pollution and CONCLUSIONS: TLR3 activation inhibits ILC2-driven innate type 2 Asthma in Children immune response to Alternaria through the production of type I inter- ferons. Activation of TLRs or exogenous IFN-b may serve as a new ther- Hesam Movassagh1, Mary Prunicki, MD PhD1, Eric Smith2, Diane Dun- apeutic strategy to treat allergic airway diseases. ham2, Xiaoying Zhou1, German Aleman Muench3, Pejman Soroosh, PhD3, Kari Nadeau, MD PhD FAAAAI4; 1Stanford University, 2Sean N Parker Center for Allergy and Asthma Research, Stanford School of Medicine, 3Janssen Research and Development, 4Stanford Univ School Medicine. RATIONALE: Although it is recognized that exposure to ambient air pollution containing particulate matter with a diameter of less than 2.5 micrometers (PM2.5) is responsible for more than a million cases of child- hood asthma per year, the underlying mechanisms remain to be precisely addressed. It has not been demonstrated whether increased levels of expo- sure to PM2.5 is associated with dysregulation of monocytes in healthy and asthmatic children, or if pollution primes monocytes to develop a hyperin- flammatory response termed ‘‘trained immunity’’. METHODS: We characterized phenotypic and functional markers spe- cific to monocyte subsets from 56 children (6-8-year-old) using mass cytometry (CyTOF). Analyses were performed by manual gating and R programming. We utilized an in vitro approach to train monocytes with

PM2.5 and then assess their response upon secondary stimulation with house dust mite or lipopolysaccharide.

RESULTS: Increased exposure to PM2.5 was associated with elevated numbers of classical monocytes and the reduction of non-classical mono- cytes in children. Heterogenous sub-clusters of each monocyte subset further demonstrated both phenotypic and functional markers differen- tially regulated in children exposed to low vs high PM2.5. Exposure to high levels of PM2.5 predisposed children with asthma to develop a mono- cyte signature distinct from that of healthy controls. PM2.5-mediated