J ALLERGY CLIN IMMUNOL Abstracts AB1 VOLUME 147, NUMBER 2

Penicillin Allergy Evaluation in Pregnancy poly(I:C) challenged mice with acute and chronic nebulization. No 001 Impacts Antibiotic Utilization and Neonatal respiratory or CNS toxicities were demonstrated at 50x the therapeutic Clinical Outcomes nebulized dose. CONCLUSIONS: MIDD0301 is a promising NCE that, following Jamie Waldron, MD1, Nerlyne Desravines, MD2, Kim Boggess, MD3, nebulized administration, safely reduces AHR and inflammation in allergic Mildred Kwan, MD PhD FAAAAI4; 1University of North Carolina Chapel murine asthma models and is further efficacious in reducing inflammatory Hill, 2University of North Carolina at Chapel Hill, 3UNC, 4University of sequelae of bacterial and viral lung infections. North Carolina. RATIONALE: Penicillin (PCN) allergy is commonly reported, but many Significant Hypogammaglobulinemia in Patients are erroneously labeled. Pregnancy is associated with high antibiotic 003 Receiving CAR T-cell therapy usage, with indications including prophylaxis for surgical Caesarean 1 1 1 section delivery and group B streptococcus (GBS) colonization, a leading Sara Barmettler, MD , Nancy Yang , Jocelyn Farmer, MD PhD , Aidan 2 1 cause of neonatal sepsis. PCN allergy evaluation has the potential to Long, MD FAAAAI , Marcela Maus, MD/PhD , Carlos Camargo, MD 1 1 2 significantly impact both maternal and neonatal clinical outcomes, how- DrPH ; Massachusetts General Hospital, Mass General Hospital. ever, proactive drug allergy evaluations during pregnancy remain RATIONALE: Chimeric antigen receptor T- (CAR T) cell therapy has underutilized. revolutionized the treatment of relapsed and refractory hematologic METHODS: Pregnant women with listed PCN allergy underwent PCN malignancies. The two first FDA-approved CAR T-cell therapies, skin testing and graded Amoxicillin challenge in outpatient Allergy clinic tisagenlecleucel and axicabtagene ciloleucel, target the CD19+ receptor between 13-38 weeks gestation (n546). Patients who passed the on B-cells, and have potential adverse effects including B-cell aplasia and Amoxicillin challenge were de-labeled in the electronic medical record hypogammaglobulinemia. There are sparse data on immunologic and continued routine obstetric care. Retrospective chart review of women outcomes in these patients. who maintained PCN allergy status served as controls (n5105). METHODS: We performed a retrospective evaluation of patients RESULTS: Of the women tested, 94% had their PCN allergy de-labeled. receiving CAR T-cell therapy in a large healthcare system. We evaluated Of those in the tested group who required antibiotics, 59% received a demographics, indication for CAR T-cell therapy, frequency of penicillin and 96% a beta-lactam (compared to 7% and 40% of controls, immunologic evaluation, and hypogammaglobulinemia pre- and respectively). The majority of peripartum indications were for infection post-CAR T-cell therapy. Hypogammaglobulinemia was stratified as prophylaxis (GBS and surgical); peripartum antibiotic use, maternal length mild (Immunoglobulin G [IgG] <650mg/dL), moderate (IgG of stay, and postpartum complications were not significantly different <400mg/dL) or severe (IgG <200mg/dL). between the two groups. Infants of tested mothers had significantly shorter RESULTS: We identified 101 patients who received tisagenlecleucel or 5 lengths of stay and decreased neonatal sepsis scores despite similar rates of axicabtagene ciloleucel for diffuse large B-cell lymphoma (n 88), 5 5 NICU admissions and neonatal complications compared to controls. follicular lymphoma (n 11), and CNS lymphoma (n 2). Of 59/101 CONCLUSIONS: Our results suggest that proactive penicillin allergy patients with immunoglobulins evaluated prior to therapy, 35 (35%) had evaluation during pregnancy is efficacious, can enhance narrow-spectrum hypogammaglobulinemia: 27/35 (77%) mild, 6/35 (17%) moderate, and penicillin and beta-lactam antibiotic use and can impact the duration of 2/35 (6%) severe. Following CAR T-cells, 72/81(89%) patients with hospitalization and neonatal sepsis scores. We encourage broader utiliza- immunoglobulins evaluated had hypogammaglobulinemia: 22/72 (31%) tion of prenatal PCN allergy testing. mild, 41/72 (57%) moderate, and 9/72 (13%) severe. The median time to nadir IgG levels was 2 months (interquartile range 1-6 months) post-CAR Nebulized MIDD0301 is Efficacious in Allergic T-cell therapy. In the 46 patients who had both pre- and post-CAR T-cell 002 and Microbial Lung Inflammation Models therapy immunoglobulins evaluated, immunoglobulin levels decreased significantly post therapy (692mg/dL pre- vs. 392mg/dL post-; p <0.0001). Leggy Arnold1, Brandon Mikulsky, BS2, M. S. Rashid Roni, MS, RA1, CONCLUSIONS: Following CAR T-cell therapy, most patients were Daniel Knutson1, Md Yeunus Mian1, Gene Yocum3, Charles found to have hypogammaglobulinemia. Future studies are needed to Emala, MD3, Nicolas Zahn1, Daniel Webb1, James Cook4, Douglas Staf- evaluate if hypogammaglobulinemia is associated with worse clinical ford1; 1UW Milwaukee, 2Pantherics Inc., 3Columbia University, 4UW- outcomes including excess infections and mortality. Milwaukee. RATIONALE: MIDD0301 is a novel new chemical entity (NCE) drug that targets GABAA receptors in the lung. This unique mechanism of drug action for asthma avoids common therapeutic targets, such as glucocorti- coid and b-adrenergic receptors that are subject to tolerance and adverse effects. MIDD0301 is expected to have broader clinical utility compared to current inhaled and oral treatments due to alleviation of Th1 and Th2 mediated lung inflammation, in addition to the relief of airway hyperres- ponsiveness (AHR). METHODS: Three discrete models of murine lung inflammation were used to evaluate the efficacy of nebulized MIDD0301 in reducing inflammation and AHR: 1) allergic asthma resulting from ovalbumin and house dust mite challenge; 2) steroid resistant lung inflammation induced with intranasal challenge of LPS and INFg, and; 3) a viral lung infection model induced with intranasal challenge of poly(I:C). Lung and blood levels of MIDD0301 were assessed following nebulized administration. Respiratory and CNS toxicity were evaluated by plethysmography and rotarod. RESULTS: MIDD0301 has excellent water solubility that enabled nebulized dosing. Reduction of AHR in ovalbumin and house mite dust challenged mice was observed at doses comparable to albuterol. MIDD0301 improved inflammation and lung function in LPS/INFg and AB2 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

SARS-CoV-2 entry factors are expressed in ICAM-1, and ICAM-5), replication of RV1A, and increased expression of 004 nasal, ocular, and oral tissues: implications for a virus and interferon-related gene (IFIT1). These findings provide COVID-19 prophylaxes/therapeutics evidence that a viral process may be contributing to the inflammation associated with EoE in some individuals. Ivan Lee1, Tsuguhisa Nakayama1, Sizun Jiang1, Yury Goltsev1, Christian Schurch€ 1, Bokai Zhu1, David McIlwain1, Pauline Chu1, Han Chen1, Food Reintroduction after Passing an Oral Food Alexandar Tzankov2, Matthias Matter2, Jayakar Nayak1, Garry Nolan1; 006 Challenge: A Cross-Sectional Structured 1Stanford University School of Medicine, 2Institute of Medical Genetics Interview-Based Assessment of Barriers, and Pathology, University of Basel, Switzerland. Challenges, and Impact on Quality of Life RATIONALE: Tissue tropism is one key to understanding the pathogen- Christina Ditlof1, Roxanne Hummel1, Samantha Wong, MSc, RD1, Mara esis of SARS-CoV-2, the causative agent of the ongoing severe acute 1 1 1 respiratory disease pandemic COVID-19. We characterized the protein Alexanian-Farr, MSc, RD , Slavka Zahrebelny , Jennifer Hoang , Lisa Hung1, Julia Upton, MD1, A. D. E. L. L. E. ATKINSON, MD, FRCP1, expression of the essential SARS-CoV-2 receptor, angiotensin-converting 1 1 1 1 enzyme 2 (ACE2), and the critical SARS-CoV-2 entry factor, trans- Maria Asper, MD , David Hummel, MD , Thomas Eiwegger, MD ; Hos- membrane protease, serine 2 (TMPRSS2), in human aerodigestive and pital for Sick Children. ocular tissues to gain insights into initial SARS-CoV-2-host interactions. RATIONALE: Asymptomatic sensitization and equivocal history often results in long periods of avoidance. In the case of a negative OFC METHODS: Immunofluorescent staining was simultaneously performed neg on tissue microarrays consisting of normal human head & neck tissues. (OFC ), the patient must reintroduce the previously avoided food on a Tissues from SARS-CoV-2-infected patients were collected during regular basis. This population allows for the evaluation of the impact of autopsy. Imaging was performed using confocal microscopy, and quanti- food allergy delabelling and investigation of challenges linked to food fication of fluorescent intensity was done using a custom open-source introduction. software in ImageJ. METHODS: The validated Food Allergy Quality of Life Questionnaire – RESULTS: ACE2 and TMPRSS2 protein expression localize to a variety Parent Form, Child Form, and Teenager Form (FAQLQ-PF, CF, TF), and motivators and barriers for food reintroduction were assessed in a Canadian of human airway, ocular, and oral epithelial surfaces, suggesting that neg SARS-CoV-2 has the capability to enter through all mucosal surfaces of the cohort of 96 parents, children and adolescents with an OFC via a struc- face. Notably, ACE2 and TMPRSS2 are both very highly expressed in the tured interview. Using the FAQLQs, quality of life (QoL) was compared to a matched cohort of food allergic pediatric patients and caregivers (n590). motile cilia of the nasal mucosa. Finally, SARS-CoV-2 Spike transcripts are neg readily detected in the nasal epithelia of SARS-CoV-2-infected patients. RESULTS: Overall QoL in the OFC cohort was significantly better in 6 6 6 CONCLUSIONS: ACE2 & TMPRSS2 are expressed on nasal, ocular, and parents (1.92 0.19 vs 3.02 0.18, p<0.0001) and children (2.65 0.25 6 5 6 6 oral epithelial surfaces, and are notably present within the motile cilia of vs 3.93 0.25, p 0.001) but not adolescents (3.16 0.31 vs 3.91 0.23) the airway. As breathing occurs primarily through the nasal passage, the compared to the matched food allergic cohort. This effect was independent dense motile cilia in the nasal epithelia are predicted to readily encounter of the type and amount of food consumed. Information given by clinicians SARS-CoV-2 during viral transmission and serve as a predominant initial/ post-OFC was a primary motivator for food reintroduction. The most early site of infection. Prophylaxes and therapeutics for COVID-19 should, important barriers to reintroduce the culprit food were fear of a reaction therefore, focus on a nasal route of administration. Similarly, proper eye or dislike of the food. protection should be worn during certain circumstances CONCLUSIONS: Parents and children benefit from food allergy delabelling demonstrated through improvement in QoL irrespective of Picornavirus Infection of Esophageal Epithelial the amount of food reintroduced. The information given by clinicians after 005 Cells a negative OFC to promote successful food reintroduction is of clinical importance. Vinay Goswamy1, Paul Fichtinger, BS2, Elizabeth McKernan, BS1, Sameer Mathur, MD PhD FAAAAI3; 1University of Wisconsin - Madison, 2University of Wisconsin, 3University of Wisconsin School of Medici. RATIONALE: Eosinophilic esophagitis (EoE) is a disorder characterized by inflammation and fibrosis in the esophageal tissue. There are mechanistic parallels between EoE and other Th2 inflammatory conditions including asthma. One of the contributors to inflammation in asthma is viral infection. We hypothesized that viral infection of esophageal epithelium may also contribute to inflammation in EoE. METHODS: We cultured immortalized esophageal epithelial cells (EPC2-hTERT) as a monolayer with Interleukin-13 (IL-13) to replicate the esophageal environment in EoE. Picornaviruses (Rhinovirus 1A, Rhinovirus 16, and Enterovirus D68) were used to infect EPC2 cultures for 48 hours. RNA samples were collected for analysis of viral replication and for gene expression from the EPC2 cells using PCR. We measured Rhinovirus and Enterovirus RNA levels (for virus replication) and IFIT1 gene expression (for anti-viral response) by PCR. RESULTS: We confirmed mRNA expression of cell surface receptors for picornaviruses, specifically LDLR, ICAM-1, and ICAM-5, which are the receptors for RV1A, RV16, and Enterovirus-D68, respectively. mRNA expression of LDLR was 4 log higher than ICAM-1. Rhinovirus 1A replication was present with monolayer cultures of EPC2 cells with IL-13 (n54, p<0.001). Increased gene expression of IFIT1 confirmed anti-viral responses in the monolayer cultures of EPC2 cells (n54, p<0.001). CONCLUSIONS: In the EPC2 cell line in vitro model of esophageal epithelium, we demonstrate expression of picornavirus receptors (LDLR, J ALLERGY CLIN IMMUNOL Abstracts AB3 VOLUME 147, NUMBER 2

Identification of severe eosinophilic chronic CD40, IL-4, and IL-10. Immunoglobulins were quantified from culture 007 rhinosinusitis based on eosinophil, mast cell supernatants using multiplexed immunoassays. and basophil microparticles in nasal lavage RESULTS: With data collection and analysis ongoing, preliminary results fluids show decreased IL-10R expression on memory B cells in FA children compared to NFA children (p < 0.02). Both FA and NFA children display Toru Takahashi, MD, PhD1, Atsushi Kato, PhD1, Lydia Suh, BS1, low frequencies of IL-10+ B cells in the periphery. IL-10+ cells are Roderick Carter, BS2, Whitney Stevens, MD, PhD2, Caroline decreased among CD38+ CD27+ B cells in FA compared to NFA children Price, CCRC2, James Norton, MS2, Anju Peters, MD MSCI FAAAAI2, (p < 0.03), with emerging trends in other B cell subsets. IL-10 decreased Leslie Grammer, MD FAAAAI2, Kevin Welch, MD2, Stephanie Shintani IL-4-induced IgG4 production from PBMCs in FA children (p < 0.01), but Smith, MD2, David Conley, MD2, Sergejs Berdnikovs, PhD2, Bruce not NFA children. IL-10 also increased IL-4-induced IgE production from Tan, MD MS2, Robert Kern, MD2, Robert Schleimer, PhD FAAAAI2; purified B cells in FA children (p 5 0.05). 1Northwestern University, Feinberg School of Medicine, 2Northwestern CONCLUSIONS: These results suggest that, in comparison to NFA University Feinberg School of Medicine. children, B cells from FA children show a decreased ability to bind IL-10, RATIONALE: Microparticles (MP) are extracellular vesicles that are as well as an altered response to IL-10 with respect to IL-4-induced IgG4 released by shedding from the membrane of activated or injured cells. We and IgE production. FA children also have decreased frequencies of previously reported that eosinophil MP (EosMP), mast cell MP (MCMP) peripheral regulatory B cells. and basophil MP (BasoMP) were increased in nasal lavage fluids (NLF) collected from chronic rhinosunisitis with polyps (CRSwNP). Androgen Receptor Signaling Augments METHODS: NLF were collected from 154 CRSwNP cases. MP were 009 Regulatory T Cell Functions to Attenuate measured using flow cytometry. ECP levels were measured by ELISA. Allergic Airway Inflammation

RESULTS: Hierarchical cluster analysis of CRSwNP cases based on 1 1 1 levels of EosMP (EMR1[+]MP), MCMP (FcεRI[+]c-kit[+]MP) and Vivek Gandhi, PhD , Jacqueline Cephus, MS , Nowrin Chowdhury , Allison Norlander, PhD1, Stokes Peebles, MD FAAAAI2,DawnNew- BasoMP (CD203c[+]c-kit[-]MP) resulted in emergence of 4 main clusters; 1 1 2 Cluster[1] (null, n536): EosMPs(1.0-fold, vs. controls)/ comb, PhD ; Vanderbilt University Medical Center, Vanderbilt Univ MCMPs(0.6-fold)/BasoMPs(1.0-fold), Cluster[2] (BasoMPhigh,n549): School of Medicine. EosMP(1.2-fold)/MCMP(0.4-fold)/BasoMP(3.0-fold), Cluster[3] RATIONALE: Androgen receptor (AR) signaling decreases allergic (EosMPhigh/MCMPhigh,n544): EosMP(1.7-fold)/MCMP(1.8-fold)/ airway inflammation (AAI); yet, the mechanisms remain unclear. BasoMPs(1.2-fold), Cluster[4] (EosMPhigh/MCMPhigh/BasoMPhigh, Regulatory Foxp3+ CD4 T cells (Tregs) suppress airway inflammation, n525): EosMPs(1.9-fold)/MCMPs(2.8-fold)/BasoMP(3.4-fold). Levels but IL-33 signaling through ST2+ Tregs decreased Treg suppressive of ECP (77863009 ng/mL vs. 21761061, p<.05) and MP from other function and increased eosinophil infiltration into the airway. Therefore, cell types were higher in Cluster[4] than in Clusters[1-3], including we hypothesized that AR signaling augments Treg suppressive function to neutrophil MP (CD66b[+]MPO[+]MP, 3.1-fold vs. 1.5-fold, p<.004), dampen eosinophil infiltration and type 2 cytokine production associated with AAI. epithelial MP (E-cadherin[+]MP, 2.6-fold vs. 0.9-fold, p<.0001), basal tfm cell MP (Integrin b6[+]MP, 2.1-fold vs. 1.3-fold, p<.0001), endothelial METHODS: WT or Foxp3eGFP C57BL/6J male, female and male AR MP (CD31[+]CD41[-]MP, 1.8-fold vs. 1.0-fold, p<.0004), although there mice with inactive androgen signaling and Foxp3 Treg lineage fate-map- was no difference in platelet MP (CD31[+]CD41[+]MP, p5.11). The ping (Foxp3eGFPR26YFP) BALB/c male and female mice were intrana- proportions of comorbid asthma (60% vs. 35%, p<.02) and history of prior sally administered Alternaria alternata extract (Alt Ext) on days 0, 3, 6 surgery (64% vs. 37%, p<.02) were higher in Cluster[4] than in Clusters and 9. Ovalbumin (OVA)-specific Tregs from male or female DO11.10 [1-3]. mice were transferred into OVA-sensitized WT BALB/c female mice CONCLUSIONS: The highest eosinophil MP cluster, Cluster[4], has that were then challenged with OVA.Bronchoalveolar lavage (BAL) eosin- higher ECP levels with higher proportions of asthma and recurrent ophils and lung ST2+ Treg and Th2 cells were quantified by differential polyposis than the other clusters, indicating severe eosinophilic CRS. It staining or flow cytometry. is notable that in this cluster, mast cells, basophils and neutrophils are RESULTS: AR signaling increased the ratio of lung Tregs to Th2 cells and also highly activated along with high degrees of basal cell activation and decreased lung ST2+ Tregs and BAL eosinophils in Alt Ext challenged 5 endothelial and epithelial injury. mice (n 5-10, p<0.05). Adoptive transfer of OVA-specific male Tregs decreased eosinophil infiltration and lung IL-5 and IL-13 protein Food-allergic children have decreased expression in recipient mice compared to OVA-specific female Tregs. 008 peripheral regulatory B cells and altered B Further, after Alt Ext challenge, male Tregs were more stable, with cell responses to IL-10 increased percentage of current Tregs (Foxp3eGFP+/YFP+ cells) compared to female Tregs. Adora Lin, MD PhD1, Hemant Sharma, MD, MHS1, Pamela CONCLUSIONS: AR signaling increased Treg numbers and stability, Guerrerio, MD PhD2, Catherine Bollard, MD1; 1Children’s National and decreased ST2+ Treg leading to decreased AAI. These data provide a Hospital, 2National Institute of Allergy and Infectious Diseases. potential mechanism for decreased asthma prevalence in men compared to RATIONALE: Increases in IL-10-producing cells and allergen-specific women. IgG4 are associated with allergic tolerance, including tolerance to foods; however, B cell responses to IL-10 and the role of regulatory, IL-10- producing B cells have not been well-explored in the context of food allergy. METHODS: Blood samples were collected from food-allergic (FA) and non-food-allergic (NFA) children between 2 and 6 years of age. Flow cytometry was performed to determine the frequency of IL-10 receptor (IL-10R)+ and IL-10+ B cells. Peripheral blood mononuclear cells (PBMCs) and purified B cells were cultured with combinations of anti- AB4 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Dupilumab Treatment Leads to Clinical Asthma visits. Technology utilized consisted of a laptop and the social media 010 Remission in Patients With Uncontrolled platforms of Zoom, Skype, and Facetime. During the National COVID-19 Moderate-to-Severe Asthma With Type 2 pandemic virtual training helped to decrease risk of exposure between the Inflammation nurse educator and the patient and family. Cost effectiveness was analyzed by the quantity of visits required to indicate patient competency. Ian Pavord, MD1, William Busse, MD FAAAAI2, Elliot Israel, MD CONCLUSIONS: Nurse educators were able to successfully teach FAAAAI3, Stanley Szefler, MD FAAAAI4, Zhen Chen, PhD5, patients safe and independent administration of ordered medications and NadiaDaizadeh6, David Lederer5, Leda Mannent, MD6, Nikhil minimize the risk of exposure to COVID-19 via virtual training during the Amin, MD5, Elizabeth Laws6, Marcella Ruddy, MD5, Paul Rowe, MD6, pandemic. Yamo Deniz5, Asif Khan6, Yi Zhang5; 1NIHR Oxford Biomedical Research Centre, University of Oxford, 2University of Wisconsin School Allergological evaluation of hypersensitivity of Medicine and Public Health, 3Harvard Medical School and Brigham & 012 drug reactions to betalactams in children 4 5 Women’s Hospital, University of Colorado School of Medicine, Regen- 1 2 eron Pharmaceuticals, Inc., 6Sanofi. Isabel Torres Rojas, CME , Ana Prieto-Moreno , Maria Desamparados 2 2 2 RATIONALE: Asthma treatment response is ascertained by improvement Cervera , Diana Perez-Alzate , Francisco Javier Ruano , Maria Luisa So- 2 2 2 in >_1 key asthma outcome (exacerbations/symptom control/lung function). moza Alvarez , Paula Lopez-Gonzalez , Marıa Vazquez De La Torre , Elisa Haroun-Dıaz2, Natalia Blanca-Lopez 2, Gabriela Canto, MD, This post hoc analysis of LIBERTY ASTHMA QUEST (NCT02414854) 2 1 2 assessed dupilumab effect in patients with uncontrolled, moderate-to- PhD ; Infanta Leonor University Hospital, Infanta Leonor University severe asthma using a multicomponent endpoint representing various Hospital, Madrid, Spain. dimensions of clinical asthma remission. RATIONALE: Betalactams(BLs) are the main cause of hypersensitivity METHODS: Clinical asthma remission components (no exacerbations/ drug reactions(HDRs) mediated by specific immunological mechanism in 5-item Asthma Control Questionnaire [ACQ-5] total score <1.5/post- children. Our aim was to describe allergological evaluation of BLs-HDRs _ in our unit. bronchodilator FEV1 >80%) were assessed at Week (Wk)24/Wk52 in 348 dupilumab-treated patients (200/300mg every 2 weeks combined) and 195 METHODS: A ten-years retrospective study was carried out including matched placebo-treated patients with baseline post-bronchodilator FEV children with BLs-HDRs. Reactions were classified as immediate(IR) and 1 _ <80%, FeNO >_25ppb, and eosinophils >_150/mL. nonimmediate(NIR) depending on the onset of symptoms (<6 hour vs >6 RESULTS: Higher percentages of dupilumab-treated patients were hour). For IR, the work-up included sIgE, ST (prick, ID) and DPT; for NIR, exacerbation-free vs placebo (Wk24: 83.3% vs 61.0%; Wk52: 72.7% vs ST (delayed-ID, patch) and DPT. 46.2%). Likewise, more dupilumab-treated patients were exacerbation- RESULTS: From 510 children included the diagnosis was confirmed in free with an ACQ-5 score <1.5 vs placebo (Wk24: 57.5% vs 27.2%; Wk52: 54(10.6%) (females 55%, median-age 5(0.5-16)), being IR 11 43.1% vs 21.5%). Also, at Wk24, 103 (29.6%) dupilumab-treated patients cases(20,4%) and NIR 43(79.6%). vs 15 (7.7%) placebo-treated patients were exacerbation-free, with ACQ-5 IR: 2 children were diagnosed by sIgE, 4 by ST, and 5 by DPT, being most _ of them mild reactions (1 urticaria,3 angioedema). Only one child score <1.5, and post-bronchodilator FEV1 >80%, thereby achieving clinical remission; at Wk52, there were 70 (20.1%) vs 9 (4.6%) patients, presented bronchospasm after DPT, with good recovery. None were respectively. Among patients not achieving clinical remission, dupilumab- diagnosed by clinical history. After evaluation, 60% were diagnosed as vs placebo-treated patients still had fewer exacerbations (adjusted selective to AX, 30% as allergic to BLs and 10% as selective to CFP. annualized rate of severe exacerbations at Wk24/Wk52: 0.63/0.56 vs NIR: 4 children were diagnosed by ST and 36 by DPT, being all mild 1.51/1.46) and improved lung function and asthma control (LS mean reactions (16urticaria, 17MPE, 3urticaria/angioedema). Three cases with severe reactions reported were diagnosed by clinical history change at Wk24/Wk52: 0.20/0.22L vs 0.02/0.03L [FEV1] and 21.33/21.51 vs 21.00/21.11 [ACQ-5 score]). (AGEP,EEM,hepatitis). After evaluation, 70,5% were diagnosed as CONCLUSIONS: Dupilumab treatment could enable patients with selective to AX, 16% as allergic to BLs, 9% as selective to CFP and uncontrolled moderate-to-severe asthma to achieve a stringent and novel 4,5% as selective to CLAV. multicomponent endpoint representing clinical asthma remission. CONCLUSIONS: In BLs-HDRs in children NIR are more frequent than Dupilumab substantially reduced exacerbations and improved lung IR. Clinical history and ST are insufficient for establishing the diagnosis, function and asthma control in patients who did not achieve clinical being necessary DPT. According to our results this is a safe remission. diagnostic-method, inducing in the majority of cases mild reactions.

Implementation of Virtual Training Visits During 011 the Coronavirus Pandemic: a Nursing Perspective

Linda Trotto, RN, BSN, CRNI1, Christopher Vanname, RN1, Timothy Kingas, RN1; 1Specialty Pharmacy Nursing Network, Inc. RATIONALE: Coronavirus (COVID-19) has created a need for alterna- tive practices to provide safe patient care in home infusions. The use of virtual platforms to conduct patient training in the self-administration of ordered medications will prove to be a viable teaching method. METHODS: Web-based meetings, social media platforms and educa- tional tools have assisted in cohesive virtual teaching among the organization’s nurse educators. Evaluation of nurse educator surveys helped to determine the overall effectiveness and educational experience of the virtual training. RESULTS: March 1, 2020 through June 30, 2020, a total number of 2257 visits were performed. Live visits equaled 1875 (83%) compared to 382 (17%) virtual trainings. There was no difference found in the number of visits to reach self-administration competency between live and virtual J ALLERGY CLIN IMMUNOL Abstracts AB5 VOLUME 147, NUMBER 2

In pediatric patients who have penicillin skin Obesity is Associated with an Increased 013 testing with minor determinants, an oral 015 Prevalence of Penicillin Allergy challenge isn't needed Sarah Abbassi1, Eugenio Capitle, MD2, Radhika Trivedi, BA1, Alan Michael D’Netto, MD1, Dayne Voelker, MD2, Miguel Park, MD3; 1Mayo Wolff, MD3; 1Rutgers University, 2Rutgers-New Jersey Medical School, Clinic School or Graduate Medical Education, 2Washington University 3Department of Veteran. School of Medicine, 3Mayo Clinic. RATIONALE: Penicillin allergy is the most frequently reported drug RATIONALE: Penicillin skin testing (PST) and oral drug challenges are allergy. While epidemiologic data has shown an increased risk of atopy and two methods to prove penicillin tolerance. The current standard is PSTwith asthma in obesity, there is conflicting evidence for the relationship between Pre-Pen (benzylpenicilloyl polylysine) and Penicillin G followed by direct atopy and drug allergy. There are also no studies on the prevalence of oral challenge with amoxicillin. We hypothesized that in the pediatric penicillin allergy in individuals who are obese, nor on the atopic status of population oral drug challenge is not needed following PST if minor obese patients with penicillin allergy. Because of the ramifications determinant mixtures are included in PST. associated with penicillin allergy labels, including use of broader spectrum METHODS: A retrospective chart review of pediatric patients aged 18 or antimicrobials and antimicrobial resistance, it is important to understand less undergoing PST from January 2008- May 2018 was performed. Each the epidemiology of penicillin allergy. The aim of this study is to determine chart review detailed the age, gender, PST results, direct oral challenge, if the prevalence of penicillin allergy is increased in obese patients. subsequent beta lactam use, and any documented adverse reaction. Patients METHODS: The 2012-2014 National Inpatient Sample database (NIS) were broken down into two study groups: Group 1- PST negative without was queried to identify patients with a diagnosis of obesity. ICD-9 code immediate oral challenge, Group 2- PST negative with immediate oral V14.0 was used to designate a history of penicillin allergy among the challenge. analytic sample. Diagnosis of asthma, allergic rhinitis, angioedema, RESULTS: 452 pediatric PSTs were performed during the study period. urticaria and atopic dermatitis were recorded. Patient demographic Of these 452 patients, only 231 had subsequent penicillin antibiotic characteristics including race, age, and gender were also collected. The exposure. 209 patients were in group 1 and 22 patients were in group 2. prevalence of penicillin allergy and associated atopic comorbidities in the Group 1 had 10 patients (4.8%) with adverse reactions with subsequent obese subset was compared to non-obese controls from the database. penicillin antibiotic exposure following PST alone. Group 2 had 2 patients RESULTS: Of 2,268,842 obese patients in the NIS, 4.3% were found to (10%) with adverse reactions following PST and direct oral challenge. have a documented penicillin allergy which was significantly more than the When comparing PST alone to PST and oral drug challenge, there was no 2.8% prevalence in the non-obese subgroup (p<.0001). Obese patients had significant difference noted in rate of adverse reactions (p-value50.35). a 55% increased odds of penicillin allergy compared to non-obese patients, CONCLUSIONS: To document penicillin tolerance in the pediatric OR 1.55 (1.54-1.55), p<.0001. population, PST with minor determinants alone can be used as a single CONCLUSIONS: Obese patients have a statistically higher documented method without the need for oral drug challenge. penicillin allergy compared to non-obese patients.

Multiple drug allergies as a risk factor for IgE 014 mediated penicillin drug allergy in a pediatric population

Dayne Voelker, MD1, Michael D’Netto, MD2, Miguel Park, MD3; 1Wash- ington University School of Medicine, 2Mayo Clinic School of Graduate Medical Education, 3Mayo Clinic. RATIONALE: Risk factors for underlying IgE mediated penicillin drug allergy is poorly described in the pediatric population. We reviewed electronic medical records to further characterize the risk of multiple reported drug allergies on patients with a listed penicillin drug allergy. METHODS: We performed a retrospective chart review of patients aged 0-18 who underwent penicillin skin testing (PST) from January 2001-July 2019. Each chart review detailed the age, sex, PST result, and drug allergy history. Multiple drug allergy was defined as >_ 2 listed drug allergies in the electronic medical record. Patients were divided into two groups: Group 1- multiple reported drug allergies, Group 2- single reported penicillin allergy. Groups were then analyzed and compared based off PST results. Odds ratio were calculated and a p value <0.05 was determined to be significant. RESULTS: 999 patients underwent PST. 251 patients had multiple reported drug allergies. 748 patients had only penicillin listed as a drug allergy. Of the 251 patients in group 1, 29 (11.5%) had a positive PST and 222 (88.5%) had a negative PST. In groups 2, 42 (5.6%) patients had a positive PST and 706 (94.4%) had a negative PST. When comparing group 1 to group 2: odds ratio52.19, 95% CI 1.3-3.6, p-value50.0019. CONCLUSIONS: Multiple reported drug allergies could be a risk factor for IgE mediated penicillin allergy. In pediatric patients with multiple reported drug allergies, penicillin skin testing should be considered over direct drug challenge alone as these patients are at higher risk for an IgE mediated penicillin drug allergy. AB6 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Ceftriaxone Allergy in Pediatric Population Anaphylaxis(48%) followed by Urticaria(42%). Diagnose was confirmed 016 by DPT 44%, ST 40% and clinical history 15%. SNIRD:Aryl-propionics were the most frequent elicitors(69%) followed Morgan Gold1, Daniel Sehayek2, Sofianne Gabrielli, MSc3, Elissa by Pyrazolones(54%), being the most common entities MPE and Non- Abrams, MD FRCPC4, Andrew O’Keefe, MD5, Jennifer immediate urticaria(31%respectively). Diagnose was confirmed by DPT Protudjer, PhD6, E. L. A. N. A. LAVINE7, Tracy Pitt8,A.D.E.L.L.E. 85%, ST 8% and clinical history 8%. ATKINSON, MD, FRCP7, Thomas Eiwegger, MD7, Christine Differences were observed between both groups when the diagnosis was McCusker, MD MSc3, Moshe Ben-Shoshan, MD FAAAAI3; 1McGill made by ST(p50,022) or DPT(p50,07). University, Montreal, Quebec, Canada, 2Universite Laval, Quebec City, Concerning clinical entities and culprit-NSAIDs we observed that Quebec, Canada, 3Division of Allergy and Clinical Immunology, Ibuprofen induced more AE(p50,012) and desquamative exan- Montreal Children’s Hospital, Montreal, Quebec, Canada, 4Section of thema(p50,042), Dexketoprofen, Etoricoxib and Paracetamol induced Allergy and Clinical Immunology, University of Manitoba, Winnipeg, more MPE(p50,01;p50,012;p50,035 respectively), and Pyrazolones Manitoba, Canada, 5Faculty of Medicine, Memorial University of more anaphylaxis(p>0,05). Newfoundland, St John’s, NL, Canada, 6University of Manitoba, CONCLUSIONS: SNIUAA was more common than SNIRD, being Winnipeg, Manitoba, Canada, 7Division of Allergy and Clinical pyrazolones the most frequent elicitors followed by arylpropionics. In Immunology, U of T, Hospital for Sick Children, Toronto, ON, Canada, SNIUAA the most frequent clinical entity was anaphylaxis whereas in 8Queen’s University, Kingston, Ontario, Canada. SNIRD were mild reactions (MPE,non-immediate urticaria). In both RATIONALE: Ceftriaxone is a widely used antibiotic in children and groups the majority of diagnoses were established by DPT. although uncommon, ceftriaxone-triggered hypersensitivity can be life-threatening. We evaluated the demographics, clinical history and The Association of Multiple Drug Allergies and management of children reporting immediate drug hypersensitivity 018 Vocal Cord Dysfunction Assessed by the reactions to ceftriaxone. Pittsburgh VCD Index METHODS: Ceftriaxone allergy was suspected in 15 children presenting Megan McCarty1, Anisha Prabakaran, PA1, Merritt Fajt, MD FAAAAI2, to the Montreal Children’s Hospital ED. Data were collected using a 2 1 2 standardized questionnaire completed by the patients’ parents. Andrej Petrov, MD FAAAAI ; UPMC, University of Pittsburgh Medical RESULTS: Among the patients, 11 (73%) were male, with a median Center. age at reaction of 6.2 years (Interquartile Range: 2, 12.75). After expo- RATIONALE: Vocal cord dysfunction (VCD) is a functional disorder of sure, 13 (86.7%) had symptoms lasting for 1 to 3 days. Three patients the upper airway that can mimic allergic reactions. The Pittsburgh VCD (20%) had previously used ceftriaxone. Five (33.3%) reported symptoms Index (PVCDI) is a validated questionnaire with high sensitivity and consistent with anaphylaxis (defined as involvement of two organ sys- specificity that can help distinguish VCD from asthma. We hypothesized tems/hypotension within 1 hour of exposure). that patients with multiple drug allergies would score higher on the PVCDI Six of the fifteen children had no known co-morbidities, while 4 had food as compared to patients with no or few drug allergies. allergies, 1 had asthma, 5 had eczema and 2 had other diseases that do not METHODS: We recruited 51 subjects aged 21-86 years from the 5 require recurrent ceftriaxone treatment. Five patients had a parental history Allergy-Immunology clinic. Subjects were classified with no (n 21), 5 5 of drug allergy; 2 to morphine and 3 to penicillin. Among all patients, 10 few (1-2) (n 17), or multiple (3+) drug allergies (MDA) (n 13) based on _ (66.7%) underwent intradermal skin test (IDT) to ceftriaxone (20mg/ml), self-report. We administered the PVCDI that was positive if >4. The of which 3 (30%) were positive and 7 (70%) were negative. Two patients PVCDI was compared by drug allergy categories using ANOVA and were challenged with ceftriaxone, both of which had no IDT. Neither of Spearman’s rank correlation. these patients had a positive challenge to intravenous ceftriaxone. RESULTS: Subjects with MDA had a significantly higher PVCDI CONCLUSIONS: The majority of patients with suspected ceftriaxone [median score of 7 vs. 2 (few drug allergies) and 1 (no drug allergy)] 5 allergy had negative intradermal tests and therefore, challenges are often (p 0.02). There was a positive correlation between the PVCDI and 5 5 required to confirm the presence of true ceftriaxone allergy. Studies number of drug allergies (Spearmans rho 0.32, p 0.02). The correlation assessing the sensitivity and specificity of IDT for ceftriaxone are required. was also noted between PVCDI and the number of food allergies (Spearmans rho 0.35, p 5 0.012). Descriptive study of selective reactions to CONCLUSION: In this pilot study, patients with a greater number of drug 017 NSAIDs in a referral Hospital allergies had a higher PVCDI. This suggests VCD being a common comorbidity for those with MDA, or their VCD attacks being mis-labeled Ana MarAa~ Prieto-Moreno Pfeifer, CME1, Isabel Torres-Rojas1, Maria as ‘‘allergic reactions.’’ We also found a novel association between Desamparados Cervera1, Diana Perez-Alzate1, Francisco J. Ruano1, Maria self-reported multiple food allergies and VCD. Larger studies are needed, Luisa Somoza Alvarez 1, Paula Lopez-Gonz alez1, Marıa Vazquez De La but this association between PVCDI and number of allergies can warrant Torre1, Elisa Haroun-Dıaz1, Natalia Blanca-Lopez 1, Gabriela Canto, further evaluation for VCD in patients with MDA. MD, PhD1; 1Infanta Leonor University Hospital. RATIONALE: Selective reactions(SRs) to NSAIDs are increasing nowadays. Our aim was to describe these reactions in our Allergy-unit. METHODS: We included adults with suspicious of NSAIDs-HDRs in a five years period(2015-2019). Diagnosis was established by clinical-history, skin-tests(ST)(only dipyrone and paracetamol) and drug provocation-test(DPT). Cases were classified as SNIUAA or SNIDR(<24 or >_24 hours) depending on the onset of symptoms. RESULTS: We included 92 cases with confirmed SRs to NSAIDs: 79 SNIUAA(female 66%; mean-age 48.78;atopic 54%), 13 SNIDR(female 92%;mean-age 50.30;atopic 38%)(p >0,05). Patients presented a mean of 1.5 episodes, being one episode the most frequent in both(67% SNIUAA and 69% SNIDR)(p>0.05). SNIUAA:Pyrazolones were the most frequent elicitors(63%) followed by Arylpropionics(38%), being the most common entity induced J ALLERGY CLIN IMMUNOL Abstracts AB7 VOLUME 147, NUMBER 2

Basophil Activation Marker Selection, CD63 or to compare actions with and without the tool. Participants completed 019 CD203c, Improves Sensitivity of Basophil surveys assessing their knowledge and confidence in handling allergies. Activation Test Depending on the Clinical RESULTS: Use of the tool increased the proportion of correct answers for Entity in Immediate Allergic Reactions to the clinical vignettes by 63%, from 0.41 to 0.67, a difference of 0.26 (95% Betalactams CI: 0.22-0.30, p<0.0001). With the tool compared to without, participants were more likely to do antibiotic challenges in low-risk situations and more Ruben Fernandez-Santamar ıa1, Gador Bogas Herrera, MD2, Maria likely to avoid the antibiotic or consult Allergy in high-risk situations. 96% Salas3, Adriana Ariza Veguillas, PhD4, Ana Molina Bueno4, Cristobalina of participants reported using the tool would increase their confidence Mayorga, PhD5, Maria Torres JaA~Ón, MD PhD FAAAAI6, when choosing an antibiotic for a patient with an allergy, and 95% would TahiaFernandez, PhD5; 1Allergy Research Group, Instituto de use the tool in their practice. Investigacion Biomedica de Malaga-IBIMA, University of Malaga-UMA, CONCLUSIONS: A point-of-care antibiotic allergy decision support tool Malaga, Spain, 2Allergy Unit, Hospital Regional Universitario de on a widely available platform can provide allergist-designed guidance to Malaga-HRUM, Malaga, Spain, 3Allergy Unit, Hospital Regional non-allergists and is a scalable system for addressing antibiotic allergies. Universitario de Malaga-HRUM, Malaga, Spain, 4Allergy Research This tool appropriately encouraged preferred antibiotic use in low- and Group, Instituto de Investigacion Biomedica de Malaga-IBIMA, Malaga, medium-risk situations and increased caution in high-risk situations. It also Spain, 5Allergy Research Group, Instituto de Investigacion Biomedica de improved provider confidence in handling antibiotic allergies. Malaga-IBIMA, Allergy Unit, Hospital Regional Universitario de Malaga-HRUM, Malaga, Spain, 6Allergy Unit, Hospital Regional Evaluation of Alpha Gal in Vaccines and Universitario de Malaga-HRUM, University of Malaga-UMA, Malaga, 021 Medications using a Human Monoclonal IgE Spain. Antibody

RATIONALE: Basophil activation test (BAT) is a reliable in vitro tool to 1 2 evaluate immediate allergic reactions to betalactams (BL). The optimal Emily Campbell , Stokes Peebles, MD FAAAAI , Cosby Stone, MD MPH1, Jian Zhang1, Azadeh Hadadianpour1, Joshua Doyle1, Scott Smith, activation marker for BAT analysis could depend on the mechanism 1 1 2 involved. The aim of the study was to evaluate the role of CD63 and MD PhD ; Vanderbilt University Medical Center, Vanderbilt Univ CD203c in basophil activation from amoxicillin (AX) and clavulanic School of Medicine. acid (CLV) allergic patients with different clinical entities: urticaria RATIONALE: Galactose-alpha-1,3-galactose (alpha-gal) sensitivity has (URT), anaphylaxis (ANA) and anaphylactic shock (AS). emerged as a causal agent of red meat allergy and drug allergy. We aim to METHODS: Twenty allergic patients to AX (6 URT, 11 ANA and 3 AS), use the first panel of naturally-occurring alpha gal-specific human IgE 30 to CLV (12 URT, 10 ANA and 8 AS) and 18 healthy controls (HC) were mAbs from subjects with red meat allergy to develop a sensitive and included. The expression of CD63 and CD203c was simultaneously specific assay to evaluate for the presence of alpha-gal in medications, analysed after basophil stimulation with the culprit drug. blood samples, and foods. RESULTS: Higher expression of CD63 (p50.02) and CD203c (p50.03) METHODS: Full-length naturally-occurring human IgE mAb were was observed in AX-patients with URT compared with HC. In CLV- generated from a subject with anaphylaxis to alpha-gal allergy using patients with URT, higher expression was observed only for CD63 human B cell hybridoma technology. Using this IgE mAb the presence of (p50.008). Higher expression of CD63 was observed in AX-patients alpha-gal antigen in medications and vaccinations will be evaluated using with ANA compared with HC (p50.0001). Only significant differences enzyme linked immunosorbent assay (ELISA), and Western blot. Human ε were obtained in CLV-patients compared with HC (p50.0006 and Fc RI transgenic alpha-gal knock out mice will be sensitized using the IgE p<0.00001 for CD63 and CD203c respectively). No difference was mAb and exposed to cetuximab and other alpha-gal containing medica- observed between AX and CLV patients. The overall sensitivity for tions to demonstrate anaphylaxis. CD63 and CD203c was 61% and 28% in URT patients; 48% and 38% in RESULTS: Human IgE mAbs specific for alpha gal from a subject with ANA patients and 94% and 97% in AS patients. The specificity was higher anaphylaxis were able to qualitatively detect the presence of alpha-gal than 90% for both markers. allergen using ELISA assay in cetuximab. Standardization curves using CONCLUSIONS: The analysis of CD63 is more sensible in BL allergic dilutions to determine the quantity of alpha-gal in cetuximab will be patients with URT and ANA, whereas CD203c seems to be slightly more performed. Once standardizations are complete, our assay can be used to sensible in patients with AS. evaluate and quantify alpha-gal in medications and vaccinations. We anticipate that Human FcεRI transgenic alpha-gal knock out mice will Online Antibiotic Allergy Decision Support Tool demonstrate anaphylaxis to cetuximab and other alpha-gal containing 020 Improves Management of Beta Lactam Allergies products when our IgE mAb is administered prior to drug challenge in an in vivo model. Theresa Dunham, MD1, Danielle Fasani, PharmD1, Elizabeth CONCLUSIONS: Alpha gal-specific human IgE mAbs from subjects Lippner, MD1, Elwyn Moir, MMH1, Bonnie Halpern-Felsher, PhD1, with red meat allergy have the potential for use to evaluate and quantify Rebecca Gardner, MS1, Vandana Sundaram, MPH1, Anne Liu, MD1; alpha-gal antigen in current and novel therapeutics. 1Stanford University. RATIONALE: Frontline providers frequently make time-sensitive antibiotic choices, but many feel poorly equipped to handle antibiotic allergies. We hypothesized that a web-based decision support tool could improve antibiotic selection and confidence when managing antibiotic allergies. METHODS: An online decision support tool was designed in REDCap to guide non-allergists on antibiotic challenge versus avoidance or Allergy consultation when giving beta lactams to patients with antibiotic allergy labels. 102 residents, fellows, pharmacists, and attendings chose actions for six clinical vignettes with and without the tool. Paired t-tests were used AB8 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Carboplatin Skin Test Conversion: A Pilot Study Population-based incidence of new ampicillin, 022 of Onco-Gynecology – Allergy Multidisciplinary 024 cephalexin, cefaclor, and sulfonamide antibiotic Care Team for Carboplatin Hypersensitivity "allergies'' in exposed individuals with and without preexisting ampicillin, cephalexin, or Apinya Chungcharoenpanich1, Wannada Laisuan2, Ticha Limsuwan, cefaclor "allergies" MD3; 1Ramathibodhi hospital, Bangkok, Thailand, 2Ramathibodi Hospi- tal, Mahidol University, 3Ramathibodee Hospital. Eric Macy, MD FAAAAI1, Thomas McCormick, PhD2, John RATIONALE: Carboplatin is chemotherapy of choice for treatment of Adams, PhD3, William Crawford, MD4, Myngoc Nguyen, MD FAAAAI5, gynecologic malignancy. Patients received multiple course therapy have Anna Davis, PhD2, Elizabeth McGlynn2; 1SCPMG-Kaiser Permanente increase rate of hypersensitivity reaction (HSR) up to 27%. Switch to San Diego, 2Kaiser Permanente, 3Kaiser Permanente Bernard J. Tyson alternative regimens may shorten progression free survival (PFS) and School of Medicine, 4Kaiser South Bay Medical Center, 5Kaiser Perma- overall survival (OS). Rapid desensitization has been used to provide safe nente Oakland. reintroduction of carboplatin treatment. RATIONALE: There is a theoretical concern that clinically-significant METHODS: Retrospective review of consecutive patients experienced immunologically-mediated hypersensitivity occurs between beta-lactams carboplatin HSR who visit Allergy clinic, Ramathibodhi hospital from sharing side chains, unconfirmed by challenge data. The population-based June 2010 to June 2020 were collected. Onco-Gynecology – Allergy ‘‘allergy’’ incidence associated with beta-lactam use that share exact R1 multidisciplinary team workflow was established in 2016 to offer rapid sidechains, ampicillin, cephalexin, or cefaclor (ACC), with or without a access to skin test (ST). Patients who had initial negative carboplatin ST current ACC ‘‘allergy’’ has not been reported. were follow and repeated ST until conversion to positive or completion of METHODS: All courses of ACC, and for comparison trimethoprim- carboplatin treatment. Patient’s demographic data, including disease status sulfamethoxazole, used by greater than 8 million total Kaiser Permanente and severity of initial HSR to carboplatin were collected. California members in 2017 and 2018, with follow-up through January RESULTS: Seventy-one patients were included. Mean age was 57.8 years 2019, were identified along with all new antibiotic-specific ‘‘allergies’’ (SD 9.93). Majority of patients (80.3%) were recurrent disease, mostly on reported within 30 days of course initiation. second course of carboplatin. Mean carboplatin cycle before developing RESULTS: There were 1,222,045 individuals without and 15,235 with an initial HSR was 15.35 (range 6-42, SD 6.211). One-third of patients ACC ‘‘allergy’’ who received AAC or trimethoprim-sulfamethoxazole. (38.0%) had only mild cutaneous reaction, while 18.3% had anaphylactic There were 64,353 ampicillin, 1,232,384 cephalexin, 1,008 cefaclor, and shock. Skin test positive was found in 55 patients (77.5%). Of 16 patients 479,075 trimethoprim-sulfamethoxazole courses given to individuals with Initial negative ST results, 6 patients changed chemotherapy without an ACC ’’allergy’’ resulting in 167 (0.26%) ampicillin, 5,500 regimens, while all of 10 patients who continue the same regimen (0.45%) cephalexin, 8 (0.79%) cefaclor, and 8,763 (1.83%) sulfonamide converted to positive result at a median of 2.1 cycles (range 1-4). antibiotic ‘‘allergy’’ reports. There were 1,019 ampicillin, 4,909 cepha- CONCLUSIONS: Multidisciplinary team approach provided rapid lexin, 30 cefaclor, and 17,885 trimethoprim-sulfamethoxazole courses accessibility to ST to carboplatin. Interestingly all patients were finally given to individuals with a preexisting ACC ’’allergy’’ resulting in 8 converted to positive result at a median of 2.1 cycles. (0.79%) ampicillin, 44 (0.90%) cephalexin, 0 cefaclor, and 568 (3.18%) sulfonamide antibiotic ‘‘allergy’’ reports. Non-Penicillin Antibiotic Allergy in children: CONCLUSIONS: The incidence of new ampicillin, cephalexin, cefaclor, 023 Removing the Label with an Oral Challenge or sulfonamide antibiotic ‘‘allergy’’ reports is minimally increased in

1 1 individuals with a preexisting ampicillin, cephalexin, or cefaclor ‘‘allergy’’ Grant Pickett , Larraine Lyter-Reed, MSN RN FNP-BC , Meera over the baseline incidence in the population. This argues against a Gupta, MD FAAAAI2, Aikaterini Anagnostou, MD MSc PhD FAAAAI3; 1 2 3 clinically-significant immunologically mediated cross-reactivity between Baylor College of Medicine, Baylor/ Texas Children, Texas Children. beta-lactams sharing side chains in individuals with pre-existing, but RATIONALE: Non-penicillin antibiotic allergy is reported in children; unconfirmed, beta-lactam ‘‘allergy’’. Any previously reported antibiotic however, the safety of oral challenges for delabeling is currently not well- ‘‘allergy’’ appears to be a risk factor for reporting a new ‘‘allergy’’. defined. METHODS: We report on 16 non-penicillin oral antibiotic challenges over a period of 24 months (January 2016 -December 2017) in our outpatient pediatric allergy clinic. A retrospective chart review was performed for all patients with a reported non-penicillin antibiotic allergy who subsequently underwent a challenge. RESULTS: A total of 16 oral challenges were undertaken in 14 children. Otitis media was the most common reason antibiotics were prescribed, followed by pharyngitis. The reasons for evaluation were rash (50%), hives (25%), anaphylaxis (6%) and previous positive penicillin test (6%). The mean age at challenge was 8 years (range 2-14 years). Six patients were female. Twelve (74%) of the challenges were to cephalosporins, three (19%) to azithromycin, one (6%) to clindamycin. In 15/16 (94%) challenges a single dose was used versus a graded challenge in 1/16 (6%). All non-penicillin antibiotic challenges were negative, and none had positive skin testing results to the corresponding drug. One challenge performed without prior skin testing was also negative. CONCLUSIONS: In our pediatric cohort, 100% of patients reporting non-penicillin allergy were able to successfully pass an oral challenge to the corresponding drug. The impact of an antibiotic allergy label is well established; our experience suggests that oral challenges in children have a good safety profile and may be helpful in removing a non-penicillin antibiotic allergy label. J ALLERGY CLIN IMMUNOL Abstracts AB9 VOLUME 147, NUMBER 2

Corticosteroid Hypersensitivity Skin Testing at a African Americans, patients on NSAIDs, and patients in the upper 025 Large Tertiary Care Network; 2008-2018 Midwest were at higher risk of ACEI-induced angioedema.

Maria Sanchez-Valenzuela, MD1, Ismael Carrillo-Martin, MD2, The diagnosis of non-life-threatening immediate Matthew Rank, MD FAAAAI3, Gerald Volcheck, MD FAAAAI3, Miguel 027 penicillin allergy should not rest upon low sIgE Park, MD4, Alexei Gonzalez-Estrada, MD4; 1Saint Barnabas Hospital, results between 0.10 kUA/L and 0.35 kUA/L in 2Mayo Clinic Florida, 3Mayo Clinic and Foundation, 4Mayo Clinic. isolation RATIONALE: Skin testing (ST) protocols for suspected corticosteroid Marie-Line Van Der Poorten, MD1, Athina Van Gasse1, Margo (CS) hypersensitivity are not validated. We believe that confirmed hyper- 2 1 sensitivity reactions after a comprehensive evaluation are low. The study Hagendorens, MD PhD , Margaretha Faber, MD PhD , Leander De Puys- seleyr1, Jessy Elst, MD1, Christel Mertens1, Anca Chiriac3, Didier objective is to describe our experience with corticosteroid ST. 4 1 1 METHODS: We conducted a retrospective chart review of all patients Ebo, MD PhD FAAAAI , Vito Sabato, MD ; University of Antwerp, 2University of Antwerp - Belgium, 3University Hospital of Montpellier, who underwent corticosteroid ST to most of the available CS presentations 4 from January 2008 to December 2018 at our health system. ST protocols University Antwerp. included percutaneous and intradermal tests (ID) from undiluted and ten- RATIONALE: Uncertainties remain about the optimal decision threshold fold dilutions (1:10 to 1:100,000) of CS. Drug provocation tests (DPTs) for sIgE results in patients with a penicillin allergy. Historically, the cut-off were performed to some patients with negative ST results. for sIgE results has been set at 0.35 kUA/L, but recently it has been RESULTS: Twenty three patients underwent evaluation for suspected suggested that lowering the threshold to 0.10 kUA/L could improve hypersensitivity reactions to CS. The mean age was 53 years (612.1). diagnosis. This study aims to assess the clinical relevance of low sIgE Twenty-two were white (96%) and 18 were women (78%). Six patients values between 0.10 and 0.35 kUA/L for penicillins in patients who reported initial allergic symptoms to more than one CS. The most common experienced immediate reactions to amoxicillin (AmX), amoxicillin- reactions were pruritus and urticaria (44%). Oral or intravenous routes of clavulanic acid (AmC), or a non-specified penicillin and demonstrating administration (65%) triggered most of the symptoms. Suspected index CS negative skin testing. were prednisone (52%), methylprednisolone acetate (26%), methylpred- METHODS: Patients were included if they had a history of an immediate nisolone sodium succinate (17%), triamcinolone acetonide (13%), dexa- or unclear but non-severe hypersensitivity reaction to AmX, AmC or a non- methasone (13%), budesonide (4%), and beclomethasone (4%). specified penicillin and demonstrated negative skin tests to penicillin G and Hypersensitivity reactions to a specific CS were confirmed in seven AmX and/or AmC but had a sIgE result between 0.10-0.35 kUA/L to one or patients (30%); five through a positive ST, and two patients had positive more penicillin determinants (penicilloyl G, penicilloyl, ampicilloyl and/ DPT after a negative ST. However, only five patients out of 18 with a or amoxicilloyl). To elucidate the clinical significance of these low sIgE negative ST underwent DPT. results, all participants underwent a graded drug challenge (DC) with AmX CONCLUSIONS: Drug provocation test should be performed in the or AmC. setting of a negative ST and if the clinically suspicion is high during RESULTS: 47 patients, with a sIgE result between 0.1 kUA/L and 0.35 corticosteroid hypersensitivity evaluation. kUA/L for one or more penicillin determinants, were included. All DCs were uneventful without immediate and delayed symptoms, indicating low Incidence And Risk Factors of Angiotensin- b-LAB-sIgE titres to be clinically irrelevant in this population. 026 Converting Enzyme Inhibitor-Induced CONCLUSIONS: In conclusion, diagnosis of non-severe immediate or Angioedema: A Large Case-Control Study unclear penicillin hypersensitivity in patients with negative skin tests should not rest upon a low sIgE result between 0.10 kUA/L and 0.35 kUA/L Juan Garcia-Saucedo1, Ismael Carrillo-Martin, MD1, Jorge Trejo- in isolation. To avoid incorrect labelling, we propose to offer a graded drug Gutierrez, MD1, Matthew Rank, MD FAAAAI1, Gerald Volcheck, MD challenge to all such patients. FAAAAI1, Miguel Park, MD1, Alexei Gonzalez-Estrada, MD1; 1Mayo Clinic. RATIONALE: The incidence of ACEI-induced angioedema ranges from 0.1% to 0.7% affecting more women, African Americans, and adults over 65 years old. We sought to determine the incidence of ACEI-induced angioedema among different geographical regions of the U.S., comparing patients’ characteristics and risk factors. METHODS: A case-control study from 2008 to 2018 using electronic health records of an integrated health-care system across four states of the country. Cohort development software was used to obtain all ACEI prescriptions and angioedema was identified using ICD-CM codes 995.1 and T78.3 (Angioneurotic edema). RESULTS: Out of 145,101 patients who received an ACEI, 716 patients developed angioedema (0.49%; 95% CI, 0.46%-0.53%). Their median age was 66 years (Range: 21.0, 99.0), 50.4% were female, 88.5% Caucasian, and 84.8% of the cases were prescribed lisinopril. The risk of ACEI- induced angioedema was higher among women compared to men (OR 1.44; 95% CI; 1.24-1.67; P < .001), African American compared to Caucasian (OR 2.88; 95% CI; 2.14-3.89; P <.001), patients with concomitant use of NSAIDs compared to patients not on NSAIDs (OR 2.28; 95% CI; 1.85-2.8; P <.001), and in the upper Midwest compared to the Southeast (OR 1.57; 95% CI; 1.24-1.99; P < .001). Seventy-nine patients (11%) had ACEI-induced angioedema within one month of being prescribed an ACEI, and 244 (34%) during the first year. CONCLUSION: The incidence and risk factors for ACEI-induced angioedema in our cohort were similar to previous reports. Women, AB10 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Non-irritating skin test concentrations for NSAIDs were challenged to the same drug. All patients with NSAID 028 ceftazidime and aztreonam in patients with a anaphylaxis were challenged to a different NSAID. Only 3 patients documented beta-lactam allergy presented reactions to the challenged drug, 2 had a delayed rash to amoxicillin and 1 had immediate hives to cotrimoxazole, none of them had Marie-Line Van Der Poorten, MD1, Margo Hagendorens, MD PhD2, a reaction requiring epinephrine. Athina Van Gasse1, Margaretha Faber, MD PhD1, Leander De Puysse- CONCLUSIONS: DC are a simple, safe and effective method for leyr1, Jessy Elst, MD1, Antonino Romano3, Didier Ebo, MD PhD delabeling drug allergy in children. FAAAAI4, Vito Sabato, MD1; 1University of Antwerp, 2University of Ant- werp - Belgium, 3IRCCS Oasi Maria S.S., Troina, Italy, 4University An enhanced technique exploring the role of T Antwerp. 030 cells in drug allergies

RATIONALE: Optimising non-irritant concentrations (NICs) is critical to 1 2 2 3 ascertain the best balance of sensitivity and specificity of skin testing for Carla Irani , Joelle Dagher , Diane Antonios-Gholam , Marc Pallardy , Hayat Azouri-Tannous4; 1Hotel Dieu De France,St Joseph University, b-lactam antibiotics. 2 This study aims to assess the NIC for ceftazidime and aztreonam in Lebanon, Toxicology Laboratory, Saint Joseph University, Faculty of Pharmacy, Beirut, Lebanon, 3Universite Paris-Saclay, Inserm, patients with a documented hypersensitivity to penicillin G, 4 amoxicillin(+/-clavulanic acid) or cefazolin. Inflammation microbiome immunosurveillance, Toxicology Laboratory, METHODS: Patients with an immediate or non-immediate Saint Joseph University, Faculty of Pharmacy, Beirut, Lebanon. hypersensitivity reaction to Penicillin G or amoxicillin(+/-clavulanic RATIONALE: The pathophysiology of drug hypersensitivity reactions is acid) or an immediate hypersensitivity reaction to cefazolin were included. complex leading to challenges in the diagnosis. Whether the reaction is Diagnosis was based upon a history, positive skin tests (STs), sIgE immediate usually mediated by immunoglobulin E (IgE) or not, the extent antibodies, a sIgE/tIgE ratio >_0.002, or a drug challenge (DC). In of lymphocytes T (LTs) involvement in hypersesnitivity to drugs is still subsequent testing for cross-reactivity, patients underwent skin test being explored. The current diagnostic approach is mainly based on the titrations for aztreonam and ceftazidime. clinical history of the patient, skin prick tetst, biological tests and Patients demonstrating negative intradermal skin test (IDT) responses at 2 sometimes provocation tests. mg/mL, had additional tests with 20mg/mL and 200mg/mL and also METHODS: We have developed an in vitro assay which allows us to underwent a graded drug challenge. evaluate by flow cytometry, the proliferation of specific LTs in and their RESULTS: 31 patients were eligible. Two patients had positive STs for subpopulations (CD4+ or CD8+) in peripheral blood mononuclear cells aztreonam or ceftazidime at a concentration <_2mg/mL, considered of patients who recently developed allergic drug reactions. The LTs are diagnostic, leaving 29 patients for further evaluation. stained with Carboxyfluorescein succinimidyl ester and specific antibodies Immediate readings of IDTs for ceftazidime at 20mg/mL were negative in coupled to fluorochromes and stimulated, for six days, with 4 to 6 all patients. In 4/26 patients immediate readings were positive at concentrations of allergenic drug molecules. We then identified the 200 mg/mL. Immediate readings for aztreonam at 20 mg/mL were cytokines produced by these specific LTs using a cytometric bead array. negative in all patients. For 200 mg/mL, a positive IDT was observed in RESULTS: Multiple trials were conducted through the development of 19/26 patients. No delayed reactions were observed. All DCs were this assay to determine the optimal conditions of culture. Our in vitro study uneventful. required an evaluation of the cytotoxic concentrations of the therapeutic CONCLUSIONS: The NIC for ceftazidime and aztreonam can be set at molecules on human cells in order to determine the maximal concentration 20 mg/mL for immediate readings. For delayed readings the NIC can be and the optimal duration of cell culture. The minimal viability percentage increased up to 200 mg/mL. The risk of cross-reactivity between (amino) was set to 75%. The therapeutic molecules included were antibiotics, penicillins and cefazolin and ceftazdim and aztreonam cannot be nonsteroidal anti-inflammatory drugs and hypouricemic drugs. We also neglected. constructed a bioconjugate composed of Human Serum Albumin and Benzyl Penicillin (BP-HSA) that we used for beta-lactam testing. Direct challenges for delabeling drug allergy in CONCLUSIONS: Our technique can be considered as an alternative 029 pediatric patients in vitro test to confirm the diagnosis of drug allergies. Once tested and proven to be clinically correlated, this technique will be applied in clinical Sara Concha1, Josefina Castagnoli1, Florencia Neumann1, Arturo practice with a wider panel of therapeutic drugs. Borzutzky, MD FAAAAI1, Rodrigo Hoyos1; 1Pontificia Universidad Catolica de Chile. RATIONALE: In pediatric patients, skin testing for drug allergy is not always technically feasible prior to a drug challenge. Direct drug challenges (DC) are a helpful tool in delabeling drug allergy not widely used in children. METHODS: Chart review of patients who underwent DC at the Allergy Center of the UC Christus Health Network in Santiago, Chile, between 2017-2020. RESULTS: DCs were performed in 62 patients, median age 6 years (7 months – 16 years), 58% male. Drug adverse reaction history consisted of rash (81%), with delayed onset in 78%, angioedema (16%) and anaphylaxis (11%). In 86% of patients with anaphylaxis the culprit was a nonsteroidal anti-inflammatory drug (NSAID). 44% of patients had additional allergic conditions: 15% had asthma, 16% allergic rhinitis, and 10% atopic dermatitis. Most DC to antibiotics were performed in 2 steps (76%) while DC to NSAIDs were done in 3 (72%). Patients with history of a delayed rash to amoxicillin completed a three-day challenge at home. Drugs tested were amoxicillin (60%), cotrimoxazole (3%), cefadroxil (3%), acetaminophen (6%), nimesulide (9%), aspirin (6%), diclofenac (3%), and ibuprofen (3%). 44% of patients with a history of reactions to J ALLERGY CLIN IMMUNOL Abstracts AB11 VOLUME 147, NUMBER 2

Stratifying Penicillin Allergy Risk in a Pediatric suppression of IL-4 and CSF2 (fold change 1.960.4; 1.560.2, 031 Population respectively, p<0.05 compared to PHA/DEX). CONCLUSIONS: Our data provides evidence for CPI enhancement of Nicole Koutlas1, Joanne Band1, Michael Smith1, Amy Stallings, MD PBMC cytokine production associated with allergic responses and also FAAAAI1; 1Duke University. demonstrates a decrease in corticosteroid suppression of these cytokines. RATIONALE: Beta-lactams are among the safest, most used, and Mechanisms and donor selectivity of these events require further effective antibiotics, especially for common pediatric infections. investigation. However, they are also among the most frequently reported drug allergies, prompting broad-spectrum and off-label antibiotic use. Prior studies have Outcomes in Hospitalized, Organ Transplant shown most children with documented penicillin reactions tolerate oral 033 Patients with a Penicillin Allergy Label in the drug challenge and may have their penicillin allergy removed. United States, 2005-2014

METHODS: A survey detailing the drug reaction was distributed to 1 2 electronic medical record identified penicillin allergic patients seen at Jared Nelson, DO , Ismael Carrillo-Martin, MD , Wendelyn Bosch, MD2, Lisa Brumble2, Justin Oring2, Miguel Park, MD1, Alexei Duke Pediatrics South Durham from September 2019 until June 2020. This 1 1 2 survey was adapted from the 2019 JAMA article by Shenoy et al. The Gonzalez-Estrada, MD ; Mayo Clinic, Mayo Clinic Florida. patients were risk stratified into three categories: 1) low-risk—allergy RATIONALE: Having a penicillin allergy label results in the use of removed without evaluation, 2) moderate-risk—penicillin skin testing and alternative antibiotic regimens. We hypothesize that transplant patients challenging warranted, and 3) high-risk— allergy retained without with a penicillin allergy label have worse outcomes from receiving additional evaluation. Percentage of patients in each risk category was alternative regimens. analyzed. METHODS: Using data from the National Inpatient Sample database RESULTS: A total of 78 patients were included. Rashes were the most from 2005 through 2014, we used international classification of disease, common reaction reported by 92% of patients. Most reactions were ninth revision (ICD-9) codes to identify organ transplant (V42) patients delayed, with 26% being 1-5 days after starting medication and 23% more who had a penicillin allergy label (V14.0) and who were hospitalized with a than 5 days after beginning therapy. Notably, no reactions required primary infectious process. We performed a retrospective analysis to epinephrine. Of families surveyed, 78% were very interested in allergy compare their outcomes to those transplant patients that were treated for testing and only 8% were opposed. In the cohort, 3% had a high-risk the same infections, but did not carry a penicillin allergy label. reaction, 1% low-risk and 96% of patients were deemed moderate-risk and RESULTS: Of the 50,069 transplant patients identified, 1,170 (2.3%) had qualified for further evaluation. a penicillin allergy label. When compared to the control group, they had a CONCLUSIONS: Most patients have moderate-risk reactions and are higher overall rate of adverse effects from non-penicillin antibiotics (8.9% 5 interested in evaluation. Future studies aim to increase access to vs 6.3%; P .0003). However, they had shorter length of hospital stay (4.9 5 evaluations, eliminate inaccurate allergies, and determine the ability to vs 5.5 days; P .0007), lower in-hospital mortality (1.6% vs 2.7%; 5 proceed to oral challenge without skin testing. P .03), and lower rate of infections with multi-drug resistant organisms (0.3% vs 1%; P 5.02). There were similar rates of MRSA infections (1.6% Immune checkpoint inhibitors alter cytokine for both; P 5 .92), surgical wound infections (6% vs 5.5%; P 5 .52), and 032 production by human PBMC: implications for mean cost of hospitalization ($35,100.10 vs $39,711.80; P 5.7). A similar increased allergic reactions in subjects on trend was noted when evaluating patients within specific organ transplant immune checkpoint inhibitor therapy groups. CONCLUSIONS: Transplant patients who carry a penicillin allergy label Evelyn Wang1, Elena Goleva, PhD1, Kathryn Vang, MS1, Jeffrey have a higher rate of adverse effects related to the use of non-penicillin Kern, MD1, Mario LaCouture, MD2, Taras Lyubchenko, PhD3, Donald antibiotics. Leung, MD PhD FAAAAI1; 1National Jewish Health, 2Memorial Sloan Kettering Cancer Center, 3National Jewish Healh. RATIONALE: Immune checkpoint inhibitors (CPIs) have significantly improved patient outcomes for various malignancies, however, they are associated with frequent adverse events(AEs). Corticosteroids are recom- mended as first line therapy for AE management, but a subpopulation of patients are unresponsive to steroids. We hypothesized that CPIs alter cellular cytokine production leading to AEs and influence corticosteroid responsiveness. METHODS: Peripheral blood mononuclear cells (PBMC) were isolated from 10 healthy donors, and cultured with 5mg/ml phytohaemagglutinin P (PHA) in the presence of 1 mg/ml anti-PD1, anti-PDL1, with and without dexamethasone (DEX) for 24 hours. Cytokine mRNA expression was analyzed by RT-PCR. In parallel, MTT and CFSE proliferation assays examined the effects of CPIs on DEX suppression of PHA-induced PBMC proliferation. RESULTS: Presence of CPIs did not alter DEX suppression of PHA-induced PBMC proliferation. However, in nearly half the donors, CPIs increased PHA-induced PBMC production of cytokines associated with allergic responses, IL-5, IL-4, IL-17a and IL-22. Anti-PD-1 (pembrolizumab) most prominently increased IL-5 mRNA (1.960.4 fold induction compared to PHA, p<0.05), and inhibited DEX suppression of PHA-induced IL-5 (fold change 2.961.1, p<0.05). PBMC cultured in the presence of anti-PDL-1 (durvalumab) had significantly reduced DEX AB12 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

A Review of Drug Reaction with Eosinophilia labels suggested an IgE-mediated reaction by history. Efforts to improve 034 and Systemic Symptoms in the FDA Adverse accurate drug allergy labeling and de-labeling are now in progress. Event Reporting System (FAERS) Guiding Inpatient Hospital Services in Sara Bluestein1, Roger Yu2, Cosby Stone, MD MPH1, Elizabeth Phillips, 036 Performing Direct Antibiotic Challenges using MD FAAAAI FIDSA3; 1Vanderbilt University Medical Center, 2Vander- Telemedicine bilt University Medical Center & Pritzker School or Medicine, 3Prof. Timothy Chow1, Alicia Alvarez, MD1, David Khan, MD FAAAAI1; RATIONALE: Drug reaction with eosinophilia and systemic symptoms 1 (DRESS) is associated with commonly prescribed drugs, carries significant University of Texas Southwestern. morbidity and mortality, and is frequently encountered by Allergists and RATIONALE: Telehealth services can be a useful tool in remotely Immunologists in clinical practice. delabeling antibiotic allergy through increasing patient access to allergist METHODS: We reviewed the publicly available FDA adverse event expertise regarding appropriate patient selection and patient-specific reporting system (FAERS) database from 1999-2019 for reports that procedural techniques of performing drug challenges. specifically contained the term ‘‘drug reaction with eosinophilia and METHODS: Due to the COVID-19 pandemic, our university strongly systemic symptoms.’’ We sorted reports by generic drug names, number encouraged the use of telehealth for inpatient consultations. Inpatient and sex of cases, median age of cases, and reported deaths. teams contacted the allergy consult service for antibiotic allergy evalua- RESULTS: The search term for ‘‘DRESS’’ was reported from 2003 tions. After thorough chart review and discussion with the patient via onwards. From 2003-2019, 15,293 (0.09%) of 16,693,661 adverse drug telephone, recommendations and instructions were given to the primary events reported in FAERS were reported as DRESS. The overall median inpatient team to perform a graded challenge procedure. reported age of DRESS was 51 years with a distribution of 47% female and RESULTS: Nine adult patients were evaluated; eight patients underwent 43% male. The top 5 drugs associated with DRESS were allopurinol, challenge, three on the obstetrics/gynecology service and five on general vancomycin, lamotrigine, carbamazepine, and trimethoprim-sulfamethox- medicine services. For the patients who underwent challenge, the time azole. These accounted for 7398 (48.4%) reported cases and 56% of elapsed since index reaction was 5 years for 2 patients, 10 years for 3 reported deaths. There were significantly more females than males affected patients, and >20 years for 3 patients; four patients had cutaneous-only by lamotrigine DRESS (63%), p<0.0005. Death was reported in 1057 reactions, 2 patients had unknown reactions, and 2 patients had dyspnea. (6.9%) cases overall, at a median age of 61, and was highest with The antibiotics in question included penicillins (6), sulfamethoxazole- allopurinol (235/2020 (11.6%)). Increasing reports of DRESS for all trimethroprim (2), and clindamycin (1). All 8 patients passed direct reported agents were observed over time. antibiotic challenge with no immediate adverse reactions. For one patient, CONCLUSIONS: Currently, five drugs account for almost 50% of direct challenge was not recommended due to recurrent episodes of diffuse DRESS cases. Importantly, allopurinol, vancomycin, and carbamazepine hives with antibiotic administration within the past year. account for one-third of reported cases and 40% of deaths and have CONCLUSIONS: Telehealth A&I consultation in conjunction with actionable HLA risk factors suggesting a need for heightened awareness graded challenges performed by inpatient services can be used to expand and risk stratification strategies to improve prevention and early diagnosis antibiotic delabeling, particularly for low risk patients. The safety of this of DRESS. approach will require further study.

Beta-Lactam Allergy Labels among Pneumonia Delayed onset localized urticarial reactions to 035 Admissions at an Academic Children's Center 037 Dupilumab 1 1 1 1 1 1 Jennifer Xu, MD , Jennifer Shih, MD FAAAAI , Merin Kalangara, MD ; Ryan LaHood, MD , Rebecca Koenigsberg, DO , An Huynh, MD , 1 James Slaven, MS, MA2, Michelle Kussin, PharmD1, John Manaloor, Emory University. MD1; 1Riley Hospital for Children/ Indiana University School of Medi- RATIONALE: Dupilumab is an anti-IL-4 receptor monoclonal antibody cine, 2Indiana University School of Medicine. used to treat persistent uncontrolled asthma. We characterize a previously RATIONALE: The impact of beta-lactam allergy labels in the pediatric undescribed injection-site urticarial reaction in patients receiving population has not been extensively studied. Pneumonia is the most Dupilumab. common reason for pediatric hospitalizations. This study assessed the METHODS: Case series of two patients evaluated at Emory University prevalence and impact of beta-lactam allergy labels among children Hospital in 2019-2020 who developed injection-site urticaria after admitted with pneumonia over a three-year period at a large academic receiving Dupilumab. children’s center. RESULTS: Patient 1 is a 31-year-old female with history of asthma, METHODS: Inpatient charts of pneumonia admissions with a beta-lactam allergic rhinitis receiving Dupilumab 200mg biweekly. Her first injection- allergy label from January-March in 2017, 2018 and 2019 were reviewed site urticaria was after 16 doses of treatment and lasted 1-2 weeks. It and compared with pneumonia admissions without the label over the same required topical triamcinolone 0.1% cream to manage symptoms. Her time period regarding days of antimicrobial treatment, route of antimicro- blood eosinophil count was 30/mcL at the time and prior to therapy was 80/ bial therapy, and days of hospitalization. mcL. The urticarial reaction spontaneously remitted over 6 weeks despite RESULTS: There were 470 admissions for pneumonia during this time continued dupilumab. period (175 in 2017; 155 in 2018; 140 in 2019). Of the 470 admissions, 48 Patient 2 is a 72-year-old male with history of nasal polyps, chronic patients (10.2%) carried a beta-lactam allergy label (29 in 2017; 14 in sinusitis, and asthma receiving Duupilumab 300mg biweekly. He experi- 2018; 5 in 2019). There were no significant differences between those with enced a large pruritic wheal at injection site after 9 doses of treatment. His a beta-lactam allergy label to those without regarding days of antimicrobial symptoms started at time of injection and self-resolved in 3-4 days each treatment (inpatient or outpatient), route of antimicrobial therapy and days time. Symptoms were unresponsive to oral antihistamines, requiring of hospitalization. Of the 48 allergy-labeled patients, 52% were female and topical clobetasol 0.05%. Initial symptoms were more severe and improved 83% white, with a median age of 8 years old. Reactions were categorized over time, however remained persistent. into nonspecific rash (58%), GI issues (19%), hives (21%), and unknown/ CONCLUSION: Early onset, dose dependent injection-site reactions other (17%). have been documented with Dupilumab; however, our patients developed a CONCLUSION: Ten percent of pediatric admissions for pneumonia had a previously unreported delayed localized urticarial reaction months after label of beta-lactam allergy, similar to adult figures. Only 21% of these receiving therapy uneventfully. Topical steroid treatment alleviated symptoms and allowed for continuation of therapy. J ALLERGY CLIN IMMUNOL Abstracts AB13 VOLUME 147, NUMBER 2

New human immunoglobulin in Brazil: should Rituximab Desensitizations in Pediatric and 038 we use? 040 Adult Patients at a Tertiary Care Center

Caroline Ferreira, MD1, Nathalia Vital, MD1, Pedro Henrique Bubach1, Alekist Quach, MD1, Anthony Wong, PharmD1, Lulu Tsao, MD1, Angela Raissa Roque, MD1, Fernanda Pires Cecchetti Vaz1, Rafael Saldanha1, Chang, MD1, Lauren Sanchez, MD1, Fanny Li, PharmD1, Iris Otani, MD Barbara Cristina Ramos1, Maria Gabriela Viana de Sa1, Luana Medeiros1, FAAAAI1; 1UCSF. Luiza Salvador Schmid1, Rafaela Guimar~aes1, Ligia Maria O. Machado1, RATIONALE: Desensitization can allow patients who have experienced Mariana Pimentel1, Candida Rizzo, MD PhD1, Carolina Aranda1, Dirceu rituximab reactions to continue first-line treatment with rituximab. Reports Sole, MD PhD FAAAAI1; 1Federal University of Sao Paulo. of rituximab desensitization in pediatric populations are limited. RATIONALE: Primary immunodeficiencies compose a heterogeneous METHODS: Patients who received rituximab desensitization for imme- group with more than 400 diseases caused by genetic mutations, which diate hypersensitivity reactions (HSRs) between 06/2015-02/2020 were cause incompetence in the immune system. Since the 1960s, different identified through review of pharmacy records. Reaction symptoms, acute antibody preparations have been developed and started to be used. Since treatment, desensitization protocols, and outcomes were reviewed. the end of 2019, this is the only immunoglobulin provided by public health Reactions were graded using CTCAE v5.0 scoring. system. Our aim was to describe its safety and effectiveness. RESULTS: Five adult patients, age 31 [24-38] years (median [range]), METHODS: Prospective study conducted between May and June/2020, with Grade 2 initial HSRs tolerated 13 total 12-15-step 3-bag (1:100, 1:10, with follow-up of patients at the infusion center. The variables evaluated 1:1) desensitizations with no or minimal modifications. One patient were diseases, ages, time of infusion, subjective symptoms (anguish and tolerated an 8-step 2-bag (1:10, 1:1) desensitization after tolerating 3 prior fear) and objectives such as blood pressure, temperature. Patients were 14-step desensitizations. observed for 60 minutes after the procedure was completed. The Seven pediatric patients, age 13 [2-18] years received 11 total 11-15-step 3- immunoglobulin mean dose was 600mg/dL. bag (1:100, 1:10, 1:1) desensitizations. One patient with Grade 2 initial RESULTS: 82 infusions were performed at the speed recommended in the HSR tolerated an initial and one subsequent desensitization without service. Only a portion of our patients (n 5 22) received the new product, modification. The remaining 6 patients experienced Grade 2-4 break- including: patients with x-linked agammaglobulinemia (n56), APDS through HSRs during initial or subsequent desensitizations: 3 patients (n53), Hyper-IgM Syndrome (n51), ataxia-telangiectasia (n53) and (Grade 1-3 initial HSRs) completed or are continuing rituximab therapy CIVD (n57) and 2nd immunodeficiency (n52). All patients and family despite breakthrough HSRs, and 3 patients (Grade 2-3 initial HSR) stopped members were distressed and afraid of the new immunoglobulin. The 28- rituximab treatment due to reactions during initial or subsequent day-valley showed values above 500mg/dL. There was an Infusion-related- desensitizations. reactions during or immediately after 9 infusions (10.9%), a statistically Peak tolerated infusion rates ranged from 160-200mg/hr for adult and 16– higher frequency with a value already evaluated and published by our 300mg/hr for pediatric patients. service (2.1%) with other immunoglobulins (p <0.001 ). CONCLUSIONS: Published desensitization protocols safely and effec- CONCLUSIONS: Intravenous immunoglobulin is increasingly recom- tively allow adult patients to receive rituximab following HSRs. These mended for many diseases in addition to primary immunodeficiency protocols may need modification for pediatric patients. Further investiga- diseases. Although it is effective and safe, adverse reactions may occur. tions in a larger cohort with attention to previously described weight-based Longer studies are required to evaluate the effectiveness and safety of this pediatric protocols are needed to identify the safest and most effective new product. methods for rituximab reintroduction following HSR in pediatric patients.

Multiple Drug Intolerance Syndrome in 039 Fibromyalgia

Alicia Alvarez, MD1, David Khan, MD FAAAAI1; 1University of Texas Southwestern. RATIONALE: Multiple drug intolerance syndrome (MDIS) describes patients with non-immunologic reactions to >_3 drug classes. This can severely limit treatment options for affected patients. Rates of MDIS in fibromyalgia have not been previously described METHODS: 1,479 patients with a diagnosis of fibromyalgia seen within our university health system in the last year were evaluated by retrospective chart review. Based on prior studies, patients with 10 or more listed allergies were considered to have MDIS. Chi-square testing and binary logistic regression were used for analysis. RESULTS: 128 (8.65%) patients with fibromyalgia met the definition of MDIS. The average number allergies listed for fibromyalgia patients was 3.7, while the average for age and sex matched controls was 1.4. On regression analysis, patients with fibromyalgia were found to be 6 times more likely to have MDIS (OR 6.29, CI 4.74-8.36). An active diagnosis of anxiety (X2 5 13.00, p < 0.0001) or depression (X2 5 7.14, p 50.008) was associated with MDIS. A Charlson Comorbidity Index score of >_4 was associated with MDIS in patients with fibromyalgia (X2 5 41.44, p < 0.0001) and estimates a 10 year survival of 53%. Additionally, having >10 outpatient visits within the last year was associated with MDIS (X2 5 30.79, p < 0.0001 CONCLUSIONS: The association of MDIS with multiple comorbidities and frequent health care utilization in patients with fibromyalgia raises concerns that MDIS may limit therapies in these already complex patients. Additional studies are needed to explore this further. AB14 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

THE ROLE OF PIPERACILLIN AS A TRIGGER IN age- matched controls. tSNPs were selected from Europeans using 1000 041 DRUG ALLERGY. A RETROSPECTIVE STUDY Genomes Project data and genotyped with the iPlex Sequenom MassArray technology. Almudena Delgado Gonzalez 1, Marta Isabel Rodriguez Cabreros2, Iria RESULTS: Statistically significant associations were found between Roibas Veiga1, Miriam Barrios Albajar2, Marta Gema Lopez San Martin3, NIUA risk and several PLA2G4A variants. Thus, the tSNPs rs10752982, Alfredo Iglesias Cadarso3; 1Resident allergist, 2MD Allergist, 3Allergist. rs12746200, and rs2064471 were associated with a diminished risk of RATIONALE: Piperacillin, is a b-lactam, usually used for treatment of NIUA, whereas rs2049963 was associated with an increased risk. severe hospital-acquired infections. CONCLUSIONS: Our results suggest a role for PLA2G4A polymor- METHODS: We retrospectively analysed 649 medical records with a phisms in NIUA, probably by affecting splicing mechanisms. However, suspicion of drug allergy, 24 patients of which were studied for further studies are required to replicate our findings, elucidate the mecha- piperacillin-tazobactam allergy. nistic role, and evaluate the potential participation of PLA2G4A variation RESULTS: We included13 women and 11 men. Average age was 65,54 in other phenotypes induced by NSAID-hypersensitivity. years (616,31, age range 29-90). 18 patients were included per protocol; 8 of them (44,4%) presented The Burden Of Self-Reported Adverse Drug delayed reaction and 10 (55,6%) immediate reaction. 043 Reactions in Patients Referred To An Among immediate reactions; 4 patients presented anaphylaxis, 2 had Outpatient Allergy Practice At A Tertiary hypotension and 2 itching and cutaneous symptoms. 80% developed Referral Center symptoms with the first administration. Becky Buelow1, Suhita Alluri, Resident2; 1Medical College of Wisconsin/ Delayed reactions appeared 2 to 22 days after treatment was initiated, 2 average 8,71 days(66,55). Most common symptom was maculopapular Children’s Hospital of Wisconsin, MCW. rash (90%), 2 added itching and 1 skin desquamation. RATIONALE: Adverse drug reactions (ADRs) play a significant role in Allergic study included skin prick, intradermal and patch test with the main patient care. With the use of electronic health records (EHR) patients self- components involved in b-lactam allergy, also piperacillin. report ADRs, but these are not always confirmed/validated by healthcare Finally, 9 patients were diagnosed of piperacillin allergy, 6 of them providers. Studies have described the prevalence in outpatient (11.4%)/ immediate hypersensitivity and 3 delayed allergy. The rest of them were inpatient (15.9%) settings, but to our knowledge, no data is available to diagnosed with b-lactam allergy(4) or aminopenicillin allergy (1). describe self-reported ADRs in patients referred to an allergy practice. We In 5 of 9 patients with piperacillin allergy, it was carried out an oral aimed to describe such patients referred to our tertiary referral center. challenge with amoxicillin well tolerated. METHODS: An IRB-approved retrospective EHR chart review was CONCLUSIONS: -We present a descriptive study where we had a high performed at Children’s Wisconsin. Inclusion criteria included new suspicion of piperacilin allergy. patients seen in 2019. Data collected included gender, age, race, ADRs -9 patients were diagnosed of piperacilin allergy, and amoxicillin tolerance reported, and atopic conditions. Data was analyzed using frequency plots. was demonstrated in 5 of them. RESULTS: Three thousand nine hundred and fifty EMRs were reviewed; -Possibly allergy in these patients might be caused by a different side chain 1996 (50.4%) were female with a mean age of 12 years. Atopy occurred in 5 previously described in aminopenicillins. 3151 (79.8%) with Caucasian predominance (n 2886;73.1%). Nine -However, further research must be carried out, to support the findings in hundred and nine (23%) patients reported ADRs; 521 (57.1%) were this study. female. Atopy was present in 679 (74.7%) patients. Average age with self- reported ADRs was 21.5 years (range 0-86) with Caucasian predominance Cytosolic Phospholipase A2 (PLA2G4A) (n5748;82.3%). The majority of patients reported one (n5608;66.9%) or 042 Polymorphisms Associated with Acute two ADRs (n5161;17.7%), with one reporting the most at 17 ADRs Urticaria/angioedema Induced by Nonsteroidal (0.11%). Of the 1602 total drugs reported as ADRs, anti-infectives Anti-inflammatory Drugs (n5981, 61.2%) were the most common, followed by opioids (n5129;8.1%) then NSAIDs (n592;5.7%). Cutaneous only reactions Raquel Jurado EscobarResercher1, Jose Triano-Cornejo1, Inmaculada were the most common reported ADRs (n51006; 62.8%). Dona~ 2, Natalia Perez Sanchez2, Gador Bogas Herrera, MD2, Joan CONCLUSIONS: The prevalence of self-reported ADRs was higher Bartra, MD, PhD3, Jose Laguna, MD4, Maria Torres JaA~Ón, MD PhD (23%) at our allergy clinic than previously reported which highlights FAAAAI2, Jose Cornejo-Garcia1; 1Allergy Unit, IBIMA, Regional Uni- allergists’ need to address ADRs proactively. versity Hospital of Malaga, UMA, Malaga, Spain, 2Research Laboratory, IBIMA, Regional University Hospital of Malaga, UMA, Malaga, Spain, 3Unitat d’Allergia, Servei de Pneumologia, Hospital Clinic, Universitat de Barcelona, Barcelona, Spain, 4Allergy Unit, Allergo-Anaesthesia Unit, Hospital Central de la Cruz Roja, Madrid, Spain. RATIONALE: Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the main triggers of drug hypersensitivity, probably due to their high consume worldwide, with NSAIDs-induced acute urticaria/angioe- dema (NIUA) being the most frequent clinical phenotype. Nevertheless, most studies have focused on NSAIDs-exacerbated respiratory disease. NSAID-hypersensitivity occurs only in some individuals, mainly by the increased release of cysteinyl-leukotrienes from arachidonic acid due to COX-1 inhibition. Thus, individual susceptibility to NSAID-hypersensi- tivity may be under the influence of genetic factors. Cytosolic phospho- lipase A2 (cPLA2) may play a key role as this enzyme catalyzes the initial hydrolysis of membrane phospholipids to release arachidonic acid, which may be subsequently metabolized into eicosanoids. Here we analyzed for the first time the genetic variation in the cPLA2 gene (PLA2G4A) in NIUA. METHODS: Thirty-six tag single nucleotide polymorphisms (tSNPs) in PLA2G4A were evaluated in 269 NIUA patients and 300 healthy sex- and J ALLERGY CLIN IMMUNOL Abstracts AB15 VOLUME 147, NUMBER 2

The Association Between Risk Stratification out of 10 patients. Interestingly, most of the patients additionally presented 044 Models And The Likelihood of Positive an allergy to other beta-lactams, including piperacillin/tazobactam. Penicillin Skin Tests The Long-term Impact of Beta-lactam Antibiotic Margaret Kuder, MD1, John McDonnell, MD2, Katherine Weller, MD2, 046 Allergy Testing - A Matched Case-control Study 2 2 2 1 Xiaofeng Wang , Manshi Li , David Lang, MD FAAAAI ; Cleveland 1 2 2 1 2 Jason Trubiano, MD PhD , Nada Marhoon , Sara Vogrin , Kyra Chua , Clinic, Cleveland Clinic Foundation. 1 1 2 RATIONALE: One-third of penicillin skin-test positive (+ST) patients Natasha Holmes ; Austin Health, University of Melbourne. have a vague reaction history (Ann Allergy Asthma Immunol 2000;85:160). RATIONALE: Antibiotic allergy testing (AAT) improves antibiotic Direct oral challenge (DOC) has been recommended for patients with a appropriateness in the acute period post testing. We sought to examine low-risk reaction history. We analyzed the association between patient-re- the impact of AAT on long-term antibiotic prescribing. _ ported penicillin reaction history and +ST. METHODS: Patients with > 1 beta-lactam allergy that had completed METHODS: We identified patients who underwent penicillin allergy AAT between 1/5/2015 and 19/3/2019 at Austin Health (AH;Melbourne, evaluation from January 2014-December 2018. We recorded drug reaction Australia) were identified from a prospective database. Inpatient antibiotic history, demographic variables, skin testing and DOC results. Matched utilization data for all identified patients was extracted from the electronic controls (age/gender/date/testing location) were identified for +ST pa- medical record (EMR) for the 12 months pre- and post-AAT. Further, AAT _ tients. Drug reaction histories were assigned a risk category (high/ patients with > 1 AH admission (cases) were matched 1:1 from the EMR moderate/low) based on two risk stratifications (Model 1: Shenoy. JAMA with that had not undergone AAT (controls). Pre- and post-testing period 2019;312:188; Model 2: Blumenthal. JACI Pract 2019;7:2411). We used (both 12 months’ duration) were compared using mixed effects logistic logistic regression to investigate whether reaction history risk is associated regression. with +ST. RESULTS: We identified 573 patients from the AAT database; 83.4% RESULTS: Penicillin skin testing was performed in 3,391patients: 215 delabeled. In the AAT cohort there was an increase in narrow-spectrum (6.3%) had +ST; +ST were more frequent in outpatients (p<0.001), penicillins (adjusted odds ratio [aOR] 2.10, 95% CI 1.25, 3.54), increase in younger (p<0.001), and female patients (p<0.001), and were associated beta-lactam/beta-lactamase inhibitors (aOR 2.12, 95% CI 1.18, 3.90) and with history of requiring treatment (p<0.05) and seeking medical care reduction in restricted antibiotics (aOR0.21 95% CI 0.13, 0.33) used in the (p5<0.05) for reaction. Percentages of high/moderate/low risk in each 12-months post- compared with the 12-month pre-AAT. In the matched 1:1 5 model were similar in cases vs. matched controls: Model 1: 17/62/18 vs. case-control study (n 155 each arm) there was also a reduction in 11/65/23 (p50.25); Model 2: 3/53/34 vs. 2/48/50 (p50.67). Likelihood for restricted antimicrobials (OR0.48, 95% CI 0.28, 0.82), but no significant +ST in cases categorized as high-risk in Model 1 approached statistical increase in narrow-spectrum penicillins (OR1.36, 95% CI 0.72, 2.56). A significance (p50.052). reduction in number of infective readmissions was also observed in cases CONCLUSIONS: Our data confirm a substantial proportion of patients that underwent AAT (OR0.44, 95% CI 0.27, 0.73) who self-report penicillin allergy and have +ST have a low-risk history. CONCLUSIONS: AAT demonstrates sustained positive impacts with Risk histories (high/moderate/low) in +ST patients do not significantly utilization preferred antibiotics up to 12 months post testing. Further differ from negative skin test patients. Further studies will be required to impacts on the rate of infective readmissions was also noted. reconcile these data with recent reports describing successful DOC without The Role of In Vivo and Ex Vivo Diagnostic Tools prior skin testing. 047 for Antibiotic-Associated Severe Cutaneous Needlessly Avoiding Meropenem Use In Adverse Reactions 045 Hospitalized Patients Ana Copaescu, MD1; 1University of Montreal. L. Marin1,M.J.Penalver~ 1, B. Moya1, J. F. Crespo1, R. Mielgo1; 112 de RATIONALE: The use of ex vivo and in vitro diagnostic tools for severe Octubre Hospital. cutaneous adverse reactions (SCARs) is currently ill defined. RATIONALE: The administration of meropenem in hospitalized patients METHODS: Patients with antibiotic-associated SCARs (AA-SCARs) is restricted when a suspected penicillin allergy is present. This leads to the such as SJS and TEN, DRESS, AGEP, GBFDE and MPE, were prospec- use of second-line treatments that increase the risk of antibiotic resistances tively recruited from Melbourne, Australia (03/2017- 07/2020). In vivo and healthcare costs. We aimed to study the utility of a bedside meropenem testing (patch (PT) or intradermal testing (IDT)) was completed to the allergy workout in these patients. implicated drug(s) and ex. vivo testing was performed with the patient’s METHODS: A case series of 182 patients in a hospital setting with PBMC stimulated with the relevant antibiotic concentrations for T cell medical histories precluding the administration of meropenem when it dose dependent interferon-g (IFN-g) enzyme-linked ImmunoSpot assay would normally be considered a first-line treatment. Patients underwent a (ELISpot) measurement. bedside allergological workout for two hours, including skin testing and a RESULTS: 392/1,346 (29%) presented a delayed reaction and 81 (21%) 5 drug challenge test (DCT), with meropenem. with AA-SCAR met the inclusion, the majority DRESS (N 42; 51.9%). RESULTS: In 180 out of 182 (99%) patients, the initial avoidance of Of the patients’ skin tested (68/81; 84%), test positivity was higher in 5 meropenem was based on a suspected history of penicillin-allergy, while severe MPE/DRESS compared with SJS/TEN (29/39 vs 0/2, p 0.08). two patients reported a history of an adverse reaction to meropenem. An Among the 63 (78%) ELISpot assay performed, 34 (54%) were positive to allergological workout of beta-lactam allergies was accomplished in 43 out at least 1 implicated antibiotic (median SFU/ million cells, 101.5; IQR of the 180 patients labelled as suspected penicillin allergy, which 68.3-203.3). Using combined testing, 51 (63%) patients were positive to an confirmed reactivity to penicillin (7 patients), amoxicillin (7 patients), implicated antibiotic. Of the most commonly encountered phenotype, piperacillin/tazobactam (6 patients) and penicillin, amoxicillin and DRESS, 62% (26/42) patients had a positive in vivo or ex vivo test result: ampicillin (2 patients). In 7 out of 182 (4%) patients, a meropenem allergy 64% (14/22) in vivo, 58% (19/33) ex vivo, and 87.5% (7/8) for both. The was confirmed by a positive result in intradermal test (5 patients) or during sensitivity and specificity of IFN-gELISpot assay for DRESS was 58% the DCT (2 patients). Additionally, two patients also had an allergy to and 100%, respectively. penicillin, one to penicillin and amoxicillin and two to piperacillin/ CONCLUSIONS: We present the largest cohorts of IFN-g ELISpot tested tazobactam. AA-SCARs identifying a culprit antibiotic in 63% of patients. This study CONCLUSIONS: A rapid, simple and safe bedside allergy study demonstrates that using in vivo and ex vivo can improve diagnostic permitted the administration of meropenem successfully in more than 9 approach in these phenotypes. AB16 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Analysis of Anaphylaxis Events in Colorado 4weeks (13 patients, 46%). Adverse events reported included cough and 048 Public Schools, 2015-2019 fatigue. CONCLUSIONS: Patients with idiopathic anaphylaxis without mast cell Bruce Lanser, MD FAAAAI1, Sarah Blumenthal, MSN, RN2, James clonality who received omalizumab had a reduction in the frequency of Crooks, PhD, MS1; 1National Jewish Health, 2Colorado Department of anaphylactic events indicating that omalizumab can be an effective Education. treatment option in these patients. RATIONALE: Epidemiologic data regarding anaphylaxis and food allergy in schools is lacking. The Colorado Department of Education Pediatric Intensive Care Unit Admissions for (CDE) has collected anaphylaxis data since 2014. We seek to analyze 050 Anaphylaxis at Children's Medical Center in school anaphylaxis events from 2015-2019. Dallas METHODS: Colorado public school nurses are required to report details Kelly Boyd, MD1, Christopher Parrish, MD FAAAAI1, J. Andrew Bird, of every anaphylaxis event via online form. Deidentified data was obtained 2 1 2 under IRB exemption. Descriptive statistics were prepared analyzing MD FAAAAI ; University of Texas Southwestern, UT Southwestern 2015-2019 data combined to assess factors associated with anaphylaxis Medical Center. events. Annual incidence was calculated using CDE PreK-12 yearly RATIONALE: The purpose of this study was to analyze the incidence, enrollment data. trends, risk factors, and treatment of anaphylactic episodes that resulted in RESULTS: The rate of anaphylaxis in Colorado public schools ranged admission to the intensive care unit (ICU) at Children’s Medical Center in from 9.94 per 100,000 students in 2016-2017 to 12.96 in 2017-2018 Dallas. (n590-104). Events were most common in middle school (42.4%, mean METHODS: A retrospective chart review was done on patients admitted age 11.48+0.37y). Foods triggered 70.2% of reactions, with peanuts and for anaphylaxis to the ICU at Children’s Medical Center in Dallas between tree nuts causing greater than half. Anaphylaxis occurred in children 2009-2018. Charts were identified based on ICD coding related to without a known allergy in 16.8% of events. For those with a known anaphylaxis. food allergy, the percent having an action plan on file decreased every RESULTS: Fifty-seven patients met clinical criteria for anaphylaxis that year from 95.3% in 2015-2016 to 71.8% in 2018-2019. The majority of re- were admitted to the ICU. There was no increase in incidence over time, actions occurred in classrooms (50.8%). Reactions were treated within a with an average of 6 admissions per year (range 1-9). The average age at the mean of 10.04min (55.3% treated within 5min). time of admission was 9.5 years, with no significant difference between CONCLUSIONS: This is the first detailed analysis of anaphylaxis gender (30 females and 27 males). Food was the most common trigger for 5 5 occurring in all public schools within a state. Incidence remained steady anaphylaxis (n 26, 46%) followed by drugs (n 22, 39%). Only 37% of from 2015 to 2019. Schools should have policies regarding food allergies, patients had a history of allergies and 32% had a history of asthma. Fifteen specifically food in the classroom, particularly in middle school. Efforts of the patients required intubation and nine were put on an epinephrine should be made to increase the number of action plans on file for children drip. Of those that were intubated, 47% had a history of asthma. There was with a known food allergy, and increase the availability of stock 1 morbidity and 1 mortality, however the mortality was due to causes other epinephrine. than anaphylaxis. CONCLUSIONS: The incidence of ICU admissions for anaphylaxis at Clinical outcomes of patients with idiopathic Children’s Medical Center in Dallas has not increased over the past 10 049 anaphylaxis receiving omalizumab years. Anaphylaxis in pediatric patients requiring admission to the ICU is most commonly caused by food, followed by drugs. The majority of Lauren Kaminsky1, Kestutis Aukstuolis, DO2, Daniel Petroni, MD PhD pediatric patients admitted to the ICU for anaphylaxis had no previous FAAAAI3, Taha Al-Shaikhly, MBChB1; 1Penn State College of Medicine, history of allergies or asthma. 2University of Washington, 3Northwest Asthma Allergy Center. RATIONALE: Idiopathic anaphylaxis involves episodes of anaphylaxis without a specific trigger. Management includes antihistamines and mast cell stabilizers, but some patients fail to respond to this treatment. Omalizumab, an anti-IgE monoclonal antibody, is not approved for treatment of idiopathic anaphylaxis, but has been used in patients with idiopathic anaphylaxis under concurrent diagnoses of allergic asthma or chronic idiopathic urticaria. We describe the clinical response to omali- zumab in patients with idiopathic anaphylaxis without evidence of mast cell clonality. METHODS: A retrospective review of medical records at 2 separate institutions identified patients with idiopathic anaphylaxis without mast cell clonality who received omalizumab. A PubMed search also identified published cases of omalizumab use in similar patients. Information about omalizumab therapy, response pattern, and frequency of anaphylactic episodes was compiled. RESULTS: Thirteen adult and pediatric patients with idiopathic anaphy- laxis who had received treatment with omalizumab were identified from the institutions. Fifteen patients were identified through literature search. All of the patients with idiopathic anaphylaxis had improvement in symptoms following omalizumab treatment with 8 patients (29%) experiencing a partial response and 20 patients (71%) experiencing a complete response defined as no anaphylactic episodes while on omalizu- mab. The most frequently used dose of omalizumab was 300mg every J ALLERGY CLIN IMMUNOL Abstracts AB17 VOLUME 147, NUMBER 2

Assigning Causality for Abnormal Tryptases: Incidence Of Fatal Anaphylaxis: A Systematic 053 a-Gal and Other Causes of Anaphylaxis, 051 Review And Meta-analysis Of Observational Mastocytosis and More Studies. Sources Of Information Alice Knoedler, MD1, Matthew Straesser, MD2, Jeffrey Wilson, MD 1 1 2 Lucia Gonzalez-Bravo, MD1, Jimena Laiseca-Garcia1, Sabela PhD ; University of Virginia, Central Pennsylvania Asthma and Allergy. Codesido, MD1, Marianela Brandoni-Petrone1, Patricia Andrade-Garban1, RATIONALE: The diagnosis of anaphylaxis can be clinically challenging Marta Goyanes-Malumbres1, Miguel Tejedor, MD PhD1; 1Hospital Uni- but is supported by an acute rise in tryptase. Here we sought to establish the versitario Fundacion Alcorcon. incidence of cases of tryptase-confirmed anaphylaxis attributable to alpha- RATIONALE: Fatal anaphylaxis is a rare condition, with an incidence gal, a major cause of allergic reactions in our area. We also describe other ranging from 0.5 to 1 death per million person-years, existing differences causes of tryptase-confirmed anaphylaxis and other explanations for between countries. Based on a systematic review and meta-analysis, we elevated tryptase. aimed to explain the heterogeneity of study results and, if possible, METHOD: We conducted a chart review of patients who had at least one determine the pooled incidence. abnormal tryptase (>11.4 ng/mL) at the University of Virginia from 6/1/ METHODS: We did a search in PubMed/MEDLINE, EMBASE, and 2016-5/31/2020. Standard clinical criteria were used to assign a cause for WOS for observational, cohort, cross-sectional, case-control and registry the elevated tryptase. studies. The Sseries included studies with all major causes of anaphylaxis RESULTS: Elevated tryptase was identified in 172 patients. The tryptase or series with only a single major cause. was obtained shortly after anaphylaxis in 49 cases: 35 were drug/treatment RESULTS: Our study reveals a fatal anaphylaxis’s total incidence (all related, 7 were food related, 2 were sting related and 5 lacked a defined causes) of 0.44 per million person-years (0.32-0.61). We selected 47 cause. Of the 7 food-related cases, 5 developed symptoms after consuming studies meeting the criteria, including a total of 14,070 16,653 fatal mammalian meat and were found to have a positive a-Gal IgE (Range 6.4- anaphylaxis’s deaths. The Mmeta-analysis of the total group revealed >100 IU/mL). Over this same 5 year timespan 234 patients were treated in considerable heterogeneity (> 80%). the emergency department for anaphylaxis (based on ICD coding), but only USA was the country with the highest number of articles (11, 23.4%) and 26 had a tryptase drawn. Of the elevated tryptases not obtained during acute Europe was the continent with the highest number of articles (20, 42.6%). anaphylaxis, 46 patients had mast cell disease, 7 had other hematologic Australia and North America had a higher death’s incidence than Europe diagnosis, and 9 had kidney disease. The explanation was undermined in and Asia. An increase in the number of publications was observed from 61 cases. 2016 onward (42.55% of all publications). CONCLUSIONS: The frequency of tryptase-confirmed anaphylaxis Half of the articles used national death certificate databases, and the other attributed to AGS is only one case per year. In part this may be explained half, rest of them from medical registries, hospital systems, and by the fact that tryptase is rarely measured in the ED as part of anaphylaxis combinations of several databases. management. CONCLUSIONS: Our systematic review and meta-analysis is composed of 47 studies. Fatal anaphylaxis’s total incidence was 0.44 per million person-years (0.32-0.61), similar to publications from the last 20 years. The heterogeneity of our review limits the reliability of the pooled estimation.

Clinical characteristics of fatal anaphylaxis: A 052 Spanish nationwide 17- year series

Jimena Laiseca Garcia, MD1, Lucia Gonzalez-Bravo, MD1, Sabela Codesido, MD1, Marianela Managua Brandoni Petrone1, Marta Goyanes Malumbres1, Patricia Alejandra Andraden Garban1, Miguel A. Tejedor1; 1Hospital Universitario Fundacion Alcorcon. RATIONALE: Forensic series and data from clinical-administrative cohorts on fatal anaphylaxis are scarce, probably because the diagnosis of sudden death is often complex and its incidence is low. We report on the clinical characteristics of a series of sudden deaths which were investigated for anaphylaxis at the Spanish National Institute of Toxicology and Forensic Sciences (INTCF) over a 17-year period. METHODS: A total of 122 undetermined sudden deaths sent for assessment to the INTCF from different regions of Spain with anaphylaxis as the suspected cause of death underwent histological, biochemical, and clinical investigation during the years 1998-2015. RESULTS: Two certified allergists confirmed that 46 of the 122 cases were classified as fatal anaphylaxis. The results indicated a median age of 51 years (IQR529) and a male predominance (76%). The main causes of anaphylaxis were drugs (41%), Hymenoptera stings (33%), and foods (13%). A previous allergic event had been reported in both food anaphylaxis (67%) and drug anaphylaxis (53%). The deaths occurred in health care settings (37%), at home (22%), and outside the home (26.09%). CONCLUSIONS: Our findings for fatal anaphylaxis indicated a predom- inance of men and persons aged >_50 years and occurrence of death in a health care setting (one-third of cases). Two- thirds of deaths by food anaphylaxis were associated with previous food allergy and a quarter of drug anaphylaxis with drug allergy. AB18 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Effect of Prescription Drugs on Anaphylaxis 95% CI, 1.03-1.78; P 5 .028), and chronic pulmonary disease (OR, 1.53; 054 Severity and Symptoms 95% CI, 1.02-2.31; P 5 .041) showed increased odds of anaphylaxis. Compared to controls, CIA patients had a higher median hospital cost Sofianne Gabrielli, MSc1, Ann Clarke2, Judy Morris3, Jocelyn Gravel4, ($38,226 versus $25,344; P <.0001) while length of stay was not Rodrick Lim, MD5, Edmond Chan, MD FAAAAI6, Ran Goldman7, An- significantly affected. drew O, MD8, Jennifer Gerdts9, Derek Chu, MD PhD10, Julia CONCLUSION: The incidence of chemotherapy-induced anaphylaxis is Upton, MD11, Adam Bretholz1, Christine McCusker, MD MSc12, Xun 1 in 1,610 with a mortality of 2%. Patients age <18 years old and women Zhang, PhD13, Moshe Ben-Shoshan, MD FAAAAI1, Laura May Miles, are at increased risk for chemotherapy-induced anaphylaxis. Patients with LLM1; 1McGill University Health Centre, 2University of Calgary, CIA also have higher cost of hospitalization compared to controls. To the 3Sacre-Coeur Hospital, 4CHU Sainte-Justine, 5Children’s Hospital at Lon- extent of our knowledge this is the first study to report the incidence of CIA don Health Science Centre, 6BC Children’s Hospital, 7University of in the US. British Columbia, 8Memorial University, 9Food Allergy Canada, 10McMaster University, 11The Hospital for Sick Children, 12Montreal Descriptive study of Anaphylaxis reactions Children, 13Research Institute of McGill University Health Centre. 056 induced by drugs in a referral hospital RATIONALE: Anaphylactic reactions are medical emergencies present- Natalia Blanca-Lopez 1, Ana MarAa~ Prieto-Moreno Pfeifer, CME1, ing with varying levels of severity, which may be influenced by drug intake. 2 1 We aimed to assess the severity of anaphylaxis in patients taking statins, Diana Perez Alzate, MD , Isabel Torres Rojas, CME , Maria Luisa So- moza Alvarez1, Elisa Haroun-Diaz1, Francisco Javier Ruano Perez1, Ma- beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, tricyclic 3 1 antidepressants as well as proton-pump inhibitors. ria Vazquez de La Torre , Paula Lopez Gonzalez , Maria Desamparados Cervera1, Maria Gabriela Canto Diez1; 1Infanta Leonor University Hospi- METHODS: From 2011 to 2019, patients with anaphylaxis were recruited 2 3 as part of the Cross-Canada Anaphylaxis REgistry study. Research tal, Hospital Universitario Infanta Leonor, Infanta LeonorUniversity assistants collected data on patients’ demographics, co-morbidities, Hospital. clinical presentation, reaction severity using a standardized questionnaire. RATIONALE: Drugs are one of the main causes of induced-anaphylaxis, RESULTS: Over an 8-year period, 4152 patients presented with with a prevalence increasing over the last years. Our aim was to describe anaphylaxis, of which 56.6% were male, with a median age of 7.5 years drug-induced anaphylaxis(DIA) in our Allergy-unit. (interquartile range [IQR]: 2.7, 15.2). Majority (78.9%) of reactions were METHODS: We included adults with suspicious of DIA in a period of classified as severe or moderate. A total of 98 patients presenting with nine years(2010-2019). Diagnosis was established by clinical-history, anaphylaxis self-reported use of an aforementioned drug. More specif- skin-tests(ST), drug provocation-test(DPT) and/or in vitro test(quantitation ically, 28 were using beta-blockers, 36 were taking proton-pump inhibitors, of specific IgE antibodies). Atopy was determined by skin tests with a panel 23 were taking ACE inhibitors, 15 were using statins, and 6, tricyclic of aeroallergens. antidepressants. RESULTS: We included 408 cases with clinical-history compatible with Out of the 362 severe cases, 4 were using proton-pump inhibitors, 4 were DIA(female 71 %;mean-age 53,22 y.o;atopic 39%). taking ACE inhibitors, 3 were using beta-blockers and 2, tricyclic NSAIDs were the most common elicitors(46%), being Pyrazolones(59%) antidepressants. None of those with severe reactions were using statins. and Arylpropionics(35%)the main responsible. Diagnose was assessed: Severe reactions were associated with the intake of tricyclic antidepres- clinical history(62%), ST(19%) and DPT(19%). sants while controlling for age, sex, cardiac comorbidities (aOR 1.22, 95% Betalactams were the second cause(34%), being AX-CLAV(42%) and CI 1.00, 1.58). Hypotension was associated with the use of ACE inhibitors AX(41%) the most frequent involved. Diagnose:clinical history(20%), while controlling for these same factors (aOR 1.16, 95% CI 1.01, 1.33). ST(59%), in vitro test(4%) and DPT(17%). CONCLUSIONS: Use of tricyclic antidepressants and ACE inhibitors Quinolones, were the third cause(6%),with moxifloxacin(46%) being the was associated with severe anaphylaxis. Future studies should elucidate the most frequent culprit, followed by Ciprofloxacin(23%) and reasons for these findings. Levofloxacin(19%). Diagnose: clinical history(54%), ST(30%) and DPT(15%). Incidence of and Risk Factors for Chemotherapy- Contrast media were responsible for the 3% of DIA, being iodinated 055 Induced Anaphylaxis Agents in the United agents(77%) more frequent than gadolinium(23%). Diagnose: clinical States history(62%), ST (23%) and DPT(15%). Concerning perioperative reactions(3%), NMBAs were the most Leyla Bojanini1, Ismael Carrillo-Martin, MD1, Yenny Moreno involved(50%), followed by morphine (17%). Diagnose: clinical his- Vanegas, MD2, Lyda Cuervo-Pardo, MD3, Ricardo Zwiener, MD4, Alexei tory(17%), ST(50%) and DPT(17%). Gonzalez-Estrada, MD1; 1Mayo Clinic, Jacksonville, FL, USA, 2St. Eliz- Other drugs less frequent involved were: opioids (3%), proton-pumps abeth Medical Center, Boston, MA, USA, 3University of Florida, Gaines- inhibitors(1%), macrolides(0,7%), ranitidine(0.5%) and sulfamethoxa- ville, FL, USA, 4Hospital Universitario Austral, Buenos Aires, Argentina. zole(0,5%), among others. RATIONALE: The incidence of chemotherapy-induced anaphylaxis CONCLUSIONS: NSAIDS and Betalactams were the most frequent (CIA) is unknown. The objective of this study is to analyze the incidence elicitors of DIA followed by quinolones. Due to the severity of the of CIA in the United States; and to compare patient characteristics and risk reactions diagnosis was mostly obtained by clinical history and ST, factors. whereas DPT was only considered depending on the severity of the METHODS: Using the Nationwide Inpatient Sample from 2005 through anaphylaxis. 2014, we identified cases of chemotherapy administration using the clinical classification software code 224. Anaphylaxis was identified using the ICD-9 CM code 995.0 (other anaphylactic reaction) or the combination of one of the following: 995.3 (allergy, unspecified) or 995.2 (adverse drug effect), or E930-E949 with a code for acute respiratory compromise (519.11 or 786.1) or hypotension (458.9). RESULTS: Among 336,610 patients, there were 209 (0.06%) patients with CIA with a mortality of 1.9%. The mean age was 40 (69.13); 52.6% were female and 69.4% were white. Univariate analysis revealed that age <18 year old (OR 1.65; 95%; CI 1.30-2.08; P<.001), female sex (OR, 1.36; J ALLERGY CLIN IMMUNOL Abstracts AB19 VOLUME 147, NUMBER 2

Patent Blue Dye: Allergen Increasing model (once developed) may be further tuned, optimized and validated 057 includes any human (adult or pediatric) PK/PD data as well. Clinical trial simulation (CTS) leverages prior knowledge (PK and PK/PD including Leticia Domınguez-Cereijo1, M. D. Rodrıguez-Bote1, A. Conde-Alca- safety indices) about various treatments (experimental and reference) with niz~ 1, P. Guardia-Martınez1; 1Virgen Macarena University Hospital. consideration for study design constructs (e.g., sampling scheme, dose, RATIONALE: Patent blue dye (PBD) is one of the most used dyes to strata and sample size) to explore the probability of success based on this identify the sentinel lymph node during breast cancer surgery. It is prior knowledge, various design scenarios and critical assumptions [L€aer, estimated as the culprit in 5% of peri-operative anaphylaxis. We present 2009]. two cases of peri-operative anaphylaxis. The first, it is a 62 year old woman RESULTS: Both PBPK and CTS model development is underway with who presents a widespread violaceous wheal eruption immediately after the goal of informing endpoint selection, dose recommendations and study anesthetic induction and dye infiltration. The second, it is a 69 year old designs for upcoming pediatric and adult trials. All models are developed woman who presents, after 20 minutes of the surgery beginning, abrupt on validated systems with coding representations and solutions to be shared hypotension refractory to treatment and forehead and hands angioedema. with regulatory authorities. Having complementary but distinct models None of them had history of allergy or atopy. provides a framework to facilitate robust decision making. METHODS: Skin test (prick and intradermal if it is possible) and tryptase CONCLUSIONS: Key decisions regarding the development of ARS-1 for curve were made. adult and pediatric subjects with systemic allergies will be informed by RESULTS: quantitative methods using the current best knowledge regarding the drug actions and therapeutic window. This model-based framework is intended to evolve as knowledge about the drug product grows and will be a future d First case: mepivacaine, cisatracurium, propofol, remi- fentanil, cefazolin, povidone iodine and latex were nega- resource for regulatory decision making and ultimately clinical perfor- mance in the intended patients receiving treatment with ARS-1. tive (histamine 8mm). Patent blue prick (25 ng/ml) was positive 10mm. Tryptase curve: 4.2 - 3 - 3.4 (mg/L). The Heterogeneity Of State-Specific Epinephrine d Second case: mepivacaine, cisatracurium, rocuronium, 059 Training Program Listing Requirements In The propofol, fentanil, midazolam atropine, povidone iodine, United States

chlorhexidine and latex were negative (histamine 5mm). 1 1 1 Patent blue prick was negative but ID 1/100 was positive. Madison Oxford, BA , Alice Hoyt, MD ; Code Ana of The Teal Schoolhouse. Tryptase curve: 22.5 - 7.56 - 5.93 (mg/L). RATIONALE: The nation-wide incidence of food allergy continues to increase, and about 18% of K-12 students with food allergy have had a CONCLUSIONS: PBD is a new emerging allergen in peri-operative reaction at school. To combat this problem, the Code Ana Program created anaphylaxis. We may suspect and test it when it can be involved in this kind a comprehensive, online Epinephrine Training Course, designed to teach of reactions. We present two cases of peri-operative anaphylaxis caused by school faculty and staff how to recognize the signs and symptoms of PBD with different clinical manifestations from mild to severe symptoms. anaphylaxis and to administer epinephrine in an emergency. The process of When allergy is confirmed, if the patient needs a new procedure with listing the course on each state’s website revealed the complexities and dyeing, methylene blue should be tested as an alternative. differences in health-programming implementation in each state. METHODS: To determine epinephrine training requirements, we first Modeling and Simulation Strategy to Support the attempted to identify state laws pertaining to epinephrine administration. 058 Development of ARS-1 (Intranasal Epinephrine) Next, we searched for and then called and/or emailed appropriate contacts for Adult and Pediatric Subjects with Systemic in each state, starting with the Department of Health and often being Allergies referred to the Boards of Nursing or Pharmacy or the Department of Education. Jeff Barrett1; 1Critical Path Institute. RESULTS: Seven states reported web-accessible information about RATIONALE: ARS-1 (Neffy)(IN epinephrine) has been shown to exhibit epinephrine training courses. Most other states did not list 1) clear be equivalent pharmacokinetic exposure (AUC0-t) compared withrespect to guidelines on the requirements for training, 2) the process of new course IM injection with dosed with a needle and syringe (RLD), but with more approval, or 3) a database of courses that could be taken to become trained. rapid absorption. The mean hemodynamic response with ARS-1 was Finally, at least one state did not have a state-wide approval process and significantly greater and more consistent than with IM injection. based instead handled training on a local basis. on pharmacokinetic considerations and similar exposure patterns. PK/PD CONCLUSIONS: School-focused anaphylaxis-education requirements differences that may be associated with the route of administration, recep- are heterogeneous. Given the paramount importance of the recognition and tor engagement or equilibration that may be contributing factors. Various response to anaphylaxis, we hope to help states streamline the approach to modeling and simulation techniques provide a means to a) explore possible epinephrine training. factors that may contribute to PK/PD differences between ARS-1 and the RLD, b) evaluate the clinical relevance of the differences observed to date though a clinical trial simulation, and c) examine the extrapolation suit- ability of the adult clinical experience for pediatric subjects. METHODS: Both physiologically based pharmacokinetic (PBPK) and pop-PK/PD-informed clinical trial simulation (CTS) models are under development. The PBPK model will address both the likelihood that epinephrine reaches its intended site of action in adequate quantities to elicit the desired therapeutic effect and also the ability to account for size, ontogeny and maturation effects that define the pediatric population across various age strata [Barrett, 2012]. Standard inputs to build the PBPK model include physiochemical properties of epinephrine (MW, solubility, perme- ability, etc.), P450 metabolism data and any data in animal models describing biodistribution and PK/PD. Additional data from which the AB20 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Role of Neurogenic Inflammation, especially Lanadelumab as treatment for acquired 060 Calcitonin Gene-related Peptide (CGRP), in 062 angioedema with low C1-inhibitor, a 3-patient Anaphylactic Reaction of Children with Food case series Allergy Tonia Afshan1, Paul Faybusovich, DO2, Timothy Craig, DO FAAAAI3, Kenichi Tokuyama1, Shunichi Ogawa1, Takeshi Koga1, Keisuke Okada1, Theodore Kelbel, MD FAAAAI4; 1Spectrum Health / Michigan State Uni- Yutaka Ueda1, Eiji Morita1, Toshiko Itazawa, MD/PhD1; 1Department of versity / Helen DeVos Children’s Hospital Pediatrics Residency Program, Pediatrics, Saitama Medical University. 2Penn State University / Milton S Hershey Medical Center Allergy/Immu- RATIONALE: CGRP has been suggested to mediate neurogenic nology Fellowship Program, 3Penn State University / Milton S Hershey inflammation in allergic disorders, and induce symptoms which mimic Medical Center, 4Spectrum Health / Helen DeVos Children’s Hospital. anaphylaxis. In animal models of food allergy(FA), plasma CGRP levels RATIONALE: Acquired angioedema with low C1-inhibitor (AA) is a and CGRP-containing nerves are shown to increase, indicating its role in rare, serious disease. Primary management options involve treatment of anaphylaxis. Thus, we wanted to know whether CGRP mediates anaphy- underlying causes and controlling acute episodes. There is no FDA- laxis in children with FA. approved long-term prophylactic therapy for these unpredictable, debili- METHODS: The subjects were 41 children with FA who admitted to our tating, and/or life-threatening attacks of angioedema. Lanadelumab, hospital to have the oral food challenge (OFC) test. OFC induced approved to treat hereditary angioedema, has not been studied in the anaphylactic symptoms, allergic symptoms without anaphylaxis and no treatment of AA but offers a logical therapeutic target given similar symptoms in 6, 18 and 17 children, respectively. During the examination, pathophysiology between the diseases. plasma CGRP levels were examined thrice for each child; that is, before the METHODS: Three patients with AA, previously managed with icantibant challenge and 15 min and 60 min after the appearance of symptoms for the for acute symptoms, started lanadelumab as long-term therapy to prevent former 2 groups and after the last challenge for the latter group without episodes of angioedema. For a variety of reasons, rituximab was not symptoms. chosen. RESULTS: The plasma CGRP levels before the challenge were not RESULTS: The first patient is a 67-year-old male who was having statistically different among 3 groups with the mean values of 14.8, 20.6 episodes of abdominal pain and upper extremity edema approximately and 18.2 pg/ml, respectively. Furthermore, no significant changes in its every 2 weeks. The second patient is an 87-year-old male who was having levels were seen in 2 groups with allergic symptoms after the challenge. weekly episodes of abdominal pain and orofacial angioedema, the latter CONCLUSIONS: Our present results did not show the evidence that often involving his airway. The third patient is a 41-year-old female who CGRP is related to the mechanism of anaphylactic reaction after eating was having recurrent abdominal pain and bloating. After diagnosis, all foods. patients ultimately started lanadelumab. Over the following 18 months to date, the first two patients have had no episodes of angioedema and Understanding Disease Mechanisms of transitioned to monthly dosing at 6 months of therapy. The third patient has 061 Hereditary Angioedema With Potential had a 75% reduction in monthly attacks, receiving every 2 week dosing for Therapeutic Implications Through RNA the last 10 months. Sequencing Transcriptome Profiling CONCLUSIONS: Lanadelumab was successfully used to prevent episodes of angioedema in 3 patients during several months of therapy. Umesh Singh, MD PhD1, Debayoti Ghosh, PhD2, Jonathan Bernstein, 3 1 2 This is the first 3-patient case series describing treatment of AA with MD FAAAAI ; University of Cincinnati, University of Cincinnati Col- lanadelumab. Further research is warranted. lege of Medicine, 3University of Cincinnati, Bernstein Allergy Group, Inc. RATIONALE: A genetic deficiency/dysfunction of C1-esterase inhibitor (C1Inh) characterizes hereditary angioedema (HAE), manifested by episodic swellings (flares) of subcutaneous tissues, bowel walls, and upper airways. Genomic profiling of these patients during flares and quiescence, to determine variations in gene expression, can improve our understanding of HAE and recognition of novel therapeutic targets. METHODS: RNA-extracts of skin biopsies from 12 HAE (Type 1 or 2) subjects during flares and quiescence, and 6 non-HAE control patients were sequenced using directional RNA-seq. Differential-expression anal- ysis between sample types was performed using a negative binomial statistical model of read counts. Pathway enrichment analysis was performed using Ingenuity Pathway Analysis (Qiagen). RESULTS: Relevant overexpressed genes during quiescence vs. controls were matrix metalloproteinases, and chemokine ligands (CXCL-1,-2,-8). Associated overexpression of IL1B, the upstream regulator of these over- expressed genes, suggests increased neutrophil activation during quies- cence. During flares, the overexpressed genes were enriched in canonical pathways e.g., IL8 signaling, TREM1, and Th17 pathway that cause neutrophil chemotaxis, activation and release of inflammatory medi- ators. Corresponding upstream regulators of these pathways, including cy- tokines (e.g., CXCL8, IL-17A) and growth factors (e.g., TGFB1), were also overexpressed during flares. CONCLUSIONS: HAE patients have dysregulated neutrophils during flares and quiescence. Activated neutrophils trigger bradykinin production through the release of neutrophil elastase that cleave and inactivate functional C1Inh, resulting in activation of kallikrein-kinin system. These results support investigation of IL1R antagonists and TREM-1 inhibitors as alternative strategies for preventing recurrent HAE attacks. J ALLERGY CLIN IMMUNOL Abstracts AB21 VOLUME 147, NUMBER 2

Despite Prophylactic Treatments, Break-through baseline), 3.1–0.3 (87.4%), 3.4–0.1 (97.0%), and 3.0–0.3 (86.2%) attacks/ 063 Attacks Continue among Patients with month in Black, White, Hispanic, and non-Hispanic patients, respectively. Hereditary Angioedema Adverse event occurrence was comparable between race and ethnicity groups in both studies. Cristine Radojicic, MD1, Jessica Best, DHSc, PA2, Jinky Rosselli, CONCLUSIONS: Although there were few non-White and Hispanic MPH3; 1Duke Asthma, Allergy, and Aiway Center, 2BioCryst Pharmaceu- patients enrolled in these studies, the response to lanadelumab was similar ticals, Inc, 3BioCryst Pharmaceuticals. regardless of race and ethnicity. RATIONALE: There are several FDA-approved medications for prophy- lactic treatment of Hereditary Angioedema (HAE). Despite increased use Real World Data of Canadian Adults Living with of these therapies, patients continue to experience HAE attacks. We sought 065 Angioedema: Part 4 - Health Economic Burden to evaluate attack frequency in patients receiving prophylactic treatment. Jacquie Badiou1, Anne Rowe1, Michelle Cooper1, Kim Roberts1, Daphne METHODS: A chart audit study was conducted among physicians 1 2 1 3 treating HAE to collect anonymized information regarding HAE treat- Dumbrille , Robert Bick , marguerite Dao , Suzanne Kelly, PhD , Wil- liam Yang, MD FAAAAI4; 1Hereditary Angioedema Canada, 2Health Pol- ments and attacks documented within their patient’s medical record. 3 4 Physicians were primarily Allergists/Immunologists (n547) or other icy Consultant, Red Maple Trials Inc., Ottawa, ON, Ottawa Allergy specialties (n528). The study received IRB exemption. Research Corporation, Ottawa, ON. RESULTS: A total of 282 patient charts were reviewed, with an average of RATIONALE: Hereditary angioedema (HAE) is a rare inherited disorder 3.8 charts per physician. Overall, 83% of patients utilized HAE treatment characterized by recurrent painful episodes of severe swelling in different prophylaxis. The most common medications were lanadelumab-flyo parts of the body. The direct health care costs of HAE are significant but are (TakhzyroÒ, 21%), C1 esterase inhibitor (C1-INH) administered subcu- little studied. We sought to understand the health care utilization of patients taneously (HaegardaÒ, 20%), C1-INH administered intravenously with HAE in Canada (CinryzeÒ, 18%), and oral androgens (15%). Most patients (n5244, METHODS: In 2017 a comprehensive email survey was sent to all 87%) were also prescribed an on-demand (acute) medication. Among members of HAE Canada to gather information on multiple aspects of patients prescribed both acute and prophylactic medications for whom on- HAE. The data from respondents was collected and analysed as the demand usage was known, 42% used their on-demand medication monthly, percentage of respondents. Responses to questions on health care use were for an average of 0.7 times/month. Although the rate of attacks decreased analysed for this report. with prophylactic medication use, 30% of patients on prophylaxis RESULTS: The survey collected data from 113 respondent adults living experienced one attack in the past month and 52% in the past three with HAE. In the prior year, 11/79 (14%) reported <3 attacks while 34/79 _ months, for an average of 0.5 and 1.2 attacks, respectively. The attack (43%) reported >12. Routine HAE treatment was mainly performed at frequency ranged from 0.6-1.7 for TakhzyroÒ and 0.3-0.9 for HaegardaÒ home (58/75, 77.3%) but some received treatment in a hospital (12.0%) or during the past one-three months. Physicians (78%) believe patients clinic (9.3%). In response to questions regarding health care use in the past accurately report their attack frequency. year, most (43/71, 60.6%) saw a physician 1-3 times for HAE-related CONCLUSIONS: Many patients with HAE on prophylactic medication, problems but 22% had 4-10 and 10% had >10 physician visits. Planned including newer subcutaneous therapies, still experience attacks and hospital visits were made 1-3 times by 32/69 (46.4%); 7.3% went >10 require on-demand medication treatment. Attack rates should be assessed times and 33.3% not at all. Unplanned ER visits were made: never by 32/71 regularly. (45%), 1-6 times by 48%, and >7 times by 7%. CONCLUSIONS: These findings suggest that having HAE leads to Response to lanadelumab is not affected by race substantial health care costs which would be higher but for the high 064 and ethnicity: findings from phase 3 studies proportion of patients who receive treatment at home.

Timothy Craig, DO FAAAAI1, Rafael Zaragoza-Urdaz2, John Anderson, MD3, Huamin Li4, Kim Paes5, Clinical Scientist5, Hong Ren, MS6, Salome Juethner, NP7; 1Penn State University, 2Rafael H Zar- agoza Urdaz MD CSP, 3Alabama Allergy & Asthma Center, 4IAA Clinical Immunology Laboratory, 5Takeda Pharmaceuticals, Inc, 6Takeda Pharma- ceuticals, 7Takeda. RATIONALE: Increasing attention has been drawn to racial and economic disparities in health care. We thus initiated an analysis to determine the impact of race and ethnicity on lanadelumab safety and efficacy. METHODS: We searched the databases of the HELP and HELP OLE studies for minority subjects. In HELP, patients >_12 years old with HAE-1/ 2 received placebo or lanadelumab (150mg Q4W, 300mg Q4W, 300mg Q2W) for 6 months. In HELP OLE, patients received one dose of 300mg lanadelumab on Day 1 then 300mg Q2W after their first attack (rollovers), or 300mg Q2W starting on Day 1 (nonrollovers) for <_132 weeks. HELP OLE data collected up to 31August2018 were analyzed. RESULTS: HELP (N5125) included n510 Black, n52 Asian, and n5113 White patients; n59 were Hispanic, and n5115 were non- Hispanic. HELP OLE (N5212) included n510 Black, n52 Asian, n5198 White, n513 Hispanic, and n5198 non-Hispanic patients. In HELP, lanadelumab reduced attack rates from 2.0 attacks/month at baseline to 0.5 during treatment (79.0% reduction from baseline) in Black patients, and 3.7–0.4 (88.2%), 3.7–0.3 (92.5%), and 3.5–0.5 (84.1%) in White, Hispanic, and non-Hispanic patients, respectively. In HELP OLE, attack rates were reduced from 1.8–0.3 (78.3% reduction from AB22 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Berotralstat Consistently Demonstrates Like father, but not like daughter: familial cases 066 Reductions in Attack Frequency in Hereditary 068 of common variable immunodeficiency and de Angioedema (HAE) Irrespective of Baseline novo hereditary angioedema type 1/2 Attack Rate: Subgroup Analysis from the APeX- 2 Trial Angeliki Barlas1, Amin Kanani1; 1University of British Columbia. RATIONALE: Hereditary angioedema (HAE) is an autosomal dominant H. Henry Li, MD, PhD1, Jessica Best, DHSc, PA2, Sharon Murray, PhD2, condition, but spontaneous mutations can occur in 15% of cases. Genetic Heather Iocca, PhD3, Raffi Tachdijan, MD4; 1Institute for Asthma and Al- abnormalities have been found in less than 20% of patients with common lergy, Chevy Chase, MD, 2BioCryst Pharmaceuticals, 3BioCryst Pharma- variable immune deficiency (CVID). Neither of these conditions have a ceuticals, Inc, 4AIRE Medical of Los Angeles, Santa Monica, CA. known association. We present a case of a father with CVID and a daughter RATIONALE: Berotralstat is an oral plasma kallikrein inhibitor in with de novo hereditary angioedema. development for HAE attack prophylaxis. HAE is characterized by METHODS: The cases were reviewed and reported. unpredictable, episodic attacks; some patients experience frequent attacks RESULTS: 28-year-old female presented with recurrent episodes of without treatment. This analysis sought to understand whether baseline angioedema involving the extremities and abdomen and subsequently attack frequency correlates with responder rates with berotralstat. diagnosed with HAE with low C1 inhibitor functional levels on two METHODS: 121 patients were randomized to berotralstat 110 mg:150 separate occasions. Both her parents have normal C1 inhibitor functional mg:placebo daily for 24 weeks in a phase 3 double-blind, placebo- levels and there is no family history of angioedema. Her 52-year-old father, controlled study (NCT03485911). This post hoc analysis examined the however, was diagnosed with CVID following episodes of recurrent reduction of HAE attacks by baseline attack rate Cohort 1: < 2 attacks/ sinopulmonary and gastrointestinal infections, low serum immunoglobulin month; Cohort 2: >_2to< 4 attacks/month; Cohort 3: >_4 attacks/month. levels and poor specific antibody response. There is no family history of RESULTS: In Cohort 1, median baseline attack rates per month were 1.3 CVID or immune deficiency. The daughter’s condition is well controlled (berotralstat 150 mg; n5 10) and 1.7 (placebo; n5 12) which declined to with C1 inhibitor infusions prophylactically. The father has been success- 0.41 and 1.3, respectively. In Cohort 2, median baseline attack rates per fully managed with immunoglobulin replacement therapy. month were 2.7 (berotralstat 150 mg; n520) and 3.1 (placebo; n521) CONCLUSIONS: Although immune dysfunction has been described in which declined to 1.2 and 2.7, respectively. For Cohort 3, median baseline patients with hereditary angioedema type 1/2 and in patients with CVID, attack rates per month were 5.2 with berotralstat 150 mg (n510) and 4.5 familial cases of hereditary angioedema and CVID have not been with placebo (n56) and declined to 1.9 and 2.5, respectively. In Cohorts 1, described. These cases exhibit the need for further evaluation of immune 2, and 3, treatment with berotralstat 150 mg resulted in a >_50% relative dysregulation in patients with hereditary angioedema and CVID. reduction in attack rate in 70%, 55%, and 50% of patients, respectively. In addition, 60%, 45%, and 50% of patients, respectively, had >_70% relative Malignancy and Immune Disorders in Patients reduction in attack rate. 069 with Hereditary Angioedema CONCLUSIONS: These results demonstrate consistent responder rates 1 1 1 with berotralstat, adding a potential oral prophylactic option to the Peter Stepaniuk , Amin Kanani ; Division of Allergy and Immunology, treatment armamentarium for physicians. Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada. Rituximab in the Treatment of Acquired RATIONALE: Hereditary angioedema (HAE) is well documented con- 067 Angioedema dition with inherited deficiency or dysfunction of C1 inhibitor. However, its association with other immune disorders such as autoimmunity, malig- Tracy Hwangpo1; 1University of Alabama Birmingham. nancy and primary immunodeficiency is not known. RATIONALE: Acquired visceral angioedema is rare and has many causes METHODS: We reviewed the charts of HAE patients at a private allergy including allergic, NSAID-induced, hereditary C1 esterase deficiency, clinic in Vancouver, Canada. Patients were included in the study if they had acei-induced, acquired angioedema, and idiopathic angioedema. A sixty- a confirmed diagnosis of HAE based on a suggestive clinical history and one-year old woman with a history of C. difficile colitis s/p fecal transplant prior abnormally low C1 inhibitor functional testing on at least two started to have severe abdominal pain and imaging-supported visceral separate occasions. Malignancy and immune disorder diagnoses were angioedema over 1 year. Her GI specialist checked C4 and C1 esterase and based on either patient reported history of the condition or on details noted deficiency of both. Patient was referred for evaluation of acquired provided in other medical consultation letters. angioedema and treatment. On review, patient has throat swelling and 2 RESULTS: 49 patients with HAE were reviewed and we identified 6 episodes of abdominal swelling over last 2 years. patients with co-existing malignancy including 2 patients with breast METHODS: Panel of angioedema labs done to confirm diagnosis of cancer, 1 with melanoma, 1 with pancreatic cancer, 1 with renal cancer, and acquired angioedema. Flow cytometry was also done to look for 1 with cervical dysplasia and possible bladder cancer (under investigation). abnormalities of her lymphocytes. All patients were aged 50 or greater at the time of their malignancy RESULTS: Cell markers show monoclonal CD5+ B cell population. diagnosis, except the patient with cervical dysplasia who was diagnosed Prompt referral to hematology and treatment with rituximab resulted in with malignancy in her early forties. 6 patients with co-existing immune improvement and resolution of angioedema for 2 years. C4 levels were disorders were identified including 2 patients with ulcerative colitis, 2 with detectable after treatment. After 2 years, her C4 levels started to decrease rheumatoid arthritis, 1 with Sjogren’s syndrome, and 1 with hypothyroid- and monoclonal B cell population noted again. Rituximab was given with ism and chronic spontaneous urticaria. improvement in C4 levels. No angioedema episodes occurred during this CONCLUSIONS: We identified multiple HAE patients with co-existing period. malignancy and immune disorders, which may indicate an association. We CONCLUSIONS: Visceral acquired angioedema is not reported much in recommend that physicians managing HAE patients should maintain a literature and referral from GI is important to investigate the cause. If B cell high index of suspicion for these conditions. clonal population detected, prompt referral to hematology is needed . Treatment with B cell depleting therapy can help with resolution of symptoms. Following C4 levels after Rituximab treatment may help determine the need for further treatment. J ALLERGY CLIN IMMUNOL Abstracts AB23 VOLUME 147, NUMBER 2

Reduction in Attacks in Hereditary Angioedema Diagnosis of hereditary Angioedema by genetic 070 (HAE) With Berotralstat is Consistent 072 mutation of coagulation factor XII Regardless of Prior Prophylactic Treatment: A Subgroup Analysis of the Phase 3 APeX-2 Trial Natasha Ferraroni, MD1, Gabriela Yoshimoto2, Camila Veronez3, Luiza Silva2, Marina Batista2, Bruna Azevedo4,Jo~ao Pesquero4; 1GEBRAEH John Anderson, MD1, Remi Gagnon, MD MSc2, Jessica Best, DHSc, (Brazilian Hereditary Angioedema Study Group), 2UniCEUB, 3Universi- PA3, Sharon Murray, PhD3, Heather Iocca, PhD4, Karl Sitz, MD dade Federal de Sao Paulo -UNIFESP, 4Universidade Federal de S~ao FAAAAI5; 1Alabama Allergy & Asthma Center, 2Clinique Specialisee Paulo - UNIFESP. en Allerfie de la Capitale, 3BioCryst Pharmaceuticals, 4BioCryst Pharma- RATIONALE: Hereditary angioedema (HAE) may be a suspected ceuticals, Inc, 5Little Rock Allergy and Asthma Clinic, P. diagnosis when a patient presents history of abdominal pain and edema RATIONALE: Prophylactic treatment in the management of HAE is attacks. In some cases, C4, C1 inhibitor (C1-INH) (quantitative and common. Berotralstat is an oral once-daily selective plasma kallikrein functional) and C1q levels are normal, leading to the diagnostic hypothesis inhibitor that was shown to reduce HAE attack rates in a Phase 3 study of HAE with normal C1-INH. We present a patient who was referred to (NCT03485911). This post hoc analysis evaluated the efficacy of investigate for variants in exon 9 of F12 gene, and the mutation berotralstat in patients previously treated with prophylactic medications. p.Thr328Lys was found in heterozygosity. METHODS: A total of 121 patients were randomized to berotralstat 110 PATIENT PRESENTATION: A 43 year old female patient, resident in mg:150 mg:placebo daily for 24 weeks. Investigator-confirmed attacks Brasılia, Brazil, referred from the dermatology with a diagnosis of contact were analyzed for patients grouped by type of prior prophylaxis: prior C1 dermatitis. During directed anamnesis, she reported abdominal pain and esterase inhibitor (C1-INH), prior androgen, and no prior prophylaxis. edema crises, requiring hospitalization in the intensive care unit and Prior C1-INH and prior androgen categories were not mutually exclusive. undergoing exploratory laparotomy without successful diagnosis. She RESULTS: Overall, 75% of patients in the berotralstat 150 mg dose group received treatment with antihistamine and corticosteroids without and 73% in the placebo group had prior prophylactic treatment. Among improvement. C4, C1-INH (quantitative and functional) and C1q levels patients with prior C1-INH prophylaxis or prior androgen use, berotralstat were normal. Therefore, the diagnostic hypothesis was HAE with normal 150 mg significantly reduced attacks compared to placebo during the C1-INH. treatment period (C1-INH, 1.58 attacks/month vs placebo 2.84 attacks/ METHODS: Analysis for variants in exon 9 of F12 gene by Sanger month, p 5 0.012; androgens, 1.35 attacks/month vs placebo 2.60 attacks/ sequencing. We identified mutation p.Thr328Lys. month, p <0.001). Lastly, patients without prior prophylaxis had a RESULTS: Administration of icatibant for acute attacks, contraindication reduction in attacks (0.86 attacks/month compared with 1.78 attacks/ of estrogen-based hormone replacement therapy, indication for screening month in placebo; p 5 0.056). family and genetic counseling. CONCLUSIONS: In this subgroup analysis, patients with prior C1-INH CONCLUSIONS: The lack of alterations in the laboratory tests of C1- prophylaxis or prior androgen use treated with berotralstat demonstrated a INH levels and function, C4, C3 and C1q levels - hinder the early diagnosis significant reduction in attacks vs. placebo, making oral berotralstat a of HAE. Furthermore, since the main complaints of this patient are was due valuable potential preventive treatment option for patients with HAE. to dermatitis, the diagnosis was only possible after consult with an allergist. The low prevalence in the population and the non-specific clinical picture Rituximab as Treatment of Chronic Idiopathic lead to an underdiagnosis of the disease. 071 Urticaria

Saira Zafar1, Mark Weinstein2, Alan Wolff, MD3; 1Rutgers NJMS, 2Hud- son-Essex Allergy, LLC, 3Department of Veteran. RATIONALE: Conventional treatment of chronic idiopathic urticaria involves high doses of antihistamines followed by omalizumab in refractory cases, however, there are patients who do not achieve resolution of symptoms despite both of these therapies. The following case series describes two cases of chronic idiopathic urticaria successfully treated with rituximab. METHODS/RESULTS: The first patient is a 43 year-old woman with psoriatic arthritis and autoimmune thyroiditis who presented to us with chronic idiopathic urticaria. She was found to have elevated levels of anti- IgE receptor antibodies with levels greater than maximum level of detection. She was unresponsive to high doses of antihistamines, cyclosporine, prednisone, dapsone, mycophenolate mofetil, hydroxychlor- oquine, and omalizumab and ultimately trialed on rituximab with complete resolution of urticaria. Our second patient is a 49 year-old woman with multiple sclerosis, allergic rhinitis, and atopic dermatitis who was referred with humoral immunode- ficiency. She was diagnosed with common variable immune deficiency and started on SQ immune globulin therapy. She also had long-standing generalized urticaria refractory to antihistamines which responded to rituximab started by her neurologist for a flare of her multiple sclerosis. CONCLUSIONS: Use of rituximab in treatment of chronic idiopathic urticaria is not well documented in literature today and should be entertained as possible therapy for cases of treatment-resistant chronic urticaria, especially in the setting of other autoimmune conditions. AB24 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Long-term Impact of Lanadelumab on Patients lanadelumab reduced the attack rate by a mean (SD) of 91.4% (14.3; 073 with Hereditary Angioedema (HAE) Type 1/2: n534), 94.5% (11.4; n519), and 92.2% (12.4; n553) versus baseline, Patient Reported Outcome (PRO) Findings from respectively. In nonrollovers, the attack rate was reduced by 93.6% (13.9; the HELP Open-label Extension Study (OLE) n539), 89.3% (22.9; n511), and 93.2% (9.7; n528) versus baseline, respectively. The adverse event (AE) profile was comparable across the Maureen Watt1, Marcus Maurer, MD2, Giovanna Devercelli3,Kim baseline attack rate groups, with similar AE rates. Injection site reactions Paes, Clinical Scientist3, Antoine Regnault4, Julliette Meunier4,Laurine were the most common adverse event. Bunod4,MarcRiedl,MDMS5, William Lumry, MD FAAAAI6; 1Takeda CONCLUSIONS: The response to lanadelumab with respect to the Pharmaceuticals International AG, Zurich, Switzerland, 2Charite–Uni- reduction of attack frequency and safety was consistent regardless of versit€atsmedizin Berlin, Germany, 3Takeda Pharmaceutical Company baseline attack rate. Limited, Lexington, MA, 4Modus Outcomes, Lyon, France, 5University of California San Diego, San Diego, CA, 6Allergy and Asthma Research Biomarkers associated with chronic Associates, Dallas, TX. 075 spontaneous urticaria severity in children

RATIONALE: Improving HAE patients’ health-related quality of life 1 1 1 (QoL) is a continuing goal. The objective was to investigate the long-term Lydia Zhang, MD , Michelle Le, MD , Sofianne Gabrielli, MSc , Elena Netchiporouk, MD, MSc1, Luis Felipe Ensina, MD, PhD2, Shoshana benefit of lanadelumab from the patient perspective. 3 4 1 >_ GreenbergerDermatology , Sharon Baum , Fatemeh Jafarian, MD , Xun METHODS: Patients 12 years old with HAE type 1/2 who continued 5 1 1 from HELP (rollovers) received 300mg lanadelumab on day 0, then 300mg Zhang, PhD , Moshe Ben-Shoshan, MD FAAAAI ; McGill University Health Centre, 2Federal University of S~ao Paulo, 3Sheba Medical Center every 2 weeks (q2wks) after their first attack (regular dosing stage). Newly 4 5 enrolled patients (nonrollovers) received 300mg q2wks from day 0. The Israel, Chaim Sheba Medical Center, Research Institute of McGill Uni- planned treatment period was 132 weeks. QoL was assessed with the versity Health Centre. Angioedema QoL Questionnaire (AE-QoL [higher scores5poorer RATIONALE: Data on biomarkers associated with chronic spontaneous outcome]) at baseline and every 4-8 weeks, and the Treatment urticaria (CSU) severity in children are sparse. We aimed to evaluate the Satisfaction Questionnaire for Medication (TSQM-9; treatment effective- association between biomarkers and CSU severity in a registry of Canadian ness, convenience, and global-satisfaction domains [higher scores5greater children with CSU. satisfaction]) at days 364, 574, and end of study (EOS). All endpoints were METHODS: Children with CSU (reporting hives for at least 6 weeks) summarized using descriptive statistics. were prospectively recruited at the Montreal Children’s Hospital allergy RESULTS: 212 patients received treatment (n5109 rollovers; n5103 and immunology clinic from 2013 to 2019. Levels of serum tryptase, total nonrollovers). Rollovers experienced improvement in AE-QoL total and immunoglobulin E (IgE), C-reactive protein (CRP), thyroid-stimulating domain scores from day 0 to EOS (respective mean change [SD]: in total hormone, anti-thyroid autoantibodies, complete blood count and CD63 score -10.2 [17.9], functioning -11.1 [24.3], fatigue/mood -7.4 [23.8], were obtained at study entry. Weekly urticaria activity score (UAS7) was _ fears/shame -12.9 [19.2], nutrition -7.2 [26.1]), with highest improvement recorded at study entry. Uncontrolled disease was defined as UAS7>16, observed in the fears/shame domain. Nonrollovers experienced numeri- which included moderate and severe CSU (Weller et al. J Eur Acad cally greater improvement in all AE-QoL scores (respective mean change Dermatol Venereol. 2015). Univariate and multivariate logistic regressions [SD]: -19.5 [21.3], -26.2 [27.7], -11.6 [25.8], -22.2 [24.3], -18.3 [24.4]). were conducted to determine factors associated with uncontrolled CSU. Mean TSQM-9 scores showed rollovers and nonrollovers were very RESULTS: Among 85 children with CSU, 42% were male and the median satisfied with treatment effectiveness (>90), perceived treatment was age at recruitment was 9.3 years [Interquartile Range (IQR) 1.3-17.7]. convenient (>81), and were very satisfied with lanadelumab (>87). Only 20% had moderate or severe urticaria. Uncontrolled CSU was less CONCLUSIONS: The results confirm the sustained long-term improve- likely in boys [adjusted Odds Ratio (aOR) 0.79 (95%CI 0.63, 0.99)], but ments in QoL and positive impact of lanadelumab on patients’ experience associated with increased TSH [aOR 1.17 (95% CI 1.03, 1.33)], mean as observed in the HELP trial. platelet volume (MPV) [aOR 1.08 (95% CI 1.02, 1.16)], CD63 [aOR 1.012 (95% CI 1.005, 1.018)] and IgE [aOR 1.0006 (95% CI 1.0002, 1.001)], Long-term efficacy and safety of lanadelumab by while adjusting for age, tryptase and CRP. 074 baseline attack rates in hereditary angioedema CONCLUSIONS: Studies assessing the underlying mechanisms for the effect of sex, TSH, MPV, CD63 and IgE levels on CSU severity will likely Aleena Banerji, MD FAAAAI1, Marc Riedl, MD MS2, Raffi contribute to elucidate the pathogenesis and prognosis of pediatric CSU. Tachdjian, MD MPH FAAAAI3, Christina Nurse, PhD4, Ming Yu4, Sorena Kiani5; 1Massachusetts General Hospital, 2University of California, San Diego, 3UCLA Division of Allergy, Immunology & Rheumatology, 4Takeda, 5Barts Health NHS Trust. RATIONALE: In the HELP OLE study (NCT02741596), lanadelumab 300mg every 2 weeks (Q2W) effectively prevented hereditary angioedema (HAE) attacks over an extended treatment duration; we further analyzed the impact of patients’ baseline attack rate on lanadelumab efficacy and safety. METHODS: Patients >_12 years old with HAE-1/2 who continued from the HELP study (rollovers) had >_1 attack/4 weeks at baseline; they received lanadelumab 300mg on Day 0, then 300mg Q2W after their first attack in the HELP OLE. Patients who did not participate in HELP (non- rollovers) had a historical baseline attack rate of >_1 attack/12 weeks and received 300mg Q2W from Day 0. The treatment period was 132 weeks from the first dose. RESULTS: Data from 212 patients (109 rollovers, 103 non-rollovers) were analyzed. The mean (SD) baseline attack rate was 3.52 (2.48) and 2.55 (2.75) attacks/4 weeks in rollovers and nonrollovers, respectively. In rollovers with a baseline attack rate of 1–<2, 2–<3, and >_3 attacks/4 weeks, J ALLERGY CLIN IMMUNOL Abstracts AB25 VOLUME 147, NUMBER 2

Allergic Rhinitis and Chronic Spontaneous Chronic urticaria in children: a real-life study 076 Urticaria 078

Iwona Dziewa, DO1, Jamie Rosenthal, MD2, Taha Al-Shaikhly, Larissa Brandao~ 1, Chayanne Araujo, MD1, Ana Carla Moura, MD2, MBChB1; 1Penn State College of Medicine, 2George Washington Univer- Dayanne Bruscky, MD2, Ana Caroline Dela Bianca, MD PhD2,In^es Cam- sity Medical Faculty Associates. elo-Nunes1, Luis Felipe Ensina, MD, PhD1; 1Federal University of S~ao RATIONALE: The prevalence of allergic rhinitis (AR) is reported to be Paulo (UNIFESP), 2Federal University of Pernambuco (UFPE). higher among patients with chronic spontaneous urticaria (CSU). RATIONALE: Chronic urticaria (CU) is a common disease but with However, the relationship between AR and response of CSU patients to limited data in children. This study aimed to evaluate comorbidities and

H1-antihistamines is not well defined. We hypothesize that AR can modify factors related to severity and response to treatment in children with CU. patient response to H1-antihistamines. METHODS: This retrospective and cross-sectional study analyzed data METHODS: We conducted a retrospective study using TriNetX, a global from patients aged 0 to 18 years with CU, followed at two centers from federated health research network that provides access to EMRs from our January 2015 to July 2020. organization. A modified validated algorithm was used to identify CSU RESULTS: Of 125 patients, 61% were female, and 68% had chronic patients seen during 2015, who had two consecutive ambulatory visits at spontaneous urticaria (CSU). Chronic inducible urticaria (CIndU) was least 6 weeks apart with an ICD-10 code of either ‘idiopathic urticaria’, associated with CSU in 22,4%, and 9,6% had isolated CIndU. The median ‘other urticaria’ or ‘urticaria, unspecified’, and have received second- age at onset of symptoms was eight years, and the majority (59,2%) generation H1-antihistamines. We compared patients with and without reported angioedema. Atopy was observed in 66%, with asthma (53.6%) allergic rhinitis with regards to requiring the addition of omalizumab to and rhinitis (26.4%) being the most common. NSAIDs exacerbation was

H1-antihistamines for treatment of CSU over an observation period of 4- reported in 21.6%, and 7.2% had autoimmune diseases. The mean time to 5 years. We used propensity score matching to match the two cohorts for disease control since the symptoms had started was 28 months (SD630) age, sex and race. and 5.7 months (SD68.8) after the first treatment. There was no associ- RESULTS: We identified 450 CSU patients [mean age at diagnosis ation between atopy, thyroid autoantibodies, eosinopenia, and angioedema (6SD), 44.2 (616.6); 82% were females]. Prevalence of allergic rhinitis with treatment response. Most patients (88.4%) had symptoms controlled was higher than a matched cohort seen during the same time frame (55.6% with second-generation antihistamines: 45% with standard doses, 25% versus 13%, P<0.001). After excluding individuals with asthma (N5200), with twofold, and 16% with fourfold doses. Previous use of first-generation and matching for age, sex, and race, an equal proportion of CSU patients antihistamines was reported in 44%. Treatment with omalizumab and with AR (N5100) required omalizumab when compared to those without cyclosporin occurred in 9% of patients. AR (N5100) [RR51; 95% CI (0.574,1.741)]. CONCLUSIONS: Children with CU had a higher prevalence of CONCLUSIONS: Although the prevalence of AR is higher in patients angioedema, adequate but late diagnosis, and treatment, with symptoms with CSU, its presence does not predict response to H1-antihistamines. controlling about six months later. The response to standardized doses of second-generation antihistamines was inadequate, and it was necessary to Urticaria Knowledge and Management among extrapolate adult protocol to childhood. 077 Pediatric Providers in a Chicago Academic Center Omalizumab Treatment and Outcomes in 079 Chinese Patients with Chronic Spontaneous Ozge Nur Aktas1, Alan Schwartz, PhD1, Andrea Pappalardo, MD Urticaria, Chronic Inducible Urticaria, or Both FAAAAI1; 1University of Illinois College of Medicine at Chicago. RATIONALE: It is important for pediatric providers (PPs) to know how to Yudi Chen1, Yu Miao2, Ping Tu2, Marcus Maurer, MD3, Zuotao Zhao, diagnose and manage acute and chronic spontaneous urticaria (AU and MD PhD4; 1Beijing Hospital, 2Peking University First Hospital, CSU) including referral to subspecialty clinics. This study aims to explore 3Charite-Universitatsmedizin Berlin, 4Peking University. the urticarial knowledge and management among PPs in a Chicago RATIONALE: Chronic urticaria (CU) is a common skin disorder which is academic center. further divided into chronic spontaneous urticaria (CSU) and chronic METHODS: This is a cross-sectional survey study of resident physicians inducible urticaria (CIndU). Omalizumab (anti-IgE) therapy is effective (RPs) and other PPs including fellow and attending physicians, and and safe for difficult-to-treat CU based on clinical trials but little is known clinicians at the Children’s Hospital of University of Illinois. Data was about its use for CU in China. Our study was conducted to collect real- collected between July and August 2020. Nonparametric tests were world clinical data on omalizumab treatment in patients with CSU, CIndU performed to compare RPs and other PPs. and both. RESULTS: Fifty PPs completed the survey, including 27 RPs. RPs felt less METHODS: This was an observational, retrospective chart review of comfortable with the diagnosis and treatment of AU (U5 103 and 140.5, patients with CU initiating omalizumab treatment between February 2018 respectively; p<0.001 for both) and CSU compared to other PPs and May 2020 (maximum 27 months follow-up). (U5109.5, p<0.001; U5 179.5, p50.01, respectively). Concern level RESULTS: A total of 152 patients were included, 97 with CSU alone, 36 for a severe reaction and frequency of epinephrine prescription for AU and with different forms of CIndU, and 19 with both. A total of 88.2% of the CSU were similar in both groups. Concern level was not correlated with CU patients responded to omalizumab therapy. The response rate was epinephrine prescription in RPs, whereas it was positively correlated in comparable among patients with CSU, CIndU or both. The proportion of other PPs for AU (rs50.47, p50.02) and CSU (rs50.48, p50.02). Forty- patients with low total IgE levels in nonresponders was significantly higher one percent of RPs and 61% of other PPs correctly identified the CSU defi- than that of responders (61.1% vs. 16.1%, P<0.001). Besides, there were nition (p50.16). Half of the providers recommended skin prick test in CSU more patients with elevated thyroid autoantibodies in nonresponders while 34% was not sure about the recommendation. Cited referral indica- than in responders (50.0% vs. 22.6%, P50.035). The median ratio of tions were similar among all providers except family’s request being more serum IgG-anti-thyroid peroxidase to serum total IgE in nonresponders prevalent among other PPs (p50.01). was significantly higher than in responders (1.22 vs. 0.09, P<0.001). CONCLUSIONS: Knowledge gaps were identified in all PPs. This Nonresponders also had shorter treatment periods (4.5 vs 6.0 months, presents an opportunity to educate PPs regarding current practice and P<0.001) compared with responders. referral recommendations for urticaria. CONCLUSIONS: Omalizumab is highly effective in patients with difficult-to-treat CSU, CIndU or both. Responders tend to have unique immunological features and longer treatment periods. AB26 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Clinical conditions of patients with chronic Cobalamin Deficiency and the Presence of 080 urticaria during the pandemic caused by the 082 Gastrointestinal Symptoms in Patients with 2019 Novel Coronavirus Disease (COVID-19) Chronic Urticaria

Paula Argolo1, Grazielly Pereira2, G. F. Pereira1, Jorge Kalil, MD, PhD1, Sari Herman, MD, FRCPC1, Armin Abadeh, MD1; 1University of Antonio Motta1, Rosana Agondi, MD PhD1; 1University of S~ao Paulo, Toronto. 2Hospital das Clı´nicas, FMUSP, S~ao Paulo, Brazil. RATIONALE: Despite the previously reported presence of systemic RATIONALE: Chronic urticaria (CU) frequently compromises patients’ symptoms in patients with chronic urticaria, the frequency and character- quality of life and stress can be a major factor. This becomes even more istics of gastrointestinal symptoms have not been described in a Canadian important in the current worldwide COVID-19 pandemic scenario. This population. study aimed to assess how much this disease had compromised patients METHODS: A retrospective chart review of adult (age >_18) patients with with CU. chronic urticaria (skin wheals >_6 weeks) from April 2019 to February 2020 METHODS: This is a retrospective study with data collected from was conducted. Demographic characteristics, medical history, medica- electronic medical records of patients with CU. As routine outpatient visits tions, presence of gastrointestinal symptoms, and laboratory findings were were suspended due to COVID-19 pandemic, patients received phone calls abstracted from electronic medical records. to reschedule their outpatient visits and during those calls, some questions RESULTS: Of the 100 patients included in this study (24 males; 76 were asked to assess clinical condition related to CU and possible infection females; average age 46), 70 patients reported experiencing gastrointes- with SARS-CoV-2. tinal symptoms during initial consultation or follow up visits. The most RESULTS: From april to july, 2020, 140 patients received phone calls. common symptoms were gastroesophageal reflux (n542; 60%) and Nervousness was reported by 80 patients (57.1%), of which 30% reported epigastric pain (n526; 37%). Gastrointestinal symptoms were more worsening of urticaria. The use of corticosteroids was more frequent prevalent in those patients with cobalamin deficiency (serum level <_250 among patients with emotional stress due to the pandemic (20%). Obesity pmol/L), which was found in 29.3% of study population, compared to was the other comorbidity most frequently seen in these patients with CU patients without deficiency (81.5% vs 73.8%). (35%). Of the 22 patients who visited the Emergency Room, 9 (40.9%), CONCLUSIONS: To our knowledge, this was the first study to provide only five patients underwent specific investigation to COVID-19 and 2 data on the high prevalence of gastrointestinal symptoms in a Canadian (22.2%) of them tested positive – one obese patient was intubated for 24 population diagnosed with chronic urticaria. These findings highlight the days. importance of assessing patients with chronic urticaria for gastrointestinal CONCLUSIONS: During the COVID-19 pandemic, our patients with CU symptoms as they may require additional management for improved presented more frequently new episodes of emotional stress and these were quality of life. Assessment for cobalamin deficiency may also be warranted a factor associated with worsening urticaria and greater use of corticoste- as it appears to be higher in prevalence in this patient population. The roids. Obesity, in our group of patients, was very prevalent and the only significance of these findings should be prioritized and may improve the patient with CU admitted to an intensive care unit was not elderly but was understanding of chronic urticaria. obese with BMI> 35 kg/m2. Omalizumab in Chronic Inducible Urticaria: a Omalizumab in Children and Adolescents with 083 Real-Life Study of Efficacy, Safety, Predictors 081 Chronic Urticaria: A 16 Week Real-World Study of Treatment Outcome, Time to Response and Relapse Xiaoting Song1, Marcus Maurer, MD2, Yudi Chen3, Miao Yu, MS4, Zuotao Zhao, MD PhD4; 1Peking University First Hospital, 2Charite- Miao Yu, MS1, Marcus Maurer, MD2, Yudi Chen3, Zuotao Zhao, MD Universitatsmedizin Berlin, 3Beijing Hospital, 4Peking University. PhD1; 1Peking University, 2Charite-Universitatsmedizin Berlin, 3Beijing RATIONALE: The efficacy and safety of omalizumab in adult with Hospital. refractory chronic urticaria (CU) have been confirmed, but related RATIONAL: Clinical trials have shown the efficacy of omalizumab in experience in children is lacking. We have attempted to assess the efficacy some forms of chronic inducible urticaria (CIndU), but real-life evidence is and safety of omalizumab in children and adolescents with CU, and to limited. Specifically, little is known about the long-term efficacy and safety explore predictive factors and optimum dosage regimens. of omalizumab in the treatment of patients with CIndU, and predictors of METHODS: Patients aged < 18 years with antihistamine-resistant CU complete response and time to response remain unknown. were treated with 150 or 300 mg of omalizumab every four weeks. We used METHODS: This retrospective study included 36 CIndU patients (24 the recently validated Chinese version of urticaria control test (UCT) to females) treated with omalizumab for six months. Efficacy and effects on assess disease control status, children’s dermatology life quality index QoL were assessed by use of the Urticaria Control Test (UCT) and the (CDLQI) to evaluate quality of life impairment, and monitored adverse Dermatology Life Quality Index (DLQI), respectively, at baseline and each events to assess the safety. The potential factors related to onset time of visit. Adverse events were documented. omalizumab in children with CU were analyzed. RESULTS: Omalizumab showed a significant continuous improvement in RESULTS: We treated 12 CU patients (7 female, 5 male; mean age the scores of UCTand DLQI from baseline to each visit. A total of 77.8% of 10.1764.42 years, range 3–16) with omalizumab. 66.7% of the patients CIndU patients treated with omalizumab had well-controlled urticaria, and achieved a well-controlled disease status (defined as a UCT score >_ 12) as 61.1% of patients had no quality of life impairment. Higher baseline total soon as the first omalizumab administration. The UCT score significantly serum is a possible biomarker predicting complete response in CIndU increased from 2.5(0.0-5.8) at baseline to 12.0(1.25-13.75) after four (121.0 vs. 42.9 kU/L, P50.045). Slow complete responders who re- weeks (Z5-3.063, P50.002) and 15.0(13.5-16.0) after 16 weeks (Z5- sponded after 2 months are younger (33.364.5 vs. 28.066.8 years, P 3.065, P50.002). The CDLQI score decreased from 17.5(14.5-20.5) at 50.034) and have lower baseline UCT scores (4.2 vs. 2.5, P 50.031). baseline to 9.0(3.0-13.8) after four weeks (Z5-2.984, P50.003) and Five patients with complete control stopped their treatment and experi- 2.0(0.0-6.8) after 16 weeks (Z5-3.063, P50.002). No adverse events were enced a relapse after 3-14 weeks. They were successfully retreated with observed. No clinical features or laboratory factors predicting response to a complete response after the first administration. No treatment-related omalizumab treatment were found. adverse events were recorded. CONCLUSION: Omalizumab is effective and safe for children and CONCLUSIONS: Long-term treatment with omalizumab is effective and adolescents with antihistamine-resistant chronic urticaria. safe in patients with CIndU. J ALLERGY CLIN IMMUNOL Abstracts AB27 VOLUME 147, NUMBER 2

Increased Prevalence of Autoimmune Diseases 300mg (36.87) and post-600mg (33.6) mean UAS7s both reflected severe 084 in Children with Chronic Spontaneous Urticaria disease activity (28-42), no clinical change from baseline (40.5). CONCLUSIONS: Up-dosing to 600mg omalizumab q4wks for patients Michelle Le, MD1, Lydia Zhang, MD1, Sofianne Gabrielli, MSc1, Elena refractory to omalizumab 300mg q4wks does not result in clinically Netchiporouk, MD, MSc1, Sharon Baum2, Shoshana GreenbergerDerma- meaningful improvements in urticaria disease severity. tology2, Luis Felipe Ensina, MD, PhD3, Fatemeh Jafarian, MD1, Xun Zhang, PhD1, Moshe Ben-Shoshan, MD FAAAAI1; 1McGill University Comorbidities in Patients with Chronic Urticaria Health Centre, 2Chaim Sheba Medical Center, 3Federal University of 086 ~ Sao Paulo. 1 2 2 RATIONALE: Chronic spontaneous urticaria (CSU) has been found to be Mariana Fernandes, MD , Paula Argolo , Bruna Gehlen, MD , Alanna Batalha, MD2, Jorge Kalil, MD, PhD2, Antonio^ Motta2, Rosana Agondi, associated with an increased prevalence of autoimmune diseases (AIDs) in 2 1 adults. However, the prevalence of AIDs in pediatric CSU patients has yet MD PhD ; Clinical Immunology and Allergy Division, University of ~ 2 ~ to be determined. We aimed to assess the prevalence of AIDs in a cohort of Sao Paulo, University of Sao Paulo. pediatric CSU patients and to determine clinical factors associated with RATIONALE: Several comorbidities are frequently associated with AIDs chronic urticaria (CU), and some can cause worse prognosis to the disease. METHODS: Children with CSU were prospectively recruited at the The objective was to describe the frequency of comorbidities in patients Montreal Children’s Hospital Allergy and Immunology clinic from 2013 to with CU. 2019. Data on patient demographics, co-morbidities (including physician METHODS: This is a retrospective study with data collected from reported diagnosis of AIDs), and clinical characteristics were collected at electronic medical records of patients with CU followed up in a tertiary study entry through a standardized questionnaire. The Fisher’s exact test service. Epidemiological data, CU’s classification, frequency of comor- was used to compare the prevalence of AIDs in our CSU cohort to the bidities were analyzed: esophagitis/gastritis, obesity, systemic arterial general prevalence of AIDs in North American and European children. hypertension, diabetes mellitus, thyroid diseases, respiratory diseases Multivariate logistic regression was conducted to determine clinical (rhinitis and/or asthma) and psychological diseases; the frequency of factors associated with the presence of AIDs in pediatric CSU. angioedema (AE), exacerbation by NSAIDs and refractoriness to H1 RESULTS: Our analysis included 191 patients, whereby 49.2% were antihistamines. Patients were classified according to the concomitance of males and the median age was 9.4 years [IQR: 4.85, 13.65]. Prevalence of comorbidities. hypothyroidism, lupus, juvenile arthritis and type I diabetes were RESULTS: There were 102 sequentially selected patients. Respiratory significantly increased in our cohort compared to children in the general diseases were the most frequent comorbidity (42.2%), followed by population (p<0.005). Hypothyroidism was found to be associated with systemic arterial hypertension (26.5%). When patients were classified increased age (adjusted Odds Ratio (aOR):1.01 [95%CI: 1.01, 1.02]) and according to the their frequency of comorbidities, there was no statistical increased CD63 levels (aOR:1.00 [95%CI: 1.00, 1.01]). difference in relation to the frequency of angioedema, exacerbation by CONCLUSIONS: There is a significantly higher prevalence of AIDs such NSAIDs or refractiveness to antihistamines. The greater the number of as hypothyroidism, lupus, juvenile arthritis, and type I diabetes in children comorbidities, the greater the number of each disease, progressively, with CSU. Increased awareness for AIDs screening in this patient except for thyroid disease and psychic conditions. The group with four or population is suggested. more comorbidities had a higher mean age (57.3 years), longer urticaria time (12.8 years) and greater refractoriness to antihistamines (54.5%). Up-dosing to 600mg Omalizumab for Chronic CONCLUSIONS: Patients with multiple comorbidities were older, had 085 Spontaneous Urticaria: Is it More Effective longer urticaria duration and were more refractory to antihistamines, which Than 300mg? may indicate worse prognosis. The progressive increase in the number of comorbidities, in the same patient, favors the hypothesis of CU to behave Rachel Simpson1, Ariba Quidwai2, Jason Lee, MD FAAAAI1; 1Toronto as a low-grade systemic inflammatory disease. Allergists, 2Western University, London, On, Canada. RATIONALE: Chronic spontaneous urticaria (CSU) is a common condition in which omalizumab, an anti-IgE antibody, is approved for 300mg q4wks dosing as a third-line treatment. Although the majority of CSU improves after 3 months on this regimen, a proportion still remains symptomatic and thus up-dosing to 600mg omalizumab q4wks is commonly suggested afterwards despite limited evidence of its clinical effectiveness. We therefore investigated if up-dosing to 600mg omalizu- mab after failing 300mg omalizumab would result in clinically significant CSU improvements. METHODS: Sixteen CSU patients (mean age 5 33.4) presented to our clinic. UAS7 scores were done before starting 300mg omalizumab q4wks (pre-300mg), 3 months after initiating 300mg omalizumab q4wks (post- 300mg), and 3 months after initiating 600mg omalizumab q4wks (post- 600mg). Statistical analysis of mean UAS7 score differences were preformed using the Wilcoxon Signed-Ranks test. Clinical significance was done by comparing mean UAS7 to established UAS7 disease severity bands (28-425 severe activity, 16-275moderate activity, 7-155 mild activity, 1-65 mild activity). RESULTS: The mean UAS7s for the pre-300mg, post-300mg, and post- 600mg groups were 40.5, 36.87, and 33.6, respectively. There were statistically significant differences between the mean UAS7s for pre- 300mg vs. post-300mg (p50.012), post-300mg vs. post-600mg (p50.004), and pre-300mg vs. post-600mg (p50.008). However, none of the changes in mean UAS7s were clinically significant as the post- AB28 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

A Randomized Controlled Trial of an Educational their concomitant daily medication for SAD. No adverse events were 087 Handbook for Caregivers of Children with Atopic recorded for dupilumab over the study period. Dermatitis CONCLUSIONS: Dupilumab therapy effectively resulted in prompt and significant differences in clinical outcomes in patients with SAD under Jennifer Lebovidge, PhD1, Corinna Rea, MD, MPH1, Karol real-world conditions. Further studies of dupilumab will help determine Timmons, RN MS CPNP1, Sophia Delano, MD, MPP1, Kimberly the clinical efficacy and safety profile of its long-term use. Greco, MPH1, Frances DeFreitas, BS1, Felice Chan, BA1, Tiffany Jeong, BA1, Melissa Rosen, BA1, Lynda Schneider, MD FAAAAI1; 1Bos- Efficacy and Safety of Crisaborole in Patients ton Children’s Hospital. 089 With Mild-to-Moderate Atopic Dermatitis With RATIONALE: Comprehensive patient education is critical to families’ Comorbid Allergic Rhinitis or Asthma ability to manage and cope with pediatric atopic dermatitis (AD). We Jonathan Spergel, MD, PhD1, Michael Blaiss, MD FAAAAI2, Peter evaluated whether an educational handbook could improve AD symptoms, 3 4 5 caregiver confidence in AD management skills, and patient and family AD- Lio, MD , Aharon Kessel, MD , Liza Takiya, PharmD , John Werth, PhD5, Michael O’Connell, MD5, Chuanbo Zang, PhD5, Michael related quality of life. 6 1 METHODS: Caregivers of children with AD ages 1 month to 16 years Cork ; Children’s Hosp of Philadelphia, Perelman School of Med at Univ of Pennsylvania, Philadelphia, PA, 2Medical College of Georgia at were randomly assigned to the intervention arm (handbook in addition to 3 standard AD management) or the control arm (standard management Augusta University, Augusta, GA, Northwestern University Feinberg School of Medicine, Chicago, IL, 4Bnai Zion Medical Center, Haifa, alone). Outcomes were assessed using self-report questionnaires at 5 6 baseline (immediately prior to a clinical visit for AD) and at 3-month Israel, Pfizer Inc., Collegeville, PA, Sheffield Dermatology Research, follow-up. IICD, University of Sheffield, Sheffield, UK. RESULTS: 175 caregivers completed questionnaires at baseline and RATIONALE: Crisaborole ointment, 2%, is a nonsteroidal anti-inflam- follow-up. AD symptoms measured by the Patient-Oriented Eczema matory phosphodiesterase 4 inhibitor for the treatment of mild-to-moder- Measure (POEM) improved in both the handbook and control arms. ate atopic dermatitis (AD). The objective of this post hoc, pooled analysis However, the decrease in the mean POEM score in the handbook arm of the phase 3 studies CrisADe CORE 1 (NCT02118766) and CORE 2 (-4.37, 95% CI [-5.73, -3.02]) did not differ from the decrease in the control (NCT02118792) was to examine the efficacy of crisaborole in patients with arm (-3.43, 95% CI [-4.83, -2.03]; p50.3425). There were no differences mild-to-moderate AD with comorbid asthma or allergic rhinitis (AR). _ between the handbook and control arms in change in quality of life. For METHODS: Patients aged >2 years with mild-to-moderate AD were caregivers of children attending a new patient visit for AD, the increase in randomly assigned 2:1 to receive twice-daily crisaborole or vehicle for 28 the mean confidence score in the handbook arm (15.83) was significantly days. The primary outcome was Investigator’s Static Global Assessment _ greater than in the control arm (1.18; p50.0117). The majority (85%) of (ISGA) success (clear [0] or almost clear [1] with a >2-grade improvement caregivers rated the handbook as helpful in managing the child’s AD. from baseline) at day 29. Patients were stratified by history of AR or CONCLUSIONS: Among caregivers of children attending new patient asthma. visits for AD, the handbook improved confidence in AD management RESULTS: Crisaborole and vehicle were received by 163 vs 79 patients skills. The handbook shows promise as a practical resource to increase with AR (mean age, 11.7 vs 10.9 years; moderate disease, 61.4% vs 65.8%) access to patient education for pediatric AD. and by 258 vs 141 patients with asthma (mean age, 12.9 vs 12.7 years; moderate disease, 60.9% vs 66.7%). ISGA success rate (95% CI) at day 29 Early Clinical Efficacy After Dupilumab Therapy was 36.6% (28.7%-44.6%) vs 18.7% (9.7%-27.7%) in patients with AR 088 for Adult Severe Atopic Dermatitis in a Real- (difference, P50.003) and 26.7% (21.0%-32.3%) vs 18.6% (11.9%- World Setting 25.3%) in patients with asthma (difference, P50.07). ISGA clear or almost clear at day 29 occurred in 55.9% (48.0%-63.8%) vs 29.2% (18.8%-39.6%) Paloma Poza Guedes, MD PhD1, Ruperto Gonzalez Perez, MD PhD1, with AR (difference, P<0.0001) and 45.9% (39.5%-52.3%) vs 31.8% Elena Mederos Luis1, Victor Matheu, MD, PhD1, Cristina Alava1, Inma- (23.5%-40.1%) with asthma (difference, P50.008). No new safety con- culada Sanchez-Machin, MD PhD1; 1Hospital Universitario de Canarias, cerns were identified. Tenerife, Spain. CONCLUSIONS: Crisaborole demonstrates efficacy and safety in the RATIONALE: Although severe atopic dermatitis (SAD) represent less treatment of mild to moderate AD in patients with history of allergic than 20% of all patients with atopic dermatitis, in this subgroup of subjects rhinitis or asthma. quality of life is markedly disturbed. As real-world data concerning dupilumab in patients with SAD are currently scarce, we investigated the early effect of dupilumab in a selected SAD cohort in a real-world background. METHODS: Only adult patients with SAD were included. Patient demographics, medical history including comorbidities and medication use were recorded. Eczema Area and Severity Index (EASI), Scoring AD (SCORAD), validated Global Assessment scale for Atopic Dermatitis (vIGA-AD), Pruritus Numerical Rating Scale (PNRS) -prior to starting dupilumab-, atopic status (total serum IgE, skin prick test/ImmunoCAP assay, blood eosinophil level) were noted. Outcome data were collected at 4-weeks post-commencement of dupilumab (cumulative dose of 1,200 mg) including changes in clinical scores and medication use. RESULTS: All 7 patients (mean age 27616.81 y.o.) reported significant (p<0.005) improvements in the median scores at the 4-week (t4) follow- up: EASI 63.81 (60-70) at baseline (t0) to 7 (1.1-8.8) at t4; t0 SCORAD 85 (63.9-96.4) to 26.9(11.9-37) at t4; t0 vIGA-AD from 4 to 1 at t4, and a reduction in PNRS from 8 to 1 at t4. All patients could effectively reduce J ALLERGY CLIN IMMUNOL Abstracts AB29 VOLUME 147, NUMBER 2

Therapeutic Potential of Rlip Loss on Atopic Downregulation of S1P lyase expression with siRNA increased S1P level 090 Dermatitis and doubled HSV-1 titer in keratinocytes. CONCLUSIONS: Our data suggest the involvement of S1P-mediated Malvika Ramesh, MD Candidate 20231, James Tarbox, MD1, Sanjay signaling in HSVand VV replication and demonstrate that both EVand EH Awasthi, MD2, Sharda Singh, PhD2; 1Texas Tech University Health Sci- are associated with persistent changes in sphingolipid metabolism. ences Ce, 2Texas Tech University Health Sciences Center. Increased sphingoid bases and their phosphates in the skin and blood RATIONALE: Rlip knockdown protects p53 deficient mice from may be a biomarker for patients prone to disseminated viral infection. carcinogenesis and reduces inflammation. In Rlip null mice, increased oxidative stress alone was not enough to increase inflammation. Thus, Rlip Temperature changes contribute to skin barrier is necessary to translate oxidative stress into inflammation. Rlip knock- 092 dysfunction: potential implications for atopic down disrupts inflammatory signaling in atopic dermatitis through altering dermatitis and food allergy

Th1/Th2 immune genes. Here we review potentially significant genes by 1 1 2 analysis of RNA sequence pathways in a previously unknown role, atopic Jessica Hui, MD , Byung Kim, MD PhD , Taras Lyubchenko, PhD , Elena Goleva, PhD1, Donald Leung, MD PhD FAAAAI1; 1National Jew- dermatitis, in relation to partial Rlip loss. 2 METHODS: RNA sequencing (RNA-Seq) was conducted in wild-type ish Health, National Jewish Healh. and Rlip loss mice liver. RNA sequencing runs were performed in a RATIONALE: Children born in the fall are at increased risk for developing Illumina HiSeq 2500 platform with HiSeq SBS V4 kits, and reads were atopic dermatitis (AD) and food allergy (FA), two conditions associated with aligned using Tophat v2.0 to mouse reference genome mm9. skin barrier dysfunction. During an analysis of meteorological data in Denver, RNA-Seq and genome analysis lead to the identification of various we found that the most extreme 24-hour temperature fluctuations occur in the fall. This prompted us to evaluate the effect of temperature on epidermal canonical pathways upregulated/downregulated by Rlip loss. Z scores, 2+ expressing the magnitude of regulation in a positive/negative manner, were differentiation and Ca transport function of transient receptor potential vanil- loid (TRPV) ion channels involved in skin temperature sensing. attributed to each gene. Analysis of existing literature was conducted to 2+ identify new roles for these Rlip loss affected genes. METHODS: Human epidermal keratinocytes were Ca -differentiated 8 RESULTS: Analysis of RNA-Seq shows the top differentially expressed for 3 days, followed by additional studies at various temperatures (25 C, 8 8 8 upregulated genes involved in immunology canonical pathways are IL- 30 C, 37 C, 41 C). Gene expression levels of filaggrin (FLG) and TRPV1, TRPV2, TRPV3, TRPV4 were measured with RT-PCR. Real- 13RA2, ACVR1C and ALDH3A1 with Z scores of 2.127, 2.107 and 1.947 2+ respectively. time dynamics of intracellular Ca influx was assessed in live keratino- CONCLUSIONS: RNA-Seq analysis shows genes involved in immuno- cytes by flow cytometry. RESULTS: Exposure of undifferentiated keratinocytes to increased Ca2+ (cell logic pathways and inflammation are among the top affected by 2+ pharmacologic knockdown of Rlip. Upregulation of canonical pathways differentiation signal) triggered a rapid intracellular Ca influx. Cells cultured 8 8 8 including IL-13RA2, ALDH3A1 and ACVR1C through Rlip inhibition at 25 C, 30 C and 41 C exhibited significant decreases in the peak amplitude of 2+ 8 could serve a therapeutic target for the treatment of atopic dermatitis Ca influx (p<0.05), as compared to the 37 C condition. FLG expression in through reduction of inflammation. Further studies are necessary to fully differentiated keratinocytes was significantly decreased (p<0.001) in cells 8 8 8 understand the mechanism behind this process. incubated at 25 C and 30 C as compared to the cells incubated at 37 Cand 418C. Gene expression of TRPV1 and TRPV4, but not TRPV2 and TRPV3, Lipid Profiles in Eczema Herpeticum and Eczema in differentiated keratinocytes were temperature-sensitive. 091 Vaccinatum Reflect Changes that Predispose to CONCLUSIONS: Differential temperature exposures alter keratinocyte Disseminated Viral Infection responses to the Ca2+ differentiation signal, as well as FLG and TRPV expression. Further mechanistic studies of TRPVs may provide insight Evgeny Berdyshev, PhD1, Elena Goleva, PhD1, Irina Bronova, PhD1, into the effects of temperature on skin barrier dysfunction. Patricia Taylor, NP1, Anna Sofia Bronoff1, Jon Hanifin, MD FAAAAI2, Mark Slifka3,DonaldLeung,MDPhDFAAAAI1; 1National Jewish Health, 2Oregon Health & Science University, 3Oregon Health & Sci- ence Univ. RATIONALE: Atopic dermatitis (AD) is the most common inflammatory skin disease. Less than 5% of AD is complicated by eczema herpeticum (EH) and eczema vaccinatum (EV) but this has led to the CDC recommendation that all AD should not receive smallpox vaccination. Biomarkers of susceptibility to EH and EV are not known. METHODS: Stratum corneum and plasma samples from 15 AD subjects with a history of EH (ADEH+), 13 age- and gender- matched AD subjects without EH history (ADEH-), and 13 healthy controls (HC) were analyzed by liquid chromatography tandem mass spectrometry for sphingolipid content. Sphingosine-1-phosphate (S1P) and ceramide levels were also determined in plasma from seven EV subjects and seven matched AD subjects. S1P lyase was down-regulated in human primary keratinocytes to evaluate its effect on HSV-1 replication in vitro. RESULTS: Stratum corneum of ADEH+ demonstrated significantly higher levels of free sphingoid bases than HC indicating enhanced sphingolipid turnover in keratinocytes (p<0.05). Plasma of ADEH+ subjects had increased S1P/ceramide ratio versus HC (p<0.05) and ADEH-(P<0.01). S1P level in plasma from EV subjects was twice its level in ADEH- subjects (mean51533 vs 732 pmol/ml, p<0.001). AB30 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

IgG4-Related Disease (IgG4-RD) With Unique The role of metal patch testing in evaluating for 093 Combined Skin And Biliary Tract Manifestation 095 metallic prosthetic joint failure

Yela Jung1, Tejal Narsai, MD1, Ashley Sandoval, MD1, Sudhir Gupta, Levi Keller1, Alan Schocket1, Craig Hogan, MD1; 1University of MD PhD FAAAAI2; 1UC Irvine, 2University of California at Irvine. Colorado. RATIONALE: IgG4-RD is a multisystem fibroinflammatory disease RATIONALE: Metal allergy is thought to be an uncommon cause of characterized by infiltration of tissues by IgG4 plasma cells. Biliary tract or prosthetic joint failure. There exists little data on patch testing to metals in skin involvement has been documented in IgG4-RD; however, combined this context and its effect on the outcomes of this type of surgery in these skin and biliary tract involvement in IgG4-RD has not been described. patients. Furthermore, skin lesions in IgG4-RD are localized. We present the first METHODS: A retrospective analysis from January 2016 to April 2020 case of IgG4-RD with combined skin and biliary tract manifestations, and was completed on a patient cohort referred to the University of Colorado generalized skin rashes. Allergy and Immunology practice by the Department of Orthopedics for METHODS: A 55 year old male presented with painful jaundice and evaluation of metal hypersensitivity. Charts were reviewed for age, generalized macular pigmented pruritic rashes all over his body. CT biological sex, referring specialty, patch testing results, joint, revision abdomen revealed biliary obstruction, and brush washing and biopsies of status, and patient reported outcome measures. Biostatistical analysis and ampulla and skin were performed. Biopsy tissues were subjected to descriptive statistics were performed to determine patch testing perfor- histology and immunostaining. Serum immunoglobulin were measured. mance and trends among patients with suspected allergy as a cause of Patient underwent cholecystectomy and was treated with steroids and prosthetic joint failure. currently being considered for B-cell directed biological therapy. RESULTS: The sensitivity and specificity of patch testing, in general, is RESULTS: Serum IgG4 was elevated at 448mg/dl (controls 5-125mg/dl). limited when evaluating patients with metallic joint replacements. Ampula brush washings revealed 1-3 IgG4+ plasma cells. Ampullary However, the predictive value of testing results appeared to improve with tissue biopsy showed focal mildly active chronic inflammation and mild strongly positive patch testing results. Functional outcomes in patients reactive changes, laminar propria showing fibrosis, and increased IgG4 when positive results were used to choose the prosthesis demonstrated positive plasma cells (up to 12/HPF). Skin punch biopsy showed a dense objective evidence of clinical improvement. perivascular and periadnexal lymphoplasmacytic infiltrates with eosino- CONCLUSIONS: The attribution of metal allergy or hypersensitivity as a phils throughout the dermis and involving the subcutis. IgG4 and IgG cause of failure in metal prosthetic joint replacement remains unproven. immunostains demonstrated a 67% ratio respectively. Despite this shortcoming, some patients with positive histories and patch CONCLUSIONS: IgG-RD may present with generalized rashes and testing in which the results were used to modify the choice of implanted combined dematological and biliary tract manifestation. prosthesis had improved functional outcomes. Consequently, these results suggest it may be worthwhile to perform patch testing in patients with prior Clinical characterization of skin pain in children history of metal sensitivity and prior prosthetic failure. 094 with atopic dermatitis

Brian Cheng1, Amy Paller, MD1, James Griffith, PhD1, Jonathan Silver- berg2, Anna Fishbein, MD MS3; 1Northwestern University Feinberg School of Medicine, 2The George Washington University School of Med- icine and Health Sciences, 3Ann & Robert H. Lurie Children’s Hospital of Chicago, Northwestern University Feinberg School of Medicine. RATIONALE: Previous studies have identified skin pain as a symptom of pediatric atopic dermatitis (AD). However, the burden of skin pain in AD is not well-characterized. We examined associations of skin pain intensity with clinical features and functional outcomes in pediatric AD. METHODS: This was a cross-sectional, nationwide survey of 180 children (ages 5-17 years) with AD in the US. Skin pain (0-10 scale) was reported by parent proxy. Multivariable linear regression models were constructed to examine associations of skin pain intensity with AD characteristics, Patient-Reported Outcome Measurement Information System (PROMIS) pain interference, PROMIS profile, and Children’s Dermatology Life Quality Index (CDLQI). RESULTS: The mean6standard deviation age was 10.560.3 years, with 56% male, 32% African-American, and 83% moderate/severe AD. Almost half (49%) had skin pain, with mean intensity of 5.4 [95% confidence interval: 4.6-6.3]. In children with skin pain (n588), after adjusting for sex, race, age, AD severity, pain intensity was associated with frequent (5-7 days/week) itch (adjusted beta [95% CI]: 1.51 [0.61, 2.41]), bleeding (1.39 [0.42, 2.36]), weeping/oozing (1.02 [0.19, 1.85]), and cracking (0.99 [0.14, 1.85]), and with difficulty sleeping (0.95 [0.09, 1.81]), paying attention (1.24 [0.38, 2.09]), and running (1.09 [0.10, 2.07]). Skin pain intensity was associated with depression/sadness (2.21 [0.87, 3.54]), fatigue (2.22 [0.90, 3.54]), and anxiety/fear (2.31 [0.67, 3.96]) and decreased CDLQI scores (-1.75 [-2.35, -1.14]). CONCLUSIONS: Skin pain in pediatric AD is associated with hetero- geneous skin symptoms and significant QOL burden. Clinicians should consider screening for skin pain when treating children with AD. J ALLERGY CLIN IMMUNOL Abstracts AB31 VOLUME 147, NUMBER 2

Single-cell immunopathology of systemic (weighted-base) reported clear/mild, moderate, and severe AD (by PtGA), 096 contact allergy associated with corticosteroids respectively, in the past week; 90.9%, 94.5%, and 97.5%, respectively, reported >_1 atopic comorbidity, mostly hay fever (64.4%, 73.5%, 83.3%), Rebecca Hertzman1, Pooja Deshpande1, Katie White2, Rama Gangula2, asthma (51.0%, 65.5%, 77.9%), seasonal allergies (41.7%, 51.4%, 53.5%), Abha Chopra1, Ramesh Ram1, Shay Leary1, John Zic2, Jeffrey Zwerner2, and allergic rhinitis (41.3%, 50.2%, 52.2%). Similar results were observed Andrew Gibson1, Elizabeth Phillips, MD FAAAAI FIDSA3; 1Institute for when stratified by POEM; 13.7% (overall) had chronic rhinosinusitis with Immunology and Infectious Disease, Murdoch University, Western nasal polyps and 3.5% had eosinophilic esophagitis. Australia, 2Vanderbilt University Medical Center, Nashville, TN, USA, CONCLUSIONS: Worldwide, children with AD have a high burden of 3Vanderbilt University Medical Center, Nashville, TN, USA. self-reported atopic comorbidities. The burden was high even among those RATIONALE: Allergic contact dermatitis (ACD) is a classic delayed with clear/mild AD, increasing further with AD severity hypersensitivity reaction commonly associated with corticosteroids that can rarely manifest as a delayed rash following systemic administration. Real-World Effectiveness of Systemic Therapies METHODS: A 50-year old woman developed local edema and delayed 098 for Atopic Dermatitis (AD) in the United States: spreading rash following interarticular injection with dexamethasone and Analysis of a Retrospective Claims Database methylprednisolone acetate (MA). 6-months following this intradermal Marco DiBonaventura1, Marie-Helene Lafeuille2, Bruno Emond2, Mei skin testing (IDST) was positive to MA and methylprednisolone sodium 2 2 1 1 3 succinate, and IDST and patch test negative to other corticosteroids. She Sheng Duh , Iman Fakih , Natalie Yin , Daniela Myers , Claire Feeney , Joseph Cappelleri1, Jashin Wu4; 1Pfizer Inc., 2Analysis Group, 3Pfizer tolerated dexamethasone challenge. Cells were isolated from 4-mm punch 4 biopsies from 48-hour positive IDST and unaffected skin with liberase Ltd., Dermatology Research and Education Foundation. digestion and sorted on CD3. scTCR and scRNA-seq were performed using RATIONALE: Data on the real-world effectiveness of new systemic plate-based assays (Smart-seq-2). Data was filtered using Seurat and therapies for AD are needed. analysed with Visual Genomics Analysis Studio (VGAS) software. METHODS: The IQVIA Health Plan Claims dataset (September 2016- _ RESULTS: Histopathology showed a superficial perivascular dermatitis December 2019) was analyzed. Patients aged >12 years with AD (ICD-9/ with epidermal spongiosis in keeping with ACD. T-cells were 18x more 10-CM: 691.8/L20.x) who newly initiated a systemic immunosuppressant prevalent in affected skin and those from both affected and unaffected sites (methotrexate, cyclosporine, mycophenolate , and azathioprine) or dupi- _ were predominantly CD8+ T-cells that expressed CD45RO and polyclonal lumab and had >6 months continuous enrollment before and after their first TCR alpha beta. Differentially expressed genes (DEG) in T-cells from systemic therapy claim were included. Treatment patterns and rates of affected skin reflected homing (CCR7,S1PR1), T-cell activation and treatment nonresponse were analyzed. Nonresponse was defined as adding/ proliferation (TNFRS9, GRAP2, ZYG11A, ZHX1), T-cell effector differ- switching to different systemic therapy, having an AD-related inpatient or entiation (IL-21R), and stress survival (EEF1A1, IFI6) without represen- emergency room visit, or having incident staphylococcal or streptococcal tation of markers of T-cell residency (ITGAE) or regulation. skin infection. CONCLUSIONS: We demonstrate insights into the immunopathogenesis RESULTS: Overall, 3249 patients were included (mean age 40.6 years; of drug-induced ACD by showing that IDST+ methylprednisolone 54.2% female). During the baseline period, 50.7% and 76.1% used associated ACD is corticosteroid-specific and associated with a polyclonal systemic and topical corticosteroids, respectively. The distribution of 5 population of primarily CD45RO+ memory CD8+ T-cells showing systemic index treatments was dupilumab (n 2455; 75.6%), methotrexate 5 5 5 upregulation of markers of homing, T-cell activation, proliferation and (n 468; 14.4%), cyclosporine (n 180; 5.5%), mycophenolate (n 94; 5 differentiation but lacking markers of T-cell residency and regulation. 2.9%), and azathioprine (n 52; 1.6%). During follow-up, 45.4% of patients exhibited an indicator of nonresponse, with adding/switching to Children With Atopic Dermatitis (AD) Have a another systemic therapy (44.7%) being the most common. Kaplan-Meier 097 High Burden of Atopic Comorbidities: Results rates of nonresponse at 12 months varied by index therapy, with dupilumab From a Large Worldwide Survey having the lowest rate (35.4%) compared with methotrexate (59.6%), cyclosporine (68.7%), mycophenolate (70.9%), and azathioprine (67.4%; Jonathan Silverberg1, Eric Simpson, MD MCR2, Stephan P<0.01 for all comparisons). Weidinger, MD PhD3,Sebastien Barbarot4, Lysel Brignoli5, Tarek CONCLUSIONS: Most patients did not remain on therapy, although this Mnif5, Grece Saba5, Laurent Eckert, PhD6, Ana Rossi7, Dimittri Delevry8, was significantly more likely for systemic immunosuppressants than Puneet Mahajan7; 1Northwestern University, 2Oregon Health & Science dupilumab. Differences in safety could partially explain these results, University, 3University Hospital Schleswig-Holstein, 4Nantes University though healthcare resource use was similar across cohorts. This study Hospital, 5Kantar Health Division, 6Sanofi, 7Sanofi Genzyme, 8Regeneron highlights the challenges in treating patients with AD who require systemic Pharmaceuticals, Inc. treatment. RATIONALE: Recent information on the prevalence of atopic comor- bidities among children with AD is lacking. This worldwide survey describes the burden of atopic comorbidities across AD severity strata. METHODS: This cross-sectional, web-based survey of children aged 0.5–<18years was conducted in 18 countries (5 regions), with quotas for age, sex, region (urban/rural split), and weighting adjustment applied for representative population for each country. Parents (children >_12yrs) were asked whether the child had ever suffered from hay fever/asthma or been diagnosed with atopic comorbidities. Results were stratified by parent/ patient global assessment (PtGA) of AD severity and POEM in the past week. RESULTS: Among 7465 included children, 92.5% reported >_1 atopic comorbidity (84.7% in Europe [n52700]; 87.6% in Asia [n5743]; 88.5% in North America [n5980]; 95.9% in Latin America [n51959]; 98.1% in Eurasia/Middle-East [n51083]). Atopic comorbidities tended to increase slightly with increasing age (90.0% with >_1 comorbidity for 0.5–5yrs; 92.0% for 6–11yrs; 94.1% for 12–<18yrs). Overall, 4478, 2722, and 376 AB32 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Dupilumab Improves Signs And Symptoms Of Real Time Assessment of Steroid Use in Patients 099 Severe Atopic Dermatitis In Children Aged 6– 100 with Atopic Dermatitis 11 Years With And Without Comorbid Asthma Sonam Sani, MD1, Stephanie Mawhirt, DO2, Erin Banta, MD3, Amanda Mark Boguniewicz, MD FAAAAI1, Lawrence Sher2, Amy Paller, MD3, Schneider, MD4, Luz Fonacier, MD FAAAAI3; 1Winthrop University Elaine Siegfried, MD4, Zhen Chen, PhD5, Randy Prescilla, MD6, Brad Hospital, 2New York University-Winthrop Hospital, 3NYU Winthrop Hos- Shumel, MD5; 1National Jewish Health, Denver, CO, USA, 2Peninsula pital, 4NYU. Research Associates, Rolling Hills Estates, CA, USA, 3Northwestern Uni- RATIONALE: Various corticosteroids(CS) are prescribed for the treat- versity Feinberg School of Medicine, Chicago, IL, USA, 4Saint Louis Uni- ment of atopic dermatitis(AD), asthma and allergic rhinitis. Despite their versity and Cardinal Glennon Children’s Hospital, St. Louis, MO, USA, efficacy, CS are associated with several side effects. The adverse effects of 5Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA, 6Sanofi Gen- combination CS (topical/intranasal/inhaled/systemic) are important to zyme, Cambridge, MA, USA. monitor. Our aim was to monitor steroid use and side effects in patients RATIONALE: Atopic dermatitis (AD) is a chronic inflammatory skin with AD. disease that frequently occurs with atopic comorbidities, including asthma. METHODS: A simplified EMR-tool was used during each AD patient Dupilumab inhibits interleukin (IL)-4 and IL-13 signaling and is approved encounter. Data collected included corticosteroid type/potency/frequency, for treating multiple type 2 inflammatory diseases, including AD and side effects, interventions and patient counseling. asthma. Here, we evaluate the efficacy of dupilumab with concomitant RESULTS: There were 151 AD encounters assessed in 81 patients(42% topical corticosteroids (TCS) for severe AD in children with and without male, 58% female). All 151 encounters involved topical CS(TCS) use with comorbid asthma. additional CS use as follows: 33 inhaled, 20 intranasal, 14 systemic. The METHODS: In this double-blind, 16-week, phase 3 trial most common side effects while on TCS included: pigment change- (NCT03345914), 367 children aged 6–11 years were randomized 1:1:1 s(n538), atrophy(n522), easy bruisability(n510), striae(n59), to 300mg dupilumab every 4 weeks (q4w), weight-based 100/200mg telangiectasias(n59). Forty-two encounters resulted in intervention: dupilumab every 2 weeks (q2w), or placebo, with concomitant medium- decreased dose(n520), decreased potency(n54), and discontinued potency TCS. Asthma history was ascertained by caregiver report. TCS(n518). Patient counseling was documented in 134 encounters. In RESULTS: At baseline, 48%/52%/49% patients in the q4w/q2w/placebo patients without side effects, 20% had a dose adjustment (decrease dose/ groups reported a history of asthma; 52%/48%/51% patients had no history potency, discontinue), compared to 48% of those with one or more side of asthma. Baseline disease severity was comparable in both groups. At effects(p50.0004). Week 16, in both subgroups, significantly more patients receiving CONCLUSIONS: Concomitant use of different CS preparations is dupilumab q4w/q2w vs placebo achieved Investigator’s Global extremely common in AD patients. Regular monitoring of steroid use Assessment score 0/1 (with asthma:37.9%/27.0% vs 11.7%; without resulted in patient counseling in 88.7%(134/151) and real-time interven- asthma:28.1%/32.2% vs 11.1%), >_75% improvement in Eczema Area tion in 27.8%(42/151). The most frequent TCS side effects identified were and Severity Index (with asthma:65.5%/58.7% vs 25.0%; without pigment changes and atrophy. Although patients with side effects had more asthma:73.4%/76.3% vs 28.6%), and >_4-point reduction from baseline in dose adjustments, those without side effects also warranted dose adjust- Peak Pruritus Numerical Rating Scale (with asthma:48.3%/50.8% vs 8.5%; ment(20%). This suggests that a steroid monitoring tool can be helpful in without asthma:53.2%/66.1% vs 15.9%); P<0.05 for all comparisons. identifying side effects early in patients with AD. This can lead to Safety in the overall population was consistent with the known dupilumab appropriate intervention and counseling that may prevent more permanent safety profile observed in adults and adolescents. consequences. CONCLUSIONS: Dupilumab with concomitant TCS was equally efficacious in improving severe AD signs and symptoms in children aged 6–11 years with and without a history of comorbid asthma. J ALLERGY CLIN IMMUNOL Abstracts AB33 VOLUME 147, NUMBER 2

Ruxolitinib Cream Ameliorates Itch and CONCLUSIONS: This study uncovers baseline and PAR2-related 101 Inflammation in Preclinical Models of Dermatitis differences in dark vs light-PHK. As we transition toward a better under- stating of AD phenotypes, it is beneficial to consider and investigate Monika Scuron, PhD1, Brittany Fay, BSc1, Andrew Connell, MSc1, intrinsic ethnic differences in skin barrier regulation and inflammation. Michael Peel, PhD1, Paul Smith, PhD1; 1Incyte Corporation. Clinical And Epidemiological Profile Of Atopic RATIONALE: The pathophysiology of atopic dermatitis (AD) is linked to Dermatitis (AD) In A Reference Center In An aberrant JAK/STAT pathway activation. The goal of the study was to 103 characterize anti-inflammatory and anti-pruritic activity of ruxolitinib Emerging Country cream, a potent, selective JAK1/JAK2 inhibitor, during experimentally- Fernanda Vaz, MD1 1 1 induced dermatitis. , Raissa Roque, MD , Marilia Moraes, MD , Lara Teixeira1, Nathalia Vital, MD2, Caroline Ferreira, MD1, Rafael Saldanha1, METHODS: Ruxolitinib cream was tested in thymic stromal lympho- Pedro Bubach1, Danielle Harari, MD1, Carolina Aranda1, Marcia poietin (TSLP)- and fluorescein isothiocyanate (FITC)-induced dermatitis 2 3 1 mouse models using ear swelling and punch biopsy weight as efficacy Mallozi, PhD , Dirceu Sole, MD PhD FAAAAI ; Federal University of S~ao Paulo, 2Federal University of Sao Paulo, 3Universidade Federal de measures. A transgenic IL-33 mouse model (IL-33tg) of chronic, progres- sive, dermatitis was used to elucidate the effect of ruxolitinib cream on Sao Paulo. RATIONALE: dermatitis associated abnormal scratching and grooming behavior. Atopic Dermatitis (AD) is a chronic inflammatory skin Transcriptomic profiling was performed using RNA extracted from ex disease with multifactorial etiology. This study evaluated the clinical and epidemiological profile of patients with Atopic Dermatitis in a reference vivo mouse samples and normal human skin explants cultured under Th2 stimulating dermatitis-like conditions. center. METHODS: Cross-sectional study performed by analyzing the medical RESULTS: Ruxolitinib cream BID significantly (p<0.01) ameliorated both TSLP- and FITC- induced ear swelling (by 34% and 39%, records of AD patients from Jan/2018-19 in a reference center. Data were analyzed concerning sex, age, severity, treatment, concomitance with other respectively) and ear punch weight (by 39% and 36%, respectively) compared to vehicle (placebo) cream. Therapeutic and prophylactic atopic diseases, evaluation of eosinofilia and the management. RESULTS: 5 administration of ruxolitinib cream abrogated pruritus and abnormal We evaluated 240 patients (male 58.75%) with mean age of 11 years. Regarding classification, 67.08% were mild, 18.33% moderate grooming behavior in IL-33tg mice (p<0.05). Histologically, ruxolitinib and 14.59% severe according to SCORAD (Scoring Atopic Dermatitis). cream significantly reduced mast cell frequency (p<0.05) and tissue Allergic rhinitis was observed in 91.66%, asthma in 55%, IgE-mediated inflammation (p<0.01) compared to vehicle (placebo) cream. Autoimmune and neuropathology transcriptomic profiling revealed that food allergy in 11.25% and allergic conjunctivitis in 35.41%. Eosinophilia was observed in 39.16% of patients and was related to greater severity. ruxolitinib cream skin samples were significantly differentiated from vehicle (placebo) cream treated tissues. Regular hydration was reported by 68.75% of patients. Ciclosporin was CONCLUSIONS: Ruxolitinib cream has potential to significantly inhibit used by 12.08% of patients. Less than 2% are using monoclonal antibodies itch and skin inflammation. These data show that ruxolitinib cream is (MA) due to the difficulty of accessing these drugs. CONCLUSIONS: AD is a multifactorial chronic disease disease with readily absorbed into the skin and inhibits the JAK/STAT signaling pathway, resulting in amelioration of experimentally-induced dermatitis. difficult management and is associated with other atopies. Eosinophilia seems to be a marker of severity in this convenience sample and appears to Protease-Activated Receptor-2: investigating role in be an inexpensive biomarker for everyday use in our clinical practice. 102 regulation of epidermal barrier and inflammation in Hydration is the main pillar of treatment, but it had partial adherence. Atopic Dermatitis based on skin type Thereby, new strategies must be developed with these patients in order to improve adherence and quality of life through multidisciplinary teams. In Shivani Doshi1, Peter Nadeau1, Anna De Benedetto, MD1; 1University of more severe cases the use of immunosuppressants and MA was necessary. Florida. RATIONALE: Protease activated receptor 2 (PAR2) is a G-protein coupled receptor that has effects in promoting Th2-inflammation, skin barrier impairment and pruritus. Current literature supports a role of PAR2 in Atopic Dermatitis (AD). Notably, PAR2 expression is greater in dark pigmented skin. We hypothesize that PAR2 activation will have a greater effect on epidermal barrier and inflammation in primary human keratino- cytes (PHK) from dark vs light pigmented skin. METHODS: PHK were labeled as dark or light based on foreskin pigmentation. PHK were differentiated in high-Ca+2 media in the presence of a PAR2 agonist (SLIGKV-NH2) or reverse peptide. Tight Junction (TJ) integrity was assessed by trans-epithelial electrical resistance (TEER). Expression of epidermal barrier components and cytokines were evaluated at the RNA level. RESULTS: Both dark and light-PHK showed reduced TEER after PAR2- activation (p<_0.05; 100 mM). However, light-PHK had a greater degree of perturbation as compared to dark-PHK (40.8% vs 16.6% reduction, respectively). Additionally, only light-PHK exhibited significant TEER reduction after 50 mM PAR2 (p50.03). Baseline expression of CLDN1, OCLD, FLG, LOR, and KRT10 was higher in dark than light-PHK. After PAR2 activation significant reduction of FLG, LOR and KRT10 was observed only in dark-PHK (p<_0.05). Dark-PHK showed greater expres- sion of IL-18 both at baseline and after PAR2 activation (p<_0.05). No differences were observed for IL-8 and IL-33. AB34 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Patch Testing Outcomes in Patients Referred for treated patients reported greater least squares mean change (improvement) 104 Surgical Metal Allergy Concern versus placebo-treated patients in POEM sleep (21.8, 21.5 vs 20.7; P<0.0001), SCORAD Sleep VAS (23.8, 23.0 vs 22.1; P<0.05), and Kristy Semenza1, Muhammad Pasha, MD FAAAAI1; 1Albany Medical WPAI-AD (222.9, 218.7 vs 25.0; P<0.05). College. CONCLUSIONS: In JADE MONO-2, abrocitinib-treated patients re- RATIONALE: Allergic contact dermatitis can be challenging for ported greater improvement in pruritus, sleep disturbance/loss, and work different specialties regarding possible sensitization to metal implant productivity than placebo-treated patients. materials. Evaluation occurs in pre- and post-surgical settings, prompted by history of reaction to metals (ex. jewelry), or suspected reaction to a Depth and Rapidity of Response With surgical implant. We aimed to find correlations with implant material and 106 Abrocitinib and Dupilumab in Patients With patch testing results. Moderate-to-Severe Atopic Dermatitis (AD) in METHODS: Retrospective chart review was completed on 345 patients JADE COMPARE evaluated for diagnosis of ‘‘Contact Dermatitis’’ between 2013 and 2019. Peter Lio, MD1, Mark Boguniewicz, MD FAAAAI2, Andrew Alexis3, Thirty-two patients were referred specifically for metal and/or surgical 4 5 6 implant evaluation. Patients were divided into 4 groups: 1. Non-surgical Mark Lebwohl , Kristian Reich , Andrew Pink , Kenji Kabashima, MD PhD7, Robert Bissonnette8, Roman Nowicki9, Hernan Valdez10, Fan metal concerns [NS], 2. Screening (Pre-surgical without metal reaction 10 10 11 10 history [PreS:M]), 3. Pre-surgical with metal reaction history [PreS+M], Zhang , Marco DiBonaventura , Claire Clibborn , Michael Cameron ; 1Northwestern University Feinberg School of Medicine, 2National Jewish and 4. Post-Surgical [PostS] with symptoms. 3 5 : 5 5 Health and University of Colorado School of Medicine, Mount Sinai RESULTS: Of the 32 patients, NS 2/32, PreS M 4/32, PreS+M 11/ 4 32, and PostS515/32. Patch testing with North American Extended series Morningside and Mount Sinai West, Icahn School of Medicine at Mount Sinai, 5University Medical Center Hamburg-Eppendorf, 6King’s College or T.R.U.E., +/- metal tray series, +/- samples of implant were completed. 7 8 NS and PreS:M did not yield significant patch test findings. PreS+M had 3 London, Kyoto University Graduate School of Medicine, Innovaderm 9 10 11 patients with positive results to possibly relevant metals. PostS had 1 Research Inc., Medical University of Gdansk, Pfizer Inc., Pfizer Ltd. patient with possibly relevant positive patch test results to cobalt. RATIONALE: Emerging treatments for moderate-to-severe AD could CONCLUSION: Patch testing did not show significant results in present provide greater and faster improvement in AD signs and symptoms than study to support routine use for screening nor for post-surgical symptoms, current therapies. A post hoc analysis of stringent endpoints with thought to be related to implant. More studies are needed to establish abrocitinib and dupilumab was conducted using JADE COMPARE relevance of patch testing in large subsets of patients suspected of metal (NCT03720470) data. allergy. METHODS: Adults with moderate-to-severe AD were randomly as- signed 2:2:2:1 to receive oral abrocitinib 200 or 100 mg once daily, Pruritus, Sleep, and Productivity: A Post Hoc subcutaneous dupilumab 300 mg every 2 weeks after a 600-mg loading 105 Analysis of Abrocitinib Versus Placebo in dose, or placebo with background topical therapy for 16 weeks. Endpoints Patients With Moderate-to-Severe Atopic were improvement >_90% from baseline in Eczema Area and Severity Dermatitis (AD) From JADE MONO-2 Index (EASI-90), Investigator’s Global Assessment (IGA) score of 0, Patient Global Assessment (PtGA) score of 0, Dermatology Life Quality Gil Yosipovitch, MD1, Luz Fonacier, MD FAAAAI2, Sonja St€ander3, Index (DLQI) score of 0/1, SCORing Atopic Dermatitis (SCORAD) sleep John Su4, Melinda Gooderham5, Jacek Szepietowski6, Mette Deleuran7, subscore <2, Patient-Oriented Eczema Measure (POEM) score <3, and Giampiero Girolomoni8, Pinaki Biswas9, Claire Feeney10, Hernan Val- NightTime Itch Score (NTIS) <2. dez9, Ricardo Rojo9, Andrew Thorpe9, Gary Chan9, Joseph Cappelleri9, RESULTS: Among 837 treated patients, the proportions who achieved Marco DiBonaventura9, Daniela Myers9; 1Miami Itch Center, 2NYU Win- stringent responses at week 16 (abrocitinib 200 mg, abrocitinib 100 mg, throp Hospital, 3Center for Chronic Pruritus, University of Muenster, dupilumab vs placebo) were EASI-90 (48.9%, 38.0%, 38.8% vs 11.3%), 4Murdoch Children’s Research Institute, Royal Children’s Hospital, Uni- IGA-0 (14.9%, 12.6%, 6.5% vs 4.8%), PtGA-0 (7.7%, 3.9%, 3.9% vs versity of Melbourne, 5SKiN Centre for Dermatology, 6Wroclaw Medical 1.6%), DLQI-0/1 (29.7%, 21.6%, 24.0% vs 10.6%), SCORAD sleep University, 7Aarhus University Hospital, 8Universita di Verona, 9Pfizer subscore <2 (68.4%, 52.8%, 58.5% vs 32.0%), POEM <3 (21.3%, 11.7%, Inc., 10Pfizer Ltd. 12.4% vs 4.8%), and NTIS <2 (57.1%, 44.5%, 46.1% vs 31.9%). Response RATIONALE: Pruritus is the hallmark symptom of AD, often affecting rates at week 2 were higher with abrocitinib 200 mg than with dupilumab. sleep and productivity. This post hoc analysis was conducted to evaluate CONCLUSIONS: Treatment with abrocitinib 200 mg resulted in greater pruritus, sleep, and work productivity in patients with moderate-to-severe and more rapid response across stringent efficacy endpoints than AD treated with abrocitinib, an oral Janus kinase 1 selective inhibitor, in dupilumab. Response rates in the abrocitinib 100 mg and dupilumab JADE MONO-2 (NCT03575871). groups were similar. METHODS: Patients aged >_12 years were randomly assigned (2:2:1) to receive once-daily abrocitinib (200 mg or 100 mg) or placebo for 12 weeks. Patient-reported outcomes (PROs) included pruritus severity (Peak Pruritus Numerical Rating Scale [PP-NRS] and Night-Time Itch Scale [NTIS]), sleep disturbance/loss (Patient Oriented Eczema Scale sleep item [POEM sleep] and SCORing AD Sleep Visual Analog Scale [SCORAD Sleep VAS]), and work productivity (Work Productivity and Activity Impairment-AD [WPAI-AD]). Nominal P values were calculated. Correlations between measures were evaluated. RESULTS: Of 391 patients (mean age: 35.1 years) included in this analysis; 98.5%, 84.4%, 99.2%, 85.7%, and 53.7% completed the PP-NRS, NTIS, POEM sleep, SCORAD Sleep VAS, and WPAI-AD assessments at week 12, respectively. At week 12, more patients treated with abrocitinib (200 mg, 100 mg) versus placebo achieved >_4-point improvement in PP- NRS (55.3%, 45.2% vs 11.5%; P<0.0001) and >_4-point improvement in NTIS (57.0%, 42.7% vs 12.7%; P<0.0001). At week 12, abrocitinib- J ALLERGY CLIN IMMUNOL Abstracts AB35 VOLUME 147, NUMBER 2

Prednisolone Treatment Reduces Type 2 (63.1%); 28.5% and 12.1% reported asthma and contact dermatitis, 107 Inflammation In Skin Lesions Of Patients With respectively. The most common prior therapies included topical cortico- Atopic Dermatitis steroids (TCSs; low potency, 49.6%; medium potency, 42.4%; high potency, 32.7%), calcineurin inhibitors (21.5%), antihistamines (43.6%), Emma Price1, Christiane Whetstone1, Dhuha Al-Sajee, MD, PhD1, Sai and systemic CSs (17.5%); 10.5% of patients were treatment-naive. Sakktee Krisna, MSc1, Karen Howie1, Caroline Munoz1,Paul CONCLUSIONS: The majority of patients enrolled in the two phase 3 O’Byrne, MD1, Hermenio Lima, MD, PhD1, Roma Sehmi, PhD1, Gail studies had a history of allergy/inflammatory comorbidities and significant Gauvreau1; 1McMaster University. itch. Most patients used medium- or high-potency TCSs with some RATIONALE: Eosinophilia is thought to contribute to disease initiation requiring systemic steroids, highlighting the substantial burden in this and progression in chronic lesions of patients with atopic dermatitis (AD). population. We examined the effect of prednisolone on eosinophils, eosinophil progenitors (EoPs), basophils and cytokines in chronic AD lesions and House Dust Mite Sensitization is Associated clinical scores to understand the relationship between eosinophilia and 109 with Resistance to Topical Therapy in Patients disease severity. with Contact Dermatitis

METHODS: Sixteen patients with severe AD underwent 8 days of 1 1 1 systemic steroid washout. Skin was assessed and biopsies were obtained Oleksandr Litus, MD , Yuriy Bisyuk, MD , Viktor Litus , Lawrence Du- buske, MD FAAAAI2; 1Shupyk National Medical Academy of Postgrad- from lesional and unaffected skin. Patients were randomized 1:1 to placebo 2 or 0.75mg/kg-0.5mg/kg prednisolone treatment for 7 days and biopsies uate Education, Kyiv, Ukraine, George Washington University School of were obtained again from the same sites. Immunofluorescence staining Medicine, Washington, DC, USA, Immunology Research Institute of New was performed for EoP (CD34-FITC+ve, IL-5Ra-Cy5+ve, Von Willebrand England, Gardner, MA, USA. factor-TRITC-ve), eosinophils (MBP-Cy5+ve) and basophils (2D7- RATIONALE: IgE dependent sensitization can coexist with contact TRITC+ve). Lesional skin was digested for cytokine measurements by dermatitis. The course of contact eczema can be severe and resistant to multiplex array. Mann-Whitney tests compared percent change from pre- standard therapy when patients have overlapping syndromes. treatment levels. METHODS: 61 adult patients with allergic contact dermatitis were RESULTS: Clinical scores (EASI, SCORAD and IGA) and patient score studied. Contact allergy was confirmed by patch tests (European baseline POEM, were significantly reduced by prednisolone treatment compared to series). Specific IgE to Der p1, Der p 2 and Der p 10 were determined by placebo (p<0.05). DLQI showed a trend towards improvement (p50.08). ImmunoCAP. After prednisolone treatment there was 2-3-fold lower levels of eosinophils RESULTS: The most commonly identified contact allergens were nickel (p50.06) and EoP (p50.185) in lesions, and 2-fold lower levels of (26.5%), p-phenylenediamin (10.5%), textile dye mix (7.4%), fragrance eosinophils in unaffected skin (p50.62), but no difference in basophil mix I (6.5%), potassium dichromate (5.4.) and cobalt (2.5%). House dust levels compared to placebo. In skin lesions, prednisolone reduced levels of mite sensitization was confirmed in 25 (40.9%) patients. The prevalence of IL-5, IL-9, IL-10, IL-13, IL-17A, eotaxin, TNF-alpha, TARC, MIP1-beta IgE sensitization to Der p1 was 96%, Der p2 – 72% and Der p10 – 7%, (p<0.05) with trends for reduction of IL-1-alpha, IP10, IFN-gamma, and respectively. In 15 (60%) of the 25 patients in whom house dust mite MDC (p<0.10). sensitization was confirmed, local treatment with high-potency topical CONCLUSIONS: A short course of prednisolone significantly improved corticosteroids was ineffective. Eight patients (32%) responded to clinical scores in patients with severe AD, and this was accompanied by cyclosporine and two (8%) to methotrexate. Five patients (20%) did not reduced T2 and trends for reduced T1 inflammation in the lesional skin. respond to systemic treatment. CONCLUSIONS: Patients with contact dermatitis have a high incidence Disease Characteristics and Burden in Patients of sensitization to house dust mites. Such patients do not respond well to 108 With Atopic Dermatitis: Insights From Two local anti-inflammatory treatment, instead requiring systemic immuno- Phase 3 Studies of Ruxolitinib Cream modulatory treatment.

Eric Simpson, MD MCR1, Mark Lee, MD2, Kanwaljit Brar, MD3, Michael Kuligowski, MD, PhD, MBA4, May Venturanza, MD5, Kang Sun, PhD4, Darryl Toth, MD6; 1Oregon Health and Science University, Portland, OR, 2Progressive Clinical Research, San Antonio, TX, 3New York University Grossman School of Medicine, Hassenfeld Children’s Hospital, New York, NY, 4Incyte Corporation, Wilmington, DE, 5Incyte Corporation Wilmington, DE, 6XLR8 Medical Research and Probity Med- ical Research, Windsor, ON, Canada. RATIONALE: Atopic dermatitis (AD) affects ;10%–20% of children and ;5%–10% of adults worldwide, with rates varying geographically. Here, medical history including prior therapy at screening in adolescent and adult patients enrolled in two randomized phase 3 studies of ruxolitinib cream for patients with AD (TRuE-AD1 [NCT03745638], TRuE-AD2 [NCT03745651]) is reported to assess disease burden in this population. METHODS: Patients aged >_12 years with AD for >_2 years, an Investigator’s Global Assessment score of 2 or 3, and 3%–20% affected body surface area were eligible for inclusion. Medical history data were collected at screening, and descriptive statistics were used for analysis. RESULTS: Patients (N51249) had a median (range) age of 32 (12–85) years and AD duration of 15.8 (0–79.1) years. The mean (SD) baseline itch numerical rating scale score was 5.1 (2.4). Patients experienced a mean (SD) of 5.9 (16.5) flares in the last 12 months, and 38.8% had facial involvement. Skin infections requiring antibiotics was the most common AD complication (13.4%) before enrollment. Most patients had allergies AB36 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

The Effect Of Prednisolone Treatment On moisturizer (8, IQR 7-9 to 9, IQR 8-10), and sleep (7, IQR 4-9 to 8, IQR 7- 110 Histopathological Outcomes In Skin Of 9). Patients With Atopic Dermatitis CONCLUSIONS: AD control and family QOL improved after 3 months of participating in an Eczema Education Program geared to support Christiane Whetstone1, Nadia Alsaji, MD1, Emma Price1, Ruth families of young children with moderate-to-severe AD. Cusack, MD1, Roma Sehmi, PhD1, Hermenio Lima, MD, PhD1, Gail Gauvreau1; 1McMaster University. Atopic Dermatitis Phenotypes Impact RATIONALE: Hyperproliferation of keratinocytes leading to epidermal 112 Expression of Atopic Diseases Despite Similar thickness contributes to the clinical features of atopic dermatitis. Mononuclear Cell Cytokine Responses

Corticosteroids are a first line treatment rapidly reducing symptoms. We 1 1 2 examined the effect of prednisolone on histological outcomes in skin of Mohamed Taki, MD MS , Kristine Lee, MS , James Gern, MD , Rob Lemanske, MD FAAAAI3, Dan Jackson, MD FAAAAI2, Anne Marie patients with atopic dermatitis. 4 1 2 METHODS: Sixteen patients with moderate-to-severe atopic dermatitis Singh, MD ; University of Wisconsin - Madison, University of Wiscon- sin-Madison, 3University of Wisconsin School of Medicine and Public completed a double-blind, placebo-controlled study to evaluate the effect 4 of oral prednisolone on histopathological changes in skin. After a 16-day Health, University of Wisconsin. run-in period (8 days of 0.25 mg/kg prednisone, 8 days withholding all RATIONALE: The atopic march refers to the co-expression and progres- medications) patients were randomized to placebo or prednisolone at sion of atopic diseases in children, often beginning with atopic dermatitis 0.75mg/kg for 5 days, 0.5mg/kg for 5 days, tapering to 0.25 mg/kg for 5 (AD). We hypothesized that the risk of future atopic disease is modified by days. Pre- and Day 14 post-treatment patients underwent intradermal AD phenotype; moreover, we expected to find evidence of underlying challenges and 24h later four punch biopsies were collected (saline dysregulation of cytokine signaling. intradermal challenge, allergen intradermal challenge, lesional skin and METHODS: A total of 285 children were enrolled into the Childhood unaffected skin). Changes in histopathology scores were compared Origins of Asthma (COAST) study at birth and followed prospectively. between placebo and prednisolone using Mann-Whitney t-tests. AD, food allergy (FA), allergic rhinitis (AR), and asthma were assessed by RESULTS: The epidermis was two times thicker in lesional vs unaffected annual questionnaires and reports of physician diagnoses. Latent class skin (p50.0275). There was no effect of allergen or saline challenge on analyses identified 3 AD phenotypes (none/intermittent, late-onset, and epidermal thickness. Compared to placebo, 14 days of prednisolone persistent). We analyzed data from birth to 18 years of age for associations treatment significantly reduced epidermal thickness in allergen-challenged between AD phenotypes and FA, AR, asthma, allergic sensitization, skin (p50.0499) with trends for effects in unaffected skin (p50.0593) but exhaled nitric oxide (FeNO), and lung function. Peripheral blood mono- not saline-challenged (p50.1605) or lesional skin (p50.1304). There was nuclear cell (PBMC) responses (IL-5, IL-10, IL-13, IFN-g) to dust mite, no effect of prednisolone treatment on measurements of spongiosis, PHA, Staphylococcus aureus Cowan I (SAC), and tetanus toxoid were lymphocytic infiltration or neutrophilic infiltration. compared among AD phenotypes. CONCLUSIONS: Epidermal thickening in this small study of patients RESULTS: Persistent AD, but not late-onset AD, was associated with an 5 5 with atopic dermatitis is somewhat reduced after 14 days of prednisolone increased risk of FA (p 0.02), elevated total IgE (p 0.01), and decreased 5 treatment, and this improvement not does not appear to be regulated by FEV1/FVC ratio (p 0.02) throughout childhood. In contrast, both lymphocyte or neutrophil levels. persistent and late-onset AD were associated with an increased risk of asthma (p50.004) and elevated FeNO (p50.002). Longitudinal analyses Eczema Education Program improves pediatric did not reveal consistent differences in PBMC responses among AD 111 atopic dermatitis control and family quality of phenotypes. life CONCLUSIONS: Age of onset and persistence of AD differentially influence the expression of other atopic diseases. Our findings suggest Thomas Rawliuk1, Shannon Deane2, Shauna Filuk2, Jo-Anne St. Vin- peripheral blood cytokine dysregulation is not the mechanism underlying cent2, Allan Becker, MD FAAAAI2, Elinor Simons, MD PhD MS this process, which may be mediated at mucosal surfaces or secondary FAAAAI2; 1Children’s Hospital Research Institute of Manitoba, 2Univer- lymphoid organs. sity of Manitoba and Children’s Asthma & Allergy Education Centre (CAAEC). BACKGROUND: Atopic dermatitis (AD), a chronic-relapsing inflam- matory skin disease, is the most common chronic skin condition of young children and results in significant morbidity. We have developed an Eczema Education Program to support families of young children with AD. We examined the effects of these interactive education sessions on understanding, treatment adherence and symptoms. METHODS: We retrospectively evaluated children up to age 5 years with moderate-to-severe AD whose parents participated in the Eczema Education Program. At baseline and 3-months, we assessed AD manage- ment, AD severity using SCORing Atopic Dermatitis (SCORAD), and Infants’ Dermatitis Quality of Life (IDQOL) and Parental Self-Efficacy and Eczema Care Index (PASECI) quality of life (QOL) questionnaires. RESULTS: Participants (n520) had a median age of 22.6 (range 5.3-66.6) months and had suffered AD for median 4 (range 1-40) months; 62% were male and 40% had seasonal flares. Median baseline SCORAD was 52.6 (range 27.4-78.8), corresponding to moderate-to-severe AD. After 3 months, median SCORAD was 23.6 (range 6.7-56.8), with a median change of -20.7 (range -45.9 to 6.7) demonstrating overall improvement. Median IDQOL score improved from 12 (range 3-22) at baseline to 3 (range 1-13) at 3 months. Median and inter-quartile range (IQR) PASECI scores also improved for management of itch (7, IQR 5-8 to 8, IQR 7-8), J ALLERGY CLIN IMMUNOL Abstracts AB37 VOLUME 147, NUMBER 2

Effects of Dexamethasone on airway epithelial (UniProtKB; FDR58.6E-12), the latter of which included multiple 113 cells exposed to oxidative stress collagen and ADAM (a disintegrin and metalloproteinase) genes. This expression module also included a small number of cytokine/receptor Chioma Enweasor, MD1, Duane KimMedical Student1, Cameron pathway genes notable for IL23R, IL26, and IL2 and an absence of canon- Flayer, PhD1, Angela Linderholm, PhD1, Lisa Franzi1, Angela Haczku, ical T2 genes. This pathway was upregulated 1.5-fold over the cluster of MD PhD FAAAAI1; 1UC Davis. children with T2-low mild asthma, and 2.4-fold over the cluster of children RATIONALE: Glucocorticoid insensitivity may be elicited by oxidative with highly symptomatic T2-high asthma (FDRs <0.05). stress such as the one caused by exposure to the air pollutant, ozone (O3). CONCLUSIONS: Our results demonstrate a unique nasal gene expres- We previously showed that O3-induced airway hyperreactivity in mice was sion profile characteristic of urban children with highly symptomatic associated with the expression of both pro-inflammatory and antioxidant asthma and rhinitis but with minimal allergy, most notable for numerous genes. But the relationship of oxidative stress to the anti-inflammatory ef- genes related to neuronal signaling and components of Th17 signaling, fects of glucocorticoids is unclear. suggesting unique molecular mechanisms of disease. METHODS: Glucocorticoid receptor (GR) protein levels and GR DNA binding was studied in A549 and HBE cells. A549 cells were incubated in HuR-targeted Inhibition Impairs Th2 serum-free media with 0, 10, or 100mM dexamethasone for 10 hours and to 115 Proinflammatory Responses in Asthmatic CD4+ T cells mimic the effects of O3, cells were treated with 0.05mM tert-butyl hydro- peroxide (TBHP). Expression of Eotaxin2, Sod1, and Sod2 mRNA were Fatemeh Fattahi1, Jason Ellis1, Michael Sylveste1, Kristin Bahelda1, measured by qPCR. 1 1 2 3 RESULTS: GR and Eotaxin2 expression showed circadian oscillation in Samuel Hietanen , Luis Correa , Njira Lugogo, MD , Ulus Atasoy ; 1Department of Internal Medicine, Division of Allergy & Clinical Immu- both A549 and HBE cells. Eotaxin2 negatively correlated with the GR 2 DNA binding activity (r5-0.75, p<0.05 n510). TBHP did not increase nology, University of Michigan Medical School, Ann Arbor, MI, Divi- sion of Pulmonary and Critical Care Medicine, University of Michigan, A549 cell death at the concentrations studied but induced expression of 3 Eotaxin2 mRNA. Although dexamethasone inhibited Eotaxin2 induction, Ann Arbor, MI, 1.Department of Internal Medicine, Division of Allergy it did not reach statistical significance in TBHP exposed A549 cells. & Clinical Immunology, University of Michigan Medical School, 2.Divi- Interestingly, dexamethasone increased Sod1 and Sod2 gene expression sion of Allergy-Immunology, Ann Arbor VA Health System, Ann Arbor, in a dose dependent manner. MI. CONCLUSIONS: Our data suggest that glucocorticoid inhibition of RATIONALE: RNA-binding protein human antigen R (HuR, elavl1)isa Eotaxin2 gene expression may be counteracted by the presence of master regulator of gene expression in human pathophysiology. Its dysre- oxidative stress. gulation plays an important role in many diseases. We hypothesized that HuR plays an important role in human Th2 asthma (especially type 2- Airway Epithelial Gene Expression Differs high) and that its inhibition impairs Th2-inflammatory responses. 114 Across Urban Childhood Asthma Phenotypes METHODS: Peripheral CD4+ T cells were isolated from 26 heathy individuals and 45 asthmatics (23 type 2-high, 22 type 2-low, defined by Matthew Altman, MD1, Edward Zoratti, MD FAAAAI2, Andrew their blood eosinophils and FeNo levels). Isolated cells were stimulated Liu, MD FAAAAI3, Jacqueline Pongracic, MD FAAAAI4, Jessica with anti-CD3/CD28 for 4 days, then retreated with PMA, ionomycin and Gereige, MD5, Robert Wood, MD6, Gurjit Khurana Hershey, MD PhD BFA for 4 hours. GATA3 and cytokine expression were evaluated by FACS FAAAAI7, Carolyn Kercsmar, MD7, Rebecca Gruchalla, MD PhD and LEGENDplex. HuR levels were quantitated by Western and qPCR. FAAAAI8, Meyer Kattan, MD9, Stephen Teach, MD10, Alyssa Inhibition of inflammatory responses was evaluated using AICAR (AMP- Ylescupidez, PhD11, Steve Sigelman, BSN12, Peter Gergen, MD activated protein kinase activator), and CMLD-2 (HuR-specific small MPH12, Alkis Togias, MD FAAAAI13, Cynthia Visness, PhD14, Scott molecule inhibitor). Actinomycin D treatment was used to measure mRNA Presnell, PhD11, James Gern, MD15, William Busse, MD FAAAAI16, decay rates of cytokines and HuR mRNAs. Dan Jackson, MD FAAAAI15; 1University of Washington, 2Henry Ford RESULTS: HuR protein levels in CD4+ T cells (both non-activated and Hospital, 3Children’s Hospital Colorado, 4Ann & Robert H. Lurie Chil- activated) was significantly higher in asthmatics (especially type 2-high) dren, 5Boston Medical Center - Shapiro Center, 6Johns Hopkins Univer- compared to the controls. The expression and secretion of Th2 cytokines sity School Medicine, 7Cincinnati Children’s Hospital Medical Center, were significantly higher in asthmatics (especially type 2-high) compared 8Univ. Texas Southwestern Medical Center, 9Columbia University Medi- to the controls. AICAR inhibited several cytokines in both groups of type cal Center, 10Children’s National Hospital, 11Benaroya Research Institute, 2-low and type 2-high. While CMLD-2 significantly decreased cytokines 12NIH/NIAID, 13NIAID/NIH, 14Rho, Inc., 15University of Wisconsin- in type 2-high asthmatics, AICAR mainly decreased the levels of the HuR Madison, 16University of Wisconsin School of Medici. in the type 2-low asthmatics. RATIONALE: Children living in low-income urban environments CONCLUSIONS: Our data shows HuR dysregulation in type 2-high experience high asthma morbidity. Prior phenotyping of these children asthma and that interfering with HuR action may ameliorate cytokine has identified a subgroup with low levels of allergy (T2-low) but highly production. This suggests potential HuR-targeted therapies to treat asthma. symptomatic asthma. Assessment of the airway epithelium in these children can provide important mechanistic insights into disease pathogenesis. METHODS: We performed RNA-sequencing of nasal brush samples from 123 children in the Asthma Phenotypes in the Inner City (APIC) cohort. These children were previously clustered into 5 phenotypes according to metrics of T2 biomarkers, lung function, rhinitis and asthma symptoms, and asthma severity. Differential gene expression was assessed by modular analysis. RESULTS: The cluster of children characterized by T2-low highly- symptomatic asthma and rhinitis had significantly increased expression of a module of 875 genes. This module was highly enriched for Neuroactive ligand-receptor interaction genes (KEGG; FDR52.3E-5), Olfactory trans- duction genes (KEGG; FDR52.6E-4) and Extracellular matrix genes AB38 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Detergent Induces Active Release of IL-33 from small cell samples. How the cellular differential determined by traditional 116 Airway Epithelial Cells and Promotes Innate cytospin preparations compared to novel CyTOF analysis is not well Type 2 Response in the Lungs known. We developed a CyTOF protocol to identify major immune cell populations from sputum samples and compared the results with those Kenzo Ohara1, Koji Iijima, PhD2, S. M. O’Grady3, Hirohito Kita, MD2; obtained from cytospin. 1Mayo Clinic Arizona, Asahikawa Medical University, 2Mayo Clinic Ari- METHODS: Induced sputum was obtained from an ongoing study zona, 3University of Minnesota. evaluating airway inflammation in older adults with asthma to prepare RATIONALE: The prevalence of asthma and allergic airway diseases has both: a) cytospin slides to measure cellular differential (H&E staining), and increased since the 1960s. The use of dishwasher and household detergents b) CyTOF. Sputum cells for CyTOF were barcoded, labeled with showed a similar trend, leading us to hypothesize that increased exposure antibodies conjugated to distinct metal isotopes, and acquired on to detergents might contribute to development of allergic diseases. The CyTOF2 (Fluidigm). Following initial data normalization and bead goal of this project was to test this hypothesis by using in vitro and in vivo removal, cell identification based on DNA content and exclusion of dead models. cells (cisplatin staining), the resulting data was analyzed using Cytobank. METHODS: We exposed normal human bronchial epithelial (NHBE) Neutrophils were identified with CD66b+EPX-CD16+ and eosinophil with cells that overexpress the IL-33 gene to sodium dodecyl benzene sulfonate CD66b+EPX+CD16low gating. (SDBS) as a model for detergent. Various pharmacologic agents were used RESULTS: Cytospin slide analysis of induced sputum from 7 subjects (mean to dissect the mechanisms for IL-33 release. SDBS was also administered age 68.9), provided samples with a wide variation of airway eosinophils (0- intranasally (i.n.) to na€ıve BALB/c mice. 13.2%) and neutrophils (0-32.4%). CyTOF analysis from the same samples RESULTS: Exposure to SDBS induced IL-33 release from NHBE cells. (high viability, mean live cells 88.6%) revealed a similar cellular distribution The dose-response curve was bell-shaped, and the maximum effect was of eosinophils and neutrophils as measured from cytospin. observed at a 3-fold lower concentration (i.e. 50 mg/ml) than the critical CONCLUSION: Pilot data from samples of induced sputum suggest that micelle concentration for SDBS. At this concentration, more than 90% of cellular differentials determined from cytospin correlates well with cell NHBE cells were alive, released ATP extracellularly and showed increase distribution obtained from a novel CyTOF technique. CyTOF analysis of in intracellular calcium concentration. IL-33 release was abolished by sputum samples also provides additional benefits, to measure cellular treating the cells with purinergic receptor antagonists or oxygen radical activation and further differentiation of cellular subtypes using few scavengers or by chelating extracellular calcium. Moreover, the levels of numbers of cells. type 2 cytokines in lung homogenates were increased in mice exposed to SDBS in vivo. Immune Predictors of Death versus Survival in CONCLUSIONS: Exposure of airway epithelial cells to a low concen- 119 COVID-19 ICU Pneumonia Patients on tration of detergents induces active release of IL-33 likely through the Mechanical Ventilators pathway(s) involved in cellular stress responses. Detergents may dysre- Natalia Antonevich1, Andrei Hancharou1, Alena Rynda1, Marina Dot- gulate the homeostasis of epithelium and promote development of type 2 2 2 1 1 immune responses to environmental allergens. senko , Eduard Dotsenko , Alena Halavach , Oxana Timohina , Yana Minich1, Darya Babrukevich1, Lawrence Dubuske, MD FAAAAI3; 1The Estrogen Decreases The Expression Of Tmem178 Institute of Biophysics and Cell Engineering of National Academy of Sci- 117 In Differentiated Airway Epithelium ences of Belarus, Minsk, 2Belarusian State Medical University, Minsk, Belarus, 3George Washington University School of Medicine, Washing- Kimberly Stelzig1, Y. Prakash, MD, PhD1; 1Mayo Clinic. ton, DC, USA, Immunology Research Institute of New England, Gardner, RATIONALE: We have previously shown that the gene expression of MA, USA. TMEM178, which encodes a novel suppressor of NFAT1c inflammation, RATIONALE: The outcome of COVID-19 associated pneumonia is decreases with the progression of asthma severity. Given the marked sex strongly related to the host immune response. This investigation seeks to bias in asthma, we sought to determine if estrogen can regulate the expres- identify immune markers of the clinical outcome COVID 19 pneumonia in sion of Tmem178 in differentiated airway epithelial cells. an ICU. METHODS: Human bronchial epithelial (HBE) cells were grown at the METHODS: 18 patients with PCR and chest CT confirmed diagnosis of air-liquid interface on collagen-coated porous cell culture inserts. During severe/critical COVID-19 pneumonia were included in the study. Patients the 3-week differentiation process, the HBE cells were treated with 10 nM were treated in an ICU and required ventilation (IMV). 10 patients died (D) b-estradiol (E2) or vehicle. Total cellular RNA was extracted with the and 8 survived (S). Blood samples from 19 healthy donors (HD) controls RNeasy Mini Kit (Qiagen) and cDNA was synthetized with the were also assessed. Blood myeloid (myeloid suppressor cells, monocytes, Transcriptor Reverse Transcriptase Kit (Roche). Quantitative RT-PCR dendritic cells (DC)) and lymphoid cells (T, B, ILC, NK, NKT cells and was performed with the LightCycler Green 480 SYBR Green I Master on subsets) subsets as well as neutrophil and monocyte activation markers the Roche LC480 Light Cycler (ABI). (CD35, CD32, CD88, CD282) were assayed. Nonparametric statistics, RESULTS: We found that E2-treated differentiated airway epithelial cells cluster and ROC analysis were applied. expressed significantly lower levels of Tmem178 when compared to RESULTS: More than 100 parameters analyzed in COVID-19 patients vehicle-treated controls (p-value < 0.05). allowed definition of considerable alteration of both lymphoid and myeloid CONCLUSIONS: We have identified a novel mechanism by which immune compartments. 3 parameters were associated with unfavorable estrogen can promote lung inflammation, which has significant implica- outcomes: decreased frequencies of myeloid DC (mDC) and increased tions for the sex bias in asthma. numbers of M-MDSC and B-cells. Cluster analysis using these selected parameters precisely divided patients in the ICU into 2 groups: D and S. Comparison of CyTOF analysis with cytospin for ROC analysis allowed calculation of the sensitivity and specificity of each 118 sputum cell differential parameter and cut-points (mDC – 95.9%/100%/<0.02%; M-MDSC – 85.7%/86.2%/>12.6%; B-cells – 91.8%/86.2%/>19.1%). 1 1 1 Janette Birmingham , Juan Wisnivesky , Alex Federman , Jonathan CONCLUSIONS: Extremely low frequencies of mDC in peripheral 2 1 1 1 Federman , Adeeb Rahman , Brian Lee ; Icahn School of Medicine at blood, 4-5 fold increased content of M-MDSC, and an increased relative 2 Mount Sinai, Yeshiva University. content of B cells in COVID 19 patients versus HD were identified as RATIONALE: Mass cytometry or CyTOF (Cytometry by Time-Of- predictors of death in COVID-19 associated pneumonia patients ventilated Flight) provides analysis of multiple cell populations and markers using in an ICU. J ALLERGY CLIN IMMUNOL Abstracts AB39 VOLUME 147, NUMBER 2

Blood Dendritic Cells, Monocytes and Myeloid- serum tryptase(rs50.378, p50.057). The TNSS showed no significant cor- 120 derived Suppressor Cells in Patients with relation with mediator production. COVID-19 Associated Pneumonia CONCLUSIONS: Aspirin-induced increases in TNSS+ scores correlated with biomarkers of acute mast cell degranulation. Assessment of lower Andrei Hancharou1, Alena Rynda1, Yana Minich1, Natalia Antonevich1, respiratory and extra-respiratory symptoms improves current symptom Oxana Timohina1, Alena Halavach1, Darya Babrukevich1, Marina Dot- scores for monitoring aspirin-induced reaction severity in AERD. The senko2, Eduard Dotsenko2, Lawrence Dubuske, MD FAAAAI3; 1The TNSS+ may be useful to standardize the assessment of reaction severity in Institute of Biophysics and Cell Engineering of National Academy of Sci- future clinical and research settings. ences of Belarus, Minsk, 2Belarusian State Medical University, Minsk, Belarus, 3George Washington University School of Medicine, Washing- Expert Advice on Managing Severe Asthma: An ton, DC, USA, Immunology Research Institute of New England, Gardner, 122 Interactive Decision Support Tool Provides MA, USA. Real-Time Expert Recommendations

RATIONALE: Little is known about function and dynamic changes in the 1 1 1 myeloid compartment in COVID-19 patients. This study analyzes the Zachary Schwartz , Carolyn Skowronski, PharmD , Anne Roc, PhD , Bradley Chipps, MD FAAAAI2, Nicola Hanania, MD, MS3, Linda myeloid cells subsets counts in COVID-19 patients. 4 5 5 1 METHODS: 57 patients with PCR and chest CT confirmed diagnosis of Rogers , Eileen Wang, MD , Michael Wechsler, MD ; Clinical Care Op- tions, 2Capital Allergy and Respiratory Dis. Ctr, 3Baylor College of Med- COVID-19 pneumonia were included in the study. Patients were divided 4 5 into 2 groups: severe/critical (S/C) patients (n518) which were treated in icine, Mount Sinai, National Jewish Health. ICU and required IMV; and moderate (M) patients (n539) which received RATIONALE: To help clinicians make personalized recommendations oxygen support through nasal mask. Blood samples from 19 healthy donors for patients with severe asthma, we developed an online tool based on (HD) controls were also used. Granulocytic and monocytic myeloid- treatment choices from 5 experts for customizable patient scenarios. The derived suppressor cells (G/M-MDSC), monocytes (Mon), myeloid and goal was to provide real-time recommendations for severe asthma based on plasmacytoid dendritic cells (mDC and pDC) were assayed using Attune patient-specific characteristics and to identify variances between the NxT flow cytometer. Nonparametric statistics were used. treatment strategies of experts and community clinicians. RESULTS: Greater CD15+ G-MDSC and M-MDSC (HD - 0.37 (0.25- METHODS: Asthma experts provided treatment recommendations for a 2.37)%, M - 3.99 (2.44-7.89)%, S/C - 13.10 (4.17-20.19)%, combination of patient variables totaling 70 possible scenarios based on: p5<0.000001) frequency (%) and absolute counts (/ml) in both S/C and d FeNO M compared with HD, with greater frequency in S/C patients (p< d Blood eosinophils 0.0001). Redistribution of Mon subsets towards intermediate (HD - 5.4 d Allergic phenotype (3.0-15.7)%, M - 16.2 (12.2-20.8)%, S/C - 25.8 (22.6-30.9)%, d IgE p50.0001) was noted. Decrease of mDC (HD - 0.233 (0.165-0.270)%, d Other allergies/comorbidities M - 0.135 (0.100-0.190)%, S/C - 0.020 (0.003-0.070)%, p5<0.000001) d Body weight and pDC subsets was observed in both groups of patients more significant d in S/C (p< 0.01). Childbearing potential CONCLUSIONS: COVID-19 is characterized by decrease of mDC and We then developed a decision support tool (http://bit.ly/asthmaIDST) pDC counts, increase of MDSC and redistribution of Mon towards where clinicians can customize a patient scenario using these variables intermediate subsets. and then select their intended treatment plan. Afterwards, experts’ treat- ment recommendations for that specific patient case are shown, and if Assessing Systemic Symptoms During Aspirin discordant, clinicians are asked if expert recommendations changed their Challenge in Aspirin Exacerbated Respiratory 121 planned treatment. Disease (AERD) RESULTS: Among the 5 experts, there was concordance in treatment selection across specific asthma patient scenarios. For example: Patrick Staso1, Pingsheng Wu2, Tanya Laidlaw, MD FAAAAI3, Kather- ine Cahill, MD1; 1Vanderbilt University Medical Center, 2Vanderbilt Uni- d For chronic urticaria, most added an anti-IgE biologic versity School of Medicine, 3Harvard Medical School. d For allergic asthma with FeNO < 20 ppb; eosinophils < RATIONALE: Aspirin-exacerbated respiratory disease (AERD) is the 150 mL; no atopic dermatitis, chronic rhinosinusitis, or clinical triad of nasal polyposis, asthma, and respiratory reactions to nasal polyps, most added an anti-IgE biologic cyclooxygenase-1 inhibitors. Extra-respiratory, gastrointestinal, and cuta- d For atopic dermatitis, chronic rhinosinusitis, or nasal neous symptoms have been reported in association with elevations in polyps, most added an anti–IL-4 receptor biologic serum tryptase. Scoring systems are available to assess upper airway symptoms during desensitization, but none capture lower respiratory and To date, over 93 patient scenarios have been entered in the tool by 54 extra-respiratory symptoms. unique clinicians. Next steps include detailed analysis of variance between METHODS: Thirty subjects with AERD underwent a standardized oral planned treatment of experts vs clinicians. aspirin challenge protocol. Total nasal symptom score (TNSS), spirometry, CONCLUSIONS: An expert-guided online decision support tool can urine and serum were collected at baseline, at the onset of a respiratory provide personalized, real-time recommendations for treating severe reaction, and for the following 3-hours. Four additional questions about the asthma. presence and severity of headache, gastrointestinal, cutaneous, and lower respiratory symptoms on a scale of 0-5 were included with the TNSS to generate the TNSS+. A higher score denoted more severe symptoms. Spearman correlation was determined between the maximum increase in symptom score and the maximum change from baseline in urinary leukotriene (uLT)E4, prostaglandin D2 metabolite (uPGD-M), and serum tryptase levels. RESULTS: An oral aspirin challenge elicited a clinical reaction in 29 subjects. The maximum change in TNSS+ correlated with the maximum change in uLTE4(rs50.411, p50.03), uPGD-M(rs50.522, p50.004), and AB40 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Fraction of exhaled nitric oxide measured by NO Use of Impulse Oscillometry to Detect Vocal 123 breathÒ correlate with airway hyperreactivity 125 Cord Dysfunction

Yosuke Kamide, MD PhD1, Hiroaki Hayashi, MD1, Yuto Hamada1, Julia Smith1, Alyssa Osheim1; 1Greater Austin Allergy, Asthma and Kiyoshi Sekiya1, Akio Mori, MD PhD1, Masami Taniguchi, MD, PhD2; Immunology. 1Sagamihara National Hospital, 2Shonan Kamakura General Hospital. RATIONALE: Vocal cord dysfunction (VCD) is the inappropriate RATIONALE: Measurement of fraction of exhaled nitric oxide (FeNO) adduction of the vocal cords during the inspiratory phase. Diagnosing concentration in the breath of patients with asthma is non-invasive and VCD can be difficult because expected flow volume loop abnormalities are useful method to assess eosinophilic or type 2 airway inflammation. not noted frequently. To diagnose through laryngoscopy, the symptoms However, results vary with the type of device used. The association must occur during testing. We hypothesized a difference in R5 low between airway hyperreactivity (AHR) and FeNO measured using NO frequency resistance of Impulse Oscillometry (IOS) in VCD compared breathÒ (Bedfont Scientific, Maidstone, UK) is unknown. with asthma patients. METHODS: We included 62 consecutive patients with asthma who METHODS: GAAAI collected 71 records of children and adults with underwent FeNO quantification (NO breathÒ) and AHR examination at asthma (confirmed or suspected) and/or vocal cord dysfunction (confirmed our hospital. The exclusion criteria were administration of systemic or suspected) who underwent spirometric and oscillometric testing. A corticosteroids, pregnancy and current smoking habit. AHR was detected multivariate logistic regression was utilized to analyze whether oscillo- using histamine. metric testing result z-scores (R5 z-score, R5-20 z-score, AX z-score) were RESULTS: The FeNO value was negatively correlated with AHR (r5 significantly different based on whether the patient had asthma, VCD, or -0.3915, p50.037). This outcome was confirmed both ICS-positive and both. The spirometric results (FEV1 %pred, FVC %pred, FEV1/FVC) -negative patients. Additionally, FeNO was positively correlated with the were also analyzed for differences. eosinophil count in the blood. RESULTS: No findings among oscillometric or spirometric measure- CONCLUSION: FeNO measured using NO breathÒ is associated with ments were found to be significantly different among patients with asthma AHR using histamine. (n551), VCD (n52), and both (n518). For VCD patients relative to asthma patients, the associate p-value is 0.574 for the predictor R5 z-score. COVID-19, severe asthma and biologicals For asthma/VCD patients relative to asthma patients, the associate p-value 124 targeting type 2 inflammation: results in a is 0.960 for the predictor R5 z-score. third-level hospital in Madrid, Spain. CONCLUSIONS: The results of this study questions the value of IOS as an investigative tool for diagnosing patients with VCD through R5 z- 1 1 Alicia Domınguez Estirado , Gabriela Zambrano Ibarra, MD , Filip scores. Patients in all groups will continue to be added. Further analysis 1 1 SkrabskiAllergologist , Francisco Javier De Castro Martınez, MD , Julia will include an asymptomatic/symptomatic variable. De Pedro, MD1, Maria Pilar Sanz Sanz, MD1, Jose Zubeldia, MD1, Elena Rodriguez, MD1; 1Hospital General Universitario Gregorio Maran~on. Combined assessment of serum periostin, YKL- RATIONALE: Our aim was to describe the ratio and severity of COVID- 126 40, and bronchial hyperresponsiveness in 19 infection in patients with severe asthma treated with biologics. asthmatic children METHODS: A total of 58 patients with severe asthma treated with biologics under follow-up in our Allergy and Pneumology Unit of Hospital Heysung Baek, MD1, Junhong Park2, HaYoung Won3; 1Hallym Univer- Gregorio Maran~on were included. Demographic data, clinical character- sity Kangdong, 2Hallym University Kandong Sacred Heart Hospital, istics, laboratory and radiological findings, pulmonary function test and 3Kangdong Sacred Heart Hospital, Hallym University College of changes in clinical control (by ACT), were obtained by reviewing Medicine. electronic medical record system and telephone interview. RATIONALE: Serum level of periostin has been studied as a biomarker RESULTS: The mean age was 52.15 6 16.3 years, and 72.4% were for type 2 inflammation in asthma patients. In addition, serum levels of female. Twenty-five patients (43%) were characterized by allergic (mean human chitinase-3-like protein 1 (YKL40) have been found to be related to total IgE 476 KU/l, eosinophiles 400/microliter), and the rest by asthma severity and airway remodeling. We explored the relationship eosinophilic non-allergic phenotype of asthma (mean eosinophiles 430/ between serum periostin, YKL-40, and bronchial hyperresponsiveness microliter). They received omalizumab (53.4%), mepolizumab (32.7%) (BHR) in asthmatic children. and reslizumab (15.5%). METHODS: The study included children aged 6–15 years who were COVID-19 was confirmed in one patient (1.7%) by serological test (IgG+). either asthmatic (n5 75) or healthy controls (n 5 29). We measured the There was a forty-six-year-old man, with severe allergic asthma treated patients’ serum levels of periostin and YKL-40 and performed pulmonary with omalizumab for 38 months, with 1100 eosinophiles/microliter, total function tests, including baseline measurements, post-bronchodilator IgE 110 KU/l, without comorbidities. In April 2020, he reported fever, inhalation tests, exercise bronchial provocation tests (BPTs), and meth- cough and dyspnea without hypoxemia, treated with increased dosage of acholine BPTs. inhaled corticosteroids, with good control and FEV1 preserved, not RESULTS: Children with asthma had significantly higher periostin levels requiring hospital admission. [86.7 (71.0–104.0) vs 68.3 (56.0–82.0) ng/mL; P 5 0.006] and higher Seventeen patients (29.3%) were suspected cases, one of them with YKL-40 levels (29.0 [15.0–39.5] vs 27.7 [14.0–34.1] ng/mL; P 5 0.034) pneumonia and another one with asthma exacerbation requiring hospital than the healthy controls. Serum levels of admission, both without infection confirmation neither by SARS-CoV-2 periostin were significantly correlated with the maximum decrease in % PCR nor serology. The others had mild symptoms, with neither admissions FEV1 after exercise and fractional exhaled nitric oxide (FeNO) and blood nor changes in treatment. eosinophil levels but were not significantly associated with lung function. CONCLUSIONS: In our patients with severe asthma receiving bi- Serum levels of YKL-40 were significantly associated with the Z-score of ologicals, the rate of COVID infection was low (1.7%). None of them FEV1 and BHR to methacholine but were not significantly associated with had severe COVID-19 infection. BHR to exercise or FENO or blood eosinophil levels. J ALLERGY CLIN IMMUNOL Abstracts AB41 VOLUME 147, NUMBER 2

A National Survey of Asthma Specialist to increase knowledge on how to appropriately implement counseling at 127 Perspectives on Physical Activity in Asthma each patient encounter utilizing a time-efficient approach.

Basil Kahwash, MD1, Karen Gregory, DNP APRN-BC RRT AE-C2, Lisa Relationship of Rhinitis and Respiratory Allergy Sharp, PhD3, Sharmilee Nyenhuis, MD FAAAAI3; 1Vanderbilt University, 129 and Asthma Phenotypes in an Urban Birth 2Oklahoma Allergy and Asthma Clinic, 3University of Illinois at Chicago. Cohort

RATIONALE: NHLBI guidelines recommend regular physical activity 1 2 (PA) for patients with asthma. Healthcare provider (HCP) counseling Sima Ramratnam, MD MPH , Agustin Calatroni, MA MS , Leonard Bacharier, MD FAAAAI3, Meyer Kattan, MD4, George O, MD5, Robert represents an effective approach to optimizing patient physical activity. 6 7 8 However, current exercise rates among asthma patients are sub-optimal, Wood, MD , Cynthia Visness, PhD , Dan Jackson, MD FAAAAI , James Gern, MD8; 1University of Madison Wisconsin, 2Rho Federal Systems Di- suggesting that counseling may be improved. We aimed to understand PA 3 4 counseling behaviors among HCPs involved in asthma management. vision, inc., Washington University, Columbia University Medical Cen- ter, 5Boston University School of Medicine, 6Johns Hopkins University METHODS: A voluntary 15-item survey assessing providers’ self- 7 8 reported awareness of PA recommendations and their current clinical School Medicine, Rho, Inc., University of Wisconsin-Madison. practices was sent to 979 randomly selected HCP members of the AAAAI. RATIONALE: Our objective was to test for associations between rhinitis Data was analyzed using SigmaPlot. symptoms and respiratory phenotypes through age 10 years in urban RESULTS: The overall response rate was 9.3% (91/979). Respondents children. were physicians (100%) and Allergists/Immunologists (96%) who re- METHODS: Chronic nasal symptoms (starting at age 1) and seasonal ported an average of 18.1612.3 years in independent practice. Average rhinitis symptoms (starting at age 4 years) were assessed yearly in The respondent age was 50.6611.8 years old and 50% were male. Over half Urban Environment and Childhood Asthma study, a high-risk urban birth 5 (58%) reported that they personally engaged in >_150 minutes/week of cohort (n 442). Longitudinal patterns of wheeze, allergic sensitization moderate to strenuous PA. Eighty percent of participants were not aware of and lung function through age ten were used to identify six respiratory specific PA guidelines for patients with asthma, yet 66% acknowledged phenotypes: 1) low wheeze, low atopy (‘‘LW-LA’’); 2) transient wheeze, evidence for improved asthma outcomes with moderate exercise. A large low atopy (‘‘TW-LA’’); 3) moderate wheeze, low atopy (‘‘MW-LA’’); 4) majority of respondents believed that patients with asthma (97%) and low wheeze, high atopy (‘‘LW-HA’’); 5) moderate wheeze, high atopy severe asthma (84%) should pursue exercise. While 90% of respondents (‘‘MW-HA’’); 6) high wheeze, high atopy, low lung function (‘‘HW-HA- support incorporating exercise counseling into asthma care, only 69% LF’’). Differences in chronic and seasonal rhinitis symptoms among regularly counsel their asthma patients about PA. phenotypes were examined using longitudinal data analyses. CONCLUSIONS: HCPs in our survey cohort recognized PA as an RESULTS: Rhinitis in the first year was common in all groups, but nasal important component of asthma care but were often unaware of specific symptoms differentially associated with wheeze and atopy thereafter. guidelines. Additional research that identifies barriers and facilitators to Chronic rhinitis symptoms were more prevalent in the three wheezing exercise counseling in asthma specialists is needed to address the currently phenotypes (HW-HA-LF, MW-LA, and MW-HA) compared to the ; low levels of PA in asthma patients. transient wheeze and low wheeze groups ( 75% increase in symptoms over the first 10 years, p<0.001). Seasonal rhinitis symptoms were most Asthma care provider perspectives on exercise prevalent (>2-fold increase) in the two high-atopy groups with wheeze 128 promotion in people with asthma: an (MW-HA and HW-HA-LF, p<0.001). examination of knowledge, practices, barriers, CONCLUSIONS: Among high risk, urban children, chronic rhinitis is and facilitators most prevalent in children among the three persistent wheezing respiratory phenotypes, while seasonal rhinitis is most prevalent in children among the Sharmilee Nyenhuis, MD FAAAAI1, Karen Gregory, DNP APRN-BC high atopy respiratory phenotypes with wheezing. These close relation- RRT AE-C2, Basil Kahwash, MD3, Lisa Sharp, PhD1; 1University of Illi- ships between trajectories of wheeze and rhinitis in early life suggest nois at Chicago, 2Oklahoma Allergy and Asthma Clinic, 3Ohio State. shared pathogenic mechanisms. RATIONALE: Rates of physical activity (PA) among asthma patients are low. Provider counseling on PA can be effective, but little is known about asthma providers’ views on the role of PA counseling in clinical practice. METHODS: A 15-item theory-based survey was designed to explore asthma specialist’s practice, knowledge, barriers and facilitators related to PA counseling in asthma patients. Survey was emailed to a random sample of current AAAAI members. RESULTS: The survey response rate was 9.3% (91/979) and 96% were Allergy/Immunology physicians. Knowledge gaps identified included: how to counsel patients based on PA guidelines (37.5%), which patients to refer (18.2%) and how to refer patients (19.3%) to a supervised exercise program. Barriers to PA counseling cited were limited time during patient visit (44.5%), lack of knowledge on how and where to refer patients for exercise (44.5%), and prioritizing other health behaviors (ie. weight loss, smoking cessation; 29.6%). Interventions deemed to be helpful to facilitate PA counseling included: e-mail to practitioners containing written infor- mation about exercise in asthma (71.9%), a practitioner education session about exercise in patients with asthma (77.5%), an electronic/web-based form/prescription pad with exercise referral information (57.5%), posters in waiting areas encouraging patients to ask about exercise (62.5%), and patient handout with information on exercising with asthma (83.8%). CONCLUSIONS: Additional efforts for PA counseling by asthma providers is essential. Promoting PA counseling may require approaches AB42 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Association Between Exposure to Outdoor Air Assessing Asthma Control By Frequency Of High 130 Pollution and School Absenteeism Among 132 Systemic Corticosteroid And/or SABA Asthmatic Children Prescriptions In US Administrative Claims Data

Tricia Morphew1, John Graham, PhD2, Kara Rubio, MPH3, Norman Marko Mychaskiw, BSRPh, MS, PhD1, Sangtaeck Lim, MPH1, Susan Anderson, MSPH4, Deborah Gentile, MD5; 1Morphew Consulting, Colilla, PhD, MPH1, Randall Brown1; 1Teva Branded Pharmaceutical LLC, 2Clean Air Task Force, Boston, MA, 3Women for a Healthy Envi- Products R&D Inc., West Chester, PA, USA. ronment, 4Anderson Environmental Health, 5Community Partners in RATIONALE: Guideline-defined assessment of asthma control incorpo- Asthma Care. rates elements of symptom burden (impairment) and exacerbation risk. RATIONALE: Pittsburgh failed the American Lung Association’s 2020 Commonly used questionnaires assess control primarily in terms of ‘‘State of the Air’’ report for ozone, and daily and long-term fine particle impairment but provide little information about varying risk levels.

(PM2.5) outdoor air pollution (OAP). The purpose of this study was to eval- However, use of systemic corticosteroids (SCS) and frequent need for uate the relationship between OAP exposure and school absenteeism in short-acting beta-agonists (SABA) may be indicative of high symptom asthmatic children from Clairton School District, which is adjacent to a burden, disease relapse, severity, and exacerbation risk. coke works facility in the Pittsburgh region. METHODS: Using data from a retrospective analysis of IBM/Watson METHODS: School absence rates were collected across four academic MarketScanÒ claims database, we explored the extent of uncontrolled years (2014/15–2017/18). Asthma diagnosis was ascertained by written asthma, defined according to numbers of SCS and/or SABA prescriptions parent/guardian report to the school nurse. OAP exposure data, including filled within one year.

PM2.5, ozone, and sulfur dioxide (SO2), was obtained from the nearby RESULTS: Of the 579,955 patients included, 54.3% were classed as GINA 1, Liberty monitor. The relationship between OAP levels and daily school 24.8% as GINA 2/3, and 20.9% as GINA 4/5. The proportions of GINA 1 absence rates was evaluated using Poisson regression with adjustment patients with prescription fills within one year for >_2SCS,>_3 SABA, or either for confounding factors. (>_2SCSor>_3 SABA) were 13.5%, 18.8%, and 28.6%, respectively. For GINA RESULTS: The school absence rate in students with asthma was 11% 2/3 patients, these proportions were: 19.8%, 31.7%, and 43.4%; and for GINA

(p<0.05) and 8%(p50.07) higher on days when daily average PM2.5 was 4/5 patients: 31.7%, 44.6%, and 59.1%, respectively. Using a stricter definition 10-11 and 12-15, respectively, versus <10 mg/m3. Long term exposure for impaired asthma control: For GINA 1 patients, 5.1% had >_3 SCS, 10.3% measured by 28-day moving daily average corresponded to a 22% higher had >_4 SABA, and 14.5% had either (>_3SCSor>_4 SABA) prescription fills school absence rate when >15 versus <10 mg/m3 (p<.05). The rate was within one year. For GINA 2/3 patients, these proportions were: 9.0%, 18.8%,

18% higher when one-hour SO2 maximum during school hours was >30 and 25.1%; and for GINA 4/5 patients: 17.6%, 29.5%, and 39.7%, respectively. versus <30 ppb (p<.05). Increased ozone did not significantly correspond CONCLUSIONS: These data suggest high prevalence of impaired asthma to increased school absenteeism, after adjustment for confounding factors. control and exacerbation risk across all disease gradations, and indicate

CONCLUSIONS: Elevated daily and long-term PM2.5 exposure and one- substantial need for relief medication among cohorts traditionally hour SO2 maximum during school hours were associated with increased described as ‘‘moderate’’ or ‘‘mild’’. school absence rates in students with asthma. Mitigating efforts to reduce OAP are needed to protect the health of at-risk children and decrease Comorbidities in Asthma: Not a Numbers Game related school absences. 133

Analysis of Serum Allergen Screening Results of Jonwei Hwang1, A. Reddy, BS1, Sharmilee Nyenhuis, MD FAAAAI1; 131 2061 Patients with asthma in Taiyuan Area 1University of Illinois at Chicago. RATIONALE: Studies investigating influence of the quantity of comor- Kathy Kong1, Yangyang Wei1,J.I.N.G.Ma2, Xiaojing Wang1; 1The bidities on asthma control in real-world populations have been sparse. First Hospital of Shanxi Medical University, 2Shanxi Cardiovascular Herein, we analyze the influence of comorbidities and multi-morbidity on Hospital. asthma control in a real-world population. RATIONALE: To analyze the rate of sensitization to allergens among METHODS: A regression analysis of the Asthma IQ dataset was patients with asthma in Taiyuan area, and explore the effect of sex, age, and performed to determine the influence of individual comorbidities and seasons on allergen distribution to guide clinical prevention and treatment. multi-morbidity on asthma control. ACT score was used to define METHODS: A total of 2,061 patients with asthma who received uncontrolled (<20) and poorly controlled asthma (£15). Adult comorbid- outpatient and inpatient care in the hospital from June 2017 to June 2019 ities included were eczema, rhinitis/sinusitis, gastroesophageal reflux were selected as research subjects. Western Blot was used to detect 19 disease (GERD), current/past tobacco use, second-hand smoke exposure, serum allergen-specific IgE antibodies. Chi-square test was used to obstructive sleep apnea (OSA), depression and overweight (BMI325)/ compare positive allergens and degree of sensitization between patients obesity (BMI330). Pediatric comorbidities included were eczema, OSA, of different gender and age groups in various seasons. rhinitis/sinusitis, and second-hand smoke exposure. RESULTS: Among 2061 patients in Taiyuan region, at least 1 allergen was RESULTS: A history of tobacco use (OR51.58, 95% CI 1.11-2.23) and positive in 1321 patients, with a positive rate of 64.1%. The top three obesity (OR51.73, 95% CI 1.22-2.44) were significantly associated with allergen positive rates were: house dust mites (26.5%), mixed mold poorly controlled asthma in adults. Being overweight (1.50, 95% CI 1.24- (17.8%), dwarf ragweed /artemisia / humulus / cheneweed (17.4%). The 1.82), obese (1.78, 95% CI 1.47-2.14), or having a history of tobacco use top four allergens causing the most severe symptoms were dwarf / ragweed (1.77, 95% CI 1.44-2.18) was associated with uncontrolled asthma in / artemisia / humulus / quinoa, cat dander, crab, and shrimp. Furthermore, adults. In adults and children, eczema was significantly associated with positive rates for many allergens were higher in males than in females, and uncontrolled asthma (Adults: 1.80, 95% CI [1.20-2.70], children: 1.44, these rates decreased with age. In winter, the number of patients with 95% CI 1.00-2.06). Second-hand smoke was significantly associated with allergic diseases was more than other seasons (P < 0.001, respectively). both uncontrolled (1.41, 95% CI [1.05-1.88]) and poorly controlled (1.70, CONCLUSIONS: The most common allergens are house dust mite, 95% CI [1.03-2.83]) asthma in children. The number of comorbidities was mixed mold, and ragweed /artemisia/ humulus / cheneweed. There are not significantly associated with uncontrolled/poorly controlled asthma. significant differences in the positive rates of allergens in patients of CONCLUSIONS: We identified specific comorbidities in a real-world different sex and ages, and in different seasons. In winter, the population of asthma population that physicians should address when treating asthma patients allergies in Taiyuan area increase significantly. to assess their risk of poor control. Future studies should investigate relation- ships between treatment of comorbidities with asthma control and severity. J ALLERGY CLIN IMMUNOL Abstracts AB43 VOLUME 147, NUMBER 2

Asthma care during the COVID-19 pandemic: Separate models evaluated ‘Inattentive’ and ‘Hyperactive-Impulsive’ 134 Differences in attitudes and expectations subscale scores. between physicians and patients RESULTS: Among children with complete data (n5311), in a model adjusting for sex, age, race/ethnicity, maternal asthma, material hardship, Nonie Arora, MD, MBA1, Desmond Lowe, BS2, Nadeen Sarsour, BS2, environmental tobacco smoke, RWWC in infancy predicted higher total Hannah Jaffee, MS3, Sanaz Eftekhari, BA3, Laurie Carpenter, MSW4, AHDH scores (Relative Risk (RR) 51.66, P50.019). The association was Priya Bansal, MD FAAAAI5, Alan Baptist, MD MPH FAAAAI4; 1Univer- observed among girls (RR52.7, P50.002) but not boys (RR51.2, P50.54; 2 sity of Michigan, Internal Medicine, University of Michigan Medical Pinteraction50.066). RWWC predicted higher Inattention (RR51.7, School, 3Asthma and Allergy Foundation of America (AAFA), 4Univer- P50.007), but not Hyperactive-Impulsive symptoms (RR51.4, P50.14). sity of Michigan, Division of Allergy and Clinical Immunology, 5Asthma CONCLUSIONS: Girls with increased PNS responses in infancy and Allergy Wellness Center. (RWWC) had higher ADHD risk at age 8-14. The increased PNS response RATIONALE: Specific behaviors and beliefs that asthma patients and associated with one ADHD subtype. Altered PNS activity may thus physicians have during the COVID-19 pandemic are unknown. The goal of represent a shared biological pathway leading to asthma and risk for this study was to understand differences in attitudes and expectations ADHD Inattentive-subtype. related to COVID-19 between physicians and patients. METHODS: An anonymous survey was distributed through email and Physical Distancing –A Role in Keeping Viral- social media channels to adult patients with asthma for a 3-week period 136 Induced Asthma at Arm's Length? between April-May 2020. A separate survey was sent to physicians. The 1 surveys asked about demographic information, including asthma-specific Catherine Freeman, MBBch BAO MRCPI , Matthew Rank, MD FAAAAI2, Thomas Grys, PhD1, Catherine Bolster, MT1, John Lewis, demographics, specific challenges due to COVID-19, and attitudes/ 1 1 2 behaviors during COVID-19. MD ; Mayo Clinic Arizona, Mayo Clinic and Foundation. RESULTS: A total of 1171 patients and 225 physicians completed the RATIONALE: Community transmission of severe acute respiratory surveys. Overall, patients with asthma and physicians had large differences illness Coronavirus-2 (SARS-CoV-2) in Arizona was noted in March regarding COVID-19 expectations. Patients were more likely to believe 2020. It was our hypothesis that the associated implementation of physical that individuals with asthma are at a higher risk to get COVID-19 (37.5% distancing and masking led to a decline in circulation and detection of vs. 12.0%, p<0.001), would require hospitalization from COVID-19 common respiratory viruses. (90.7% vs. 62.2%, p<0.001), and should not go to work (62.7% vs METHODS: Nasopharyngeal swabs processed with the Biofire, Film Array respiratory panel at Mayo Clinic Arizona were reviewed from 11.9%, p <0.001). Patients also faced increased financial difficulties st st obtaining their medications due to COVID-19 more often than physicians January 1 2017 to July 31 2020. A total of 13,324 nasopharyngeal swabs anticipated (28.0% vs 16.4%, p< 0.001). Among patients, those with were analyzed. severe asthma (n5102, 8.7% of patients) were significantly more impacted RESULTS: Between April and July 2017- 2019 (Period A) a mean of 262 (e.g., became unemployed [OR 2.15] and had difficulty getting asthma tests were performed monthly, falling to 128 for the corresponding months meds [OR 2.37]) compared to those with mild or moderate asthma. of 2020 (Period B). A reduction in the monthly mean number of positive CONCLUSIONS: Patients with asthma and their physicians have tests (Period A 71.5; Period B 2.8) and mean positivity rate (Period A markedly different attitudes and opinions regarding care during COVID- 25.04%; Period B 2.07%) was observed. Rhinovirus/enterovirus was the 19. There are also differences in attitudes and experiences between patients most prevalent virus, with a monthly mean of 21.6 cases (30.2% of with severe asthma and those with mild/moderate asthma. Such differences positives) for Period A and 2 cases (72.7% of positives) for Period B. have important implications for patient care. Positivity for a second virus occurred in a mean of 2.1 positive tests (3.3%) in Period A but was absent in Period B. Infant rhinorrhea and watery eyes and CONCLUSIONS: Implementation of distancing and masking coincides 135 adolescent Attention Deficit Hyperactivity with a marked reduction in respiratory virus detection and likely circula- Disorder tion. This is noteworthy in asthma, where higher respiratory virus transmission is associated with increased asthma exacerbation. Data Matthew Perzanowski, PhD1, Virginia Rauh, ScD1, Bruce Ramphal1, from the fall/winter of 2020 will help clarify the potential role for Luis Acosta, MD1, Lori Hoepner2, Frederica Perera, PhD3, Julie distancing and masking as a mitigation strategy, not only for SARS-CoV-2 Herbstman, PhD1, Rachel Miller, MD FAAAAI4, Amy Margolis1; but also for people with asthma who are triggered by viral infection. 1Columbia University, 2SUNY Downstate, 3Columbia Center for Chil- dren, 4Icahn School of Medicine at Mount Sinai. RATIONALE: Comorbidity between asthma and attention deficit hyper- reactivity disorder (ADHD) is well documented. Parasympathetic nervous system (PNS) activity is a known but less well-acknowledged underlying mechanism of asthma and ADHD, with differing risks observed among boys and girls. We previously reported associations between infant rhinorrhea and watery eyes without a cold (RWWC), and school age asthma morbidity with evidence of underlying PNS dysregulation. Increased PNS activity has been associated with ADHD Inattentive but not Hyperactive-Impulsive symptoms. We hypothesized that infant RWWC would predict adolescent ADHD symptoms. METHODS: With Columbia’s Center for Children’s Environmental Health birth cohort, mothers were queried about their child’s RWWC and wheeze symptoms every 3 months in the first year of life and ADHD symptoms at age 8-14 years (DuPaul ADHD-Rating Scale). ADHD Total score in the highest quartile for sex was the primary outcome measure. AB44 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Different childhood asthma phenotypes based patients, even though asthmatics had a lower odds of testing positive 137 on humidifier disinfectant exposure with SARS-CoV-2. Further investigation to be able to understand which factors in asthmatic patients contribute to more severe COVID-19 infection So-Yeon Lee, MD PhD1, Mi-Jin Kang2, Min Jee Park1, Hyun-ju Cho3, is ongoing. Eun Lee, PhD4, Sungsu Jung5, Song-I Yang6, Soo-Jong Hong, MD FAAAAI1; 1Asan Medical Center, University of Ulsan College of Medi- A study on Bone mineral density among cine, 2Humidifier Disinfectant Health Center, Asan Medical Center, 3In- 139 asthmatic children on inhaled corticosteroids ternational St. Mary’s hospital, Catholic Kwandong University College attending a tertiary care hospital at Mysuru 4 of Medicine, Chonnam National University Hospital, Chonnam National 1 2 1 5 Thanuja B , Savitha Ramaraj ; Mysore Medical College and Research University Medical School, Pusan National University Yangsan Hospital, 2 6Hallym University Sacred Heart Hospital, Hallym University College of Institute, Mysore Medical College. Medicine. RATIONALE: There are conflicting reports about the effect of ICS RATIONALE: Exposure to humidifier disinfectants can increase the risk (inhaled corticosteroids) on BMD (bone mineral density). So, we studied of asthma but the characteristics of humidifier disinfectant-related asthma the effect of long-term (>6 months) ICS therapy on BMD in asthmatic are currently unclear. To investigate the characteristics of polyhexa- children. We hypothesised that there would be no difference in BMD methylene guanidine hydrochloride (PHMG)-induced asthma. among children on long-term ICS and their normal counterparts. METHODS: This general population-based birth cohort study utilized METHODS: 60 asthmatic children (5-18 years) on ICS for at least 6 data from the Panel Study of Korean Children from 2008 (n 5 846). months, attending asthma clinic at a tertiary care hospital in India (Mysuru) Spirometry, bronchial provocation tests, detailed history recording, and were compared against 60 age-and-sex matched controls. BMD was done physical examinations were performed on seven-year-old patients. in all the subjects by whole-body Dual-energy X-ray Absorptiometry based on fan-beam technology. RESULTS: The recent wheeze group without humidifier disinfectant 2 exposure was associated with a reduction in forced expiratory volume in 1 RESULTS: Mean total BMD (g/cm ) in children on low, medium and high 6 6 6 second (FEV )/forced vital capacity (z score 5-0.971; 95% CI, -1.460 to dose steroids was 0.771 0.114, 0.613 0.192, 0.564 0.104 respectively 1 5 -0.482). FEV in the recent wheeze group with PHMG exposure decreased (p 0.026). Mean total BMD in children on ICS for 6-12 months and 1 6 6 5 compared to that in the healthy group without humidifier disinfectant expo- more than 12 months was 0.611 0.172 and 0.623 0.173 (p 0.795) sure (z score 5 -0.806; 95% CI, -1.492 to -0.119). Bronchial hyperrespon- respectively. 18.9% of children on medium to high dose ICS had a low total siveness did not increased in the recent wheeze group with exposure to BMD while none on low-dose ICS did. While 38.7% on ICS for 6-12 PHMG. Long-term exposure to low-intensity PHMG before age three months had a low trochanteric BMD, 68.9% of those on ICS for more 5 was associated with asthma symptoms. than 12 months had a low BMD in the trochanter (p 0.018). CONCLUSIONS: The asthma phenotype associated with low intensity CONCLUSIONS: exposure to PHMG is characterized by decreased lung function and low 1. Dose and duration are the important determinants of effect of ICS positive rates of bronchial hyperresponsiveness. These findings suggest therapy on BMD. that asthma related to PHMG exposure may constitute a different 2. Children on medium to high dose long-term ICS therapy have a mechanism of asthma pathophysiology. significantly low BMD. 3. Trochanter is the ideal site for monitoring BMD. Asthma as a predictor of more severe outcomes 138 in COVID-19 infection Recommendation: we recommend annual monitoring of BMD in all children on medium to high dose steroids for more than 12 months. Lauren Eggert1, Shu Cao1, Ziyuan He2, Gopal Krishna Dhondalay, PhD3, Shirley Jiang1, William Collins, MD4, Sayantani Sindher, MD1, Kari Nadeau, MD PhD FAAAAI5, R. Sharon Chinthrajah, MD1; 1Stanford Uni- versity School of Medicine, 2Stanford University, 3Sean N Parker Centre for Allergy & Asthm, 4Stanford, 5Stanford Univ School Medicine. RATIONALE: There has been conflicting initial data regarding the effect of comorbid asthma on severity of illness with COVID-19 infection. Multiple studies have demonstrated an increased prevalence of asthma among hospitalized patients, but more recent studies have not shown an increased risk of severe infection in patients with asthma. Our objective is to understand the impact of asthma as a predictor of severe disease in COVID-19 patients at Stanford Hospital. METHODS: SARS-CoV-2 RT-PCR positive patients tested at Stanford Hospital were identified and hospitalization status, asthma history, de- mographics, co-existing conditions, complications caused by COVID-19, and clinical outcomes were noted. Inpatients were defined as hospitalized within 14 days of a positive test. RESULTS: From March 1 to July 3, 2020, 80331 patients were tested for SARS-CoV-2 at Stanford Hospital and 2626 (3.3%) tested positive; 202 (7.7%) patients were hospitalized. Significantly less SARS-CoV-2 positive patients had a diagnosis of asthma compared to those who tested negative (7.7% vs 11%, p<0.001, odds ratio50.66). Among 202 inpatients, 35 (17%) had severe COVID-19 infection with an ICU admission, with a higher incidence rate in the asthmatic patients (30.3% vs 14.0%, p50.037, odds ratio52.66). CONCLUSIONS: In our cohort of 202 hospitalized patients at Stanford Hospital, the odds of severe COVID-19 infection with an ICU admission among asthmatic patients is 2.66 higher compared to non-asthmatic J ALLERGY CLIN IMMUNOL Abstracts AB45 VOLUME 147, NUMBER 2

Outdoor Allergies are Associated with (OR51.84; IC 95% 1.39-2.44), emergency room visits (OR51.78; IC 95% 140 Increased Oral Corticosteroid Use in Children 1.44-2.21), nighttime symptoms (OR52.89; IC 95% 2.34-3.53) and with Allergic Asthma in New York City: A updated immunization (OR50.62; IC 95% 0.41-0.96). Single-Center Retrospective Study CONCLUSIONS: There are differences in associated factors for RW between genders. Identification of these differences could be useful to Angela Chan, MD1; 1NYP Hospital- Columbia. approach and management of RW between boys and girls. RATIONALE: Sensitization and exposure to environmental allergens is well known to be related to asthma morbidity; however, individual Early life food allergen sensitization and risk of populations may vary with respect to specific risk factors associated with 142 childhood asthma in an infant bronchiolitis exacerbations. Among children with asthma in our urban community cohort practices, we sought to better characterize children with the allergic asthma Anna Arroyo, MD MPH1, Lacey Robinson, MD2, Ruth Geller, MHS3, phenotype to identify allergic predictors of poor asthma outcomes. 4 5 6 METHODS: This is a single-center retrospective chart review using Susan Rudders, MD MS , Jonathan Spergel, MD, PhD , Cindy Bauer , Ashley Sullivan, MPH MS3, Kohei Hasegawa, MD MPH2, Carlos Ca- electronic health records of 264 children (3 to 21 years) with asthma in 2 1 2 New York City, with outpatient encounters at NYPH-Weill Cornell margo, Jr, MD DrPH ; Stanford School of Medicine, Harvard Medical School, Massachusetts General Hospital, 3Massachusetts General Hospi- Medicine from January 2015 to April 2019. Descriptive statistics were 4 5 5 5 tal, Harvard Medical School, Boston Children’s Hospital, Children’s used to define allergic (N 213) and nonallergic (N 54) groups. Logistic 6 regression models were used to assess the association between allergy Hospital of Philadelphia, Phoenix Children’s Hospital. status and asthma severity. RATIONALE: The relation of infant food sIgE to asthma remains unclear. RESULTS: Among children with allergic asthma, 48.4% had both indoor We examined the relationship between food sIgE patterns and incident and outdoor allergies. Subjects with indoor and outdoor allergies had asthma at age 5 years. METHODS: We analyzed data from a multicenter, prospective cohort increased odds (ORunadj 3.65; 95% CI 1.36-9.76, p50.010) of having persistent asthma, compared to having indoor allergies alone. Compared study of infants hospitalized with bronchiolitis. We measured sIgE to 5 to the non-allergic group, subjects with outdoor allergies had increased foods at enrollment (median age, 3 months) and in early childhood (median age, 45 months) using ImmunoCAP. Four sensitization patterns were: odds (ORunadj 7.29; 95% CI 1.44-37.01, p50.017) of asthma exacerbations requiring oral steroids. There were no associations between the degree of never, early transient, late-onset, and persistent sensitization to any food sensitization and asthma exacerbations, severity or control. allergen. Asthma was defined as parent report of clinician-diagnosed CONCLUSIONS: In this cohort, outdoor allergies is an important risk asthma by age 5 years plus either asthma medication use or asthma factor for asthma exacerbations over degree of sensitization, or presence of symptoms during ages 4-4.9 years. Logistic regression models examined indoor allergies. In addition to avoidance measures, this higher risk subset the relation of sIgE patterns with incident asthma. of patients may benefit from aggressive medication regimens including RESULTS: Of 920 infants followed longitudinally, 573 (62%) provided consideration of targeted allergen immunotherapy, to improve asthma early childhood blood samples. At age 5 years, 161/570 (28%) had asthma. outcomes. The prevalence of food sensitization was 93/570 (16%) during infancy and 160/570 (28%) during early childhood. The prevalence of sensitization Associated factors with recurrent wheezing in patterns was: never, 370 (65%); early transient, 40 (7%); late-onset, 107 141 infants: is there difference between the (19%), and persistent, 53 (9%). Early transient was not associated with genders? asthma (P>0.20), while late-onset and persistent were (both P<0.01). After adjustment for age at enrollment, sex, race/ethnicity, and maternal asthma Herberto Chong Neto1, Wellington Ferreira2, Gustavo Wandalsen, MD3, – compared to ‘‘never’’ group – asthma was more likely in late-onset Dirceu Sole3, Emanuel Sarinho4,Decio Medeiros5, Elaine Prestes6, Paulo (adjusted OR 1.70, 95%CI 1.07-2.70, P50.02) and possibly in persistent Camargos7, Nelson Rosario, MD PhD FAAAAI8; 1Universidade Federal (adjusted OR 1.58, 95%CI 0.85-2.94, P50.15). do Parana, 2Federal University of Parana, 3Federal University of S~ao CONCLUSION: Late-onset food sensitization during early childhood Paulo-EPM, 4University Federal of Pernambuco, Brazil, 5Federal Univer- was associated with higher odds of incident asthma. Temporal variations in sity of Pernambuco, 6Para State University, 7Federal University of Minas food sensitization during early childhood may influence asthma risk. Gerais, 8Federal University of ParanA~¡. RATIONALE: Identify associated factors for recurrent wheezing (RW) infants between the genders. METHODS: Cross-sectional multicentric study using the standardized questionnaire from the Estudio Internacional sobre Sibilancias en Lactantes (EISL). The questionnaire was applied to parents of 9,345 in- fants aged 12 to 15 months at the time of immunization/routine visits. RESULTS: One thousand two hundred and sixty-one (13.5%) males and nine hundred sixty-three (10.3%) females have had RW (>_ 3 episodes), respectively (p<0.001). Associated factors for RW for male were maternal smoking during pregnancy (OR51.41; IC 95% 1.08-1.81), >10 colds episodes (OR53.46; IC 95% 2.35-5.07), air pollution (OR51.33; IC 95% 1.12-1.59), molds at home (OR51.23; IC 95% 1.03-1.47), afrodescendants (OR51.42; IC 95% 1.20-1.69), bronchopneumonia (OR51.41; IC; 1.11- 1.78), severe episodes of wheezing in the first year (OR51.56; IC 95% 1.29-1.89), treatment with bronchodilators (OR51.60; IC 95% 1.22-2,1) treatment with oral corticosteroids (OR51,23; IC 95% 0.99-1,52). Associated factors for RW for females were passive smoking (OR51.24; IC 95% 1.01-1,51), parents diagnosed with asthma (OR51.32; IC 95% 1,08-1,62), parents with allergic rhinitis (OR51.26; IC 95% 1.04-1.53), daycare attendance (OR51.48; IC 95% 1.17-1,88), colds in the first 6 months of life (OR52.19; IC 95% 1.69-2.82), personal diagnosis of asthma AB46 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Association Between Olfactory Function and Pediatric Severe Asthmatics in a Southern US 143 Asthma In Adults 145 State Face Multiple Challenges and Barriers to Care Hyo-In Rhyou1, Woo-Yong Bae1, Young-Hee Nam, MD1; 1College of Medicine, Dong-A University, Busan, Korea. Robbie Pesek, MD1, Brandi Whitaker, PhD2, Erhan Ararat, MD2, Amika RATIONALE: Chronic rhinosinusitis (CRS) and allergic rhinitis (AR) are Sood, MD3, Matthew Pertzborn, MD2, Amber Davidson, MSW4, Kim common asthma-associated upper airway diseases. Olfactory dysfunction, Cobb, MA, RRT-AE-C4, Kristin Hines, BS, RRT, AE-C, CPFT4, Callie a common symptom among these patients, is an increasingly recognized Margiotta3, Jessica Turner, allied health5, Akilah Jefferson6, Tamara condition, associated with reduced quality of life and major health Perry, MD FAAAAI7; 1University of Arkansas for Medical Sciences, outcomes. However, there are few studies on association between cognitive 2University of Arkansas for Medical Sciences and Arkansas Children’s function and asthma. Hospital, 3Arkansas Children, 4Arkansas Children’s Hospital, 5University METHODS: A total of 146 asthmatic patients aged >18 years were of Arkansas for Medical Scien, 6UC San Diego, 7UAMS/Arkansas analyzed retrospectively from August 2019 to February 2020. Olfactory Children. function was assessed using the Sniffin’ stick test or YSK olfactory RATIONALE: Severe asthmatics account for 5-10% of all asthma function test. We compared clinical parameters between hyposmic and diagnoses but are responsible for significant health care utilization. normosmic patients. Identifying barriers to care is a key step to improving outcomes and RESULTS: Of the total participants, 68 (46.6%) showed olfactory reducing healthcare costs. dysfunction (hyposmia n531; anosmia n537). Patients with more severe METHODS: Subjects, 2-21 years, referred to the Arkansas Children’s olfactory dysfunction had longer asthma duration and higher proportion of Severe Asthma clinic were enrolled in a prospective database. Data CRS, nasal polyp, and aspirin exacerbated respiratory disease compared collected includes demographics, asthma history, social determinants of with those with normosmia. Age (odds ratio: 1.044, 95% confidence health, and psycho-social evaluation of subjects and caregivers. interval: 1.009-1.081, P50.012), general health status (3.304, 1.231-8.863, RESULTS: Twenty-five subjects with a mean age of 11.5 years (6 3.94) 0.018), CRS (2.589, 1.155-5.804, P50.021), and nasal polyp (3.306, 1.1- have been enrolled to date. 54.5% are male, 77.3% are African-American/ 9.94, 0.033) were significantly associated with olfactory dysfunction. Black, and 90.9% have Medicaid. Average households consist of 4 CONCLUSIONS: Olfactory dysfunction was largely observed (46.6%) in members with 42% of families living below the national poverty level adults with asthma, which was more prevalent in older adults than in ($26,200) and 20% experiencing food insecurity. Less than 25% of younger adults. Poor health status, CRS, and nasal polyp were more caregivers have a college degree. Subjects had a mean of 3.16 (6 2.76) associated with olfactory dysfunction. exacerbations requiring systemic corticosteroids yearly and a mean of 7.3 (6 4.61) lifetime hospitalizations related to asthma. Mean Composite Do Airborne Mold Counts Predict Asthma Asthma Severity Index was 6.96 (6 5.36) and Asthma Control Test was 144 Exacerbations? 16.33 (6 6.38) at baseline. Twenty-four percent of parents had concern regarding their child’s mental health and nearly 20% were receiving mental Kelsey Kaman, MD1, Christopher Randolph, MD FAAAAI2; 1Yale Uni- 2 health services. Pediatric Symptom Checklist-17 lacked clinically signif- versity, Center for Allergy, Asthma & Immunology. icant elevations. Mean caregiver scores on the Connors-Davidson RATIONALE: Airborne fungal spore counts including Alternaria, Resilience Scale fell in the 2nd quartile (mean 5 77.76, 6 20.37). Cladiosporium, Ascospores, Aspergillus, Epicoccum, Agrocybe and CONCLUSIONS: Severe asthmatic children in Arkansas have a high Basidiospores have been correlated with asthma exacerbation requiring disease burden, multiple socioeconomic and psycho-social challenges, and ER visits and hospitalizations in children and adults with asthma, caregivers with low resilience. Reduction of these barriers will be critical particularly those sensitized to mold. Airborne fungi have also been for improving asthma control and reducing healthcare utilization. suggested as a possible etiology for ‘‘thunderstorm asthma’’ driven more commonly by grass pollen. We hypothesized there would be a correlation between airborne mold and asthma exacerbations reflected in ER visits, nonurgent outpatient visits and hospitalization. METHODS: Longitudinal retrospective and prospective analysis was conducted for April –October from 2013-2020 of asthma exacerbations reflected by de-identified EMR documented ER visits and hospitalizations at a 243-bed teaching communtiy hospital. Airborne mold counts were derived from our National Allergy Bureau certified in hospital station and correlation was investigated. RESULTS: A total of 3772 asthma cases were included in this study (13% inpatient, 50% nonurgent outpatient and 37% ER) over 814 days. Patients ranged in age from 1m to 86yrs old, 64% were female and 36% were male. There were an average of 4.643 asthma exacerbations per day (range 0-14; std. deviation 2.39). Average mold count was 12,221.26 (range 4-533,914; median 5545.5). Linear regression model yielded a correlation coefficient of 0.017 suggesting no significant correlation. CONCLUSIONS: There is no significant correlation between daily un- speciated airborne mold counts and asthma exacerbations presenting to the ER, nonurgent outpatient or admitted to a community hospital over the period of 2013-2020. Analysis of the subsequent days after maximum mold counts for asthma exacerbations may provide a correlation as with pollen, and is in progress. J ALLERGY CLIN IMMUNOL Abstracts AB47 VOLUME 147, NUMBER 2

Clinical and Economic Burden of Patients with nocturnal (57%/43%, 54%/39%, 48%/35%) symptoms and >_1 exacerba- 146 Uncontrolled Severe Asthma with Low Blood tion in the prior year (59%, 57%, 50%). Eosinophil Levels in the United States CONCLUSION: In this real-world study of specialist-treated patients with SA, sex and age had meaningful effects on patient characteristics. Laren Tan1, Joan Reibman2, Chris Ambrose, MD MBA3,Yen Female sex and younger age were associated with greater disease burden, Chung, pharmd3, Pooja Desai4, Jean-Pierre Llanos Ackert4, Meghan Moy- suggesting a need for increased monitoring and/or intervention. nihan5, Joseph Tkacz, MS5; 1Loma Linda University Medical Center, 2New York University School of Medicine, 3AstraZeneca, 4Amgen, Baseline Asthma Impairment and Risk ä 5IBM Watson Health. 148 Questionnaire (AIRQ ) Control Level is RATIONALE: Further investigation is needed to quantify the clinical and Associated with Future Risk of Exacerbations economic burden of severe asthma patients with low eosinophils untreated David Beuther1, Kevin Murphy, MD2, Robert Zeiger, MD PhD with biologics. 3 4 5 METHODS: Severe asthma patients aged 12+ with blood eosinophil (eos) FAAAAI , Robert Wise , William McCann, MD FAAAAI , Joan Reib- man6, Maureen George, PhD RN AE-C7, Ileen Gilbert8, James Eudicone8, count data were selected from the IBM MarketScan claims databases 8 9 9 10 1 between 1/1/2013 and 6/30/2018 (most recent eos5index date). Inclusion Hitesh Ghandi , Karin Coyne , Melissa Ross , Bradley Chipps ; Na- tional Jewish Health, Denver, CO, 2Boys Town National Research Hospi- criteria were 1) blood eos level <300 cells/uL, 2) continuous enrollment for 3 12 months preceding/following index, 3) meets both the HEDIS definition tal, Boys Town, NE, Departments of Allergy and Research and Evaluation, Kaiser Permanente Southern California, San Diego and Pasa- of persistent asthma and the GINA definition of severe asthma, and 4) an 4 absence of biologic treatment, other major respiratory diagnoses, and any dena, CA, Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 5Allergy Part- malignancy 12 months preceding/following index. Patients were stratified 6 into <150 cells/mL and >_150 and <300 cells/mL cohorts. Patient ners, Asheville, NC, New York University School of Medicine, New York, NY, 7Columbia University School of Nursing, New York, NY, 8As- characteristics, asthma treatment, exacerbations, levels of disease control, 9 10 and all-cause and asthma-related healthcare costs were reported during the traZeneca, Wilmington, DE, Evidera, Bethesda, MD, Capital Allergy & 12-month post-index period. Respiratory Disease Center, Sacramento, CA. RESULTS: The sample included 6,260 patients with an eos count <300 RATIONALE: The Asthma Impairment and Risk Questionnaire ä cells/mL: 3,403 (54.4%) <150 cells/mL and 2,857 (45.6%) >_150 and <300 (AIRQ ) is a 10-item, yes/no, composite control tool cross-sectionally _ cells/mL. Mean [SD] age of the sample was 54.8 [14.2]; 64% were female. validated in a study of asthma patients aged >12 years. This interim report ä Eighteen percent of patients presented an asthma exacerbation; 19% of the from the ongoing year-long longitudinal assessment of AIRQ evaluates ä sample presented either uncontrolled or sub-optimally controlled disease the relationship of baseline AIRQ control category with patient-reported based on the frequency of asthma-related hospital admissions, ER visits, or exacerbations over the subsequent six months. corticosteroid fills. Annual all-cause and asthma-related total healthcare METHODS: Patients completed monthly online surveys regarding costs were $25,845 and $2,802, respectively, and was inversely related to exacerbation-related oral corticosteroid use, emergency room/urgent care level of disease control. visits, and hospitalizations. Logistic regressions were performed using ä CONCLUSIONS: Nearly 1 in 5 severe asthma patients with low AIRQ control categories (well-controlled[WC], not well-controlled eosinophils and untreated with biologics experience exacerbations and [NWC], very poorly controlled[VPC]), age, sex, race, and BMI as _ _ have less than optimal control within one year, demonstrating a potential covariates, and >1or>2 exacerbations as dependent variables (odds- unmet need. ratios[OR] and Wald Confidence Limits[CL]). RESULTS: 1057 patients completed >_1 survey over 6 months (mean[SD] Effects of Sex and Age on Characteristics of surveys completed: 5.4[1.3]); 70.1% female; age 43.9[19.4] years; 21.5% 147 United States Patients With Severe Asthma non-white; BMI 30.6[8.7]; AIRQä control category: WC 35.5%, NWC 38.4%, VPC 26%. Thirty-eight percent of patients reported >_1 and 23% Njira Lugogo, MD1, Elizabeth Judson2, Erin Haight2, Frank Trudo, MD2, reported >_2 exacerbations (WC: 20.4% >_1, 17.5% >_2; NWC: 37.3% >_1, Bradley Chipps, MD FAAAAI3, Jennifer Trevor, MD4, Chris Ambrose, 37.0 % >_2; VPC: 42.3% >_1, 45.5% >_2). AIRQä control category, age, sex MD MBA2; 1University of Michigan, 2Astrazeneca, 3Capital Allergy (>_1 exacerbation only), and BMI were significant in both exacerbation- and Respiratory Dis. Ctr, 4University of Alabama at Birmingham. level models. ORs for future exacerbations relative to baseline AIRQä RATIONALE: This study examined the effects of sex and age on clinical control category for NWC vs WC were 2.0 (95% CL 1.5-2.8) for >_1 characteristics of specialist-treated US severe asthma (SA) patients. exacerbation and 2.2 (95% CL 1.5-3.2) for >_2; VPC vs WC were 4.9 (95% METHODS: CHRONICLE is an observational study of adult, specialist- CL 3.4-7.0) for >_1 exacerbation and 4.5 (95% CL 3.0-6.7) for >_2. treated SA patients receiving biologics, maintenance systemic corticoste- CONCLUSIONS: Baseline AIRQä identifies patients at increased risk of roids, or uncontrolled on high-dosage inhaled corticosteroids with future exacerbations. AIRQä could prompt patients and providers to additional controllers. For patients enrolled February 2018–February discuss options to optimize asthma control. 2020, demographic and clinical characteristics were examined by sex and age at enrollment (18–49, 50–64, or >_65 y). RESULTS: Of 1884 enrolled patients, 69% were female. Mean age at enrollment was 54 y. Female patients had more depression (19% vs 9%), more anxiety (16% vs 8%), higher mean BMI (34.2 vs 31.4), more daytime/nocturnal (55%/41% vs 50%/35%) symptoms, poorer St. George’s Respiratory Questionnaire scores (median: 45 vs 36). More female patients had >_1 exacerbation in the prior year (58% vs 52%). With older age (18–49, 50–64, >_65 y), more patients were male (29%, 31%, 35%), while fewer were Black (20%, 22%, 11%) or Hispanic (11%, 8%, 6%). As age increased, former smoking (23%, 30%, 39%), COPD (4%, 8%, 14%), hypertension (17%, 33%, 43%), and hypercholesterolemia (6%, 18%, 24%) increased, while allergic rhinitis (57%, 53%, 48%) and nasal polyps (12%, 7%, 3%) decreased. Fewer older patients had daytime/ AB48 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Perception of burden of oral and inhaled Wheezing patterns in childhood and body mass 149 corticosteroid adverse effects by asthmatic 150 index, blood pressure, and lung function in patients school-aged children

Vickram Tejwani1, Hsing-Yuan Chang, MD, MPH2, Annie Tran, MPH2, Catalina Acosta1, Maribel Casas1, Judith Garcia2; 1Isglobal Institute of Tonya Winders3, Rachael Moloney, MPH2; 1Johns Hopkins University, global health, 2Isglobal, Insitutite of Global health. 2Center for Medical Technology Policy, 3Allergy & Asthma Network. RATIONALE: This study evaluates the associations between wheezing RATIONALE: Patient perceptions of oral and inhaled corticosteroid patterns in childhood and (BMI), blood pressure, and lung function at 7 (OCS and ICS) adverse effects (AEs) may influence their compliance to years of age. these therapies for asthma. However, AE burden has yet to be fully METHODS: This study used data from the INMA multicenter popula- elucidated in an asthmatic population. We sought to characterize the level tion-based mother and child cohort including three Spanish regions of burden from OCS and ICS AEs within this population. (n51,164). Wheezing information was assessed through questionnaires METHODS: We distributed an online survey to patients within the at 1.5, 4 and 7 years of age and four wheezing patterns were defined: never, Allergy and Asthma Network and Asthma UK. A list of 25 OCS and 9 ICS early, late, and persistent wheezers. At 7 years, weight, height, and blood AEs were compiled from a targeted literature search and supplemented by pressure were measured and spirometry test was performed. We calculated feedback from a pilot survey. Respondents were asked to rate these AEs on the age- and sex- specific z-scores for BMI, blood pressure, and lung a scale from 1 to 5, ranging from least to most burdensome. Respondents function parameters. were then asked to select the one AE they would eliminate by switching RESULTS: In our study population, 53% of children reported at least one treatment. wheezing episode up to age of 7 years. Persistent wheezing was associated RESULTS: Among 124 respondents, 119 had asthma, with 54 reporting a with higher systolic blood pressure among females (b 5 0.32, 95% CI 5 severe asthma diagnosis. Eighty-two reported short course OCS use and 24 0.08 - 0.57) and lower systolic blood pressure among males (b 5 -0.18, reported long course OCS use (>30 days) in the past 12 months, and 105 95% CI 5 -0.34 – -0.02) (p-value for interaction 5 0.01) in comparison reported daily ICS use. The three most burdensome OCS AEs were weight with never wheezing. Persistent, but also early wheezers, presented both a gain/obesity, decreased bone mineral density, and increased risk of lower forced expiratory volume in one second (FEV1) and FEV1/Forced vi- infection/infectious complications. The top AEs to be eliminated were tal capacity ratio, especially in males (FEV1/FVC b 5 -0.64, 95% CI 5 weight gain/obesity, bone/osteoporosis-related fracture, and sleeplessness. -0.95, -0.34; p-value for interaction50.03). No association was observed The three most burdensome ICS AEs were pneumonia, hoarse/croaky between wheezing patterns and BMI at 7 years of age. voice, and oral thrush. These were the same AEs most desired for CONCLUSION: the presence of persistent wheezing up to age 7 years can elimination. affect blood pressure and lung function in school-aged children in a sex- CONCLUSIONS: Understanding the most burdensome OCS and ICS specific manner. Further investigation is needed to clarify the mechanisms AEs from the asthma patient perspective provides more clarity on patient behind these associations. treatment preferences. Efforts at mitigating these AEs could potentially improve compliance. J ALLERGY CLIN IMMUNOL Abstracts AB49 VOLUME 147, NUMBER 2

Analysis Of COVID-19 In Adult Asthmatic between flavonoid nutrients and alpha diversity. Peonidin intake was pos- 5 5 151 Outpatients tively associated with richness (rho 0.59, padj 0.01) and phylogenetic di- versity (rho50.58, padj50.02). Dietary anthocyanidins also correlated with 1 ~ Maria Somoza Alvarez, MD , Ana MarAa Prieto-Moreno richness (rho50.48, padj50.05). Pfeifer, CME1, Isabel Torres Rojas, CME1, Maria Desamparados Cer- CONCLUSIONS: These preliminary results indicate significant differ- vera1, Diana Perez-Alzate1, Maria Vazquez de La Torre1, Elisa Haroun- ential relationships between dietary flavonoid intake, atopy, and asthma Diaz1, Francisco Javier Ruano1, Paula Lopez-Gonzalez1, Natalia clinical features and invite further investigation into the potential role of Blanca-Lopez1, Gabriela Canto, MD, PhD1; 1Infanta Leonor University the gut microbiota. Hospital. RATIONALE: During the SARS-CoV-2 pandemic, the Infanta Leonor The ASTHMAXcel PRO Mobile Application for University Hospital (Madrid, Spain) was one of the most affected, assisting 153 Adult Patients: Evaluating User Satisfaction 2,968 COVID-19 patients (March-April 2020). Our aim was to analyse the and Adoption epidemiological and clinical characteristics of COVID-19 in adult 1 2 1 asthmatic outpatients in our allergy unit. Anjani Singh, MD , Obumneme Njeze, BS , Emine Cosar , Savneet 1 3 4 1 METHODS: Clinical and epidemiological characteristics were analysed Kaur , Brian Hsia, MD , Sunit Jariwala, MD FAAAAI ; Albert Einstein 2 by consulting the electronic medical records system for the previous year, College of Medicine/Montefiore Medical Center, Montefiore Medical 3 4 as well as via telephone interview made by two allergists in May 2020. Center/Albert Einstei, Mount Sinai Hospital, Albert Einstein/Montefiore RESULTS: We included 217 patients (>_16 years old), from which 26 Medical Cente. (12%) were probable and three confirmed COVID-19. BACKGROUND: The ASTHMAXcel PRO mobile application has been Pneumonia was diagnosed in three patients from the probable group. linked to favorable clinical and process outcomes among adult asthma Emergency assistance was required for 24% of them, and only one was patients. admitted to hospital not needing intensive care. OBJECTIVE: We assessed the impact of ASTHMAXcel PRO on patient From the confirmed cases, two were diagnosed with pneumonia and only satisfaction with the user interface and app adoption. one admitted to hospital with no intensive care assistance. METHODS: ASTHMAXcel PRO is a mobile app with videos and quiz When comparing probable and confirmed cases with non-COVID-19 questions that educate patients and promote self-management. During app patients, we found an increase in the asthma control treatment (33% vs 1%, field testing, we administered the Questionnaire for User Satisfaction P <0.0001 respectively) and in b2-agonists (59% vs 3%, P <0.0001). (QUIS) and Unified Theory of Acceptance and Use of Technology Uncontrolled asthma was more frequent in patients with COVID-19 (30% (UTAUT) surveys at baseline and 4 weeks. Both QUIS and UTAUT had vs 7%, P <0.0001). As all patients were recruited during the pollen season, domain-specific and total score values. The paired 2-sample t-test we investigated allergic rhinoconjunctivitis, being similar in both groups evaluated change from baseline to the 4-week session for each domain (59% vs 57%, P 5 0.812). and total scores. 5 CONCLUSIONS: In our study, adult asthmatic allergic outpatients do not RESULTS: 28 patients (female 21) ranging from 20-70 years enrolled. A seem to be at risk of developing severe COVID-19. Nevertheless, SARS- total of 25 patients completed surveys for both baseline and 4-week. In the CoV-2 causes mild asthma exacerbation which triggers the need for asthma QUIS total score group, there were statistically significant increases from 5 control in these patients. baseline to 4-weeks (199 vs 226.4, p 0.04), while one of six QUIS Domain groups, Screen Domain, showed statistically significant results Relationships Between Dietary Flavonoid from baseline to 4-weeks (27.0 vs 32.4, p50.0189). UTAUT total scores at 152 Intake, Gut Microbiota, And Asthma Clinical baseline and 4-week (64.2 vs 69.8, p50.002) also showed significant Features improvements with using the ASTHMAXcel application. All four of the UTAUT domains: Performance Expectancy, Effort Expectancy, Social Michelle El-Hosni1, Ariangela Kozik, PhD1, Molly Cook1, Research Lab Influence, and Facilitating Conditions (16.2 vs 17.5, p50.02; 17.0 vs 18.3, Tech1, Alan Baptist, MD MPH FAAAAI1, Nicole Schafer1, Clinical p50.0098; 14.2 vs 15.9, p50.0008; 16.8 vs 18.0, p50.01) showed Research Coordinator1, Lesa Begley, MS1, Yvonne Huang, MD1; 1Univer- statistically significant results from baseline to 4-weeks. sity of Michigan. CONCLUSION: ASTHMAXcel has been associated with improved user RATIONALE: The anti-oxidative and anti-inflammatory effects of satisfaction and adoption outcomes in adult patients. Larger studies are flavonoids are well-established. However, less is known regarding poten- needed to validate these results. tial associations between dietary flavonoids, the gut microbiome, and clinical features of asthma. METHODS: Extensive nutrient analysis and clinical data were collected from 127 asthmatic (n5 80) and non-asthmatic (n547) adults enrolled in a prospective observational cohort study (CAARS) at the University of Michigan. Asthmatic patients were subcategorized as taking inhaled corticosteroids (ICS) (n546) and those not taking ICS (n534). Control groups were defined as atopic (n525) and non-atopic (n522) (IgE, p<0.01). Fecal samples from 44 of the 127 participants were processed for 16S ribosomal RNA gene sequencing to characterize gut microbiota composition. R analysis software was used to examine relationships between dietary patterns and clinical features. RESULTS: Asthmatic patients demonstrated mild-moderate disease (FEV1 % predicted mean589.23, sd519.06). FEV1 % predicted levels inversely correlated with eriodyctoyl intake in both asthma +ICS (rho5

-0.38, padj50.02) and non-ICS cohorts (rho5 -0.46, padj50.02). Within the atopic control group, blood neutrophil levels were inversely associated with intake of quercetin (rho5 -0.55, padj50.02), epicatechin (rho5 -0.54, padj50.03), and flavanols (rho5 -0.52, padj50.03). Gut microbiome data within the asthma +ICS subgroup demonstrated a positive correlation AB50 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Medication adherence was greater in a digital phone encounters and 75% of video encounters were linked to e-consent 154 asthma platform consisting of controller and completion (p<0.05). rescue vs. controller inhalers alone CONCLUSION: While e-consent is preferable to verbal consent within the context of virtual cohort studies, larger trials are necessary to validate Rahul Gondalia, PhD1, William Anderson, MD FAAAAI2, Leanne these findings. It would be of great interest to determine how e-consent Kaye1, Heather De Keyser, MD3, Meredith Barrett, PhD1, Stanley participation impacts attrition patterns. Szefler, MD FAAAAI3, David Stempel, MD FAAAAI4; 1ResMed, 2Chil- dren’s Hospital Colorado, University of Colorado School of Medicine, Development of a Novel, Interactive, Electronic 3Breathing Institute, Children’s Hospital Colorado, University of Colo- 156 Pediatric Asthma Diary for Self-Report of rado School of Medicine, 4Propeller Health. Symptom Severity and Disease Impact by RATIONALE: Use of inhaler electronic medication monitors (EMMs) Young Children With Asthma and mobile applications (‘‘app’’) for asthma is associated with higher Marci Clark1, Carla Romano1, Oyebimpe Olayinka-Amao1, Diane Whal- controller medication adherence. The objective was to assess whether 1 1 2 2 adherence was higher in patients using EMMs for both controller and ley , Rebecca Crawford , Purnima Pathak , Caterina Brindicci , Kristin Garg2, Kattayoun Kordy2, Francois Everhard2, Francesco Patalano2, rescue vs. controller inhalers alone. 3 3 3 3 METHODS: Patients aged >_12 years using inhaled controller medication Zach Roesler , Thomas Sutton , Oskar Goransson , Ross Landles , Chris- tel Naujoks2, Jessica Marvel2, Dorothy Keininger2; 1RTI Health Solutions, enrolled in a digital asthma platform (2017-2019) consisting of EMMs and 2 3 an app that tracked inhaler use and provided asthma education, controller Novartis Pharma AG, frog. use insights and medication reminders. When used alongside rescue RATIONALE: No comprehensive diary is available to assess the severity inhaler EMMs, the app included additional features to promote engage- and impact of asthma symptoms for self-completion by children aged 6-11 ment, e.g. short-acting beta-agonist trends and personalized trigger years. We developed a novel electronic pediatric asthma symptom diary identification. Patients were included if they completed an Asthma (ePASD) administered via an animated digital application with visuals, Control Test (ACT) at enrollment. Analyses included the first 90 days of sounds, and written and audible text to facilitate self-report by young EMM use. Linear mixed-effects models estimated age-adjusted associa- children with asthma with varying reading levels. tions between EMM-recorded adherence with controller only vs. controller METHODS: Development of the ePASD was conducted following FDA and rescue EMM use, overall and by ACT (<_15; 16-19; >_20). PRO guidance and good research practices. It included: a targeted literature RESULTS: Among 5105 patients (mean age: 39 years), 57%, 22% and review and semistructured interviews with three experienced clinicians to 21% had an ACT<_15, 16-19 and >_20, respectively. Using both controller gain an initial understanding of pediatric asthma symptoms and impacts on and rescue EMMs (vs. controller EMMs alone) was associated with 4.7% daily activities; concept elicitation (CE) interviews with 44 (30 US; 14 UK) (95% CI: 2.6, 6.9; P<0.01) higher absolute percentage adherence. children with asthma and their caregivers to elicit key symptoms and core Improvements were greatest in patients with ACT<_15 (5.9%; 95% CI: impacts of asthma; and cognitive debriefing (CD) interviews with 21 US 3.0, 8.9; P<0.01), while lower and non-significant in patients with ACT 16- children to assess relevance, understanding, and interpretability of the 19 (3.4%; 95% CI: -1.3, 8.1; P50.15) and ACT>_20 (3.3%; 95% CI: -1.1, ePASD items. 7.6; P50.13). RESULTS: Key measurement concepts identified from literature and CONCLUSIONS: EMM use with both rescue and controller inhalers was clinician interviews included cough, wheeze, difficulty breathing, chest associated with higher adherence, suggesting that a more comprehensive tightness/discomfort, nighttime awakening, and daytime activity limita- digital experience of inhaler use may improve adherence. tions. CE interviews confirmed concept saturation was achieved for the primary asthma-related daytime and nighttime symptoms and core Utilizing the ASTHMAXcel PRO Mobile Platform impacts. Children in the CD interviews found the ePASD items clear, 155 to Conduct a Virtual Cohort Study During the understandable, and comprehensive. COVID-19 Pandemic CONCLUSIONS: The ePASD is a novel patient-reported outcome instrument designed to facilitate self-completion by children aged 6 to Emine Cosar1, Savneet Kaur1, Anjani Singh, MD2, Obumneme 11 years with mild to severe asthma who may or may not read Njeze, BS1, Brian Hsia, MD3, Sunit Jariwala, MD FAAAAI4; 1Albert Ein- independently. Interviews with pediatric patients demonstrated the stein College of Medicine, 2Albert Einstein College of Medicine/Mont, ePASD to be appropriate and feasible for children in this age group with 3Mount Sinai Hospital, 4Albert Einstein/Montefiore Medical Cente. a range of reading abilities. RATIONALE: The COVID-19 pandemic resulted in widespread disrup- tions to on-site clinical studies. We therefore sought to utilize our patient- facing ASTHMAXcel mobile platform to conduct a virtual cohort study and determine patient preferences throughout the process. METHODS: We recruited adults with persistent asthma from primary care clinics within the Montefiore Health System (Bronx, NY). During the baseline visit, patients completed either electronic consent (e-consent) reviewed and signed through our project’s REDCap database or verbal consent administered via telephone. The subsequent enrollment process was completed either through a secure video platform or by phone. Following consent, we conducted field testing and formative and summa- tive evaluation feedback to iteratively refine our ASTHMAXcel mobile platform. Statistical analysis was completed with the chi-square test. RESULTS: 28 patients (female: 21, mean age: 45.5 6 15.2) participated in the study with 18 and 10 completing the e-consent and verbal consent respectively. Of the 18 individuals in the e-consent group, 3 utilized the secure video platform, while 15 used the phone to complete the consent process. Of the 10 participants in the verbal consent group, 1 utilized the secure video platform, while 9 used the phone. Whereas 85.7% of the study population utilized the phone to complete the consent process, 62.5% of J ALLERGY CLIN IMMUNOL Abstracts AB51 VOLUME 147, NUMBER 2

Impact of a Digital Asthma Intervention on The lack of use of telemedicine in our population is not associated to 157 Short-acting Beta-agonist (SABA) Medication socioeconomic status, level of education or access to technology. 75% of Use Among Medicaid-enrolled Children in our population was not aware that telemedicine was an option for patient Southwest Detroit care. 68% of our population will consider to use telemedicine prior consulting to ED next time. Meredith Barrett, PhD1, Rahul Gondalia, PhD1, Carolynn CONCLUSIONS: Despite the socioeconomic hardship that our popula- Rowland, RN2, Alex Hill, MA3, Elliot Attisha, MD4, Leanne Kaye1, Ter- tion face every day Bronxcare caregivers and patients are ready to use esa Holtrop, MD5; 1Propeller (during work); ResMed (current), 2Kids’ telemedicine as part of asthma care and potentially decrease emergency Health Connection, 3Detroit Health Department (during work), Wayne visits. However, health care providers and the hospital need to offer this State University (current), 4Detroit Public Schools Community District, service explicitly making it more available for the caregivers. 5Kids’ Health Connections. Note: During covid 19 pandemic telemedicine was started in our ED with RATIONALE: Digital asthma interventions have been associated with good response. improved outcomes, but evidence among Medicaid-enrolled participants remains limited. We aimed to evaluate the impact of a digital asthma Phenotyping patients based on longitudinal intervention, combined with a collaborative asthma education program, on 159 heterogeneity of engagement patterns with the SABA use among children in Detroit. ASTHMAXcel PRO mobile health application METHODS: Children (ages 6-13) with asthma living in four ZIP codes of Savneet Kaur, Emine Cosar1, Obumneme Njeze, BS2, Anjani southwest Detroit were eligible to participate in the program sponsored by 3 4 5 1 the Detroit Health Department. Participants were recruited by Kids Health Singh, MD , Brian Hsia, MD , Sunit Jariwala, MD FAAAAI ; Monte- fiore Medical Center, 2Montefiore Medical Center/Albert Einstei, 3Albert Connection (KHC) to enroll in an asthma education program supplemented 4 5 with electronic medication monitors (EMMs) to capture the date and time Einstein College of Medicine/Mont, Mount Sinai Hospital, Albert Ein- of SABA use, and a companion smartphone app to provide education, stein/Montefiore Medical Cente. feedback and reminders. Caregivers and providers were invited to monitor RATIONALE: The ASTHMAXcel PRO mobile application delivers the data and discuss trends with KHC. Paired t-tests (?50.05) estimated asthma education and assesses and tracks patient-reported outcomes change in mean daily SABA use and SABA-free days from first to last (PROs), which are collected via in-app quizzes and push notifications. month of participation. We seek to identify distinct patient phenotypes based on heterogeneity of RESULTS: 51 participants enrolled, had > 60 days of EMM data and were engagement patterns. included in analyses (median age: 12 years, with a mean of 8.4 months of METHODS: Adult patients with persistent asthma completed virtual data). From the first to last month, mean SABA use decreased from 0.68 to study sessions at baseline (app download), 2 weeks, and 4 weeks. The 0.25 puffs/day (-0.43, 95% CI: -0.67, -0.20; p<0.001), and mean SABA- number of PRO items submitted by each user was tracked through the app’s free days increased from 25.2 to 28.1 days/month (2.9 days, 95% CI: 1.7, administration panel and leaderboard, and used to evaluate app usage 4.1, p<0.001). 76% of participants improved their number of SABA-free patterns. We evaluated user interface satisfaction and acceptance through days, while 7.8% maintained and 15.7% worsened. the QUIS and UTAUT questionnaires, respectively. 6 CONCLUSIONS: Analysis demonstrated a statistically significant reduc- RESULTS: A total of 25 patients answered a mean 8.4 ( 8.2) PROs from 6 tion in SABA use and an increase in SABA-free days among Medicaid- app download to 2 weeks and a mean 2.1 ( 4.4) PROs from 2- to 4 weeks. enrolled children in a digital asthma intervention in southwest Detroit. Four phenotypes were identified: never engaged (4, 16%); low engagers with subsequent decrease (10, 40%); late engagers (low engagers with Are Caregivers Of Pediatric Patients With subsequent increase) (4, 16%); and high engagers with subsequent 158 Asthma Willing To Use Telemedicine To disengagement (7, 28%). Of those who never engaged, 3 (75%) had a Prevent Emergency Room Visits? high school diploma or lesser education and reported improved satisfaction between baseline and 4 week (p < 0.03). For the late engagers, 3 (75%) Jully Padam1; 1BronxCare. were tech school or college graduates. For the high engagers with RATIONALE: The probability to use telemedicine is related to level of subsequent disengagement, satisfaction improved between baseline and education, age and previous experience with technology. However, we 4 week (p < 0.03). would like to know if these conclusions can be extrapolated to South Bronx CONCLUSIONS: Phenotyping e- health users regarding engagement Population, an inner-city community with polyculture background and over time, rather than simply a single metric such as total app usage time, epicenter nationwide of asthma, seeking for an alternative of Asthma care allows for opportunities in delivering personalized push notification to decrease the load on emergency department. content and assessing differences in clinical outcomes among different METHODS: Survey provided to caregivers of children and adolescent subtypes. between 1 to 21 years of age with previous diagnosis of asthma who were consulting to Bronx Care Pediatrics Emergency Department due to Acute Asthma Exacerbation. Survey was designed to assess Asthma exacerbation understanding, severity of the exacerbation at time of the visit, medication compliance, accessibility to physician follow up, access to technology at home, familiarity with telemedicine, and level of education and likelihood to use telemedicine as part of Asthma care. RESULTS: Most of our surveyed population were from Hispanic background (66.7%) followed by African American background (30.3%) and the remainder were Caucasian and Asiatic background. Our patient pool consisted of patients with age less than 10 years (54.4%) with a second peak (27.27%) between the ages 11 to 15 years. 72.7% of our patient had a mild asthma exacerbation at the time of ED visit as per PASS (between 0 to 2). It was remarkable to find that 100 % of our population had smartphones and 66% had other type of technology at home including full wi-fi access. AB52 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

(1) DNA methylation biomarkers in nasal and detection of Human Rhinovirus (GAM P50.012 Baseline, P50.003 160 epithelium for severe asthma in children respiratory illness). In baseline samples adjusted for season, time to respiratory Illness or exacerbation related to the presence of Tao Zhu1, Xue Zhang, PhD2, Xiaoting Chen, PhD2, Anthony Brown1, Staphylococcus or Corynebacterium which delayed respiratory events, Matthew Weirauch, PhD2, Theresa Guilbert, MD, MS3, Gurjit Khurana and Haemophilus, which associated with more imminent illness and exac- Hershey, MD PhD FAAAAI2, Jocelyn Biagini Myers, PhD3; 1California erbation. In season and age adjusted analysis, interactions during respira- National Primate Research Center, University of California Davis, 2Cin- tory illness events between the exacerbation-associated SMAD3 cinnati Children’s Hospital Medical Center, 3Cincinnati Children. transcriptional module and a bacterial network primarily comprised of RATIONALE: Severity assessment is essential for asthma management. Streptococcus and Haemophilus increased risk of exacerbation DNA methylation (DNAm) plays a critical role in asthma pathogenesis. (OR514.71, P50.02). The purpose of this study was to identify nasal epithelial DNAm CONCLUSIONS: Upper airway microbiota co-vary with seasonal trends differences associated with asthma severity in children and explore the in respiratory illness and asthma exacerbation. Specific microbial-host effect of environmental exposures. interactions at baseline or during respiratory illness events influence risk of METHODS: This study included 33 non-severe and 22 severe asthmatic exacerbation. children. Nasal epithelial DNA methylation modification (all children) and gene expression (17 children) were analyzed. The correlation between Endogenous hydrogen sulfide is directly DNAm and gene expression was assessed. Computational approaches were 162 correlated with age and inversely correlated performed to evaluate the enrichment of binding of transcription factors with intensive care length of stay in children (TFs) and histone modifications. Differentially methylated CpG positions with respiratory syncytial virus (RSV) (DMPs) associated with environmental exposures and predictive of severe bronchiolitis asthma were explored. Jose Rojas-Camayo1, Nadiya Druzhyna1, Antonella Casola1, Roberto RESULTS: We found 816 DMPs and 10 differentially methylated regions 1 1 associated with asthma severity. The DNAm levels of 39 DMPs Garofalo ; University of Texas Medical Branch. significantly correlated with gene expression. Three DMPs that predict RATIONALE: Hydrogen sulfide (H2S) is an endogenous gasotransmitter asthma severity were identified. Out of 816 DMPs, 11 DMPs were that is involved in the regulation of important physiological functions in the associated with exposure to air pollution and 16 DMPs were associated respiratory tract. We have recently described previously unknown antiviral with exposure to secondhand smoke. Six DMPs were simultaneously properties of H2S in RSV-infected airway epithelial cells and mice, but its associated with asthma status, allergy asthma, total IgE, environment IgE, role in naturally-acquired RSV infections remains to be determined. 5 and fractional exhaled nitric oxide (FeNO) in an independent cohort of METHODS: Children <24 months of age (n 63) hospitalized due to children. Around the 816 DMPs, 3 histone marks and several TFs known to RSV bronchiolitis were enrolled and nasopharyngeal secretions (NPS) be involved in asthma were enriched. were collected for H2S measurement by an analytic method based on the CONCLUSIONS: DNAm marks in nasal epithelium were associated with fluorogenic probe 7-azido-4-metthylcouramin. Clinical data were asthma severity in children and some marks were also associated with collected and disease severity was categorized, including need for inten- clinical characteristics in previous studies. As promising markers for sive care. Age in all admitted patients and length of stay in intensive predicting severity, these DMPs may be influenced by environmental care were correlated with H2S levels. Spearman’s Rho was used for statis- exposures and regulate gene expression. tical analysis. RESULTS: In all 63 patients admitted due RSV bronchiolitis, age was

Upper Airway Microbiota Relates to Season and directly correlated with H2S levels measured in NPS (rho 5 0.380, 161 Asthma Exacerbations p50.02). In 18 patients who required intensive care, length of stay in the pediatric intensive care unit was inversely correlated with H2S levels Kathryn McCauley1, Kaitlin Flynn, PhD2, Vincent DiMassa, MPH1, (rho 5 -0.490, p5 0.039). Douglas Fadrosh1, Kole Lynch1, Petra LeBeau, ScD3, Agustin CONCLUSIONS: In patients admitted with RSV bronchiolitis, infants 4 3 5 Calatroni, MA MS , Brett Jepson , Michelle Gill, MD PhD , James and younger children have lower H2S levels, and in those requiring inten- 6 6 7 Gern, MD , Dan Jackson, MD FAAAAI , Matthew Altman, MD , Susan sive care lower H2S levels were correlated with longer intensive care stay. 8 1 2 Lynch, PhD ; University of California, San Francisco, Benaroya H2S in the airways may have a protective role against severe RSV lower Research Institute, 3Rho, Inc., 4Rho Federal Systems Division, inc., 5UT respiratory tract infections in children. Southwestern Medical Center at Dallas, 6University of Wisconsin-Madi- son, 7University of Washington, 8Asthma, Immunology & Allergy Assoc. RATIONALE: Seasonal variation in respiratory illness and exacerbation in pediatric populations with asthma is well described but poorly under- stood. We hypothesized that nasal microbiota covaries with seasonal clinical trends and that season-specific microbial-host interactions during respiratory illness influence risk of exacerbation. METHODS: Bacterial (16S rRNA) and fungal (ITS2) profiling was performed on longitudinally collected nasal secretion samples from children with asthma during periods of pulmonary health (Baseline, n594 samples) and their first subsequent respiratory illness (n597). Data were analyzed in conjunction with extant clinical and nasal transcriptional modules using R. Generalized linear (mixed) models were utilized to identify seasonal differences in incidence or microbiota composition (P<0.05). RESULTS: Exacerbation and respiratory illness events co-varied simi- larly with season [Generalized Additive Mixed Models (GAMM) P50.039, P5<0.001, respectively]. So too did upper airway bacterial [Generalized Additive Model (GAM) P50.001 baseline, P50.016 respi- ratory illness] and fungal (GAM P50.006 respiratory illness) composition J ALLERGY CLIN IMMUNOL Abstracts AB53 VOLUME 147, NUMBER 2

Association of the Gut Microbiome and de Bruxelles, Brussels, Belgium, 6Chest Diseases Department;Federation 163 Metabolome with Wheeze Frequency in of translational medicine EA 3070;ALYATECÒ, Strasbourg, France. Childhood Asthma RATIONALE: It has been suggested that Treg were deficient in allergic asthma. Our aim was to characterize Treg response after Kathleen Lee-Sarwar1, Sandra Dedrick2, Babak Momeni2, Rachel Dermatophagoides pt. (Dpt) challenge in mite allergic asthma. Kelly1, Robert Zeiger, MD PhD FAAAAI3, George O’Connor4, Megan METHODS: 20 GINA I asthmatics, allergic to mite were exposed to Dpt Sandel5, Leonard Bacharier, MD FAAAAI6, Avraham Beigelman, MD (46ng/m3 of Derp1) and placebo (pcb) in an Environmental Exposure MSCI FAAAAI6, Nancy Laranjo1, Diane Gold, MD1, Jessica Lasky- Chamber (AlyatecÒ). Early (EAR, 20% drop in FEV1) and Late Su1, Augusto Litonjua, MD MPH7, Yang-Yu Liu1, Scott Weiss, MD Asthmatic Response (LAR, 15% drop in FEV1) were assessed. Blood sam- MS8; 1Channing Division of Network Medicine, Brigham and Women’s ples were collected before and 6h after exposure. Treg Hospital and Harvard Medical School, Boston, MA, USA, 2Boston Col- (CD4+CD25++FoxP3+) and their molecules implicated in the function lege, Department of Biology, Chestnut Hill, MA, USA, 3Departments of (ICOS, PD1 and CD39) and in the lung recruitment (CCR4) of Treg Allergy and Research and Evaluation, Kaiser Permanente Southern Cali- were measured by flow cytometry (FACSAriaÒ). Subjects were catego- fornia, San Diego and Pasadena, CA, USA, 4Pulmonary Center and rized in 3 groups according asthmatic response: EAR, Dual or no asthma. Department of Medicine, Boston University School of Medicine, Boston, RESULTS: 13 subjects exhibited a dual, 4 EAR and 3 no asthmatic MA, USA, 5Department of Pediatrics, Boston Medical Center, Boston, response. No change was observed for Treg (%CD4). PD1, CCR4 and MA, USA, 6Division of Pediatric Allergy, Immunology and Pulmonary CD39 (%Treg) increased (p <_0,05) after Dpt as well as after pcb. The CCR4 Medicine, Department of Pediatrics, Washington University School of and CD39 increase was higher after Dpt (p<_0,05) vs pcb. No difference Medicine, St Louis, MO and St Louis Children’s Hospital, St Louis, according to asthmatic response (A, D, N) was observed. At T0, dual MO, USA, 7Division of Pediatric Pulmonary Medicine, Golisano Chil- responders exhibited higher CCR4 levels on Treg compared to non- dren’s Hospital at Strong, University of Rochester Medical Center, Ro- responders (p<0.05). Methacholine PD20 was inversely correlated with chester, NY, USA, 8Channing Division of Network Medicine, Brigham CD39+Treg (Pearson coefficient: -0.4 et p<0.01). and Women’s Hospital and Harvard Medical School, Boston, MA, USA. CONCLUSIONS: Mite exposure induced an increase of expression of RATIONALE: While the gut microbiome has an established role in molecules on Treg with suppressive function (CD39) and implicated in the asthma development, less is known about its contribution to morbidity in lung migration (CCR4). Dual responders exhibited more CCR4 on Treg at children with asthma. In this ancillary study of the Vitamin D Antenatal baseline. Our results suggest that there was no deficit of expression of Asthma Reduction Trial (VDAART), we analyzed the gut microbiome and recruitment and function markers. metabolome of wheeze frequency in children with asthma. METHODS: Microbiome profiling by 16S rRNA gene sequencing and CXCL1 Levels as a Biomarker of Systemic metabolomic profiling by mass spectrometry were performed on fecal 165 Inflammation in Severe Asthma samples collected from 3 year-olds with parent-reported doctor-diagnosed 1 1 asthma. We tabulated the proportion of quarterly questionnaires in which Galyna Yeryomenko , Tetyana Bezditko , Lawrence Dubuske, MD FAAAAI2; 1Kharkiv National Medical University, Kharkiv, Ukraine, parents/guardians reported wheeze between months 39 and 63 of life 2 (‘‘wheeze proportion’’). Associations of bacterial taxa with wheeze George Washington University School of Medicine, Washington, DC, proportion were tested in negative binomial regression models including USA, Immunology Research Institute of New England, Gardner, MA, potential confounders and associations of metabolites with wheeze USA. proportion were tested in correlation, linear regression and pathway RATIONALE: This study assesses the activity of systemic inflammation analyses. Microbe-metabolite and microbial correlation networks were by evaluating the level of fractalkine CX3CL1 (Fr) in patients with asthma constructed. (As) alone or in combination with diabetes mellitus type 2 (DM2T). RESULTS: In 111 children with asthma, several bacterial taxa were METHODS: 49 patients (Pts) with severe As were assessed, divided into: associated with wheeze proportion. Among those with higher wheeze Group (Gr) 1 Pts with isolated As (18 Pts) and Gr 2 had As + DM2T (22 proportion, Veillonella spp. were enriched (log2FoldChanges: 3.1 for V Pts). The control Gr included 9 volunteers. Fr levels were measured. dispar (FDR 5 0.01); 3.2 for V parvula (FDR 5 0.01); 3.1 for unidentified RESULTS: In Gr 1, the median level of Fr was 47.00 ng / ml; in Gr 2 – Veillonella spp. (FDR 5 0.02)) and Bifidobacterium longum was depleted 99.60 pg / ml, and in the control Gr - 45.11 [42.83; 45.75] pg / ml. Analysis (log2FoldChange -2.1, FDR 5 0.01). Histidine pathway metabolites were of duration of AS and Fr level showed a relationship in pts with As history enriched in those with higher wheeze proportion (p<0.05 using two more than 10 years (p <0.01). Changes in Fr during the period of different pathway analysis methods). V dispar and V uniformis correlated exacerbation and onset of exacerbation duration revealed an average value 6 with each other and with numerous metabolites. of 95.3 7.58 pg / ml for the As group, with Fr a prognostic marker for CONCLUSIONS: Gut microbiome features are associated with wheeze onset duration. Levels of Fr in As patients is statistically significant (p frequency in children with asthma, suggesting an impact of the gut <0.001) exceeding the levels in the control Gr. There was a progressive microbiome on morbidity in childhood asthma. increase in the level of Fr with addition of comorbidity in the Gr of patients with concomitant DM2T, being 2.2 times greater compared to control Gr. EEC exposure to mite in allergic asthma induces CONCLUSIONS: CX3CL1 levels are increased in As with DM and are 164 an increase of function and recruitment indicative of exacerbation and increase with durations of exacerbation of molecules on blood Treg. AS.

Virginie Doyen1, Anh Poirot2, Myriam Maumy-Bertrand3, Nathalie Do- mis4, Naji Khayath2, Francis Corazza5, Frederic De Blay6; 1Clinic of Im- muno-Allergology, CHU-Brugmann, Brussels, Belgium, Translationnal Laboratory Research, ULB223, Universite Libre de Bruxelles, Brussels, Belgium, 2Chest Diseases Department, Strasbourg University Hospital, Strasbourg, France, 3Advanced Mathematics Research Institut (IRMA), Strasbourg, France, 4ALYATECÒ Environmental Exposure Chamber, Strasbourg, France, 5Immunology Laboratory, CHU Brugmann, Brussels, Belgium, Translationnal Laboratory Research, ULB223, Universite Libre AB54 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Interleukin-26 is a Novel Biomarker for Asthma values were obtained: 9.5 (7.1; 11.8) pg /ml versus 3.7 (2.9; 4.4) pg /ml 166 Inflammation Associated with Systemic versus the control group ( p 5 0.039). Inflammation and Lung Function in Obese CONCLUSIONS: Levels of IL-13 can be marker of allergic inflammation Asthmatics in patients with FA. Increase of IL-13 may have special value for FA patients with normal total IgE serum levels. Igor Kaidashev1, Yanina Avramenko1, Olga Izmailova1, Oksana Shly- kova1, Lawrence Dubuske, MD FAAAAI2; 1Ukrainian Medical Stomato- Vagal sensory neurons sense allergens to logical Academy, Poltava, Ukraine, 2George Washington University 168 regulate Type 2 inflammation School of Medicine, Washington, DC, USA, Immunology Research Insti- Theo Crosson1, JO-CHIAO WANG2, Katiane Roversi3, Tuany Eich- tute of New England, Gardner, MA, USA. 3 3 3 3 RATIONALE: IL-26 is a potential biomarker of inflammation in wald , Mohammad Balood , Maryam Ahmadi , Sebastien Talbot, PhD ; 1 2 3 asthmatics. Universite de Montreal, University of Montreal, Universitede METHODS: The study included 10 healthy subjects (controls), 10 obese Montreal. subjects without lung pathologies, 10 non-obese asthmatics (NOA) (BMI – RATIONALE: Vagal sensory neurons were previously shown to amplify 18.5–24.9 kg/m2), and 40 obese asthmatics (OA) (BMI – 25.0–49.9 kg/ lung immune cell activity in response to inhaled antigens through the m2). Spirometry with reversibility and both exhaled breath condensate release of neuropeptides. However, the cellular mechanisms by which (EBC) and blood samples collected. IL-26, interleukin-4 (IL-4), inter- these sensory neurons are activated after allergen exposure are unknown. leukin-10(IL-10), and high sensitive C reactive protein (hs-CRP) were Here, we investigate the ability of vagal nociceptors to directly sense measured by ELISA. Receiver Operating Characteristic (ROC) area under allergens through the Fc?R1 receptor. the curve (AUC) was used assessing IL-26 as a biomarker. METHODS: We used Calcium Imaging, In Situ Hybridization, and RT- RESULTS: NOA had reversible airway obstruction, reduced FEV1, qPCR to assess the functional expression of the Fc?R1 in vagal sensory neurons in na€ıve mice and allergen sensitized mice. We also knocked out of FEV1/FVC, FVC 25/75, and positive post bronchodilator test (PBT), + significantly increased serum levels of IL-10, IL-4, and slightly increased the Fc?R1g specifically in TRPV1 neurons to investigate the role of the IL-26, with significantly increased exhaled IL-26 versus controls. The neuronal Fc?R1/IgE signaling in House dust mites and Ovalbumin models obese subjects had normal spirometry without obstruction, or differences or allergic airway inflammation. in serum IL-26, IL-10, and IL-4 versus controls but significantly increased RESULTS: The number of neurons expressing functional Fc?R1 € hs-CRP with no difference in exhaled IL-26, IL-10, and hs-CRP versus increased from 4% in naıve to 11% in ovalbumin sensitized mice, with controls. OA had reduced FEV1, FEV1/FVC, and FEV25–75 versus NOA mRNA level of Fcer1g in FACS sorted nociceptors increasing by 8-fold. In with elevated IL-26, IL-10, IL-4, and hs-CRP versus controls with partial addition, knocking out the receptor in sensory neurons significantly similarity with both NOA (elevated IL-26, IL-10, and IL-4) and obese reduced the infiltration and activation of leucocytes in bronchoalveolar subjects (elevated hs-CRP). OA had reduced exhaled IL-26 versus NOA fluid compared to wild type mice in both mouse models of allergic airway and elevated exhaled IL-10 versus obese subjects. Exhaled IL-26 inflammation. distinguished NOA from controls, ROC analysis (area: 0.9700) showed CONCLUSION: We conclude that targeting Fc?R1/IgE signaling on 100% sensitivity/ 80% specificity; asthmatics versus non-asthmatics; and sensory neurons is a relevant approach to treat allergic airway (area: 0.9620) showed 94% sensitivity and 80% specificity distinguishing inflammation. all asthmatics from non-asthmatics (area: 0.9280) showing 94% sensitivity /80% specificity. CONCLUSIONS: IL-26 is novel biomarker for asthma inflammation.

Interleukin-13 as a Marker of Allergic 167 Inflammation in Patients with Fungal Asthma

Tatyana Novikova1, Eduard Dotsenko1, Lawrence Dubuske, MD FAAAAI2; 1Belorussian State Medical University, Minsk, Belarus, 2George Washington University School of Medicine, Washington, DC, USA, Immunology Research Institute of New England, Gardner, MA, USA. RATIONALE: Fungal asthma (FA) is characterized by frequent exacer- bations, rapidly growing irreversible changes in distal bronchi with 10% of FA failing inhaled glucocorticosteroids requiring systemic steroids. Immune markers of FA are needed. METHODS: 104 patients of Minsk Regional Clinical Hospital were assessed for FA including allergy skin testing, allergen specific IgE antibodies by immunoblotting , serum total IgE and interleukin (IL) -13 by ELISA. RESULTS: FA patients showed increased sensitivity to both one or several fungi allergens. About half of the FA patients with confirmed fungal sensitization (48 %) had a combination of fungal sensitization with other types of sensitization. A combination of fungi and house dust mite sensitization occurred most often, but there was also a combination of increased sensitivity to fungi and pollen and animal allergens. About 23% of sensitized patients had normal levels of total IgE 78 (65.7;92.8) ME/ml. In patients with combined sensitization and normal total IgE, higher IL-13 J ALLERGY CLIN IMMUNOL Abstracts AB55 VOLUME 147, NUMBER 2

(1) Associations of PAI-1 Promoter 14(35.5) cells/mL(p<0.001) at t4 and even significant improvements in 169 Polymorphism and African Ancestry with lung function were recorded from median FEV1(IQR) 64.5(32.0)% at t0 to Asthma in the GALA2 cohort 93.0(38.75 )% at the 4-month assessment (p<0.001). No adverse events were recorded for mepolizumab over the 16-week study period. Joong Cho1, Angel Mak, PhD2, Donglei Hu, PhD2, Sam Oh, PhD MPH2, CONCLUSIONS: Mepolizumab therapy effectively resulted in signifi- Scott Hunstman, MS2, Celeste Eng, BS2, Harold Farber, MD, MSPH3, cant early clinical and biological outcomes in a selected cohort of patients William Rodriguez-Cintron, MD4, Denise Serebrisky5, Shannon with type 2 inflammation severe asthma in a real-world setting. Whether Thyne, MD6, Luisa Borrell, DDS, PhD, MPH7, Jose Rodriguez- these responses are safe and sustained over time, still remains to be Santana, MD8, L. Keoki Williams, MD MPH FAAAAI9, Max assessed in subsequent real-word investigations. Seibold, PhD10, Esteban Burchard, MD2, Rajesh Kumar, MD FAAAAI11; 1Ann and Robert H. Lurie Children, University of Illinois College of Med- Steroid Stewardship – Survey Results & icine, 2UnivCrsity of California, San Francisco, 3Texas Children, 4Veter- 171 Awareness Strategies 5 ans Caribbean Health Care System, Jacobi Asthma and Allergy for 1 1 1 Chi, 6UCSF School of Medicine, 7Lehman College, City University of Jackie Eghrari-Sabet , Tonya Winders ; Allergy & Asthma Network. New York, 8Centro de Neumologia Pediatrica, 9Henry Ford Health Sys- RATIONALE: The most common treatment for severe asthma is the tem, 10National Jewish Health, 11Ann & Robert H. Lurie Children. prescription of oral corticosteroids (OCS) but even short-term low-dose RATIONALE: Plasminogen activator inhibitor-1 (PAI-1) promoter vari- use of OCS can result in serious health problems. Side effects are ants and African ancestry both are associated with asthma. We evaluated significant in both short-term and long-term use and are pronounced in the independent and joint effects of a gain of function (GOF) PAI-1 pro- disparate communities. moter variant and African ancestry on asthma odds. METHODS: Key messages have been developed by an interprofessional METHODS: Latinx subjects aged 8-21 years (1736 with asthma and 1747 work group to address the OCS stewardship issues.An additional healthy controls) from the GALA2 study were classified using African Awareness Campaign has been developed to address the need to educate ancestry dichotomized at the 5th quintile. The variant (rs1799768) was patients on the side effects of long-term steroid use. dichotomized as wild type (GG) or risk allele (either heterozygous AG RESULTS: Key messages address people with asthma in minority or low- or homozygous AA). Using logistic regression, we evaluated the indepen- income communities related to outcomes, death rates and emergency room dent and joint effects of a PAI-1 GOF polymorphism and African ancestry visits and may be worse during the flu season with the presence of COVID- proportion on asthma odds, controlling for confounding variables 19.Messaging also contains that while OCS can be an important tool in RESULTS: Subjects were 50% male, 13.2 (SD 3.5) years old, and had care, during COVID-19, their use may prevent hospitalization and stresses mean African ancestry proportion of 0.14 (SD 0.12). Compared to those the importance of primary care or specialist care. with the wild type and African ancestry at the 1st-4th quintile, subjects at the CONCLUSIONS: OCS has historically been overused, with significant top 5th quintile of African ancestry and the risk genotype had an increased side effects in an already vulnerable population.With awareness and odds of asthma (OR: 1.47, p 5 0.003). Neither subjects with the risk geno- stewardship, asthma treatment can meet patient needs and provide healthy type and at the lower quintiles (OR51.07, P50.39) nor those with the high- outcomes for every patient, regardless of race, geographic location or est quintile of African ancestry and wild type genotype (OR 1.11, p50.50) income. had an increased odds of asthma. In subgroup analysis, Puerto Rican sub- jects with the risk genotype and elevated ancestry retained this association (OR: 1.43, p 5 0.035) but Mexican subjects with lower mean African ancestry did not. CONCLUSIONS: A GOF promoter variant in PAI-1 and higher African ancestry proportion was synergistically associated with an increased odds of asthma.

Real-World Rapid Response to Mepolizumab in 170 the Uncontrolled T2 Severe Asthma Endotype

Ruperto Gonzalez Perez, MD PhD1, Paloma Poza-Guedes, MD, PhD1, Elena Mederos-Luıs1, Victor Matheu-Delgado, MD, PhD1, Cristina Alava-Cruz 1, Inmaculada Sanchez-Machın1; 1Hospital Universitario de Canarias. RATIONALE: Real-world data are lacking on the impact of mepolizumab in patients with Type 2 inflammation-driven severe asthma (SA). Herein, we assessed the prompt effect -16-weeks after initiation- of mepolizumab over a selected SA cohort in a real-world setting. METHODS: We selected 17 non-consecutive patients with polarized type 2 severe uncontrolled asthma according to the GINA Guidelines. Patient demographics, medical history, asthma diagnosis, exacerbation history, medication use and health care resource demand were recorded. Patients completed the, Asthma Control Test (ACT). Spirometry (prior to starting mepolizumab), atopic status (total serum IgE, skin prick test/ImmunoCAP assay, blood eosinophil level) were recorded. Outcome data were collected at 4-months post-commencement of mepolizumab including change in ACT, medication use, lung function and blood eosinophil levels. RESULTS: Patients reported a significant improvement in symptom control (ACT increase), from ACT median (IQR) 13.5(5) at baseline (t0) to 22.0(7) at the 4-month (t4) follow-up. Blood eosinophil levels were significantly reduced from median (IQR) 800(360) cells/mLatt0to AB56 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Efficacy of Omalizumab against Aspirin- age at mepolizumab initiation (index date), >_2 mepolizumab administra- 172 hypersensitivity and Overproduction of tions 6 months post-index, >_12 months of continuous enrollment before Cysteinyl Leukotrienes in Aspirin-exacerbated (baseline) and after (follow-up) the index date, and a medical claim for one Respiratory Disease: A Randomized Trial of the pre-specified comorbidities during baseline. Asthma exacerbations and OCS-use were compared between baseline and follow-up periods for Hiroaki Hayashi, MD1, Yuma Fukutomi, MD2, Chihiro Mitsui, MD2, Keii- each of the non-mutually exclusive comorbid subgroups. chi Kajiwara, BSc2, Kentaro Watai2, Yosuke Kamide, MD PhD2,Maki RESULTS: Patient subgroups were identified with the following comor- Iwata, MD2, Kisako Nagayama2,YutoNakamura,MD2, Yuto Hamada2,Ya- bidities: Atopy (N5468); Obesity (N5171); Depression/Anxiety suhiro Tomita, MD PhD1, Kiyoshi Sekiya2, Takahiro Tsuburai, MD PhD3, (N5173). After initiating mepolizumab, the mean rate of exacerbations Akio Mori, MD PhD2, Kenji Izuhara4, Keiko Wakahara, MD PhD5,Nao- was reduced in all groups: 48% in atopy, 52% in obesity, 38% in zumi Hashimoto, MD PhD5, Yoshinori Hasegawa, MD PhD5,MasamiTa- depression/anxiety (p<0.0001). All subgroups also had significant de- niguchi, MD, PhD6; 1Clinical Research Center, National Hospital creases in mean number of OCS claims (atopic 33%; obesity 38%; Organization Sagamihara National Hospital and Department of Respiratory depression/anxiety 31%; p<0.001) and OCS bursts (atopic 40%; obesity Medicine, Nagoya University Graduate School of Medicine, 2National Hos- 48%; depression/anxiety 37%; p<0.001) compared to baseline. pital Organization Sagamihara National Hospital, 3St. Marianna University CONCLUSIONS: This study demonstrates that patients with asthma and School of Medicine, 4Saga Medical School, 5Nagoya University Graduate atopy, obesity or depression/anxiety have significantly fewer exacerbations School of Medicine, 6Clinical Research Center, National Hospital Organi- and reduced OCS use in a real-world setting following treatment with zation Sagamihara National Hospital and Shonan Kamakura General Hos- mepolizumab. Holistic patient care for severe asthma is critical and pital Center for Immunology and Allergology. mepolizumab provides tangible clinical benefit despite the complexities of RATIONALE: Aspirin-exacerbated respiratory disease (AERD) is charac- medical comorbidities. terized by severe asthma, nonsteroidal anti-inflammatory drugs (NSAIDs)- hypersensitivity, nasal polyposis, and leukotriene overproduction. The most Impact of baseline clinical asthma important pathogenesis of AERD is mast cell activation and serious 174 characteristics on the response to eosinophilic inflammation in the respiratory tract. Lifelong NSAIDs-hyper- mepolizumab: a post hoc meta-analysis of two sensitivity cannot be completely suppressed by systemic corticosteroid therapy. Phase III trials Omalizumab, anti-IgE antibody, strongly suppresses the activation of mast Mark Liu, MD FAAAAI1, Camille Taille2, Jason Lee, MD FAAAAI3, cells and eosinophils. Therefore, we hypothesized that omalizumab would 4 5 6 suppress leukotriene overproduction and induce NSAIDs tolerance in AERD. Steven Smith, PhD MSc , Steve Mallett, MSc , Neil Martin, MD , Peter Howarth, MD6, Steven Yancey, MS MBA4, Catherine Lemiere, MD METHODS: We performed a double-blind, randomized, crossover, 7 1 placebo-controlled, single-center study at Sagamihara National Hospital MSc ; Pulmonary and Critical Care Medicine, Johns Hopkins Asthma 2 ^ (Kanagawa, Japan) between August 2015 and December 2016. Allergic and Allergy Center, Baltimore, MD, USA, Hopital Bichat, AP-HP- 3 patients aged 20–79 years with AERD diagnosed by systemic aspirin Nord, Universite de Paris, F-CRIN CRISALIS, Paris, France, Toronto Al- lergy and Asthma Clinic, Toronto, ON, Canada, 4GSK, Research Triangle challenge were randomized (1:1) to a 3-month treatment with omalizumab 5 6 or placebo, followed by at least an 18-week washout period as a crossover Park, NC, USA, GSK, Stockley Park, Uxbridge, Middlesex, UK, GSK, 7 design. The primary endpoint was the difference in area under the Brentford, Middlesex, UK, Universite de Montreal, Montreal, QC Can- ada, Hopital^ du Sacre-Cœur de Montreal, Montreal, QC Canada. logarithm level of urinary leukotriene (LTE4) concentration vs time curve RATIONALE: Severe asthma is associated with a broad range of (AUC[Before-24h]) during oral aspirin challenge. phenotypes. We assessed whether select baseline clinical characteristics RESULTS: Sixteen patients completed the study. AUC(Before-24h) of uri- could influence the efficacy of mepolizumab in patients with severe nary LTE4 during oral aspirin challenge was significantly lower in the oma- lizumab phase than in the placebo phase [median interquartile range, 51.1 eosinophilic asthma (SEA). (44.5–59.8) vs 80.8 (65.4–87.8)] (p<0.001). Ten patients (62.5%) devel- METHODS: This was a post hoc meta-analysis of data from the Phase III _ _ oped oral aspirin tolerance up to cumulative doses of 930 mg in the oma- MENSA and MUSCA studies. Patients aged >12yrs with SEA and >2 lizumab phase (p<0.001). No severe adverse events, including exacerbations were randomized to 4-weekly placebo or mepolizumab 100 anaphylaxis, occurred. mg subcutaneously for 32/24 weeks (MENSA/MUSCA). We assessed: annual rates of clinically significant exacerbations (primary endpoint); CONCLUSIONS: Omalizumab treatment inhibited urinary LTE4 over- production and respiratory tract symptoms during oral aspirin challenge, proportions of patients achieving complete asthma control (Asthma resulting in aspirin tolerance in more than 50% of patients with AERD. Control Questionnaire [ACQ]-5 score <0.75); changes from baseline in pre-bronchodilator forced expiratory volume in 1 second (FEV1), St Managing Patients with Severe Asthma and George’s Respiratory Questionnaire (SGRQ) total score, and ACQ-5 score. 173 Common Comorbidities of Atopy, Obesity & Analyses were performed by: age at asthma onset (<18/18–40/>_40 years); _ Depression/Anxiety: Real-world Effectiveness lung function (% predicted FEV1 <60/60–80/>80%), airway reversibility _ of Mepolizumab (>12/<12% change in FEV1), and asthma control (uncontrolled vs par- tial/complete control [ACQ-5 score >_1.5/<1.5]) at baseline. Nestor Molfino, MD MSc1, Thomas Casale, MD FAAAAI2, Jared RESULTS: Overall, 936 patients received mepolizumab or placebo. Silver, MD; PhD1, Michael Bogart, PharmD1, Elizabeth Across age, lung function, and airway reversibility subgroups, mepolizu- 3 3 3 1 Packnett, MPH , Donna McMorrow, BS , Juan Wu, ScD , Beth Hahn ; mab reduced exacerbation rates by 49–63% versus placebo. FEV1, SGRQ 1GlaxoSmithKline, 2University of South Florida, 3IBM Watson Health. total score, and ACQ-5 score were also improved with mepolizumab versus RATIONALE: Mepolizumab has been shown to improve severe asthma placebo across the majority of age and lung function subgroups. Patients control in clinical trials. However, physicians treat holistically and were more likely to achieve complete asthma control with mepolizumab consider comorbid conditions when selecting therapy. Atopy, obesity, versus placebo, irrespective of baseline asthma control (odds ratio mepoli- and depression/anxiety affect patients with asthma at an increased rate, yet zumab/placebo [95% confidence interval]: 2.28[1.47,3.54] and 2.31 few studies have examined asthma therapy with these comorbidities. This [1.38,3.87] for baseline ACQ-5 scores >_1.5 and <1.5). study examined the impact of mepolizumab in patients with severe asthma CONCLUSIONS: Mepolizumab is beneficial for patients with SEA who and atopy, obesity or depression/anxiety. have a broad range of baseline clinical characteristics. METHODS: Retrospective claims database analysis of patients with FUNDING: GSK (meta-analysis: 208115[MEA115588/NCT01691521; commercial/Medicare supplemental insurance with asthma, >_12 years of 200862/NCT02281318]). J ALLERGY CLIN IMMUNOL Abstracts AB57 VOLUME 147, NUMBER 2

_ Treatment with Tezepelumab Reduces Serum (pre-bronchodilator forced expiratory volume in 1 second [FEV1] >30%, 175 Interleukin (IL)-5 and IL-13 in Patients with <85% predicted; Asthma Control Questionnaire [ACQ]-6 score >_1.5). Severe, Uncontrolled Asthma to Levels Prespecified subgroup analyses of change from baseline in trough FEV1 Approaching those Observed in Healthy (Week 24) and annualized rate of moderate/severe exacerbations (Weeks Individuals 1–52) were conducted in patients with BMI <30 (non-obese) and >_30 kg/m2 (obese) for FF/UMEC/VI 100/62.5/25mcg (n5261/145) versus Tuyet-Hang Pham1, Janet Griffiths, PhD1, Gene Colice, MD2, Jane FF/VI 100/25mcg (n5244/163), and FF/UMEC/VI 200/62.5/25mcg Parnes, MD3, Claudia Chen4, Bill Cook5; 1Translational Science and (n5248/160) versus FF/VI 200/25mcg (n5243/163). Experimental Medicine, Research and Early Development, Respiratory RESULTS: Mean (SD) BMI in the <30 and >_30 kg/m2 subgroups was 25.3 & Immunology, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, (2.94) and 35.8 (5.71) kg/m2, respectively. Similar improvements in trough 2 MD, Late Respiratory & Immunology, BioPharmaceuticals R&D, Astra- FEV1 were observed following addition of UMEC to FF/VI in the non- Zeneca, Gaithersburg, MD, 3Amgen, Thousand Oaks, CA, 4Biometrics, obese and obese subgroups, respectively (124mL [95% CI: 69, 179] and Late Respiratory and Immunology, BioPharmaceuticals R&D, AstraZe- 85mL [14, 155] with FF/UMEC/VI 100/62.5/25mcg versus FF/VI 100/ neca, Gaithersburg, MD, 5Respiratory & Immunology, Bio- 25mcg, and 84mL [29, 140] and 103mL [34, 172] with FF/UMEC/VI Pharmaceuticals Medical, AstraZeneca, Gaithersburg, MD. 200/62.5/25mcg versus FF/VI 200/25mcg). As in the overall population, RATIONALE: In the PATHWAY phase 2b study (NCT02054130), exacerbation rates were lower in both subgroups when UMEC was added tezepelumab significantly reduced exacerbations and inflammatory to FF/VI 100/25mcg, but no additional reductions were observed when biomarker levels in adults with severe, uncontrolled asthma. This post UMEC was added to FF/VI 200/25mcg. hoc analysis evaluated changes in serum levels of IL-5 and IL-13 after te- CONCLUSIONS: The response to FF/UMEC/VI in subgroups defined by zepelumab treatment, relative to levels observed in healthy individuals. BMI was consistent with the overall population, suggesting that obesity METHODS: Adults with severe, uncontrolled asthma were randomized to may not substantially alter treatment response to FF/UMEC/VI. tezepelumab 70mg every 4 weeks (Q4W), 210mg Q4W, 280mg every 2 FUNDING: GSK study 205715/NCT02924688. weeks, or placebo for 52 weeks. Immunoassays were used to determine serum IL-5 and IL-13 levels (measured in pg/mL; Quanterix, Lexington, Pharmacokinetics Of Indacaterol/Mometasone MA) in PATHWAY participants and healthy individuals who were not 177 Furoate In Healthy Chinese Volunteers: Results PATHWAY participants (Bioreclamation, Westbury, NY). Data are From A Randomized, Open-label, Parallel-group reported as mean (6 standard deviation). Study RESULTS: At baseline, serum IL-5 and IL-13 levels were nominally Yun Liu1, Weie Cao1, Yijun Wang1, Soniya Vaidya2, Jian Sun3, Yingying significantly higher in PATHWAY participants than in healthy individuals 3 4 3 1 (p<0.0001). Baseline IL-5 levels were 1.40 (62.84) and 1.14 (61.77) in Wang , Hanns-Christian Tillmann , Chenyu Qian ; Central Laboratory, the tezepelumab 210mg (n5128) and placebo (n5133) groups, respec- Shanghai Xuhui Central Hospital, Shanghai, China, Shanghai Engineering 6 5 Research Center of Phase I Clinical Research & Quality Consistency tively, versus 0.44 ( 0.31) in healthy individuals (n 50). Baseline IL- 2 6 6 Evaluation for Drugs, Shanghai, China, Novartis Institutes for BioMed- 13 levels were 0.06 ( 0.09) and 0.06 ( 0.08) in the tezepelumab 3 5 5 ical Research, Cambridge, MA, United States, China Novartis Institutes 210mg (n 89) and placebo (n 101) groups, respectively, versus 0.02 4 (60.02) in healthy individuals. At week 52, serum levels of IL-5 and IL- for BioMedical Research Co, Ltd, Shanghai, China, Novartis Pharma 13 in placebo patients were similar to baseline levels (IL-5, 1.03 AG, Basel, Switzerland. [61.06], n5120; IL-13, 0.06 [60.10], n593), whereas levels in the teze- RATIONALE: Once-daily indacaterol/mometasone furoate (IND/MF) is pelumab 210mg group were nominally significantly reduced (IL-5, 0.45 an inhaled long-acting b2-agonist/inhaled corticosteroid (LABA/ICS), [60.58], n5112; IL-13, 0.03 [60.03], n580; p<0.0001) and approached recently approved for maintenance treatment of asthma. those observed in healthy individuals. Pharmacokinetics of IND and MF after once-daily oral inhalation of CONCLUSIONS: In patients with severe, uncontrolled asthma, tezepe- IND/MF low- (150/80 mg), medium- (150/160 mg) and high-dose (150/ lumab reduced serum IL-5 and IL-13 to levels approaching those observed 320 mg) for 14 days were assessed in healthy Chinese volunteers. in healthy individuals. METHODS: In this randomized, open-label, parallel group, multiple- dose study, healthy volunteers (n537; 18-45 yrs; body weight, >_50 kg; CAPTAIN: Effects of Body Mass Index (BMI) on BMI, 18–30 kg/m2) received one of three treatments (1:1:1) – IND/MF 176 Response to Triple Therapy in Patients With low-, medium- or high-dose once-daily, via BreezhalerÒ, for 14 days. Inadequately Controlled Asthma on Inhaled Pharmacokinetic parameters of IND and MF following single (Day 1) Corticosteroids/Long-acting b2-agonists (ICS/ and multiple (Day 14) once-daily doses of IND/MF low-, medium- and LABA) high-dose were calculated. RESULTS: In total, 36 volunteers completed study. After single or Diego Maselli1, Sarah Chang, PhD2,AndrewFowler3,MarkLiu,MD multiple inhalations of all doses of IND/MF, IND (Tmax, 0.25–0.38 h) and FAAAAI4, Michael Manning5, David Mannino, MD2, Joseph Spahn, MD6, MF (Tmax, 1–2 h) were rapidly absorbed. Steady state exposures of IND Agne Zarankaite3, Edward Kerwin, MD FAAAAI7; 1University of Texas were similar among all groups; mean Cmax values were 448, 547 and 458 Health at San Antonio, San Antonio, TX, USA, 2GSK, Research Triangle pg/mL and mean AUC0–24h values were 2630, 3000 and 2510 h*pg/mL Park, NC, USA, 3GSK, Stockley Park West, Uxbridge, Middlesex, UK, for the low-, medium-, and high-dose groups, respectively. Steady state 4Johns Hopkins Asthma and Allergy Center, Baltimore, MD, USA, 5Allergy, Cmax and AUC0–24h of MF increased with increasing dose; mean Cmax Asthma and Immunology Associates, Scottsdale, AZ, USA, 6GSK, Research values were 71.7, 146 and 223 pg/mL and mean AUC0–24h values were Triangle Park, NC, USA, 7Crisor LLC Research, Clinical Research Institute 538, 1180 and 1870 h*pg/mL for low-, medium- and high-dose groups, of Southern Oregon, Medford, OR, USA. respectively. RATIONALE: The CAPTAIN study showed that adding umeclidinium CONCLUSIONS: IND and MF were systemically available shortly after (UMEC) to fluticasone furoate/vilanterol (FF/VI) improved lung function inhalation. The absorption rate and exposure of IND were comparable and symptom control in uncontrolled asthma. As response to inhaled across IND/MF low-, medium- and high-dose groups. Those of MF therapy may vary by bodyweight, we evaluated outcomes in CAPTAIN in increased with increasing MF dose. subgroups defined by BMI. METHODS: CAPTAIN was a Phase IIIA, randomized, double-blind, 24–52-week, parallel-group study in adults with uncontrolled asthma AB58 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Which Severe Asthma Patients Are Switching, 100/25mcg (n5206/201), and FF/UMEC/VI 200/62.5/25mcg (n5204/ 178 Stopping, or Continuing Biologic Treatments? 204) versus FF/VI 200/25mcg (n5205/201). RESULTS: Of 2436 patients in the intent-to-treat population, 1181 (48%) 1 2 Weily Soong, MD FAAAAI , Chris Ambrose, MD MBA , Donna Cars- had CV risk. Similar improvements in trough FEV1 were observed in pa- tens2, Frank Trudo, MD2, Wendy Moore, MD3, Reynold Panettieri, tients with/without CV risk, respectively, with FF/UMEC/VI 100/62.5/ MD4; 1Alabama Allergy & Asthma Center, 2AstraZeneca, 3Wake Forest 25mcg versus FF/VI 100/25mcg (108mL [95% CI: 46, 169]; 112mL [51, School of Medicine, 4Rutgers University. 173]), and with FF/UMEC/VI 200/62.5/25mcg versus FF/VI 200/25mcg RATIONALE: With growing use of biologics for severe asthma (SA), we (81mL [20, 142]; 103mL [42, 164]). As in the overall population, exacer- sought to understand factors associated with switching/stopping versus bation rates were lower in both subgroups when UMEC was added to FF/ continuation of biologics. VI 100/25mcg, but there was no clear pattern of response in subgroups METHODS: CHRONICLE is an observational study of US adults with when UMEC was added to FF/VI 200/25mcg. Safety profiles were similar SA. Asthma treatments were collected beginning 12 months before across subgroups. enrollment. We compared demographic and clinical characteristics of CONCLUSIONS: Improvements in lung function occurred following patients enrolled from February 2018–February 2020 receiving biologics addition of UMEC to FF/VI irrespective of CV risk. Effects on moderate/ who switched biologics within a 6-month period, stopped biologic use for severe exacerbation rates were less consistent. >_6 months without switching, or continued biologic use without switching/ FUNDING: GSK (study 205715/NCT02924688). stopping. RESULTS: 1294 patients had 1494 biologic uses (654 omalizumab, 366 Efficacy of oral Dexamethasone versus oral mepolizumab, 307 benralizumab, 119 dupilumab, and 47 reslizumab). Of 180 Prednisone in school-aged asthmatics treated these patients, 134 switched, 101 stopped, and 1222 continued use. Patients in the Emergency Department at an Academic who stopped (vs continued, switched) were younger at diagnosis (mean age Medical Center

25 vs 28, 29 y), more often managed by pulmonologists (60% vs 45%, 1 2 3 48%), more often Medicaid-insured (16% vs 9%, 13%), less often Joseph Howard , Jay Lieberman, MD FAAAAI , Daniel Dibaba, PhD , Qi Zhao, PhD1, Annette Carlisle, MD4; 1University of Tennessee Health employed full-time (34% vs 42%, 46%), and had more asthma-related 2 disability (15% vs 8%, 9%), more maintenance systemic corticosteroid use Science Center, University of Tennessee Health Science Center/ Le Bon- heur Children’s Hospital, 3Tennessee Clinical and Translational Science (27% vs 13%, 19%), and worse Saint George’s Respiratory Questionnaire 4 scores (mean 53 vs 41, 46). Of those who continued (vs switched, stopped), Institute at University of TN Health Science Center, University of Ten- fewer experienced an exacerbation in the prior year (54% vs 69%, 70%), nessee Health Science Center/Le Bonheur Children’s Hospital. and fewer reported daytime (47% vs 58%, 70%) and nocturnal (35% vs RATIONALE: Recent studies suggest oral prednisone (PRED) and 49%, 51%) symptoms. dexamethasone (DEX) are equally efficacious in treatment of asthma CONCLUSIONS: More than 90% of SA patients treated with biologics exacerbation in the emergency department (ED). Furthermore, DEX is continued them. Those continuing less frequently reported exacerbations suggested as potentially superior given improved palatability and fewer and symptoms. Stopping biologics was more common among pulmonol- doses required. Subsequently, our institution transitioned from PRED to ogist-managed patients and was associated with greater disease burden and DEX. We hypothesize that both treatments will be equally efficacious in a lower socioeconomic status. much larger, predominantly African American (AA) population. METHODS: A retrospective review of 2068 charts was conducted on CAPTAIN: Effects of Cardiovascular Risk on patients age 5-18 that presented to the ED for asthma exacerbation and 179 Response to Triple Therapy in Patients With received either PRED or DEX. Demographic information (gender, smoke Inadequately Controlled Asthma on Inhaled exposure, controller medications) was obtained. Primary endpoints Corticosteroids/Long-acting b2-agonists (ICS/ included return to the ED or additional corticosteroid within 14 days. LABA) Secondary endpoints included admission at initial presentation and within 30 days of initial presentation. Statistical analysis was performed using a Nicola Hanania, MD, MS1, Zelie Bailes2, Sarah Chang, PhD3, Andrew logistic regression model adjusted for age, smoke exposure, and atopy. Fowler2, Robson Lima3, David Mannino, MD3, Mark Millard4, Joseph RESULTS: Primary endpoint results showed no statistical difference in Spahn, MD3, Steve Weinstein, MD FAAAAI5, Robert Nathan, MD the association between treatment and need for additional steroid within 14 FAAAAI6; 1Baylor College of Medicine, Houston, TX, USA, 2GSK, days (OR50.94, 95% CI: 0.6-1.48, p 5 0.784). However, secondary Stockley Park West, Uxbridge, Middlesex, UK, 3GSK, Research Triangle endpoint results demonstrated that patients receiving PRED were at a Park, NC, USA, 4Baylor Scott & White Texas Lung Center, Dallas, TX, reduced risk of admission at initial presentation compared to DEX USA, 5Allergy and Asthma Specialists Medical Group and Research Cen- (OR50.55, (0.43, 0.71)). More patients that received DEX were on daily ter, Huntington Beach, CA, USA, 6Asthma & Allergy Associates, P.C. and ICS compared to PRED (33% vs 26%, p<0.0001). Research Center, Colorado Springs, CO, USA. CONCLUSIONS: Findings of this study suggest that oral DEX is equally RATIONALE: In the CAPTAIN study, adding umeclidinium (UMEC) to as efficacious as oral PRED in treating asthma exacerbation in a hetero- fluticasone furoate/vilanterol (FF/VI) improved lung function and symp- geneous, predominantly AA population. tom control in patients with uncontrolled asthma. Here, we evaluate outcomes in subgroups defined by cardiovascular (CV) risk. METHODS: CAPTAIN was a Phase IIIA, randomized, double-blind, 24– 52-week, parallel-group study in adults with uncontrolled asthma (pre- _ bronchodilator forced expiratory volume in 1 second [FEV1] >30%, <85% predicted; Asthma Control Questionnaire [ACQ]-6 score >_1.5). Change from baseline in trough FEV1 at Week 24 (prespecified) and annualized rate of moderate/severe exacerbations (Weeks 1–52; post hoc) were eval- uated in stable patients with/without CV risk at screening (>_1 past/current arrhythmia, congestive heart failure, coronary artery disease, myocardial infarction, cerebrovascular accident, hypertension, diabetes, hypercholes- terolemia) for FF/UMEC/VI 100/62.5/25mcg (n5198/208) versus FF/VI J ALLERGY CLIN IMMUNOL Abstracts AB59 VOLUME 147, NUMBER 2

Corresponding doses of mometasone furoate receive either IND/GLY/MF medium-dose or high-dose via BreezhalerÒ, 181 (MF) in once-daily inhaled fixed-dose once-daily for 14 days. The pharmacokinetic parameters of IND, GLYand combination (FDC) of indacaterol/mometasone MF were calculated by non-compartmental analysis. furoate (IND/MF) and indacaterol/ RESULTS: Of 22 volunteers who completed the study, PK analysis glycopyrronium/mometasone furoate (IND/GLY/ included 20 volunteers (11 in medium-dose group and 9 in high-dose MF): results from randomized clinical studies group) and 2 were excluded due to protocol deviations. At steady state (Day 14), median Tmax was 0.25 h for IND, 0.08 h for GLYand 0.5 h for Roland Buhl1, Huib Kerstjens2, Ivan Nikolaev3, Soniya Vaidya4, Chris- MF. Cmax and AUC0–24h of IND (mean Cmax: 449 and 395 pg/mL; mean tian Bartels3, Monish Jain4, Juergen Jauernig3, Ioannis Kottakis3, Chenyu AUC0–24h: 2340 and 2250 h*pg/mL, for medium-dose and high-dose Qian5, Hanns-Christian Tillman6; 1Pulmonary Department, Mainz Uni- respectively) and GLY (mean Cmax: 354 and 368 pg/mL; mean AUC0– versity Hospital, Mainz, Germany, 2University Medical Center Gronin- 24h: 723 and 713 h*pg/mL, for medium- and high-dose respectively) were gen, Groningen, The Netherlands, 3Novartis Pharma AG, Basel, similar between medium- and high-dose groups. Cmax (140 and 240 pg/ Switzerland, 4Novartis Institutes for BioMedical Research, Cambridge, mL) and AUC0–24h (885 and 1890 h*pg/mL) of MF were approximately MA, USA, 5Novartis Institutes for BioMedical Research, Shanghai, 2-fold in high-dose versus medium-dose group. China, 6Novartis Institutes for Biomedical Research Translational Medi- CONCLUSIONS: IND, GLY and MF were rapidly absorbed after cine, Basel, Switzerland. administration. The exposure of IND and GLY were comparable between RATIONALE: IND/GLY/MF and IND/MF are both once-daily (o.d.) the IND/GLY/MF medium-dose and high-dose groups and that of MF FDCs, recently approved for maintenance treatment of asthma. They have increased with increasing dose of MF. been developed with different MF doses with the goal to tailor therapy to a patient’s needs. Dupilumab Efficacy in GINA-Defined Difficult- METHODS: MF doses at the corresponding strengths in IND/MF and 183 to-Treat Type 2 Asthma Patients in the LIBERTY IND/GLY/MF FDCs were determined via in-vitro assessments and studies ASTHMA QUEST Study to evaluate potential PK/biopharmaceutical interactions between IND, 1 2 3 Ò Klaus Rabe , J. Mark FitzGerald , Mario Castro, MD MPH , Ian GLY and MF when combined for delivery via the Breezhaler device 4 5 and further evaluated using population PK analysis in Phase III studies. Pavord, MD , Jorge Maspero, MD FAAAAI , William Busse, MD FAAAAI6, Nadia Daizadeh7, Benjamin Ortiz8, Nami Pandit-Abid7, Paul Pharmacokinetic parameters of MF at the matching doses in IND/MF 7 8 8 1 and IND/GLY/MF in Chinese healthy subjects were compared. Rowe, MD , Amin Nikhil , Yamo Deniz ; LungenClinic Grosshansdorf RESULTS: In IND/GLY/MF, an increase in MF fine particle mass was and Christian-Albrechts-University of Kiel and Christian-Albrechts Uni- observed compared with corresponding nominal MF doses in IND/MF due versity of Kiel (member of the German Center for Lung Research [DZL]), 2University of British Columbia, 3University of Kansas School to pharmaceutical interaction with GLY. To maintain comparability, 4 nominal dose of MF was adjusted from 320 mg in IND/MF to 160 mgin of Medicine, NIHR Oxford Biomedical Research Centre, University of Oxford, 5Fundacion CIDEA, 6University of Wisconsin School of Medi- IND/GLY/MF (high-dose ICS), and from 160 mg in IND/MF to 80 mgin 7 8 IND/GLY/MF (medium-dose ICS). Population PK analyses and Chinese cine and Public Health, Sanofi, Regeneron Pharmaceuticals, Inc. healthy volunteer PK studies showed comparable systemic plasma MF RATIONALE: Dupilumab, a fully human monoclonal antibody, blocks trough concentrations and steady state exposure, respectively, at corre- the shared receptor component for interleukin-4/interleukin-13, key and sponding MF doses of the two FDCs. central drivers of type 2 inflammation. In phase 3 QUEST CONCLUSIONS: MF 80 mg and 160 mg in IND/GLY/MF o.d. (NCT02414854), dupilumab 200/300mg every 2 weeks vs placebo reduced formulations provide similar ICS systemic exposure to MF 160 mg and severe exacerbations and improved pre-bronchodilator FEV1 in patients 320 mg in the IND/MF o.d. formulations, respectively in Chinese healthy with uncontrolled, moderate-to-severe asthma. Treatment effects were subjects. MF doses for IND/GLY/MF and IND/MF are matched at greater in patients with elevated baseline type 2 biomarkers (blood eosin- _ _ corresponding medium (IND/GLY/MF 150/50/80 mg, and IND/MF 150/ ophils >150cells/mL or fractional exhaled nitric oxide [FeNO] >25ppb). 160 mg) and high-dose (IND/GLY/MF 150/50/160 mg and IND/MF 150/ Recent GINA guidelines recommend add-on biologic treatment for pa- 320 mg) levels. tients with severe type 2 asthma, defined as having any of the following criteria: blood eosinophils >_150cells/mL; FeNO >_20ppb; sputum eosino- Pharmacokinetics Of Indacaterol/ phils >_2%; evidence of clinically allergen-driven disease; and/or need 182 Glycopyrronium/Mometasone Furoate In for maintenance oral corticosteroids. This analysis assessed dupilumab ef- Healthy Chinese Volunteers: Results From A ficacy in patients with baseline eosinophils >_150 cells/mL, and FeNO Randomized, Open-Label, Parallel-Group Study >_20ppb, and evidence of allergic asthma (total serum IgE >_30IU/mL and >_1 perennial aeroallergen-specific IgE >_0.35kU/L). Wenyuan Qi1, Wei Xue1, Kexin Li1, Soniya Vaidya2, Jian Sun3, Yingying METHODS: Annualized severe exacerbation rates during the 52-week Wang3, Hanns-Christian Tillmann4, Chenyu Qian3; 1Clinical Trial Center, treatment period were analyzed using negative binomial regression Beijing Hospital, National Center of Gerontology, Institute of Geriatric models, and change from baseline in pre-bronchodilator FEV1 (L) at Medicine, Chinese Academy of Medical Sciences, P.R, China, 2Novartis Week 12 using mixed-effect models with repeated measures. Institutes for BioMedical Research , Cambridge, MA, United States, 3No- RESULTS: Baseline characteristics were generally similar across treat- vartis Institutes for BioMedical Research, Shanghai, China, 4Novartis In- ment groups. In patients with GINA-defined type 2 asthma, dupilumab stitutes for BioMedical Research, Basel, Switzerland. combined (n5337) vs placebo (n5197) reduced severe exacerbations by RATIONALE: Once-daily indacaterol/glycopyrronium/mometasone fu- 57.4% (95% CI: 42.0–68.8; P<0.0001), and improved FEV1 (least squares roate (IND/GLY/MF) is the first inhaled long-acting muscarinic antago- mean difference at Week 12 [95% CI]: 0.24L [0.16–0.31]; P<0.0001). nist/long-acting b2-agonist/inhaled corticosteroid (LABA/LAMA/ICS) CONCLUSIONS: Dupilumab reduced severe exacerbations and approved for maintenance treatment of asthma. The steady-state pharma- improved lung function in patients with uncontrolled, moderate-to-severe cokinetics (PK) of IND, GLY and MF were characterized in healthy asthma with a type 2 phenotype defined by multiple parameters as per Chinese volunteers following multiple once-daily oral inhalations of GINA guidelines. IND/GLY/MF medium-dose (150/50/80 mg) or high-dose (150/50/160 mg). METHODS: In this randomized, open-label, parallel-group, Phase I study, 24 healthy volunteers aged 18–45 years were randomized 1:1 to AB60 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Long-Term Efficacy of Dupilumab in Patients and/or topical steroid for ages 0-18 was at a rate of 43%, with 32% of off- 184 With Asthma With an Allergic Phenotype label prescriptions affected. Rolled Over From LIBERTY ASTHMA QUEST: CONCLUSION: FP-MDI is prescribed at a high off-label rate across LIBERTY ASTHMA TRAVERSE Study multiple pediatric specialties spanning a disease severity of mild through severe, and often in concurrence with other steroids further increasing risk Lawrence Sher1, Jonathan Corren, MD2, Ian Pavord, MD3, Nadia Daiza- of growth and adrenal suppression. The higher rate of off-label prescribing deh4, Benjamin Ortiz5, Michel Djandji4, Yamo Deniz5, Paul Rowe, MD4; by pediatric pulmonologists, caring for children with the most severe 1Peninsula Research Associates, 2David Geffen School of Medicine at disease, was expected. However, high rates observed in other specialties is UCLA, 3NIHR Oxford Biomedical Research Centre, University of Ox- concerning. ford, 4Sanofi, 5Regeneron Pharmaceuticals, Inc. RATIONALE: Dupilumab, a fully human mAb, blocks the shared Factors Associated With Increased Asthma receptor component for interleukin-4/interleukin-13. Dupilumab effi- 186 Exacerbations After Stopping Biologic cacy/safety in asthma have been demonstrated up to 52 weeks. The Treatment open-label extension (OLE) TRAVERSE study (NCT02134028) assessed n 1 2 dupilumab long-term safety/efficacy in patients who completed phase 2/3 Jacob Maddux , Matthew Rank, MD FAAAAI , Molly Jeffery, PhD , Jonathan Inselman3, Ragina Lam4, Nilay Shah5; 1Mayo Clinic and Foun- studies. This analysis assessed long-term efficacy in patients with/without 2 >_ >_ dation, 3. Division of Health Care Policy and Research, Department of an allergic phenotype (total serum IgE 30IU/mL and 1 perennial 3 aeroallergen-specific IgE >_0.35kU/L at QUEST baseline) rolled into Health Sciences Research, Mayo Clinic, Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, 4Mayo TRAVERSE from the phase 3 QUEST study (NCT02414854). 5 METHODS: Annualized rate of severe asthma exacerbations (AER) and Clinic Alix School of Medicine, Scottsdale, AZ, Division of Health Care Policy and Research, Department of Health Sciences Research, change in FEV1 were assessed in 868/662 allergic/non-allergic QUEST participants with persistent asthma receiving add-on subcutaneous dupilu- Mayo Clinic. mab 300mg q2w up to 96 weeks. RATIONALE: There is limited information about factors that are RESULTS: 89.7% of QUEST patients completed the OLE. Dupilumab associated with outcomes after stopping asthma biologics. treatment in QUEST resulted in lower unadjusted AER vs placebo in METHODS: Individuals who stopped asthma biologics after at least 6 allergic (0.520 vs 0.964) and non-allergic (0.521 vs 1.134) patients. AER months of treatment were identified in a large insurance database from were further reduced with dupilumab during the OLE regardless of 2003-2019. The primary outcome used to assess failure after stopping patients’ allergic status or QUEST treatment regimen (dupilumab- treatment was an increase of 50% or more in the asthma exacerbation rate dupilumab/placebo-dupilumab, allergic: 0.332/0.375; non-allergic: after the first 6 months after stopping treatment compared to the 6 month period before biologic initiation. Asthma exacerbations were defined as 0.330/0.321). LS mean improvement in FEV1 during QUEST (dupilumab vs placebo) of 0.36L vs 0.19L and 0.35L vs 0.19L for allergic and non- hospitalization with a primary diagnosis of asthma or in a secondary allergic patients, respectively, continued during the OLE with LS mean position with a respiratory diagnosis in the first position, emergency changes at Week 96 for dupilumab-dupilumab/placebo-dupilumab of department visit with a primary diagnosis of asthma, or a pharmacy fill for 0.39L/0.33L and 0.35L/0.39L in allergic and non-allergic patients, a systemic corticosteroid within 1 month of an outpatient visit. respectively. RESULTS: Characteristics associated with a decreased odds of failure CONCLUSIONS: Long-term efficacy with dupilumab was observed in after stopping treatment were lack of pulmonologist or allergist visits (OR asthma patients with and without an allergic phenotype. Patients who [95% CI]: 0.273 [0.127, 0.586]) and the number of Charlson Conditions 0- switched from placebo to dupilumab for the OLE showed similar lung 1 vs. 4+ (0.645 [0.445, 0.936]). Sex, age, and insurance type were not function benefits and exacerbation reductions to those originally on associated with failure after stopping biologic treatment. dupilumab, confirming the early dupilumab results from QUEST. CONCLUSIONS: People with asthma receiving biologic therapy were less likely to experience increased asthma exacerbations after stopping Off-label Prescribing Of Inhaled Corticosteroids therapy if they had not seen an asthma specialist during the 6 months before 185 In Children With Asthma treatment initiation or if they had a decreased number of comorbid conditions. This may suggest their biologic treatment was not intended to S. A. Mahady1, T. P. Lefeber2, D. Rich2, D. P. Skoner2; 1West Virginia treat asthma; alternatively, this may reflect suboptimal patient selection for University School of Medicine, Morgantown, WV, Department of Internal biologic treatment when an asthma specialist is not part of the treatment Medicine & Pediatrics, 2West Virgnia School of Medicine, Department of decision. Pediatrics. RATIONALE: Inhaled corticosteroids (ICS) are the treatment of choice for persistent asthma; however, prescribed in off-label doses can increase a child’s risk of adrenal or growth suppression. The goal of this study is to determine the rate and trends of off-label prescribing of FP-MDI in 4-11- year-old children where only the 44-mcg dose is approved by the FDA. METHODS: A retrospective analysis was performed of 45,222 pre- scriptions of inhaled, nasal, and topical steroids across 354 sites prescrib- ing ICS across a state-wide university medical system over a 4.5-year period. Data included prescribing care site, number of prescriptions, patient age, severity of disease, type of ICS, dosage, and concurrent prescriptions of nasal and topical steroids. RESULTS: Total off-label prescribing of FP-MDI to children age 4-11 was 43%. Highest off-label prescribing sites include pediatric pulmonol- ogy (58%), family medicine (45%), pediatric hospital units (40%), pediatricians (35%), and pediatric allergy/immunology (14%). The severity diagnosis with the most off-label prescriptions is ‘‘unspecified uncomplicated asthma’’. Concurrent prescribing of FP-MDI plus a nasal J ALLERGY CLIN IMMUNOL Abstracts AB61 VOLUME 147, NUMBER 2

Comparing Machine Learning Models for HARQ data from both trials were pooled and individual HARQ items most 187 Identifying Chronic Cough Using Diagnosis and frequently rated as a 4 or 5 were summarized using descriptive statistics. Medication in the Electronic Health Records RESULTS: Among 2044 randomized and treated patients (COUGH-1, N5730; COUGH-2, N51314), 2000 completed HARQ at baseline. The Vishal Bali, PhD1, Xiao Luo, PhD2, Priyanka Gandhi, BS2, Zuoyi pooled mean (SD) baseline total HARQ score was 39.7 (13.4). Triggers or Zhang, PhD3, Wei Shao, PhD3, Zhi Han, PhD3, Vasu symptoms most frequently rated as severe or frequent included coughing Chandrasekaran, PhD1, Vladimir Turzhitsky, PhD1, Anna more when awake than asleep (70.0%), clearing your throat (58.2%), Roberts, MIS4, Megan Metzger, MS4, Jarod Baker, MS4, Carmen La cough brought on by singing or speaking (54.2%), and tickle or lump in Rosa, MD1, Jessica Weaver1, Paul Dexter5, Kun Huang, PhD3; 1Center your throat (52.4%). for Observational and Real-World Evidence, Merck & Co., Inc., 2Purdue CONCLUSIONS: Patients with RCC or UCC frequently reported triggers School of Engineering and Technology, 3Indiana University School of and symptoms associated with their cough, with the most frequent/severe Medicine, 4Regenstrief Institute, Inc., 5Eskenazi Health. problems being coughing while awake and throat-related sensations. RATIONALE: Chronic cough (CC), a cough of eight or more weeks is often multifactorial and can impair patients’ quality of life. We investi- Comorbid Conditions and Medical History gated the potential of machine learning models for CC prediction using the 189 Among Patients with Refractory or diagnoses and medications in the electronic health records (EHRs). Unexplained Chronic Cough in Two Phase 3 METHODS: We constructed two cohorts of 18-85 years old patients using Clinical Trials (COUGH-1 and COUGH-2) EHRs of a large statewide academic system and a public county hospital. Peter Dicpinigaitis, MD1, Surinder Birring, MD2, Lorcan 23,573 CC patients were identified by the rule-based algorithm with an 3 4 5 6 outpatient visit and available medical history of 120 days from the index McGarvey, MD , Alyn Morice, MD , Ian Pavord, MD , Jaclyn Smith , Carmen La Rosa, MD7, Qing Li7, Allison Martin Nguyen7, Jonathan date; and an equal number of patients with a cough that did not meet the 7 7 7 1 criteria of CC. We used diagnosis and medication data to simulate claims Schelfhout , Anjela Tzontcheva , David Muccino, MD ; Jack D. Weiler Hospital, 2King’s College, London, UK, 3Queen, 4University of Hull, data for CC prediction. We used the original diagnosis name to capture the 5 6 7 contextual information between diagnosis and medication. The medication University of Oxford, University of Manchester, Merck & Co., Inc. information is standardized with the National Drug Code Directory, which RATIONALE: Patients with refractory chronic cough (RCC) or unex- was then mapped to the medication category. An NLP method was used to plained chronic cough (UCC) often have comorbid diseases associated construct the data representation for the learning models. The machine with cough (RCC) and/or receive treatments for conditions presumed to be learning models, including Logistic Regression (LR), Support Vector related to their cough (RCC/UCC). The medical histories of patients with Machine (SVM), k-Nearest Neighbor (kNN), and Random Forest (RF) RCC or UCC enrolled in two phase 3, randomized, placebo-controlled were compared. studies of the P2X3 receptor antagonist gefapixant were assessed. RESULTS: LR, SVM, kNN and RF gained sensitivity of 0.83, 0.85, 0.71 METHODS: Patients enrolled in COUGH-1 (NCT03449134) and and 0.84, respectively, and specificity of 0.78, 0.81, 0.67 and 0.79, COUGH-2 (NCT03449147) were included. Eligible patients for both _ _ respectively. SVM performed better than the other three models. trials were >18 years of age, diagnosed with RCC or UCC (>1 year), and _ CONCLUSIONS: SVM by using only medication and diagnosis in the scored >40 mm on the cough severity visual analog scale. Medical history, claims data can predict majority of the CC patients. Additionally, including comorbidities and prior medications, was collected from medical symptoms extracted from clinical notes may further improve performance records. 5 of the models. RESULTS: A total of 2044 patients were included (COUGH-1, N 730; COUGH-2, N51314). Patients were predominately female (COUGH-1, Cough Triggers and Symptoms Among Patients 74%; COUGH-2, 75%) with a median (range) cough duration of 9 (2–59) 188 with Refractory or Unexplained Chronic Cough and 7 (1–75) years in COUGH-1 and COUGH-2, respectively. Common in Two Phase 3 Trials of the P2X3 Receptor comorbid diagnoses included asthma (COUGH-1, 43%; COUGH-2, 40%), Antagonist Gefapixant (COUGH-1 and COUGH-2) gastroesophageal reflux disease (COUGH-1, 40%; COUGH-2, 40%), and allergic rhinitis (COUGH-1, 20%; COUGH-2, 15%). Prior medication Alyn Morice, MD1, Surinder Birring, MD2, Peter Dicpinigaitis, MD3, classes included medications for acid-related disorders (eg, esomeprazole, Lorcan McGarvey, MD4, Ian Pavord, MD5, Jaclyn Smith6, Carmen La omeprazole; COUGH-1, 59%; COUGH-2, 52%), anti-inflammatory or Rosa, MD7, Qing Li7, Allison Martin Nguyen7, Jonathan Schelfhout7, An- anti-infective medications including steroids (eg, budesonide, predniso- jela Tzontcheva7, David Muccino, MD7; 1University of Hull, 2King’s Col- lone; COUGH-1, 34%; COUGH-2, 28%), and analgesics including lege, London, UK, 3Jack D. Weiler Hospital, 4Queen, 5University of neuromodulators commonly used off-label to manage cough (eg, codeine, Oxford, 6University of Manchester, 7Merck & Co., Inc. gabapentin, morphine; COUGH-1, 48%; COUGH-2, 39%). RATIONALE: Patients with chronic cough often report sensitivity to CONCLUSIONS: Patients enrolled in COUGH-1 and COUGH-2 repre- tussive and nontussive stimuli that subsequently induces their cough. The sented a heterogeneous RCC and UCC patient population, with medical frequency and severity of these triggers and cough-related symptoms in histories consistent with treatment of identified or presumed conditions patients with refractory or unexplained chronic cough (RCC or UCC) are associated with chronic cough. less well characterized. METHODS: COUGH-1 (NCT03449134) and COUGH-2 (NCT03449147) were phase 3, randomized, double-blind, placebo- controlled trials of the P2X3 receptor antagonist gefapixant. Eligible patients were >_18 years of age, diagnosed with RCC or UCC for >_1 year, and had a >_40 mm score on the cough severity visual analog scale. At baseline, patients completed the Hull Airway Reflux Questionnaire (HARQ), a 14-item questionnaire designed to assess triggers and symptoms associated with airway reflux on a scale of 0 (no problem) to 5 (severe or frequent problem), with a maximum total score of 70. Baseline AB62 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Characterizing Unexplained Chronic Cough In The fourth patient’s work up, including WES, has not revealed a 190 The Primary Care Setting monogenetic cause. He is currently treated with prednisone and infliximab. CONCLUSIONS: Early identification of monogenic causes of infantile Patel AK1, Guo A1, Vu T-HT2, Patel GB1, Peters AT1; 1Division of Al- IBD can guide use of biologic therapy, necessity for bone marrow lergy and Immunology, Department of Medicine, Northwestern Univer- transplant, or the avoidance of specific treatments. Workup significantly sity Feinberg School of Medicine, Chicago, IL 60611, United States, changed management in 3 of 4 patients, highlighting the importance of co- 2Division of Epidemiology, Department of Preventive Medicine, North- management between specialties for individualized treatment. western University Feinberg School of Medicine, Chicago, IL 60611, United States. Cancer mortality in a cohort of 202 common ~ RATIONALE: Unexplained chronic cough (UCC) is a cough lasting at 192 variable immunodeficiency patients from Sao least 8 weeks with no etiology identified despite a thorough investigation. Paulo, Brazil, followed for up to forty years UCC is routinely evaluated by primary care providers. Data on UCC in the Luiz Fonseca, MD, PhD1, Myrthes Barros, MD, PhD2, Cristina primary care population remains limited. 3 4 METHODS: This was a retrospective study of patients with chronic cough Kokron, MD, PhD , Octavio Grecco, MD, MSc , Ana Barreto, MD, 5 6 1 ~ 2 (CC) who were evaluated at primary care provider (PCP) clinics between PhD , Jorge Kalil, MD, PhD ; Universidade de Sao Paulo, Hospital 3 2015-2018. Patients with at least 3 PCP visits for a primary diagnosis of das Clınicas, Faculdade de Medicina da USP, Brazil, Hospital das Clıni- cas, FMUSP, S~ao Paulo, Brazil, 4Hospital das Clınicas, Faculdade de Me- cough within 6 months and a minimum of 8 weeks between the first and 5 third visits were included. Charts were reviewed for 3.5 years from the dicina USP, Hospital das Clinicas, Faculdade de Medicina da USP, 6 ~ initial PCP visit. Descriptive statistics were utilized to characterize UCC Brazil, Faculdade de Medicina da USP, Sao Paulo, Brazil. patients clinically. RATIONALE: We observed an increase in cancer incidence and mortality RESULTS: Twenty-seven out of 61 (44%) of CC patients had UCC. among our common variable immunodeficiency (CVI) patients over the Median age was 64 (IQR524), and median BMI was 27 (IQR57). 70.4% last decade. We hypothesized that such trend might be associated with of UCC patients were female. Despite 40.7% of UCC patients having 2 or delays in diagnosis of CVI; we also investigated whether cancer patients more chest X-rays and 37% having chest CT imaging ordered by PCP and/ were more prone to have had their immunodeficiency diagnosed later than or specialists, their cough remained unexplained. 37% of UCC patients had non-cancer patients. 2 or more antibiotic courses, and 22.2% had 2 or more oral corticosteroid METHODS: We compared the delay in the diagnosis of CVI over the last courses without benefit. 34.4% of all CC patients were referred to decade with those from the previous 30 years of follow-up of our 172- specialists (23% pulmonary, 9.8% otolaryngology, 8.2% gastroenterology, patients cohort. We also compared Kaplan-Meier survival curves from 8.2% allergy-immunology), but 33.3% of referred patients continued to patients admitted to care on the last decade with those from the preceding have no explanation for their cough. thirty years. CONCLUSIONS: Chronic cough remained unexplained in almost 50% of RESULTS: Delays in diagnosis of CVI have remained fairly constant over patients presenting to PCP clinics despite extensive workup and therapeu- the forty years of existence of our cohort, at about 10 years, both on the last tic trials. Further clinical characterization will inform future research and decade and on the the preceding 30 years. Survival curves are also similar treatment directions. for both periods analysed. Thirty-nine patients died, 13 of them from cancer (6 from stomach cancer, 4 from lymphomas), ten of those 13 cancer Multidisciplinary Approach to Evaluation and deaths ocurring since 2010. Delays in the diagnosis of CVI for patients 191 Treatment of Infantile Onset Inflammatory dying from cancer were similar for those dying from other causes and also Bowel Disease not different for patients surviving to this day. CONCLUSIONS: We noticed an increase in cancer deaths among our Courtney Cotter, DO1, Melissa Keeley, MD2, Ismaeel Hashemi, MD2, patients in recent years, what was particularly noticeable for stomach Nicholas Hartog, MD FAAAAI2; 1Spectrum Health/ Helen DeVos Chil- cancer. Our findings did not point to delays in diagnosing CVI as a culprit, dren, 2Spectrum Health/ Helen DeVos Children’s Hospital. so the causes of this trend warrant a careful search in order to improve RATIONALE: Children with inflammatory bowel disease symptoms patients’ prognosis. prior to two years of age are classified as infantile onset inflammatory bowel disease (IBD) which may be caused by monogenetic immunologic disorders. METHODS: Patients at Helen DeVos Children’s Hospital who presented from July 2016 to July 2020 with IBD symptoms prior to 2 years were included. Four patients met criteria. RESULTS: The patients presented between three days and seventeen months. Whole exome sequencing (WES) was used in 3 patients and targeted chronic granulomatous disease gene (CGD) was used in one. We identified a definitive monogenic immunodeficiency in two patients: CYBB (c.338-3 C>A) and WDR1 (c.1646 C>T; c.1271 T>G). The patient with WDR1 deficiency underwent a matched unrelated hemato- poietic stem cell transplant with resolution of colitis. The patient with the CYBB variant was started on triple-therapy. His IBD is controlled on prednisone, mesalamine, and vedolizumab. TNF inhibitors have been avoided. WES revealed a nonsense loss of function variant in CFH (c. 1924A>T) in the third patient. Further workup is pending to determine clinical signifi- cance. This patient failed infliximab therapy and cytokine panel revealed elevated IL-1b, a potential therapeutic target. J ALLERGY CLIN IMMUNOL Abstracts AB63 VOLUME 147, NUMBER 2

Microbiota Suppresses Innate Type 2 Immune Mental Health Concerns among Primary 193 Responses in the lungs in Mice 195 Immunodeficiency Patients and their Caregivers

Koji Iijima, PhD1, Takao Kobayashi, PhD1, Rinna Tei, MD1, Lisa Till2, Nouf Alsaati1, Kathleen Webber1, Michael Keller, MD1, Linda Herbert, William Moor2, Purna Kashyap2, Hirohito Kita, MD1; 1Mayo Clinic Ari- PhD1; 1Children’s National Hospital. zona, 2Mayo Clinic Rochester. RATIONALE: Patients with primary immunodeficiency disorders (PID) RATIONALE: Microbiota promotes generation of regulatory T cells and and their caregivers must enact major life changes in order to manage their may be involved in development of or protection from immune-mediated illness. We hypothesized that the targeted population would report diseases. However, our knowledge is limited regarding the role for psychosocial concerns related to PID and that severity of diagnosis and microbiota in allergic airway diseases. The goal of this project was to time since diagnosis would affect these concerns. address this question directly by using a germ-free (GF) mouse model. METHODS: Caregivers of children with PID (ages 0-17 yrs) and children METHODS: Na€ıve C57BL/6 mice were housed in a GF condition or with PID (ages 8-17 yrs) were recruited from a pediatric immunology specific pathogen-free (SPF) condition during pregnancy and after birth. clinic to complete PROMIS surveys on REDCap. Parent surveys assessed The steady-state immune status was analyzed by a multiplex cytokine anxiety, depression, fatigue, sleep disturbance, emotional support, and assay and Nanostring gene expression assay. Innate type 2 immune informational support. Child and parent proxy surveys assessed fatigue, responses in the lungs were compared by exposing these mice intranasally anxiety, depression, pain interference, mobility, and peer relationships. (i.n.) to extract of fungus Alternaria. Each measure resulted in a t-score. Correlations and independent samples RESULTS: At steady-state, the total numbers of CD3+ T cells and B220+ t-tests were completed. B cells in the lungs were lower in GF mice as compared to SPF mice. In RESULTS: Participants were 29 caregivers and 11 children (Mean age 5 contrast, plasma levels of total IgE and IgG1 were elevated in GF mice. 8.1 years; Mean time since diagnosis 5 3.68 years; 32% female; 79% By comprehensive protein and mRNA expression analyses, the lung levels Caucasian). 13 participants were classified as mild PID and 16 as severe of IL-1a, IL-1b, IL-10, and a transcription factor Rorc were lower in GF PID. Greater time since diagnosis was related to greater child depressive mice as compared to SPF mice. When na€ıve mice were exposed i.n, to symptoms, pain and fatigue, (p<.05). Greater parent-reported emotional Alternaria extract, GF mice produced higher amounts of type 2 cytokines and informational support was correlated with less time since diagnosis and lower amount of IL-10 in the lungs. No differences were observed in (p<.05). Caregivers of children with severe PID perceived more child Alternaria-induced IL-33 release or IL-33-induced innate type 2 response peer relationship challenges than caregivers of children with mild PID in two conditions. (p<.05). Other mean group differences existed but were not significant. CONCLUSION: Microbiota modulates type 2 immune responses in the CONCLUSION: These findings provide insight about psychosocial lungs. Steady-state and low-grade inflammation in response to colonized concerns in PID patients and their caregivers. Time since diagnosis and microbes may suppress aberrant allergic immune responses to inhaled specific PID experiences may affect psychosocial functioning. A larger allergens. sample will need to be investigated to better understand the population.

Undetectable IgE Level Associated with Assessment of Telomere Length in Patients with 194 Increased Risk of Malignancy 196 Primary Immune Deficiency

John McDonnell, MD1, Katherine Weller, MD1, Jeff Albert, Ph D2, Fred Andrea Sitek1, Avni Joshi, MD FAAAAI1; 1Mayo Clinic. Hsieh1, Robert Burton1; 1Cleveland Clinic, 2Case Western Reserve RATIONALE: Short telomere syndromes are accelerated aging syn- University. dromes, often leading to multi-organ disease including a variety of immune RATIONALE: Previous studies have explored the relationship between defects. It is unclear if patients with primary immune deficiency (PID) have serum IgE levels and therisk of malignancy. We aimed to examine the telomere attrition, which may contribute to disease severity and the association between undetectable serum IgE and malignancy risk and development of associated comorbidities. evaluate the differential effects of undetectable IgE on cancer type. We METHODS: We undertook a retrospective chart review of patients in our hypothesized that undetectable IgE levels could increase odds of first PID clinic that underwent telomere length testing at Mayo Clinic malignancy in general and hematologic malignancy in particular. Rochester, Minnesota. FlowFISH telomere length testing was performed METHODS: This retrospective cohort study reviewed all serum IgE at Johns Hopkins University reference laboratory. levels performed on adults at a single academic center from 1998-2020. A RESULTS: Fifty-two patient charts were screened and 24 were included total of 40,069 subjects met the inclusion criteria (age at least 18 years and in the study. The median age was 38 years with equal distribution amongst at least 1 IgE measurement). the sexes. 19 of these 24 patients (79%) had short lymphocyte telomere Logistic and multinomial regression were performed, controlling for sex, length. IgA deficiency, pulmonary parenchymal disease with low lung race, age, high IgE (>114 IU/mL), HIV status, and immunodeficiency diffusion capacity (DLCO; P50.05) and liver disease were associated with status. The primary outcome measure was development of first malig- lymphocyte telomere attrition. nancy; secondary outcome measures included type of malignancy CONCLUSIONS: Short lymphocyte telomere length may help define a developed. more severe phenotype of PID. This may offer potential therapeutic RESULTS: Subjects were 35.2% male, mean age 51.3 years, and 85.2% overlaps with short telomere syndrome manifestations. white. 17.2% (n5 6,898) of subjects developed a first malignancy during the study period. Undetectable IgE levels were associated with increased odds of first malignancy (n5550, OR 1.54, 95% CI (1.35 to 1.75), p < 0.001). Undetectable IgE levels were associated with increased odds of hematologic malignancy in subjects who developed a malignancy (n5183, OR 1.99, 95% CI (1.39 to 2.85), p < 0.001). CONCLUSIONS: Presence of an undetectable IgE level in adults is associated with increased risk of first malignancy and hematologic malignancy in a large clinical cohort. AB64 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Genetic Panel Testing for Primary Relationship of Blood Eosinophil Counts of 197 Immunodeficiency Diseases 199 Adults with Diabetes as a Risk Factor for Coronary Artery Disease Kelsey Lecerf, MD1, Benjamin Prince, MD MCSI FAAAAI2, Rebecca Scherzer, MD FAAAAI2; 1The Ohio State University/Nationwide Chil- Alexander Babazadeh, MD1, Shawn Mathew, MD1, Sairaman dren’s Hospital, 2Nationwide Children’s Hospital. Nagarajan, MD MPH1, Bibi Khartoon, MD1, Rauno Joks, MD FAAAAI1; RATIONALE: Advances in genetic testing have allowed for increased 1SUNY Brooklyn Health Sciences University. diagnosis of primary immunodeficiency diseases (PIDDs). Over 400 RATIONALE: Elevated serum eosinophil levels have been shown to be PIDDs have been recognized with the majority being monogenic defects. associated with multiple immune disorders. We have previously shown We aimed to examine the demographics and outcome of genetic testing for eosinophilia as a biomarker for coronary artery disease (CAD). The PIDD at a large pediatric tertiary hospital. relationship of HBA1C which reflects diabetes control has not been METHODS: A chart review was performed on all patients in whom a 207 evaluated with respect to eosinophil counts. We hypothesized that HBA1C gene PIDD panel was ordered from January 1, 2017 through March 31, levels may correlate with blood eosinophil counts. 2020. Data gathered included patient demographics, past medical and METHODS: We tested our hypothesis through a retrospective chart family history, specialty of ordering provider, inpatient or outpatient analysis of adult diabetic patients (n560) of our ambulatory endocrinology setting, PIDD panel results, genetic counseling, and changes to treatment. clinic at the University Hospital of Brooklyn. Patient data included HbA1c RESULTS: Of the 97 patients that had the panel performed, 72% were and CBC with differentials over three points in time. Absolute eosinophil ordered in the outpatient setting. The most common ordering specialties count (AEC) was non-normal therefore logarithmized. Spearman correla- were Immunology (36%), Rheumatology (22%), Hematology/ tion analysis and generalized linear mixed models (GLMM) were Immunology/Rheumatology multidisciplinary clinic (19%), and conducted to identify factors predicting AEC. Hematology (11%). 31 pathogenic variants, 16 increased-risk variants, RESULTS: The Raw Spearman correlation was –0.06 between contem- and 219 variants of uncertain significance (VUS) were discovered. Sixteen poraneous HbA1c and AEC. There was no significant association patients had clinically significant mutations, eight patients had a diagnosis (p50.142) using a mixed linear model to predict log(AEC) from established, and two patients required bone marrow transplant (ICF contemporaneous HbA1c. Log(AEC) was not predictable based on prior syndrome; hypomorphic RAG1 SCID). Twenty-five patients required HbA1c (p50.558). Also, the extent of change from prior AEC was not further functional or genetic testing. Eight patients had negative panels. predictable from the extent of change from prior HbA1c (p50.861). CONCLUSIONS: In this study of patients who had a PIDD gene panel as CONCLUSIONS: There has been no significant association of AEC and part of their work-up, 8% of patients had a diagnosis established, 16% had HbA1c from contemporaneous HbA1c as well as over time. Future studies clinically significant variants identified, and 26% required further func- should consider analyzing the association of other markers of diabetic tional or genetic testing. Two patients underwent a bone marrow transplant status or glycemic control in predicting AEC as a forerunner to CAD. based on the diagnosis. Genetic testing for PIDDs has the potential to alter treatment options, provide prognostic information, and change counseling Use of Benralizumab in Refractory Eosinophilic recommendations. 200 Cystitis Improves Symptoms and Reduces Bladder Eosinophils Hospitalizations and Critical Illness in Adult 198 Primary Immunodeficiency Patients Cheshil Dixit1, Travis Bullock, MD2, Laura Kahle3, Manoj Warrier, MD FAAAAI3; 1Saint Louis University, 2Urology of St. Louis, 3Allergy, Arun Dhir1, Persia Pourshahnazari, MD1, Catherine Biggs, MD1; 1Uni- Asthma & Food Allergy Centers. versity of British Columbia. RATIONALE: Eosinophilic cystitis (EoC) is a rare bladder condition RATIONALE: Adult patients with primary immunodeficiency (PID) face defined by an eosinophilic infiltrate of the bladder. Current treatment high morbidity and mortality, but sparse literature is available describing modalities include oral medications, oral/intravesicular steroids, and this population. We hypothesized that compared to patients without PID, bladder surgery including total cystectomy. Benralizumab is a monoclonal this population would experience a greater burden of comorbidities and be antibody that blocks the alpha subunit of the IL-5 receptor, and thus more likely to require intravenous antibiotics, hospital admission, and reduces eosinophil production and survival. intensive care. METHODS: We present three female patients (71, 57, and 21 years-old) METHODS: Charts of patients seen at the Saint Paul’s Hospital Primary with EoC refractory to standard treatment who were prospectively treated Immunodeficiency Transition Clinic from February 2018 to June 2019 with benralizumab 30 mg every 4 weeks starting in 2018. Patients were were retrospectively reviewed. 24 patients were diagnosed with PID (8 assessed for changes in clinical symptoms (suprapubic pain, dysuria, monogenic, 16 non-monogenic) and 12 patients were deemed immune urgency, frequency, and hematuria) and by cystoscopy with biopsies. competent. Ages ranged from 18 to 70. Statistical analysis was performed RESULTS: The patients treated with benralizumab reported a reduction in using Fisher’s exact test. symptoms, had decreased bladder eosinophils, and required fewer RESULTS: Amongst patients with PID, 29.2% were hospitalized 3 or treatments with intravesicular steroids. All patients had a significant more times, 33.3% required 3 or more courses of antibiotics, and 25.0% reduction in bladder eosinophils to < 1/HPF. Two of three patients had at least 1 ICU admission. Comparatively, amongst patients with no discontinued benralizumab for reasons unrelated to treatment and had PID, 8.33% were hospitalized 3 or more times, 8.33% required 3 or more worsening of symptoms along with increased bladder eosinophilia. In the courses of antibiotics, and no patients required ICU. Patients with remaining patient, symptomatic and histologic response has been monogenic PIDs were more likely to require ICU admission compared sustained. to patients with a non-monogenic PID (p50.0011) and those with no PID CONCLUSIONS: Effective treatment for EoC is not well defined, and (p50.0018). The mean number of comorbidities was similar between both there are a paucity of surgery/steroid-sparing treatment options in EoC. groups. Benralizumab should be considered as a treatment option in patients with CONCLUSIONS: Patients with PIDs, particularly those with monogenic refractory EoC, and these results suggest that response could be sustained. PIDs, show a high frequency of recurrent hospitalizations, IV antibiotic Further studies are needed to properly elucidate the role of benralizumab in use, and intensive care admissions. Though we found no difference in the EoC. number of comorbidities between the groups, our findings suggest that patients with PIDs have the potential to deteriorate quickly and warrant close attention from their healthcare teams. J ALLERGY CLIN IMMUNOL Abstracts AB65 VOLUME 147, NUMBER 2

Overlay Between Th1 and Th2 pathways in infection. The most differentially expressed gene, Chi3l1, was restricted 201 Patients with Common Variable to CXCR5+ cDC2. Immunodeficiency and Allergic disease CONCLUSIONS: cDC1 and cDC2 DEG differ in TH1 (B6 Lm), TH2(Hp and BALB/c Lm) and TH17 (Cr) infection, but in all settings Cxcr5 and Seemal Awan1, Pavan Nataraj2, Martin Maldonado-Puebla2, Pooja Dave3, Chi3l1 were expressed by cDC2. CXCR5 deficient cDC2 fail to express Veronica Mark3, Zachary Falk3, Annette Aldous4, Daniel Ein, MD Chi3l1. FAAAAI5; 1National Institutes of Health, 2George Washington University Hospital, 3George Washington University School of Medicine, 4Milken The Role of Antisense RNA in Gene Expression Institute School of Public Health, 5George Washington University Medi- 203 After Treatment with Autophagy Modulators cal Cen. RATIONALE: Common Variable Immunodeficiency (CVID) is defined Kristina Antuna, MD by low serum immunoglobulins, history of recurrent sinopulmonary RATIONALE: This study explores how molecular determinants of gene infections, and blunted response to immunization. It can be associated regulation contribute to the inflammatory response of MSCs in the with immune dysregulation. Though not well documented, it has been presence of autophagy modulators. It is our hypothesis that antiRNA clinically suspected that CVID may be associated with allergic disease. We contributes to gene regulation in cells that are exposed to inflammation set out to determine a possible connection. stimulation in the presence of autophagy modulators. METHODS: This retrospective study was conducted at the George METHODS: We utilized a subset of MSCs termed ‘‘marrow-isolated Washington University. Study patients were identified with ICD-10 adult multilineage inducible’’ (MIAMI) cells. These cells were initially diagnoses of primary immunodeficiencies in an electronic medical record treated with IFNg to stimulate the inflammatory response. The autophagy (EMR). Of 541 patients with one or more such diagnoses, 88 patients had a modulators tamoxifen (TX) and chloroquine (CQ) were concurrently used confirmed diagnosis of CVID. to activate and inhibit autophagy in MIAMI cells, respectively. By RESULTS: Of the 88 patients, 43 (48.9%) patients were diagnosed with comparing mRNA between treatment groups, changes in gene expression allergic rhinitis by an Allergist with 7 (78%) out of 9 patients reporting were assessed. RNA sequencing was matched to online databases to improvement in symptoms with allergen immunotherapy. 22 of the 88 uncover molecular determinants of gene expression regulation. patients underwent skin testing of which 20 (91%) were found to be RESULTS: AntiRNA should typically decrease mRNA expression. For positive. Of the 88 patients, 46 (52.3%) patients were receiving IVIG example, IL-6 mRNA expression was decreased after stimulation with replacement therapy. 21 (45.7%) of these 46 patients were asked if IVIG IFNg and TX. However, the antiRNA for the inflammatory gene PYCARD helped their allergic symptoms of which 18 (85.7%) of the 21 patients did not affect gene expression regardless of treatment. We found that many reported improvement. Interestingly, the mean Immunoglobulin E (IgE) of these direct relationships remained. was found to be 67.5 and mean eosinophils were 200. CONCLUSIONS: Further gene expression studies which will include CONCLUSIONS: The high incidence of allergic disease, positive skin other RNA species will be needed to discover all determinants of mRNA testing, and elevated IgE and eosinophils in these patients suggests a expression in the presence of TX or CQ. potential interaction between Th1 and Th2 immunity that might explain COVID-19 and Common Variable why patients with CVID have allergic disease. An improvement in allergic Immunodeficiency symptoms in CVID patients on IVIG further points to a possible 204 connection between allergic disease and CVID. Marina KaminskiUniversity graduate1, Gabriela Yoshimoto2, Luiza 1 1 3 1 2 Transcriptional Features of TH1, TH2, and TH17 Silva , Ana Garcia , Natasha Ferraroni, MD ; UniCEUB, UniCEBu, 3 202 priming migratory dendritic cells – a common Clinica Ferraroni. role for CXCR5 and Chi3l1 RATIONALE: Common Variable Immunodeficiency (CVI) is rare primary immunodeficiency. The COVID-19 pandemics rised the risc os Miranda Curtiss1, Natalia Ballesteros Benavides1, Beatriz infection in these patients. Leon-Ruiz, PhD1, Alexander Rosenberg2, Chris Scharer3, Travis Ptacek4, METHODS: We describe a 27 year old male patient with CVI, in regular Casey Weaver, MD1, Troy Randall2, Frances Lund, PhD2; 1University of replacement of human immunoglobulin (600mg/kg), with parotiditis and Alabama at Birmingham, 2University of Alabama Birmingham, 3Emory night sweating. The diagnosis os COVID was suspected. Two days later, he University, 4University of North Caroline Chapel Hill. presented diarrhea. The diagnosis of COVID-19 was made by blood test RATIONALE: In a mouse infection model with the nematode -serology and a RT-qPCR for SARS-CoV-2. He received azithromycin, + zinc, ivermectin and vitamin D, and he received human gammaglobulin 1 Heligmosomoides polygurus (Hp), TH2 responses require CXCR5 DC. + week in advance. The significance of CXCR5 DCs in TH1orTH17 infections is unknown. RESULTS: IgM anti-SARS CoV-2 serology of 4.73 AU / ml (Reference We probed the transcriptomes of migratory DCs in response to Hp (TH2), <1) and IgG negative. In addition, a C-reactive protein test was requested, Citrobacter rodentii (Cr)(TH17), and Leishmania major (Lm) infection which showed a high result 8.712 mg/dL. Chest CT scan was ordered and (BALB/c mice: TH2, C57BL/6 mice: TH1). We further parsed the transcrip- tomics of draining lymph node DCs to identify gene signatures associated showed no changes related to early stages of viral infections. IL-6, 5 with CXCR5+ DC. fibrinogen and D-dimer were normal. At the time of infecction IgG 1150 5 5 METHODS: Wildtype mice were infected with Hp larvae or Cr by (700-1600mg/dL), IgA 28 (70-400mg/dL), IgM 19 (40-230mg/dL). gavage. Irradiated mice reconstituted with a 1:1 ratio of wildtype CONCLUSIONS: The literature is scarce with regard to the relationship (CD45.1) and CXCR5 deficient (CD45.2) bone marrow were infected between primary immunodeficiencies and SARS CoV-2 infection, how- with either Hp larvae or intradermal Lm. Migratory dendritic cells were ever, there is a consensus that patients with primary immunodeficiencies sorted from mesenteric lymph nodes (msLN) of Hp or Cr infected mice mostly present more severe conditions when infected with this virus. and popliteal lymph nodes of Lm infected mice into CD103+ (cDC1) and Fortunately, this patient recovered well, and progressed to cure of the viral CD11b+ (cDC2) subsets, then underwent RNA seq. In chimeric mice DC syndrome. CT chest scan was unremakable. To our knowledge, this is the were also sorted by the congenic marker CD45. first report of parotidis in a patient with CVI and COVID-19. RESULTS: Thousands of differentially expressed genes (DEG) were found in cDC1 and cDC2 from Hp, Cr and Lm infected mice. Cxcr5 and Chi3l1 were expressed by cDC2 in Hp, Cr and Lm. In contrast, few DEG were identified between CXCR5+ and CXCR5- cDC2 during Hp or Lm AB66 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

A Case of Mild COVID-19 in a Teenager with obesity and congenital heart disease was asymptomatic. More cases are 205 Common Variable Immunodeficiency and needed to better understand risk factors in pediatric patients with primary Granulomatous Interstitial Lung Disease on immunodeficiency and COVID-19. Replacement Immunoglobulin and Infliximab Cellular and humoral immunity in patients Yatyng Chang1, Daniel Urschel, MD1, Vivian Hernandez-Trujillo, MD 207 infected with the SARS-CoV-2 virus at general FAAAAI2, Jose Calderon, MD1; 1Nicklaus Children’s Hospital, Division hospital of Allergy and Immunology, Miami, FL, 2Allergy and Immunology Valeria Brandao~ 1, Thaıs T. Saito1,Debora S. Guterres1, Grasiele Lima1, Care Center of So. 1 2 3 RATIONALE: Common variable immunodeficiency (CVID) is a disorder Sara Tencarte , Ana Carolina Dos Santos , Marina Laubi , Roselene Lourenc¸o4, Octavio Grecco, MD, MSc5, Myrthes Toledo Barros8, Myrthes of the immune system. Patients are generally diagnosed in their 6 6 7 1 adolescence and require regular immunoglobulin replacement. Due to T. Barros , Cristina Kokron , Ana Karolina Marinho, DO ; Conjunto ~ 2 their immune dysregulation, they are at increased risk of infections, Hospitalar do Mandaqui, Sao Paulo, Brazil, Universidade Nove de Julho, ~ 3 ~ 4 autoimmune disease, and cancer. Sao Paulo, Brazil, Universidade Nove de Julho, Sao Paulo, Brazil, Con- ~ METHODS: To describe a case of mild COVID-19 in a patient with CVID junto Hospitalar do Mandaqui and Universidade Nove de Julho, Sao 5 ~ 6 and granulomatous interstitial lung disease on replacement immunoglob- Paulo, Brazil, Hospital das Clınicas Universidade de Sao Paulo, Hospital ~ 7 ulin and infliximab. das Clınicas University of Sao Paulo, Hospital das Clınicas University of 8 ~ RESULTS: The patient is a 15 year old female with CVID, granulomatous Sao Paulo Medical School, Hospital das Clı´nicas, FMUSP, Sao Paulo, interstitial lung disease, and hepatosplenomegaly with pancytopenia and Brazil. portal hypertension. She receives weekly SCIG and monthly infliximab. In RATIONALE: The cellular immune response seems to have a central role July, an uncle who visits frequently tested positive for COVID-19. Mother, in the pathophysiology of COVID-19. Few studies have analyzed father, and brother subsequently had mild nasal congestion and tested lymphocyte subpopulations and clinical outcomes. We evaluated clinical positive for COVID-19. Our patient developed symptoms of headache and and immunological characteristics of patients infected with the SARS- nasal congestion, for which Azithromycin was prescribed and symptoms CoV-2 virus and described the outcomes during hospitalization. resolved. No fever, cough, shortness of breath, or loss of sense of smell or METHODS: Prospective and descriptive study carried with adult patients, admitted with a diagnosis of COVID-19 confirmed by RT-PCR. We taste was reported. No hospitalization was required. Her most recent labs + + + with lymphocyte subsets revealed normal CD4 and CD8 T cell levels, low evaluated lymphocytes subsets (CD3 , CD4 , CD8 , CD19), serum immu- CD19 B cell levels, and normal immunoglobulins. Follow up COVID-19 noglobulin levels (IgG, IgM, IgA) and described the mean hospital stay PCR testing 1 month later remains positive. outcomes, need for intensive care, mechanical ventilation and death. CONCLUSIONS: There are concerns regarding persons with immuno- RESULTS: Of the 165 patients included, 65% were male, with an average deficiency being at higher risk of serious illness from COVID-19. of 58.7 years. The most related initial symptoms were dyspnea (80%), However, our patient’s clinical course suggests that certain types of fever (74%) and cough (70%). Among the reported comorbidities, 58% had immunodeficiency or immunomodulators may potentially limit the obesity, 47% systemic arterial hypertension and 25% diabetes. We observed that 40% lymphopenia, 43% reduction in CD3+, 46% reduction cytokine storm which causes some COVID-19 complications. Further + + + studies are needed. in CD4 , 50% reduction in CD8 and 39% reduction in CD19 . The average levels of IgG, IgM and IgA were 1,285, 121 and 296mg / dL, DiGeorge Syndrome and COVID-19 in Two respectively. We identified 3 patients with selective IgA deficiency and 206 Pediatric Patients all were discharged. Regarding the outcome, 28% required intensive care unit, 24% mechanical ventilation conditions and 23% of the patients Eilaf Fallatah1, Yatyng Chang1, Jose Calderon, MD1, Vivian Hernandez- died. Trujillo1; 1Nicklaus Children’s Hospital. CONCLUSIONS: Lymphopenia, reduction of CD8+, CD4+ and CD3+ RATIONALE: Immunocompromised patients, including those with cells were frequent in hospitalized patients, inferring greater clinical primary immunodeficiency, may be expected to have more severe severity. However, we identified three patients with selective IgA defi- COVID-19 disease. However, the evidence is unclear as limited cases ciency whose outcome was hospital discharge. have been reported. Hispanic ethnicity and obesity also appear to confer risk of more severe disease in adults. METHODS: Two pediatric patients with DiGeorge syndrome and COVID-19 are described. RESULTS: A 12-year-old female with DiGeorge syndrome with hypo- gammaglobulinemia on monthly immunoglobulin replacement and T cell lymphocytopenia, congenital heart disease, and VP shunt, presented to the ED with headache and an episode of emesis. Brain CT and shunt series were obtained to rule out shunt malfunction, both normal. Immediate family members were diagnosed with COVID-19 and our patient also tested PCR positive. She was treated with supportive care. Repeat COVID- 19 PCR testing 3 weeks later was still positive, although asymptomatic. A 13-year-old Hispanic male with DiGeorge syndrome, obesity, and congenital heart disease with immediate family members diagnosed with COVID-19 also tested PCR positive. Three family members required hospital admission, one of which required ICU admission and remains on supplemental oxygen. He had history of normal T lymphocytes and low IgM. Despite a complex medical history, he remained asymptomatic. Both patients had history of normal mitogens. CONCLUSIONS: Pediatric patients with primary immunodeficiency, specifically those with DiGeorge syndrome, may not necessarily be at increased risk of severe COVID-19 disease. One Hispanic patient with J ALLERGY CLIN IMMUNOL Abstracts AB67 VOLUME 147, NUMBER 2

Intravenous Immunoglobulin for Treatment of Two novel variants in signal transduction and 208 Severe Coronavirus Disease 19 (COVID-19) – A 210 activator of transcription 1 (STAT1) coiled-coil Literature Overview region cause STAT1 gain of function in an infant presenting with Pneumocystis jiroveci Syed Rizvi1, Huub Kreuwel2; 1Octapharm, 2Octapharma. pneumonia (PJP) and CMV viremia RATIONALE: COVID-19 was declared a global pandemic in March 2020. Previous experiences with SARS-Cov-2 showed that the main Tina Banzon, MD1, Sandra Burchett, MD1, Andrew Wehrman, MD1, Pui pathogenesis and pulmonary dysfunction lay in the overall cytokine Lee, MD, PhD1, Craig Platt, MD PhD1; 1Boston Children’s Hospital. dysregulation. Intravenous immunoglobulin (IVIg) has been recognized RATIONALE: Gain-of-function (GOF) mutations in STAT1 are associ- for its anti-inflammatory and immunomodulatory effects ated with a diverse phenotype, including chronic mucocutaneous candidi- METHODS: Based on evidence, clinicians have hypothesized that IVIg asis and autoimmunity. We report a 5-month-old boy presenting with PJP, therapy may improve the prognosis of critically-ill COVID-19 patients. A CMV viremia, and immune-mediated hepatitis with novel compound het- literature search was performed using the search terms: Corona, COVID- erozygous in-frame deletions in the coiled-coil region of STAT1. 19, IVIg, and Immunoglobulin. 10 published reports describing the METHODS: Next generation sequencing (Prevention Genetics), flow beneficial effects of IVIg in treating COVID-19 were identified. cytometry, quantitative PCR. RESULTS: A retrospective, multicenter cohort study that included 325 RESULTS: A 5-month-old male presented with PJP and CMV viremia. adult critical patients demonstrated early high-dose IVIg administration Immune phenotyping revealed mild T cell lymphopenia (CD3+: 1,029 improves the prognosis of critical COVID-19 patients. A retrospective cells/mcL, CD4+: 686 cells/mcL, CD8+: 258 cells/mcL) and normal T cell review of 58 patients with severe COVID-19 pneumonia compared proliferation to mitogens. B and NK cell numbers were normal or high. outcomes in those receiving high-dose IVIg treatment < 48 hours versus Sequencing of genomic DNA revealed novel biallelic variants in the > 48 hours after admission to ICU. Results demonstrated high-dose IVIg coiled-coil region of STAT1 (c.496_504del, p.Leu166_Asp168del, het- received < 48 hours after admission to ICU resulted in reductions in the erozygous; c.489_497del, p.Glu164_Leu166del, heterozygous). Neither use of mechanical ventilation, hospital/ICU stay, and 28-day mortality in variant is in gnomAD, and surprisingly, neither variant was found in either patients with severe COVID-19 pneumonia. An observational study con- parent. Functional assays were consistent with STAT1 gain-of-function. ducted in 10 COVID-19 patients demonstrated short-term moderate-dose The patient had increased IFN-g and IFN-a-mediated STAT1 phosphory- corticosteroid combined with high-dose IVIg reversed severe, deterio- lation and low Th17 cell percentage (0.09%). There was also increased rating COVID-19 patients who failed initial low-dose therapy. Three pub- expression of downstream IFN-stimulated genes: flow cytometry showed lished papers were identified using IVIg in pediatric COVID-19 patients baseline surface expression of CD64 and CD169 and quantitative PCR who presented with Kawasaki-like or PMIS (Pediatric COVID-associated showed increased expression of IFI44, ISG15, and Ly6E compared to Multi-system Inflammatory Syndrome). healthy controls. CONCLUSIONS: It may be useful to consider high-dose IVIg at the time CONCLUSIONS: We report PJP, CMV viremia, and immune-mediated of initiation of respiratory distress to potentially promote satisfactory hepatitis in a patient with novel compound heterozygous STAT1 variants. clinical recovery and reduce burden of care for COVID-19 patients. These variants are closely positioned in the coiled-coil domain, where numerous GOF mutations have been reported previously. To the best of An effective approach for recombinant our knowledge, this is the first report of an in-frame deletion causing 209 production of select SARS-CoV-2 proteins in increased STAT1 activity. Work is ongoing to determine whether one or Escherichia coli both variants is pathogenic.

Sayeh Agah1, Catherine Thorpe2, Martin Chapman, PhD FAAAAI2, Sa- bina Wuenschmann, PhD2; 1Indoor Biotechnologies, 2INDOOR Biotech- nologies, Inc. RATIONALE: Individuals with asthma may be at higher risk of becoming severely ill from COVID-19 which targets the respiratory tract and may cause asthma exacerbations. Serological testing can be useful to assess the true spread of COVID-19 and help protect vulnerable individuals. The SARS-CoV-2 spike and nucleocapsid proteins are the primary viral antigens against which antibodies are raised. We developed an efficient method for production of select SARS-CoV-2 proteins in E. coli to facilitate the development of diagnostics, research, and drug discovery. METHODS: SARS-CoV-2 Spike-RBD, full-length Nucleocapsid, and Nucleocapsid RNA binding domain (BD), were expressed in E. coli under IPTG induction. The proteins were purified using multi-step chromatog- raphy techniques. The purity of the SARS-CoV-2 proteins was assessed by LC-MS/MS, and their IgG reactivity tested using COVID-19 positive patients’ sera by ELISA. RESULTS: The Spike-RBD and Nucleocapsid proteins were expressed with high yields. The purified proteins had a relative abundance of >95% as assessed by LC-MS/MS with only trace contamination of host cell proteins. All three proteins showed high IgG reactivity (titers >1/10,000) against COVID-19 sera (n550), with Spike-RBD and Nucleocapsid RNA- BD exhibiting the highest sensitivity. CONCLUSIONS: Production of high quality SARS-CoV-2 proteins is feasible in E.coli and the purified proteins will provide useful tools to study the immune responses involved in COVID-19 including antibody and T cell responses, epitope mapping, diagnostics and drug discovery. AB68 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Germline RUNX1 Deficiency Predisposes to alemtuzumab she had a clinical response with cessation of gastrointestinal 211 Allergy and Autoimmunity bleeding and entered remission on abatacept as a maintenance therapy. CONCLUSIONS: We believe this is the first case of successful treatment Keith Sacco1, Karen Laky, PhD1, Min (Jenny) Li, PhD1, Matt of severe autoimmune enteropathy following a neonatal heart trans- Merguerian, MD PhD2, Kathleen Craft2, Lea Cunningham, MD3, Paul plantation with the combination of abatacept and alemtuzumab. Liu, MD PhD2, Pamela Guerrerio, MD PhD1; 1National Institute of Al- lergy and Infectious Diseases, NIH, Bethesda, MD, 2National Human Undiagnosed, familial cold auto-inflammatory Genome Research Institute, NIH, Bethesda, MD, 3National Cancer Insti- 213 syndrome (FCAS) masquerading as COVID-19 tute, NIH, Bethesda, MD. cytokine storm

RATIONALE: The Runx1 transcription factor decreases GATA3 and IL-4 1 1 1 expression and Th2 skewing and promotes Th1/Th17/Tregulatory (Treg) Dilawar Khokhar, MD , James Baker, MD FAAAAI ; University of cell development and function. We hypothesized that patients with Michigan. germline RUNX1 deficiency would be predisposed to allergic and/or RATIONALE: A patient presented in early April with fever and markers for autoimmune disease. acute inflammation that appeared to be cytokine storm from COVID-19. METHODS: Thirty-one patients (17 female; median age 42 years, range Molecular and antibody testing for COVID-19 and other infections were 2-74) with confirmed RUNX1 mutations were evaluated. Peripheral blood negative. Genetic testing was undertaken to identify a cause for his symptoms. was obtained to evaluate hematologic variables, total and allergen specific CASE: The patient is a 49-year-old male who initially presented In April IgE, and lymphocyte immune phenotypes. with a high fever, apparent pneumonia and elevated inflammatory markers RESULTS: 29/31 patients had a positive allergic history; 21 had allergic suggestive of cytokine storm from COVID-19. His history was notable for rhinitis, 16 allergic conjunctivitis, and 20 mild-moderate eczema controlled a prolonged hospitalization complicated by hyponatremia, hypokalemia, with topical glucocorticoids and emollients. Seven patients had doctor- pulmonary embolism and peripheral neuropathy. Extensive evaluation by diagnosed asthma with 1 patient receiving mepolizumab for eosinophilic Endocrinology, Rheumatology, Neurology and Infectious Disease failed to asthma. Four reported oral allergy syndrome. Two patients had IgE- identify a cause for his symptoms. During our evaluation we obtained a mediated food allergy to flounder and egg, respectively, and two had history of cold sensitivity and frequent febrile illness during his childhood biopsy-proven eosinophilic esophagitis. Five patients reported autoimmune in Bulgaria. He also reported fever symptoms during winters in Michigan disorders including mixed connective tissue disease, Hashimoto’s thyroid- and after minor trauma, and these were associated with arthralgias. itis, Sjogren’s syndrome, alopecia universalis and systemic Juvenile RESULTS: Screening of 201 immune associated genes revealed a variant in idiopathic arthritis. Median total IgE and eosinophil counts were within PLCG2; c.1596 G>T, which causes as sequence change replacing tryptophan the normal range (73.35 IU/mL; range 16 – 635 IU/mL and 215/mcL; range with cysteine at amino acid 532 of the PLCG2 protein. While this variant has 0-1000/mcL, respectively). Median CD4 and CD8 T cells counts were not been previously described, it is in an exon area associated with FCAS. within the normal range, although patients exhibited an increased frequency CONCLUSION: Patients with FCAS can have a clinical presentation of memory CD4+ T cells, decreased CD4:CD8 ratios, and decreased Tregs compatible with COVID-19 cytokine storm. Broad ranging genetic in peripheral blood when compared to healthy controls. screening is important to perform on patients with non-COVID-19, CONCLUSIONS: Patients with germline RUNX1 deficiency exhibit an cytokine storm-like presentations to identify novel gene variants poten- increased prevalence of atopic and autoimmune disorders, demonstrating tially causing these symptoms. The findings in this patient suggest that this an important role for Runx1 in tolerance development in humans. variant may be pathogenic and associated with a FCAS phenotype.

Successful treatment of severe autoimmune Schnitzler Syndrome With Extremely Elevated 212 enteropathy in a pediatric heart transplant 214 IL-6 Responds To Anti IL-1 Receptor Antagonist recipient with abatacept and alemtuzumab Kevin Diehl, Zaynab Ashoor1, Timothy Craig, DO FAAAAI2; 1Cairo 2 Elizaveta Kalaidina1, Elisabeth Utterson, MD1, Mai He, MD PhD1, University, Penn State University. Megan Cooper, MD PhD1; 1Washington University School of Medicine. RATIONALE: We previously reported Schnitzler Syndrome (SS) in a 73- RATIONALE: Disorders of immune dysregulation have been reported in year-old woman with extremely elevated levels of Il-6 and normal levels of IL- children who underwent heart transplantation in infancy. Diagnosis and 1 who responded to IL-6 receptor antagonists. SS is a rare autoinflammatory management of such disorders are challenging. Here we describe a disorder, which is defined by two major criteria: chronic urticaria and treatment approach to severe autoimmune enteropathy following heart monoclonal immunoglobulin M (IgM) or immunoglobulin G gammopathy, in transplantation in a child. combination with at least two of the following minor criteria: recurrent fever, METHODS: Flow cytometry, TCRVb spectratyping, microscopy and joint and/or bone pain, leukocytosis and/or elevated C-reactive protein (CRP). immunohistochemical staining. Usually IL-1 is elevated and treatment is directed at IL-1 receptor. RESULTS: A 21-month-old girl with medical history of dilated cardio- METHODS: We reassessed this case of SS with elevated IL-6 and myopathy necessitating heart transplantation at the age 2 months was assessed her response and adverse effects to IL-6 receptor inhibition evaluated for chronic hematochezia requiring daily transfusions of RBCs. leading to failure to control her symptoms and her response to IL-1 receptor An endoscopic biopsy showed crypt apoptosis, similar to that seen with inhibition despite a normal IL-1. acute graft-versus-host disease (GVHD). We hypothesized that these RESULTS: Because of elevation of IL-6 she was first started on sarilumab. GVHD-like changes were caused by autoreactive T cells emerged as a After months of control she experienced a resurgence of symptoms due the consequence of neonatal thymectomy and immunosuppression. Pertinent development of neutralizing antibodies. Consequently, tocilizumab was results of work-up which supported this reasoning included: recent thymic commenced; however, this was also discontinued due to decreased emigrants at 0.8% of CD4+ T cells, 2% na€ıve and 98% memory T cells in efficacy. Given the failure of anti-IL-6 agents, she was then started on an CD45RA/RO analysis, T-cell repertoire with 15 oligoclonal families, anti-TNF-alpha, which failed to control her symptoms and she had a severe serum ILR2a of 1,280 IU/mL and IgG of 1833 mg/dL. Despite treatment flare. Despite normal level of IL-1, she was started on anakinra, which for with steroids and everolimus, the patient continued to have daily many months totally controlled her symptoms. More recently, mild hematochezia which eventually required colectomy. We approached symptoms have resurfaced suggesting partial refractoriness. treatment similar to that of patients with allogeneic GVHD and initiated CONCLUSIONS: These results suggest that an anti-IL-1 receptor abatacept followed by a combination of abatacept and ruxolitinib, and, antagonist is effective in the management of Schnitzler syndrome even finally, a combination of abatacept and alemtuzumab. Following with the unusual profound elevation of IL-6. J ALLERGY CLIN IMMUNOL Abstracts AB69 VOLUME 147, NUMBER 2

Are we diagnosing too late? RAG deficiency in cytopenia (AIC). There is a lack of understanding of the clinical spectrum, 215 young adults with end organ damage treatment outcome, and biomarkers for AIC in patients with pDGS. The aim of this project is to characterize the natural history and immune Tara Saco1, Christoph Geier2, David Buchbinder3, Joseph Hernandez4, phenotype of the heterogeneous population of pDGS with AIC, ranging Svetlana Sharapova5, Alexis Cochino6, Tomas Milota7, Elema Laty- from manageable to severe, and biomarkers predicting escalation to sheva8, Emma Westerman-Clark9, Olajumoke Fadugba, MD10, Emma second-line B and/or T cell therapies. Morris11, Michael Albert12, Dimana Dimitrova13, Despina Moshous14, METHODS: In our tertiary care center we retrospectively collected data Jennifer Kanakry15, Steven Holland, MD16, Jean-Pierre de Villartay17, on clinical presentation, disease severity, immunological phenotype, Ravishankar Sargur, MBBS MD FRCPath FRCP18, Luigi treatment selection and response for patients with pDGS with AIC and Notarangelo, MD19, Jolan Walter, MD PhD FAAAAI9; 1University of age-matched controls. South Florida Morsani College of Medicine, 2Outpatient Clinic Vienna, RESULTS: Of 69 pDGS patients, 28 (40%) had a history of cytopenia. 10 Austria, 3CHOC Children’s, 4Stanford University School of Medicine, of 28 patients with cytopenia had AIC (14% of cohort). Seven patients had 5Belarusian Research Center for Pediatric Oncology and Hematology, multi-lineal AIC (Evans syndrome (ES)) and 3 had immune thrombocy- 6Alfred Rusescu Institute for Mother and Child, 7Charles University in topenia alone. 4 of 7 pDGS patients with ES had refractory cytopenias Prague, 8NRC Institute of Immunology FMBA Russia, Russian Federa- requiring second line immunomodulation. Those with refractory AIC had tion, 9University of South Florida, 10University of Pennsylvania, 11UCL both evidence of antibody deficiency (ADS) and lower na€ıve T cell counts Institute of Immunity and Transplantation, 12Dr von Haunersches Kinder- (94 cells/uL), compared to pDGS patients with mild AIC (355 cells/uL) spital, Lidwig-Maximilians-Universitat, 13National Institute of Allergy and the general population. Three of the 4 received rituximab and one and Infect, 14Necker-Enfants Malades University Hospital Paris, 15Na- patient is stabilized on sirolimus and high dose subcutaneous tional Institute of Allergy and Infectious Diseases, 16NIH, 17Institut Ima- immunoglobulin. gine Hopital Necker Enfants Malades, 18Northern General Hospital, CONCLUSIONS: AIC is common in pDGS and may be treatment- 19NIAID/NIH. refractory. Lower na€ıve T cell count and ADS with need for immunoglob- RATIONALE: Pathogenic variants of recombination activating genes ulin replacement therapy distinguish pDGS patients with severe refractory (RAG1/2) are increasingly recognized among adult patients with antibody AIC. Second line rituximab or sirolimus may improve AIC for these deficiency syndromes. Despite their complex medical history with infec- patients. tious and non-infectious complications, identification is delayed. Our aim is to raise awareness and provide diagnostic clues for this vulnerable Systemic inflammatory syndromes with patient population. 217 immunodysregulatory phenotype: clinical METHODS: Retrospective chart review including data on demographics, characteristics, genetic findings and clinical features, laboratory evaluation and treatment. therapeutic response RESULTS: In our cohort of 17 patients, all had history of frequent 1 2 ~ childhood infections. However, combined immunodeficiency (CID) with Grazielly Pereira Pereira GF , Alex Prado, MD , Jaqueline Brandao ~ 2 2 n pathogenic RAG1/2 variants was not diagnosed until adulthood. Brandao, JC , Francine Zanetti Zanetti, FA , Nazoneth Alberto , Samu- canda alberto, NE2, Jorge Kalil, MD, PhD2, Luiz Fonseca, MD, PhD3, Fa- Bronchiectasis and non-infectious complications (autoimmune cytopenia, 4 1 vitiligo, alopecia) were common contributors to disease burden. Routine bio Castro Castro, FF , Myrthes Toledo-Barros, Barros, MAM , Leonardo 1 1 ~ immune phenotyping showed variable antibody deficiencies; however, the Mendonc¸a Mendonc¸a, LO ; Hospital das Clınicas, FMUSP, Sao Paulo, 2 3 ~ 4 ~ na€ıve T cell fraction was uniformly low (<15% of CD4+ T cells) and 5/11 Brazil, USP, Universidade de Sao Paulo, Sao Paulo University. (45%) of patients tested had detectable antibodies to cytokines, a hallmark RATIONALE: Clinical immunodysregulation phenotypes that simulate of partial RAG deficiency. All patients received immunoglobulin replace- recurrent fever inflammatory syndromes (SIFRs) have so far been reported ment therapy (IgRT), although in some cases IgRTwas initially denied due only in clinical case reports. This ‘‘clinical-immunodromic’’diagnosis has to mild hypogammaglobulinemia or normal IgG despite evidence of a great impact in the indication of correct sequencing, in the therapeutic impaired function. Out of 17, three patients successfully underwent and conduct and without monitoring these patients. Due to the rarity of each three are awaiting hematopoietic stem cell transplantation (HSCT). syndrome, practical and real-life data on SIFRs that mimic autoinflamma- CONCLUSIONS: Although RAG-CID is being increasingly detected tory diseases are scarce worldwide. among adults, genetic diagnosis is delayed. Patients may not easily be METHODS: Retrospective analysis of clinical, genetic and therapeutic approved for IgRT. Disease burden is often high when definitive diagnosis data on SIFRs that mimicked autoinflammatory diseases followed from is achieved, and HSCT could be considered. As specific immune 2015 to 2020. phenotyping may not be available for outpatient Allergists/ RESULTS: Twenty eight patients had the final diagnosis of immunodys- 5 Immunologists, upfront genetic testing is a feasible alternative to identify regulatory syndrome. The majority (n 22) started in the pediatric age these patients, expedite IgRT approval and improve treatment outcomes group, with 65% of the males having ALPS-like phenotype. The average pre- and post-HSCT. global diagnostic delay was 10 years. Recurrent fever with long-term periods was more frequently found in patients with ALPS-like phenotypes Clinical and Treatment History of Patients with (87.5% x 58% and 28 x 14 days - respectively). Common findings were: 216 Partial DiGeorge Syndrome and Autoimmune joint, gastrointestinal, involvement of lymphoid organs and neurological Cytopenia conditions, while infection was triggered in 40%. All patients presented with elevated inflammatory tests and thrombocytopenia, leukopenia and Priya Patel1, Emma Westermann-Clark, MD2, Sonia Joychan3, Ahmad lymphopenia were found. Laboratory markers of immunodysregulation Shaker, MD4, Boglarka Ujhazi, BS5, Cristina Meehan, BS5, Maryssa were found in 25% of patients. Ellison, BS5, Krisztian Csomos6, Sumai Gordon, BS5, Daime Genetic sequencing was relevant and had great genetic variability in 76% Nieves, APRN5, Jaz Mateus, MPH1, Irmel Ayala, MD1, Jolan of patients. IVIG and M-tor system inhibitors were the most widely used Walter, MD PhD FAAAAI5, Panida Sriaroon, MD FAAAAI5; 1Johns Hop- drugs with therapeutic success. kins All Children’s Hospital, 2James A. Haley Veterans Hospital, 3Dear- CONCLUSIONS: Clinical, laboratory signs and genetic findings of born Allergy & Asthma Clinic, P.C., 4Baycare Medical Group, immunodysregulation allow for early and adequate diagnosis. These 5University of South Florida, 6Massachusetts General Hospital. findings serve as warning signs for immunodysregulatory syndromes RATIONALE: Patients with partial DiGeorge Syndrome (pDGS) can whose final diagnosis has a major impact on clinical practice present with immune dysregulation, the most common being autoimmune AB70 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Diagnostic Dilemma on Novel Pathogenic Hereditary heterozygous FoxN1 variant with 218 Variant of Cytotoxic T-Lymphocyte Associated 220 associated T cell lymphopenia in a family Protein 4 (CTLA-4) in a Family with Chronic ITP and Immune Dysregulation Andrea D’Mello, MD1, Amara Seng1, Marissa Love, MD1; 1University of Kansas Medical Center. Priyanka Timothy, MD1, Mary Ann Miranda, MD1, Jocelyn Farmer, MD RATIONALE: Transcription factor FOXN1 is critical to thymus develop- PhD2, Jolan Walter, MD PhD FAAAAI1, Emma Westermann-Clark, MD1; ment and biallelic loss-of-function (LoF) FOXN1 mutations result in complete 1University of South Florida, 2Massachusetts General Hospital. athymia in both humans and mice. The effects of heterozygous single point RATIONALE: Inborn errors of immunity are increasingly linked to mutations in FOXN1 have been less well defined. We describe a young child autoimmune cytopenias, especially in families with immunodeficiency and and parent with T cell lymphopenia and the same heterozygous FOXN1 variant. immune dysregulation. We present a large family study with several METHODS: Genetic mutations in patient samples were identified via next members presenting with chronic immune thrombocytopenia (ITP) and generation sequencing performed by Invitae genetic testing. Lymphocyte variable combinations of immune dysregulation and infections. The subsets were assessed via flow cytometry and measurement of T cell reception proband and kindred were diagnosed with a novel variant of unknown excision circles (TRECs) was completed with state newborn screening. significance (VUS) in CTLA-4. Diagnostic approach to confirm the RESULTS: Our pediatric patient was found to have abnormal TRECs association between clinical phenotype and the pathogenicity of this novel newborn screening, nearly absent T cells, undetectable na€ıve CD4 T cells, variant is described. normal NK and B cells. Target gene sequence analysis of genes associated METHODS: Retrospective chart review yielded demographic informa- with severe combined immunodeficiency and combined immunodefi- tion, clinical history, immunological phenotype, genetic panel testing and ciency revealed a variant of uncertain significance in the FOXN1 gene treatment response. Functional testing included CTLA-4 expression and [c.961C>T (p.His321Tyr)]. The same single point mutation was identified transendocytosis assay. in the asymptomatic father, who continues to have an isolated low CD4 RESULTS: Proband a 50-year-old female, presented with recurrent count and is not on any antimicrobial prophylaxis. Our pediatric patient is pneumonia, chronic diarrhea, hypothyroidism, granulomatous interstitial currently asymptomatic on prophylactic antimicrobial agents and IgG lung disease, and ITP. Immune phenotyping confirmed hypogammaglob- supplementation despite continued severe T cell lymphocytopenia. ulinemia requiring immunoglobulin replacement therapy. Proband, along CONCLUSIONS: This is an interesting case series of T cell lymphopenia with three other family members, had a novel CTLA4-VUS (c.173G>C related to heterozygous FOXN1 single point mutation found in a patient p.Cys58Ser). Proband and her adult cousin had chronic ITP and who has a parent with the identical mutation. Heterozygous FoxN1 variant hypogammaglobulinemia; however, two children with this VUS only patients do see a gradual increase in their T cells and in our case series the had history of milk-induced colitis and asthma, respectively. father has done well without need for thymic or stem cell transplant. Internalization of CD80/86 was impaired in CTLA-4 trans-endocytosis assay performed on T cells from proband’s cousin, revealing a functional A Novel De Novo PGM3 Pathogenic Mutation impairment of CTLA-4. For the proband, abatacept (CTLA4-Ig) was 221 Identified in an Infant Presenting with initiated and resulted in marked improvement in respiratory and gastro- Abnormal TREC Assay and Severe Neutropenia intestinal symptoms along with decreased frequency of infections. 1 1 2 CONCLUSIONS: Andrew Winslow , Elizabeth Jalazo, MD , Thomas Felton, MS CGC , The segregation of clinical phenotype within the 2 1 family, functional testing, and response to abatacept support this CTLA- Eric Weimer, PhD , Nathan Montgomery, MD PhD , Michael Winstead, MD1, Timothy Moran, MD PhD1; 1University of North Car- 4 VUS as pathogenic variant. Our study highlights the importance of 2 genetic testing and functional studies in patients with immune dysregula- olina School of Medicine, University of North Carolina. tion and immunodeficiency. RATIONALE: Phosphoglucomutase 3 (PGM3) deficiency is an auto- somal recessive congenital glycosylation disorder associated with a Chronic Granulomatous Disease (CGD): variable clinical phenotype including immunodeficiency, atopy and pro- 219 Presentation at Diagnosis and Burkholderia gressive bone marrow failure. We present an infant with compound Colonization heterozygous pathogenic PGM3 mutations, including a novel de novo variant, who initially presented with an abnormal T-cell receptor excision Amrita Dosanjh, MD1; 1RCHSD. circles (TREC) assay on newborn screen. RATIONALE: Chronic Granulomatous Disease (CGD) is a primary METHODS: Rapid whole genome sequencing was performed by Perkin immune disorder characterized by serious and recurrent infections. The Elmer Genomics on Illumina next generation sequencing system. clinical presentation and diagnosis of this immune disease is often delayed RESULTS: A term Hispanic female born to non-consanguineous parents since the hallmark infections such as pneumonia are associated with presented at two weeks of life for evaluation of abnormal TREC assay on Pediatric isolated illnesses. newborn screen. Flow cytometry showed severe lymphopenia with METHODS: This study reviewed the presenting initial clinical features of decreased numbers of CD3+ T cells (305 cells/microL) and CD19+ B cells CGD utilizing a retrospective search and review of clinical medical charts (398 cells/microL), and low percentage of na€ıve CD45RA+ T cells (18%, and clinical data. The purpose of the study was to identify patients with normal 64-95%). Proliferative responses to PHA mitogens were decreased. Burkholderia respiratory infection, and to describe the clinical presentation IgM and IgA were below the limit of detection but IgE was normal for age. of the disease among a Pediatric population.The study was approved by the The patient also had severe neutropenia (100-300 cells/microL) poorly IRB as a retrosepctive chart review study. responsive to filgrastim. Targeted sequencing of 25 genes associated with RESULTS: The study identified that respiratory disease was found among severe combined immunodeficiency revealed no pathogenic variants. Rapid 62.5% of the 16 patients who had early diagnosis medical information whole genome sequencing showed two pathogenic variants in PGM3:a documented. Additionally, the mean levels of inflammatory markers were maternally inherited c.1049T>C (p.Ile350Thr) missense variant and a novel elevated. Burkholderia infection was not common presenting features, de novo c.1558C>T (p.Arg520Ter) nonsense variant. The patient underwent based on this analysis. mismatched unrelated umbilical cord transplant with successful engraftment CONCLUSIONS: The early presentation of Pediatric CGD is associated and no complications one month post-transplant. with respiratory disease, elevated inflammatory markers, but not CONCLUSIONS: We present an infant with a novel pathogenic PGM3 Burkholderia infection. mutation who presented with cellular immune deficiency and severe neu- tropenia. PGM3 deficiency should be considered for infants with abnormal TREC assay and neutropenia. J ALLERGY CLIN IMMUNOL Abstracts AB71 VOLUME 147, NUMBER 2

In-Utero Exposure to Immunosuppressive Omenn Syndrome with Autoreactive T-cell 222 Medications Resulting in Abnormal Newborn 224 development after viral infections in two Screening for Severe Combined patients with Leaky Severe Combined Immunodeficiency (SCID) Immunodeficiency (SCID)

Elisa Ochfeld1, Aisha Ahmed1; 1Northwestern University Feinberg Maria Chitty-Lopez, MD1, Jessica Trotter, MA BS1, Carla Duff, CPNP- School of Medicine, Ann & Robert H. Lurie Children’s Hospital of PC APRN MSN CCR1, Gretchen Vaughn, APRN MSN2, Benjamin Chicago. Oshrine, MD2, Gauri Sunkersett, DO2, Jennifer Leiding, MD FAAAAI1; RATIONALE: Exposure to immunosuppressive medication in-utero is an 1University of South Florida, St. Petersburg, FL, USA, 2Johns Hopkins important cause of secondary T cell lymphopenia in infancy, which can be All Children’s Hospital, St. Petersburg, FL, USA. detected via T- cell receptor excision circle (TREC) quantification on SCID RATIONALE: Leaky SCID presents with reduced but not absent numbers newborn screening. At present, there is a paucity of literature surrounding of CD3+ T-cells and lymphocyte proliferation to phytohemagglutinin management of these infants. A protocol including recommendations for (PHA) in the absence of maternal T-cells. Despite antimicrobial pharma- vaccinations and follow-up is needed to augment care. cologic prophylaxis patients remain susceptible to a variety of opportu- METHODS: Patients referred to immunology for abnormal TREC results nistic infections. T-cells without thymic maturation in leaky SCID can on NBS were identified as having in-utero exposure to immunosuppressive undergo oligoclonal expansion, particularly in response to viral infections, medications and were followed until lymphopenia improved. leading to the development of Omenn Syndrome. RESULTS: Four infants with low TRECs secondary to in-utero immuno- METHODS: Retrospective chart review. suppressive exposure were evaluated. Medication exposures included RESULTS: Patient A is a 4-month-old female with TBX1 haploinsuffi- azathioprine, infliximab, hydroxychloroquine, and fingolimod. All infants ciency, T-B+NK- phenotype, absent T-cell proliferation to PHA, and ab- were born full term. TRECs ranged from 101-206 (normal value in IL >_ sent maternal T-cell engraftment awaiting thymus transplantation. One 250 at time of test). T cell lymphopenia (CD3< 1500) was present in week after developing rhinovirus, she developed a severe eczematous 50% of cases. CD4 T cell lymphopenia was more prominent than CD8 lym- rash, erythroderma, alopecia universalis, peripheral eosinophilia phopenia. Mitogen proliferation was normal when performed (3/4 cases). (3890cells/uL), and an elevated IgE (29.3IU/mL). T-cell receptor spectra- Thrombocytosis was present in 100% of cases, and an undetectably low typing revealed an oligoclonal repertoire, along with memory T-cells effector CD4 na€ıve T cell population was present in 100% of cases. (CD4+RO+) expansion (1026cells/uL). Patient B is a 10-month-old female Severity of TREC abnormality did not correlate with presence of T cell with Rac2 gain-of-function, T-B+NK+ phenotype, absent maternal T-cells, lymphopenia. Immune abnormalities normalized in 75% patients by age and normal T-cell proliferation to PHA. She was positive for SARS-Cov-2 4 months. All vaccinations, including live vaccines, were given to all pa- antibodies with positive household contact. Two weeks later, she devel- tients by age 4 months. oped an extensive severe eczematous rash and increased atypical lympho- CONCLUSIONS: It is critical to assess for in-utero immunosuppressive cytes. T-cell receptor spectratyping is pending. Both patients were treated exposure in infants with abnormal TREC results on NBS. In the infants with topical corticosteroids. Patient A required systemic steroids and evaluated, secondary T cell lymphopenia associated with maternal immu- cyclosporine and eventually underwent unmanipulated matched sibling nosuppressive use resolved or significantly improved by age 4 months. donor hematopoietic cell transplantation at 9 months of age. CONCLUSIONS: Leaky SCID patients are at risk for infectious Characterizing Neutropenia in Severe Combined complications, that can trigger the development of auto-reactive T-cells. 223 Immunodeficiency Auto-reactive, oligoclonal T-cells can lead to organ inflammation that clinically resembles graft-versus-host disease. Topical and systemic Abeer Siddiqi1, Angela Chan, MD1, Elizabeth Garabedian, RN, MSLS2, 1 1 immunosuppression can be effective in the upfront management of Ramsay Fuleihan, MD FAAAAI , Joyce Yu, MD FAAAAI , Deepti Desh- Omenn Syndrome. pande, MD1; 1Columbia University Irving Medical Center, 2NIH. RATIONALE: Neutropenia has been observed in SCID due to ADA-1 and AK2 mutations but is less reported in other forms of SCID. We sought to determine and characterize the frequency of neutropenia in SCID. METHODS: We included all subjects with SCID in the USIDNET registry. Most (80%) had known mutations in AK2, ADA-1, PNP, FOXN1, RAG1, RAG2, LIG4, NHEJ1, DCLRE1C, IL2RG, JAK3, CD3D or IL7R. Clinical data and mortality were compared between those with vs. without reported neutropenia (defined as physician-diagnosed neutropenia) using Chi2 (Fisher’s exact)/Mann Whitney tests. RESULTS: Of the 231 individuals with SCID with a median age (at last USIDNET entry) of 6 years; IQR (1-13), 66% (152/231) were male. Neutropenia was reported in 17.7% (41/232), of which, 6 individuals reported immune neutropenia. Neutropenia by genetic mutation included ADA-1 22% (11/50), RAG-1/2 21% (6/28), IL7R 21.4% (3/14), IL2RG 8.5% (5/59), JAK3 37.5% (3/8) and AK2, 100% (2/2), PNP 50% (1/2) and LIG4 33.3% (1/3). Those with vs. without neutropenia were younger [median (IQR): 3 years (1-7) vs. 8 years (2-15) respectively, p<0.01] and neutropenia was more often reported in females [29.1% (56/79)] vs. males [11.8 % (27/152)], p<0.01. While overall reported mortality in SCID was ;18% (40/226), there was no difference between those with neutropenia (25% (10/40)) vs without (17% (31/186)), p50.26. CONCLUSIONS: Neutropenia is not uncommon in SCID. Although not associated with differences in mortality, the underlying etiologies for neutropenia, response to immune reconstitutive therapies and the potential impact on clinical outcomes require further study. AB72 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Maternal Immunosuppression for Myasthenia Detection and Characterization of Specific Anti- 225 Gravis Mimicking SCID on Newborn Screening 227 Apolipoprotein E4 IgG Antibodies in Human Plasma and an Intravenous Immunoglobulin Jenyfeer Blanco1, Anne Yates, MD FAAAAI2; 1University of Mississippi Preparation (Gammagard Liquid) Medical Center, 2University MS Medical Center. RATIONALE: Screening with T cell receptor incision circles (TREC) Alfred Weber1, Andrea Engelmaier1, Eva Minibeck1; 1Baxalta Innova- assay identifies newborns with severe T cell deficiency, including Severe tions GmbH, now part of Takeda. Combined Immune Deficiency syndromes (SCID) and other causes. RATIONALE: Apoliprotein E4 (apoE4) is the strongest genetic risk METHODS: A 3 week old Caucasian female born at 37 weeks gestation factor for Alzheimer’s Disease although the detailed method of action is by vaginal delivery to a 28 year old mother with a history of myasthenia still unclear. Kim et al (JEM 209, 2149) demonstrated that a monoclonal gravis post thyroidectomy requiring azathioprine 100 mg daily, prednisone anti-apoE4 antibody reduced the amyloid deposition in an AD mouse 10 mg daily, and omeprazole during the pregnancy and with breastfeeding. model. These data prompted us to investigate human plasma and the intra- Birth weight 2669 grams. She had a hip click, but did not have cardiac or venous immunoglobulin G (IVIG) preparation Gammagard Liquid (GGL) any other malformation. Newborn SCID screen was positive. for the presence of anti-apoE4 IgG. Breastfeeding was stopped to prevent further immunosuppression. METHODS: A direct ELISA with purified human apoE4 (Sigma) was RESULTS: At 3 weeks old she had very low total white blood cell count (0.8 used for the detection of anti-apoE4 IgG in a human reference plasma pool TH/cmm), severe neutropenia (absolute 0.03 TH/cmm), severe lymphopenia and several lots of GGL. The binding of natural occurring anti-apoE4 IgGs (absolute 0.35 TH/cmm), anemia (hemoglobin 7.9 g/dL), and borderline low was compared with that of a monoclonal and a polyclonal anti-apoE4 platelets (277 TH/cmm). Lymphocyte subsets showed profoundly low T cells preparation. Binding specificity was checked by competition studies using (absolute CD3 206 cells/uL, absolute CD4 177 cells/uL, absolute CD8 83 purified apoE4, apoE3 and apoE2. cells/uL), no B cells (CD19 <20 cells/uL), and normal NK cells (171 cells/ RESULTS: Human plasma and GGL contain anti-apoE4 IgG with EC50 uL). CBC and lymphocyte subsets were repeated weekly for one month and binding values in the low one-digit mg/mL range. Binding to plate-bound then monthly. At 3 months old, her total white blood cell count was 5.90 TH/ apoE4 was shown to be specific as it could be dose-dependently inhibited cmm, neutrophils 1.06 TH/cmm, and lymphocytes 3.95 TH/cmm. CD4 cells by apoE4 in solution and by a monoclonal anti-apoE4 antibody. In contrast, were normal (1540 cells/uL), and CD8 cells were moderately low (289 cells/ purified apoE2 and apoE3 did not dose-dependently compete with binding uL). CD19 B cells were normal (975 cells/uL). She remained healthy. She of anti-apoE4 IgG to apoE4 suggesting the presence of conformation-spe- tolerated killed vaccines but has not had live viral vaccines. cific antibodies specifically targeting apoE4. CONCLUSIONS: Taking azathioprine with prednisone during pregnancy CONCLUSIONS: Specific human anti-apoE4 IgGs, described to our best may cause secondary, reversible immune suppression in the fetus. knowledge in plasma and IVIG for the first time, add to the list of rare examples that also naturally occurring IgG antibodies can be endowed with Difference in clinical characteristics of patients specific binding to conformationally different forms of proteins. 226 with common variable immunodeficiency (CVID) according to pulmonary alterations - A cohort of Real-World Evaluation of Immune Globulin 182 patients from a Brazilian tertiary hospital 228 Subcutaneous 16.5% in the Treatment of Primary Immunodeficiency Priscila Franco, MD1, Rosana Agondi, MD PhD1, Grazielly Pereira3,Per- eira GF1, Octavio Grecco, MD, MSc2, Ana Karolina Marinho, DO2, Jeffrey Langford, MD1, Richard Herrscher, MD2, Samantha Myrthes Toledo Barros3, Myrthes T. Barros2, Jorge Kalil, MD, PhD2,Cris- Mehta, PharmD3, Lucinda Van Anglen, PharmD3; 1Langford Allergy, tina Kokron, MD, PhD2; 1University of S~ao Paulo, 2University of Sao Paulo, LLC, 2AIRCare P.A., 3Healix Infusion Therapy, LLC. 3Hospital das Clı´nicas, FMUSP, S~ao Paulo, Brazil. RATIONALE: Immune Globulin Subcutaneous (Human), 16.5% solution RATIONALE: One of the main clinical manifestations in CVID patients (IGSC 16.5%) is a subcutaneous immunoglobulin (IG) indicated for is predisposition to recurrent sinopulmonary infections that can lead to primary immunodeficiencies (PID) in adults. Approved in 5/2019, data is persistent structural lung disease. We evaluated the difference in clinical mostly limited to clinical trials. We report efficacy, safety, and tolerability characteristics between CVID patients with and without bronchiectasis. of IGSC 16.5% (CutaquigÒ) in a real-world setting. METHODS: Retrospective observational study of medical records of METHODS: We conducted a retrospective review of patients receiving IGSC CVID patients followed at a Brazilian tertiary center during 21 years. 16.5% from product availability through 7/2020. Physicians initiated therapy Demographic data, clinical characteristics, immunoglobulin levels, and in the clinic setting, with on-site nursing training. Pharmacists dispensed drug pulmonary alterations through chest CT scan were compared between two and supplies, performing comprehensive assessments upon initiation and subgroups of CVID patients divided by pulmonary characteristics. monthly. Data collection included demographics, IGSC 16.5% regimen, RESULTS: Among the 182 patients of this cohort, 40.1% had bronchi- adverse reactions, and respiratory tract infections through 52 weekly infusions. ectasis and 42.3% bronchial thickening and micronodules (BT&M) in the RESULTS: Ninety patients (age 50.2611.2, female 82%) initiated IGSC chest CT scan. The majority were female in both groups (around 56%) with 16.5% during the study period. Of these, 33 (37%) transitioned from mean age of 48 years. Symptoms begun earlier in the bronchiectasis group another IGSC product, 30 (33%) transitioned from intravenous IG, and 27 comparing with those with BT&M (13.8x19.3 years, p50.036). The mean (30%) were IG-na€ıve. Patients have completed an average number of time to diagnosis was longer in the first group (15.7x12.9 years, p50.090). 31616 weekly infusions, with 14 (16%) completing 52 infusions. Mean There was no difference between the two groups regarding sinusitis dose was 138640.4 mg/kg/week and median maximum infusion rate was incidence (around 69%). The average immunoglobulin levels before IVIG 60.8 mL/hr/all sites (min 22.1, max 93.5). Local-site reactions were replacement in the bronchiectasis and BT&M groups were: IgG reported in 60 (67%) patients and systemic reactions were reported in 50 278.1x221.4mg/dL, respectively (p50.065), and the IgG post IVIG were (56%) patients. Most common reactions were swelling (rate 0.103/ 681.6x565.8mg/dL, respectively (p50,019). The bronchiectasis group infusion) and fatigue (rate 0.129/infusion). Incidence of reactions was presented higher incidence of air trapping and mosaic pattern in the chest highest with the first infusion, then diminished significantly (local-site CT comparing to the BT&M group (11.5%x4.4%, p>0.05). p<0.001, systemic p<0.001). Overall, 35 (39%) patients experienced 53 CONCLUSIONS: The age of onset symptoms in CVID patients as well as mild to moderate bacterial respiratory tract infections, predominantly sinus the diagnosis delay increases their morbidity and mortality and is infections. Three were serious bacterial infections. associated with the development of bronchiectasis, probably due to a CONCLUSIONS: These data demonstrate IGSC 16.5% for PID is greater predisposition to infections during childhood. effective and well-tolerated in a real-world setting. J ALLERGY CLIN IMMUNOL Abstracts AB73 VOLUME 147, NUMBER 2

Impact of immunization with pneumococcal antibodies were detected among patients with available immunogenicity 229 conjugated vaccines on the aplicability of the data (n5194). diagnostic criteria for specific pneumococcal CONCLUSION: These data support previous observations that fSCIG is antibody deficiency well tolerated in clinical practice by patients with PIDD. Baxalta US Inc. (a Takeda company) funded this study and writing support. Daniela Navarrete-Cortes1, David Rodriguez-Cabezas, MD1, Marıa Cristina Mayol1, Antonia Sanchez1, Aileen Ferran1, Nicole Silva1, Con- Lower IgM levels after rituximab use is stanza Silva1, Teresa Quiroga, MD1, Katia Abarca, MD1, Rodrigo Hoyos1; 231 associated with sepsis 1Pontificia Universidad Catolica de Chile School of Medicine. Idil Ezhuthachan1, Mara Shapero2, Joanna Fishbein3, Blanka Kaplan, RATIONALE: Diagnostic criteria for specific antibody deficiency (SAD) 3 1 were established before the incorporation of pneumococcal conjugate MD FAAAAI ; Steven & Alexandra Cohen Children’s Medical Center of NY, 2Steven & Alexandra Cohen Children’s Medical Center of NY, vaccines (PCV) in immunization schedules. We evaluated the effect of 3 PCV immunization on the applicability of these criteria. Northwell Health. METHODS: We compared the serologic response to the pneumococcal RATIONALE: Rituximab is a chimeric monoclonal antibody against polysaccharide vaccine (PPV23) of 242 pediatric patients with recurrent CD20 that is widely used for treatment of autoimmune diseases and infections who completed an immunization series with either PCV10 or malignancies. In a subset of patients, rituximab has been associated with PCV13, to that of 224 PCV-na€ıve patients. Specific anti-polysaccharide infections and persistent humoral immunodeficiency. IgGs to ten serotypes (1, 3, 4, 5, 6B[26], 9V[68], 14, 18C[56], 19F[19], 23F METHODS: A retrospective cohort study was conducted on patients who [23]) were measured by ELISA. received rituximab and presented to a tertiary center for immune evaluation RESULTS: Similar serotype specific antibody levels were found between with recurrent and/or severe infections. Primary disease information, patients who received PCV10 or PCV13, irrespective of the total number of infection history and laboratory data including immunoglobulin levels and doses (3 or 4). PPV23 immunization of PCV-experienced patients lymphocyte phenotypes at presentation were collected. increased antibody levels for all serotypes, except for serotype 19. No RESULTS: 38 patients, ages 17-78, were identified; 61% were females. differences in antibody levels were found for any serotype between PCV- Infections leading to evaluation included lower respiratory infections experienced and PCV-na€ıve patients after PPV23. 22 PCV-experienced and (50%), upper respiratory infections (47%), sepsis (24%), skin infections 16 PCV-na€ıve patients had antibody levels pre/post PPV23. At baseline, (13%) and colitis (5%). Lower IgM levels were observed significantly 48% of PCV-experienced and 20% of PCV-na€ıve patients had antibody more often in patients with sepsis compared to those without (median levels >_1.3mg/mL for >_50% of the serotypes. Antibody levels increased at [IQR]: 31 [10-81] vs 12 [5-17]). We failed to find a statistically significant least 2x for >_50% of the serotypes in 59% of the PCV-experienced and 69% association between other immunoglobulin levels and lymphocyte subset of the PCV-na€ıve patients after PPV23. counts with history of skin or respiratory infections, including pneumonia. CONCLUSIONS: PCV immunization decreases the applicability of SAD CONCLUSIONS: Low IgM levels were previously reported as a risk diagnostic criteria in settings were a limited number of serotypes are tested. factor for infectious complications in rituximab-treated hematology Efforts must be made to include as many PPV23 exclusive serotypes as patients. Our study demonstrated that there was a statistically significant possible in anti-pneumococcal antibody panels in order to obtain a association between lower IgM levels and sepsis, but not other types of relayable evaluation of the serologic response against PPV23 in PCV- infections. These findings emphasize the importance of continued experienced patients. monitoring of IgM levels after rituximab therapy. Low IgM levels should prompt early evaluation and possible intervention to prevent severe Long-term Safety of Facilitated Subcutaneous infections. 230 Immunoglobulin Treatment in Patients With Primary Immunodeficiency Diseases: Interim Analysis from a Post-authorization Safety Study

Arye Rubinstein1; 1Albert Einstein College of Medicine. RATIONALE: fSCIG (facilitated immune globulin infusion 10% [hu- man] with recombinant human hyaluronidase [rHuPH20]) is a subcutane- ously administered IG, approved for patients with primary immunodeficiency diseases (PIDD). The objective of this study was to acquire data from clinical practice on long-term safety of fSCIG in patients with PIDD. METHODS: This ongoing prospective, non-interventional, uncontrolled, multicenter, post-authorization safety study was initiated in the US in November 2015 (NCT02593188) in patients >_16 years receiving fSCIG for PIDD. Dosage regimen and treatment schedule are at the discretion of the treating physician. AEs are collected from enrollment to study completion/ discontinuation. The presence of anti-rHuPH20 antibody titers is evaluated on a voluntary basis. RESULTS: This interim analysis (May 2, 2019) includes 264 patients (mean age 54.7 years; 79.2% female); 81 of whom are still under follow- up. No serious AEs (SAEs) related to fSCIG were reported. Infusions were administered at home (60.4%) or at the clinical site (39.6%), most commonly using 4-week infusion intervals. Over 98% of infusions were administered without a rate reduction, interruption, or discontinuation due to AEs. Twenty-seven patients experienced a causally related non-serious local AE (10.2%; 0.35 events/patient-year, 0.05 events/infusion), and 37 patients experienced a causally related non-serious systemic AE (14.0%, 0.72 events/patient-year, 0.10 events/infusion). No neutralizing rHuPH20 AB74 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Assessment of Immune Function Status using significant incremental costs were experienced by MS patients diagnosed 232 Polysaccharide Vaccination in Secondary with immunodeficiency, even after accounting for the various treatments Immunodeficiencies and comorbidities.

Yvelise Barrios del Pino1, Elena Mederos Luis1, Cristina Alava1, Paloma Infections and associated diseases in patients Poza Guedes, MD PhD2, Andres Franco1, Teresa Delgado1, Taida Martın1, 234 with mannose-binding lectin deficiency, Isabel Suarez1, Victor Matheu, MD, PhD1; 1Hospital Universitario de presenting to a tertiary care immunology clinic 2 Canarias, Hospital Universitario de Canarias, Tene. 1 1 1 RATIONALE: Patients with secondary immunodeficiencies (SID) can Blanka Kaplan, MD FAAAAI , Alissa McInerney, MD ; Northwell suffer complicated infections. However, it is evident that not all individuals Health. develop an impaired immune system. Here we report the results of using a RATIONALE: Clinical significance of mannose-binding lectin MBL polysaccharide vaccine (S. thyphim Vi) to assess immune system status in deficiency (MBLd) has been argued. The role of mannose-binding lectin SID patients to identify patients who may be at high risk of developing (MBL) as a disease modifier, causing other diseases to present with a more complications and may benefit from immunoglobulin replacement therapy. severe phenotype, has been suggested. METHODS: SID patients that were referred to the Immunodeficiency METHODS: We conducted a retrospective chart review of patients (ID) outpatient clinic of the Allergy Service. Vaccination consists on i.m presenting to a tertiary immunology center with recurrent and/or severe administration Typhim Vi (Sanofi Pasteur). Antibodies specific for the infections. All patients underwent immune evaluation and were found to TyphimVi vaccines were measured by the VaccZymeTM Human Anti- have undetectable MBL levels (<70ng/ml). Types of infections and Salmonella typhi Vi IgG Enzyme Immunoassay (Binding Site Group) associated diseases were recorded. before and 4 weeks after vaccination. The measurement range of the test RESULTS: 53 patients with MBLd were identified. Most (47/53) had is 7.4 - 600 U / mL. sinopulmonary infections (47/53) including sinusitis (40/53), viral upper RESULTS: Ten SID patients (8/2 female/male) were clinical evaluated. respiratory infections (25/53), bronchitis (19/53), pneumonia (15/53), Basal level of specific IgG to S. typhy ranged from <7,4 U/mL (8 patients) Streptococcal pharyngitis (9/53), otitis media (9/53). Other infections were to 22.5 U/mL. Post-vaccination specific IgG to S. typhi were performed in skin infections (6/53), sepsis (2/53), meningitis (2/53). Among 33 patients 6 individuals. 3 were classified as non-responders (7,4-8,5 U/mL) whereas with chronic sinusitis, 15/33 had chronic rhinosinusitis without polyps, 10/ 3 were classfied as responders (120.3, 283.2 and >600 U/mL) based on 33 had aspirin exacerbated respiratory disease (AERD), 7/33 chronic specific post-vaccination IgG. rhinosinusitis with polyps (non AERD), 2/33 had allergic fungal sinusitis. CONCLUSIONS: After clinical evaluation, all non-responders patients Many were atopic (44/53) with allergic rhinitis (30/44), asthma (25/44), have an indication of Ig replacement therapy to prevent life-threatening atopic dermatitis (7/44), and food allergy (7/44). Associated immunode- complications. Typhim Vi polysaccharide vaccination can be use as a good ficiencies were (13/53) were with common variable immunodeficiency (7/ and objective method to assess the immune funcion in SID patients. 13), IgG subclass deficiency (2/13), isolated IgM deficiency (2/13), other hypogammaglobulinemia (1/13), specific antibody deficiency (1/13), The Impact of Immunodeficiency on Patients transient T cell lymphopenia of infancy (1/13). Rheumatologic disease 233 Receiving Immunologic-Based Multiple was seen in 14/53 patients, hematologic disease in 8/53 and inflammatory Sclerosis Therapies bowel disease in 5/53. Other disease findings included bronchiectasis (8/ 53). Michael Runken, PharmD1, Terry Harville, MD PhD2, Joshua Noone, CONCLUSIONS: Even in the absence of other immunodeficiency, people PhD3; 1Grifols SSNA, 2University of Arkansas Medical Sciences, 3Uni- with MBLd have recurrent infections, most commonly sinopulmonary. versity of North Carolina at Charlotte. Further research, comparing infections, severity and associated illnesses in RATIONALE: Immunologic-based therapies have become commonly those with patients with different MBL levels is warranted to define its used to treat multiple sclerosis (MS), with potential adverse effects on clinical significance. patient’s immunity. This study assesses the impact on healthcare resource utilization and costs among patients receiving rituximab, ocrelizumab, and natalizumab. METHODS: Using the Pharmetrics Plus administrative insurance claims database (2014-2019), MS patients were identified, who had no history of immunodeficiency prior to treatment, at least one-year pre- and post- treatment index, with >30% compliance with treatment. Treated MS pa- tients were aggregated and comparisons were made one year and beyond post index between those diagnosed with immunodeficiency, or not. Patients were Greedy matched on treatment plus all significant (p<0.10) demographic and clinical characteristics. RESULTS: 3,976 MS patients receiving rituximab, ocrelizumab, or natalizumab were identified with 190 diagnosed with immunodeficiency subsequent to treatment. Rituximab association with immunodeficiency included, 10.2% of MS patients, and 27.9% of all immunodeficiency. MS patients subsequently diagnosed with immunodeficiency had increased likelihood to be hospitalized (16.3% vs 7.8%, p<0.01), pneumonia (4.7% vs 1.7%, p<0.01), chronic sinusitis (8.4% vs 4.9%, p50.03), higher hospitalization ($13,413 vs $2,425, p50.02), and total costs ($119,121 vs $100,121, p50.01), but not significantly different medication costs ($76,592 vs $79,677, p50.34). Matched results highlighted similar differences in total costs ($103,927 vs $91,243; p50.04) and all non-MS medication costs ($24,349 vs $18,117, p50.05). CONCLUSIONS: Cohorts of patients with immunodeficiency became evident with each of the three immunologic-based treatments. Ominously, J ALLERGY CLIN IMMUNOL Abstracts AB75 VOLUME 147, NUMBER 2

Assessing Severity in Common variable immune prominent increase in the frequency of Tfh, p <0.0001, while this differ- 235 deficiency (CVID) using the "Ameratunga Score- ence is much lower in patients with infections only (n514) p 5 0.0424. AS" CONCLUSIONS: The increased frequency of Tfh cells with an increase in PD-1 expression in CVID patients with non-infectious complications Rafaela Guimaraes1, Luiza Schmid2,Lıgia Machado2, Mariana Pimen- may indicate a suppression of B cell terminal differentiation through this tel3, Maria C^andida Rizzo4, Carolina Aranda1, Dirceu Sole, MD PhD pathway. FAAAAI5; 1Federal University of Sao Paulo, 2UNIVERSIDADE FED- ERAL DE SAO~ PAULO - UNIFESP, 3Federal University of S~ao Paulo, Evaluating Safety, Tolerability, and Efficacy of 4UNIVERSIDADE FEDERAL DE SAO~ PAULO -UNIFESP, 5Universi- 237 Subcutaneous Human Immunoglobulin 16.5% dade Federal de Sao Paulo. Administered at Modified Dosing Regimens in RATIONALE: A proportion of patients with CVID evolves with a Patients with Primary Immunodeficiency prominent T cell defect leading to a more severe phenotype with Diseases – Study Design opportunistic infections, being considered by some experts as Late Onset 1 2 Combined Immunodeficiency (LOCID). The aim of the study was to assess Isaac Melamed, MD , Sudhir Gupta, MD PhD FAAAAI , Roger Kobayashi, MD FAAAAI3, Michael Eppolito, MBA4, Joanna the severity of CVID using the ‘‘AS’’, which focuses mainly on cumulative 4 4 5 1 damage to organs such as result of infections, autoimmunity or Maltese, BSN , Syed Rizvi , Ai Kobayashi ; IMMUNOe Health Centers, 2University of California at Irvine, 3Allergy Asthma & Immunology As- inflammation. 4 5 METHODS: We retrospectively study charts of patients with CVID, seen soc, Octapharma, Midlands Pediatric. at a Reference Center, and applied the "AS". The score is based on the RATIONALE: Immunoglobulin (Ig) concentrates have been successfully severity of the complications of each organ, classified as mild 5 1point used to treat patients with primary immunodeficiency disorders (PID). (without long-term morbidity), moderate 5 5points (short and long-term Many patients opt to use subcutaneous route of administration (SCIg) for morbidity) and severe 5 10points (fatal or with the potential to severe the convenience, flexibility and minimal systemic side effects. This study disability). plans to evaluate safety, tolerability, and efficacy of a SCIg 16.5% at RESULTS: We evaluated 29 charts (69% male), with a median of age modified infusion regimens in adult and pediatric PID patients. 36.3 y. The lung was the most affected organ, with manifestations in 69%, METHODS: The prospective, open-label, non-controlled, 3-arm, multi- mainly bronchiectasis (58.6%). Gastrointestinal complications such as centre, phase 3 study will monitor the safety, tolerability, and efficacy of severe enteritis were the second most frequent (20.7%). Autoimmune SCIg 16.5% administered at modified infusion regimens. Sixty-five adult manifestations were present in 41.4%, mainly cytopenias. Three patients and pediatric patients with a confirmed diagnosis of PID currently on a had some type of malignancy. The total score in the analyzed population stable dose of SCIG treatment will be enrolled and assigned to 1 of 3 ranged from 0 to 47. Patients with a score above 35 had CD4 lymphopenia cohorts to receive doses of SCIg 16.5% (Cutaquig) over a 32-week period during evolution in 75% of cases. (Cohort 1: increased volume at each infusion site (up to 60 mL/site); CONCLUSIONS: The "AS’’ can be a useful tool for the identification of Cohort 2: increased infusion rate (up to 240 mL/hr/all sites); Cohort 3: patients with LOCID, in addition to providing a linear assessment of the every other week dosing). evolution of each patient, as well as a strategy until the genetic clarification RESULTS: The co-primary objectives are to compare total IgG trough to differentiate the CVID from the monogenic CIVD-like. levels achieved by weekly infusions to every other week infusions, to assess safety and tolerability of SCIg 16.5% being administered according Frequency of Follicular T cells in a cohort of to 3 different infusion parameters, and to assess efficacy parameters when 236 Brazilian Common Variable Immunodeficiency switching from weekly infusions to every other week infusions. Secondary (CVID) patients objectives will evaluate quality of life, along with additional evaluations of safety and efficacy of SCIg 16.5% administration. Cristina Kokron, MD, PhD1, Fernando Zilinski, biomedicine, MScstu- CONCLUSIONS: The investigators of this study hope to provide dent2, Bianca Santos, MSc, PhDstudent2, Erica Coutinho, MSc2, Juliana modified infusion regimens to offer patients dosing flexibility to accom- Apostolico, PhD3, Milena Andrade, MScstudent2, Ana Karolina modate their personal schedules or reduce the number of injection Marinho, DO4, Myrthes Barros, MD, PhD2, Octavio Grecco, MD, MSc2, Jorge Kalil, MD, PhD2; 1Hospital das Clınicas, Faculdade de Me- dicina, USP, 2Faculdade de Medicina, Universidade de S~ao Paulo, 3Uni- versidade Federal de S~ao Paulo, 4University of Sao Paulo Medical School. RATIONALE: CVID is the most common form of antibody deficiency and is a group of conditions which hallmark is hypogammaglobulinemia. Follicular T lymphocytes (Tfh) are essential to assist B cells in the production of antibodies. Our objective was to evaluate the frequency of circulating follicular T cells in CVID patients with and without non- infectious complications. METHODS: In this prospective study, 73 CVID patients followed at the Primary Immunodeficiency Outpatient Clinic from the Division of Clinical Immunology and Allergy of Hospital das Clinicas (HCFMUSP) and 24 healthy controls were studied. Fourty milliliters of peripheral blood were collected, peripheral blood mononuclear cells obtained and cell surface immunophenotyping was performed by flow cytometry. RESULTS: Among the 73 patients, mean age of patients was 43,4 years and 39 were women. Among the 24 controls, the mean age 38,6 years and 14 were women. We observed an increased frequency of circulanting Tfh cells (CD4+CXCR5+PD-1+) in CVID patients when compared to controls with p <0.0001. When we divided CVID patients according to the clinical phenotype, we observed that, compared to the control group (n524), the group with non-infectious complications (n559) showed a more AB76 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Long-Term Safety, Efficacy, and Tolerability of hospitalized (total n594, 47 each, 23.4% vs 6.4%, p50.02), with 238 Subcutaneous Human Immunoglobulin 16.5% in significantly higher total costs ($129,292 vs $71,640, p50.05). Patients with Primary Immunodeficiencies CONCLUSIONS: The additional costs (more than $60,000 in total costs) and high prevalence of immunodeficiency among rituximab-treated MS Sudhir Gupta, MD PhD FAAAAI1, Roger Kobayashi, MD FAAAAI2, patients (13.1% of treated), warrants further analysis of the impact of Isaac Melamed, MD3, Syed Rehman4, Ai Kobayashi5, jose-fernando treatment and the possible unmasking of primary immunodeficiency. Mandujano, MD6, Bob Geng, MD7, Bruce Ritchie, MD8; 1University of California at Irvine, 2Allergy Asthma & Immunology Assoc, 3IMMUNOe Risk Factors for Mortality from COVID-19 in a Health Centers, 4Asthma & Allergy Center, 5Midlands Pediatrics, P.C, 240 New York Inner city Epicenter 6Children’s Health, 7Rady’s Children hospital San Diego, 8University of Mariam Majzoub1, Rauno Joks, MD FAAAAI2; 1Center of Allergy and Alberta, Canada. 2 RATIONALE: Primary Immunodeficiencies (PID) patients require life- Asthma Research, SUNY Brooklyn Health Science University, SUNY- long Immunoglobulin (Ig) therapy. In a follow-up study, medium-to-long HSC. term safety, efficacy and tolerability data of a subcutaneous human normal RATIONALE: Being the epicenter of COVID-19 in USA, New York’s immunoglobulin 16.5% were evaluated in adult and pediatric PID patients. inner city areas were the most affected during Spring. Reviewing the METHODS: The prospective, multicenter, open-label, non-controlled, clinical profiles of affected individuals allows us to identify risk factors for single-arm, phase III study enrolled 27 adult and pediatric PID patients COVID-19 mortality. with a mean age of 39.26 years (range 6-73; 10 subjects aged < 17 years; METHODS: We collected data from 109 charts of COVID PCR+ adult 5 5 63% female). Patients received weekly or bi-weekly doses of SCIg 16.5% patients (Survivors n 54; Non-survivors n 55) admitted to University (Cutaquig) with the option of increased infusion volume (up to 60 mL/site) Hosiptal of Brooklyn (Mar 2020-Jun 2020) for COVID related symptoms. and rate (up to 240 mL/hr/all sites) over a 42-month period. EMR review included demographic profile, comorbidities, vital signs at RESULTS: Twenty-seven patients received a mean dose of 0.169 g/kg presentation and medications administered. News2 Score, which quantifies overall (range among different age groups: 0.127 – 0.166 g/kg). One abnormal vital signs, and Charlson Comorbidity Index (CCI) were serious bacterial infection (SBI; type bacteremia/sepsis) was recorded in calculated for each patient. one adult patient for an overall rate of 0.018 SBIs per person-year. Of the Statistical analysis was performed using T test and Chi-square test 6 204 reported adverse events (excluding infusion site reactions and RESULTS: The age of survivors was significantly lower (67.1 11.3) than 6 infections), only 7 (headache, nausea, chills, pyrexia) were assessed as non-survivors (74.4 10.5) (P<0.01). 65% (36/55) of deaths were men 5 6 being related to the study drug; all of these events were non-serious. There (P 0.1). Length of stay was longer in survivors (12.78 15.1days Vs. 6 5 were no infusion site reactions in 96.6%. 44.4% of patients experienced 8.2 9.8 days); P 0.04. 6 infusion site reactions, with most being mild-to-moderate in intensity. News2 Score was significantly higher in non-survivors (9.38 2.81 Vs. 6 Serum IgG trough levels remained relatively constant (> 5g/L) throughout 6.76 3.1 in survivors) (P<0.01). There were no difference in CCI (4.2 6 6 5 the study. 2.7 in survivors Vs. 4.71 2.0; p 0.28). 5 CONCLUSIONS: This study demonstrated that subcutaneous human 40.7% (22/54) of survivors received steroids Vs. 21.8% (12/55); P 0.03. normal immunoglobulin 16.5% is well-tolerated, safe and effective for No difference in use of hydroxychloroquine, azithromycin and full dose 5 5 5 long-term use in patients with primary immunodeficiency diseases. anticoagulation (p 0.91, p 0.14, p 0.79 respectively). Nonsurvivors had more cancer (8/55 Vs. 2/54; P50.04). There were no Impact of Immunodeficiency on Multiple significant difference in presence of hypertension, hyperlipidemia, dia- 239 Sclerosis Patients Receiving Rituximab betes, CAD, CHF, asthma and COPD. CONCLUSIONS: Elderly patients with early signs of COVID should Terry Harville, MD PhD1, Michael Runken, PharmD2, Joshua Noone, seek prompt medical care. Patients with higher News2 Score at presen- PhD3; 1University of Arkansas Medical Sciences, 2Grifols SSNA, 3Uni- tation and those with cancer are more likely to die from COVID-19 versity of North Carolina at Charlotte. infection. RATIONALE: Rituximab is commonly utilized as an immunologic-based therapy for Multiple Sclerosis (MS). Treatment results in the reduction of B lymphocytes. The unintended consequence can be antibody deficiency, which may become permanent in some, possibly via the unmasking of primary immunodeficiency. This study assesses the impact on healthcare costs and utilization in MS patients taking rituximab. METHODS: Using the Pharmetrics Plus administrative insurance claims database (2014-19), MS patients receiving rituximab were identified, who had no prior history of immunodeficiency, at least one year enrollment pre- and post-initiation of treatment, and >30% compliance. Rituximab-treated MS patients diagnosed with immunodeficiency were compared with non- immunodeficiency MS patients, and were Greedy-matched on all signifi- cant (p<0.10) demographic and clinical characteristics, and immunoglob- ulin therapy. RESULTS: 404 rituximab-treated MS patients were identified with 53 (13.1%) subsequently diagnosed with immunodeficiency, who were more likely to be hospitalized (28.3% vs 16.2%, p50.03), and diagnosed with chronic sinusitis (15.1% vs 4.8%, p<0.01). Unadjusted costs were higher for hospitalizations ($40,936 vs $7,421, p50.05), total costs ($132,463 vs $73,394, p50.01), non-MS medication costs ($80,724 vs $31,962, p50.04), and MS medication costs ($51,739 vs $41,432, p<0.01). After matching, rituximab-treated MS patients were more likely to be J ALLERGY CLIN IMMUNOL Abstracts AB77 VOLUME 147, NUMBER 2

Point-of-care assays can detect COVID-19 antibodies to SARS-CoV-2 is easier, requires fewer resources than high- 241 antibodies via serum or whole blood complexity lab testing and provides rapid results regarding individual antibody status to SARS-CoV-2. However, the specific test characteristics Charles Schuler, MD1, James Baldwin, MD FAAAAI2, James Baker, for each kit must be rigorously evaluated, as they vary substantially. MD FAAAAI1; 1University of Michigan, 2University of Michigan Allergy Immunolog. Multi-system Inflammatory syndrome in Children RATIONALE: Point-of-care (POC) antibody testing has a mixed record 243 (MIS-C): an evolving presentation of COVID-19 in in detecting prior COVID-19 infection. However, interest remains in POC the pediatric population: A Florida State antibody testing because the numerous patients in need of screening may experience and our management approach overwhelm high-complexity laboratory capacity. Farida Karim, MD1, Miry Makebish1, Pallavi Agarwal1, Callah Anto- METHODS: We enrolled subjects with and without a history of COVID- 1 1 19 infection. Exclusion criteria included a history of immunodeficiency or netti, MD ; University of Florida Pensacola. an immunosuppressed state. A positive infection history was defined by RATIONALE: Florida is among the states with the highest COVID-19 clinical COVID-19 PCR. Demographic and infection history were disease burden in the country. We have seen an emergence of multi-system recorded. We utilized commercial POC antibody tests from Healgen and inflammatory syndrome in children (MIS-C), associated with COVID-19 Access Bio Inc and tested both kits using whole blood and serum. We infection in our region and successfully treated three patients in our compared each test to a history of PCR positivity and a validated hospital. Here, we describe the diagnosis and management of MIS-C in one immunoassay (Elecsys, Roche Inc). Test characteristics were calculated of these patients. for each test. METHODS: COVID-19 associated MIS-C guidelines; A Western New RESULTS: 467 subjects enrolled, including 88 subjects with a known York Approach (PMCID 7244417) criteria [Fever > 24 hours, illness prior positive COVID-19 PCR. Symptoms among COVID-19-infected requiring hospitalization, laboratory evidence of inflammation, > 2 organ subjects included fever > 38C (59%), subjective fever (72%), myalgias system involvement and no alternative plausible diagnosis with COVID-19 (84%), rhinorrhea (47%), cough (81%), dyspnea (64%), gastrointestinal positivity/exposure] and treatment recommendations were followed for the symptoms (58%), anosmia (70%), and dysgeusia (66%). The Healgen kit management of this patient. showed 93.5%/97.6% sensitivity/specificity between whole blood and RESULTS: A 2-year-old African-American male presented with fever, serum and 95.5%/96.2% between serum testing and the immunoassay. The rash, and bilateral eye redness for 5 days with prior SARS-COV-2 exposure Access Bio kit showed 98.0%/98.7% sensitivity/specificity between whole confirmed by positive serum IgG. Clinical findings included features of a blood and serum and 93.8%/100.0% between serum testing and the Kawasaki-disease (KD)-like illness with bilateral bulbar injection, phar- immunoassay.The Roche immunoassay showed 96.6%/96.0% sensitivity/ yngitis, polymorphous rash, erythema of palms and soles, and unilateral specificity with history of PCR positivity. cervical lymphadenopathy. He had elevated inflammatory markers, CONCLUSIONS: POC COVID-19 antibody testing showed good elevated D-dimer and fibrinogen, and hypoalbuminemia. He also had concordance between whole blood and serum analyses, and excellent elevated brain natriuretic peptide with a normal echocardiogram, meeting concordance with the Roche immunoassay. POC antibody testing via MIS-C criteria of remote infection with predominant KD features. He was whole blood and/or serum may be reasonable as a screening step for prior treated with low dose aspirin, IVIG, and intravenous methylprednisolone. COVID-19 infection. He improved and was discharged after 7 days of hospitalization. CONCLUSIONS: Recognition of MIS-C in its early stages is very Does Point-Of-Care SARS-CoV-2 Antibody critical, however, in the absence of standardized management guidelines, 242 Testing Have Similar Sensitivity and the treatment gets very challenging. Therefore, global reporting of the Specificity To High Complexity Serology? detection and management of these cases is essential for developing a definitive management standard. Kelly O’Shea, MD1, Charles Schuler, MD1, Jesse Chen1, Carmen Gherasim, PhD1, Donald Giacherio, PhD1, James Baldwin, MD FAAAAI2, James Baker, MD FAAAAI1; 1University of Michigan, 2Uni- versity of Michigan Allergy Immunolog. RATIONALE: Point-of-care (POC) antibody screening for SARS-CoV-2 infection has yielded varied results. We analyzed two POC antibody testing devices to study whether these are comparable to ELISA testing done in a high complexity CLIA facility employed as a standard. METHODS: We enrolled 146 individuals, with 41 individuals having had a history of positive PCR for COVID-19. After informed consent, we obtained serum and at the same time performed a finger stick for whole blood. Autobio and MEDsan rapid IgG/IgM tests that use SARS-CoV-2 spike protein to detect antibody were performed with serum and compared to Roche’s SARS-CoV-2 immunoassay, which uses nucleocapsid protein to detect antibody. The Autobio test was also evaluated using whole blood obtained by finger stick. RESULTS: Serum testing using the Autobio kit versus the Roche immunoassay (used as the standard for comparison) revealed a sensitivity of 93.2% and a specificity of 96.1%; whole blood testing using the Autobio kit vs. the Roche immunoassay revealed a sensitivity of 90.5% and a specificity of 97.9%. Whole blood compared to serum testing using the Autobio POC kit revealed a sensitivity of 90.7% and a specificity of 99.0%. Serum testing using the MEDsan kit vs. the Roche immunoassay revealed a sensitivity of 100% and a specificity of 96.1%. CONCLUSIONS: Despite using different antigens, both the POC devices showed comparable results to the high complexity ELISA. POC testing for AB78 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Prenatal and Perinatal Risk Factors for Lower first 4 months of the pandemic. Despite significant disruption to daily life, 244 Respiratory Tract Infections in Inner-city the situation tended to enhance protective factors on asthma control. Minority Infants Further studies are needed to better guide management of pediatric asthma and evaluate socioeconomic changes occurring during the COVID-19 Maria Gutierrez1; 1Johns Hopkins University. emergency. RATIONALE: Children born in urban minority populations are at higher risk of respiratory morbidity, including lower respiratory tract infections Clinical Characteristics of SARS-CoV2 Infected (LRTI) and the ongoing COVID-19 pandemic. There is a critical need to 246 and Exposed Patients at a Tertiary Care identify risk and protective factors for LRTI in this vulnerable population. Allergy/Immunology Program in Florida METHODS: We examined 3,131 mother-child dyads from the Boston Mary Ann Miranda, MD1, Joseph Dasso2, Maryssa Ellison, BS2, Jessica Birth Cohort (BBC), a predominantly urban, low-income, minority birth 3 4 5 cohort, aiming to identify prenatal and perinatal predictors of LRTI during Trotter, MA BS , Priyanka Timothy, MD , Maria Chitty-Lopez, MD , Carla Duff, CPNP-PC APRN MSN CCR2, Daime Nieves, APRN2, infancy (0-12 months). LRTI were defined as the presence of bronchiolitis, 2 2 bronchitis, or pneumonia, as documented by ICD9/10 diagnosis codes Emma Westermann-Clark, MD , Nathan Tang , Mandel Sher, MD FAAAAI2, Mark Ballow, MD FAAAAI2, Jennifer Leiding, MD from electronic medical records. LRTI predictors were selected using 2 2 Akaike’s Information Criteria (AIC) and stepwise logistic regression. FAAAAI , Panida Sriaroon, MD FAAAAI , Jolan Walter, MD PhD FAAAAI2; 1Children’s Research Institute, 2University of South Florida, RESULTS: The strongest predictors of LRTI during infancy in this 3 4 5 University of South Florida - CRI, University of South Florida/Johns population were preterm birth (adjOR 1.64, 95%CI 1.31-2.05), multi- 5 parity (adjOR51.53, 95%CI 1.20-1.96), male sex (adjOR 1.43, 95%CI Hopkin, Johns Hopkins All Children. 1.15-1.77) and maternal overweight and obesity (adjOR51.37, 95% RATIONALE: Immunocompromised persons are logically thought to CI1.09-1.71). Breastfeeding (adjOR 0.73 95%CI 0.57-0.93), vaginal have increased risk of severe SARS-CoV-2 infection (COVID-19) and delivery (adjOR 0.75, 95%CI 0.60-0.94) and maternal age 24-35 years Florida has one of the highest number of COVID-19 cases nationally. How (adjOR 0.65 95%CI 0.50-0.85) were negatively associated with LRTI. allergic and immunologic disorders affect the clinical course of COVID-19 Interestingly, race and maternal education were comparable between is not fully understood. Hence, we characterized the demographics, infants with and without LRTI. symptoms, diagnosis, comorbidities, and disease severity of patients in CONCLUSIONS: In this sample of high-risk U.S. minority children, we our academic allergy/immunology program in Florida with SARS-CoV2 replicated some known clinical predictors of early life LRTI. Our findings infection or direct exposure to household contacts. Infection was confirmed also raise important questions as to why prenatal factors such as maternal by viral nucleic acid testing or antibody serology. obesity increase LRTI risk. Such information, along with underlying METHODS: We performed a referral-based retrospective chart review of mechanisms, if further confirmed, would inform primary prevention efforts patients described above. starting in-utero in vulnerable populations. Finally, this study motivates RESULTS: Of 18 patients, most had allergic conditions (60%) and/or further investigation into whether these susceptibility factors apply to antibody deficiency (55%). One patient was asymptomatic with severe T- COVID-19 among minority children. cell lymphopenia and another had combined immunodeficiency and untreated hypogammaglobulinemia. The median age of 12 symptomatic Implications of the COVID-19 Pandemic on patients with COVID-19 was 18 years with similar sex distribution and 245 Asthma Control and Socioeconomic Factors in divided equally as to staying home, going to emergency department or Inner-City Cohort: A Rapid Online Cross- becoming hospitalized (33% each). Six patients with COVID-19 house- Sectional Survey hold contacts were asymptomatic (2 PCR negative, 1 IgG seropositive, 3 not tested). Six of 18 had serological testing and 3 (50%) were positive for Thanaporn Ratchataswan1, Christina Yee, MD PhD1, Caroline Mortel- SARS-CoV2 IgG antibody. All hospitalized patients had comorbidities of liti1, Amparito Cunningham, MD MPH2, Lisa Bartnikas, MD1, Wanda asthma and/or obesity. All patients were treated supportively and none Phipatanakul, MD MS FAAAAI1; 1Boston Children’s Hospital, 2Harvard required respiratory support or died. University. CONCLUSIONS: This observational study suggests that in our predom- RATIONALE: The COVID-19 pandemic produced unprecedented inantly pediatric population with allergic and immune disorders, mostly disruption to many social determinants of health. We sought to explore young adults become infected and symptomatic. Comorbidity with asthma the initial impact of the COVID-19 emergency on asthma control and and obesity increases hospitalization. Whether non-asthmatic allergic health in school-age children and their families. disorders and/or immunodeficiency affects infectivity or morbidity is METHODS: We remotely surveyed the parents of children attending unclear. elementary school in a city in the Northeast, about their experiences from February-July 2020. We recorded demographic information about the children and their family members, COVID-19 associated illness and testing, asthma control, and socioeconomic factors related to health. RESULTS: The online survey was completed by 120 families. Seventy- four households (66.7%) had >_1 adult working outside the home during the state of emergency. Two children (1.7%) had documented illness with SARS-CoV-2. Documented or suspected COVID-19-related illness was reported in >_1 family member in 9.9% of households. Thirty-six children (30%) had asthma. During the initial period of the COVID-19 emergency, parents generally perceived their children’s asthma as well-controlled (52.8%) or completely-controlled (41.7%). Most families reported good adherence to asthma medications (76%), though some (11.1%) expressed reluctance to access medical care during the outbreak. Nearly all children were offered online education during school closures. Many families reported that technical and/or logistical barriers limited participation. CONCLUSIONS: Notable proportions of families reported working outside the home and experiencing COVID-19-related illness during the J ALLERGY CLIN IMMUNOL Abstracts AB79 VOLUME 147, NUMBER 2

COVID-19 Severity in Hospitalized Pediatric Characterization of T cell, B cell and Natural 247 Patients with Atopic Disease 249 Killer Cell Subsets in COVID-19 Patients

Dylan Timberlake1, Rebecca Scherzer, MD FAAAAI2, Benjamin Alena Rynda1, Andrei Hancharou1, Natalia Antonevich1, Oxana Timohina1, Prince, MD MCSI FAAAAI3, Mitchell Grayson, MD2; 1The Ohio State Yana Minich1, Alena Halavach1, Darya Babrukevich1, Marina Dotsenko2, University/Nationwide Children’s Hospital, 2Nationwide Children, Eduard Dotsenko2, Lawrence Dubuske, MD FAAAAI3; 1The Institute of 3Nationwide Children’s Hospital. Biophysics and Cell Engineering of National Academy of Sciences of RATIONALE: Data from the Coronavirus-19 disease (COVID-19) Belarus, Minsk, 2Belarusian State Medical University, Minsk, Belarus, pandemic suggests asthma is not a risk factor for severe disease in adults; 3George Washington University School of Medicine, Washington, DC, it is unclear if this applies to pediatric patients. This study was undertaken USA, Immunology Research Institute of New England, Gardner, MA, USA. to determine if pediatric patients with asthma or atopic disease had altered RATIONALE: Immune dysregulation is observed in patients with severe risk for severe disease when hospitalized with COVID-19. COVID-19 associated pneumonia. The aim of the investigation was to METHODS: A retrospective chart review was performed of SARS-CoV-2 perform analysis of immune parameters including cell count, differenti- positive patients admitted to Nationwide Children’s Hospital from March 1 ation and activation of lymphocytes from COVID-19 patients. to July 31. Charts were evaluated for history of asthma or atopic disease METHODS: 57 patients with PCR and chest CT confirmed diagnosis of (including asthma) and surrogate markers of COVID-19 severity, including COVID-19 pneumonia were included in the study. Patients were divided ICU admission, supplemental oxygen requirement, and intubation. into 2 groups: severe/critical (S/C) patients (n518) which were treated in RESULTS: 49 patients were identified as positive for SARS-CoV-2, 22 of ICU and required IMV; and moderate (M) patients (n539). Blood samples whom were admitted for COVID-19 related symptoms. Of the admitted from 19 healthy donors (HD) controls were obtained. T cell, B cell, natural patients, six patients (12%) had asthma and 18 (37%) atopic disease killer (NK) cell and innate lymphoid cell (ILC) subsets were assayed using (including those with asthma). ICU admission rate for asthma versus non- Attune NxT flow cytometer. Nonparametric statistics were used. asthma was 17% versus 12% (p50.78) and for atopic versus non-atopic RESULTS: A profound decrease of the absolute counts of T-cells, B-cells, was 17% versus 6.4% (p50.32), while supplemental oxygen rates were NK- and NKT-cells and frequencies (%) of ILC was noted both in S/C and 17% versus 16% asthma versus non-asthma (p50.98) and 22% versus 13% M versus HD (p<0.01). Frequency (%) of B-cells in S/C was increased. A atopic versus non-atopic (p50.43). Only two patients required intubation decrease in the content of naive T-cells was noted, while the content of and both had atopic dermatitis. Two patients had Multisystem TCM, TEM, TEMRA, T-reg and activated HLA-DR+ T-cells did not Inflammatory Syndrome in Children – one with allergic rhinitis and atopic change significantly in S/C compared with M but both groups had dermatitis, the other without any atopic disease. increased exhausted PD-1+ T cells counts. CONCLUSIONS: Markers of COVID-19 disease severity do not differ CONCLUSIONS: Tand NK cell lymphopenia was observed in COVID-19 based on asthma or atopic status in pediatric patients. In children, like patients, more significant in S/C. No important changes in T-cells differen- adults, the presence of asthma or atopy does not appear to alter the risk of tiation and activation were detected in with S/C or M groups accompanied by severe COVID-19. increase in exhausted T cells. Immune system anergy may explain the severe course of some COVID 19 patients and cases of reinfection. COVID-19 pandemia: Atopy and prospective 248 analysis of the clinical evolution of patients Effects of Virus Specific Short-Interfering RNAs infected with the SARS-CoV-2 virus 250 on Enterovirus D68 Induced Lung Injury

Debora S. Guterres1, Ana Carolina Dos Santos2,MarinadeAlmeidaPrado Nicholas Klaiber1, Michael McVoy1, Wei Zhao, MD PhD FAAAAI1; Meireles Laubi2, Marina Laubi2, Roselene Lourenc¸o1,MarcusVinıcius1, 1Department of Pediatrics, Virginia Commonwealth University, Rich- Rosana Agondi, MD PhD3, Ana Karolina Marinho, DO4,Valeria Brand~ao5, mond, VA, USA. Thais Saito5, Grasiela Lima5; 1Conjunto Hospitalar do Mandaqui, S~ao RATIONALE: Enterovirus D68 (EV-D68) is an emerging respiratory Paulo, Brazil, 2Universidade Nove de Julho, S~ao Paulo, Brazil, 3Hospital pathogen. We previously described siRNAs targeting the EV-D68 RNA das Clınicas Universidade de S~ao Paulo, S~ao Paulo, Brazil, 4University of dependent RNA polymerase, which were able to suppress EV-D68 Sao Paulo Medical School, 5Conjunto Hospitalar do Mandaqui. replication and cytopathic effect in vitro. We sought to assess the effects RATIONALE: A few scientific evidence is now available to date on the of intranasal application of these siRNAs in vivo, utilizing a previously es- clinical evolution of COVID-19 in atopics. The aim of this study was to tablished animal model of EV-D68 infection. assess the frequency of atopy in patients hospitalized for COVID-19. METHODS: 22 female cotton rats were infected i.n. with EV-D68. Two METHODS: A prospective study was carried out with hard descriptive hours p.i. animals were treated intranasally with either EV-D68 specific data of 4 months. During this period, 300 patients were admitted with ARS siRNAs, non-coding siRNAs or PBS. Virus associated lung injury was and positive RT-PCR for SARS-CoV-2. Clinical features, history of atopy, quantified by a veterinary pathologist utilizing a previously published total IgE and chest tomography were evaluated. peribronchiolitis scoring system. Viral VP2 capsid protein expression was RESULTS: Of all patients, 212 (70%) were male and the average age was measured using indirect immunofluorescence. RT-PCR was used to 58 years old. Of the total, 37 patients (12.3%) had a history of atopy compare levels of EV-D68 genomic RNA and inflammatory cytokine according to the following: 19 rhinitis (51.4%), 15 asthma (40.5%) and 3 expression. Viral titers, expression of cytokine genes were calculated as (1%), atopic dermatitis. Obesity was present in 32% of the evaluated geometric means 6 standard error (SE) for all animals in a group at a given atopics. The mean of atopic patients was aged for 55, 92% O2 Sat, time p.i. Student t-test was used to determine statistically significant respiratory rate 27 per minute, CT > 50% in 22 patients (7.3%) and 3 differences between two groups, using an unpaired, two-tailed test with patients died (1%). Of these who died, all were elderly (age over 60 years) significance set at p<0.05.Pulmonary pathology scores were expressed as and had comorbidities such as SH and obesity. Mean IgE total was 538UI/ the arithmetic means 6 SE for all animals in a group. ml, and 3 patients presented IgE above 2000, all of them with clinical RESULTS: Peribronchiolitis scores, VP2 expression and inflammatory suggesting atopy (AD, asthma and rhinitis). cytokine expression were all significantly reduced (p<0.05) in animals treated CONCLUSIONS: The literature reports less severe outcomes in atopic with EV-D68 specific siRNA. Viral genome copy number was lower in treated patients affected by COVID-19. In the studied group, the frequency of atopy animals, however this difference was not statistically significant (p50.06). was lower than that observed in the literature for the general population and CONCLUSION: I.N. application of EV-D68 specific siRNA was able to the tomographic impairment was lower than that of the non-atopic group. decrease virus mediated lung pathology, inflammatory cytokine expression The atopic patients who died were elderly and had comorbidities. and viral protein expression in a cotton rat model of EV-D68 infection. AB80 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Effect of cigarette smoking on M1/M2 type Visual Machine Learning and Artificial 251 Alveolar Macrophage (AM) and the restoration 253 Intelligence Application in Aeroallergen of AM by smoking cessation Identification During Spring, Summer, and Fall Pollen Season Minoru Takeuchi1, Honami Nakata1, Kent Pinkerton2; 1Kyoto Sangyo University, 2University of California - Davis. Richard Lucas, PhD1, Landon Bunderson2, James Anderson, MLT3, Dan RATIONALE: Cigarette smoking is the most important risk factor for Dalan, MD4; 1Southwest Environmental Institute, 2Pollen Sense, 3Envi- pulmonary disease. Alveolar macrophages (AM) are classified in M1 and ronmental Allergy Assays, 4MercyOne Medical Center. M2 types. It is reported that immune functions of AM are suppressed by RATIONALE: Continued validation of automated pollen identification smoking. However, the restore of AM after smoking cessation is not fully (API) is needed. We performed a side-by-side device comparison of pollen understood. Therefore, we investigated the effect of cigarette smoking and counts identified using a Burkard sampler (BS) and an Automate Pollen the restore of M1/M2 AM by smoking cessation. Sampler (APS) by Pollen SenseTM. METHODS: 8-weeks-old female C57BL/6N mice were used. METHODS: The designated gold standard device for comparison, the BS, KENTUCKY Research CIGARETTE were used. Mice were exposed to was co-located with the APS in Waterloo, Iowa. Pollen collection, the smoke of twenty cigarettes per day for 10 days by using MIPS smoking processing, and identification were performed following NAB requirements. machine. AM were recovered by Broncho Alveolar Lavage (BAL) from 1 The APS was provided by Pollen SenseTM. The APS collects particulate day to 8 weeks after smoking cessation. Dot plots and expressions of cell matter volumetrically from ambient air, automatically images the particu- surface makers (CD11c as M1 marker, CD206 as M2 marker) were lates, and uses a convolutional neural network to identify the individual pol- analyzed by FACS Calibur. TNF-a mRNA expression was evaluated by len species. For this first iteration, 57 days were compared in the fall 2019 RT-PCR. and spring-summer 2020. The top 10 pollen reported to the NAB in the upper RESULTS: Number of AM was increased by smoking. Morphology and Midwest were chosen for reporting. Accuracy is determined as the number Dot plots of AM were changed by smoking. However, Dot plots and of days a species was identified as present or absent in the APS that matches morphology were restored to the level of AM in non-smoked mice at 8 the Burkard, divided by the number of counting days x 100. weeks after smoking cessation. CD206 expression was significantly RESULTS: Accuracy: ragweed 96, mulberry 50, juniper 8, oak 46, nettle decreased by smoking, but it was restored to the non-smoke level at 8 0, grass 65, ash 58, elm 8, pine 65, birch 23. weeks after smoking cessation . CD11c expression was almost unchanged CONCLUSION: Current accuracy of APS needs continued improvement. by smoking. TNF-a mRNA expression was significantly decreased by Varying correctness in pollen species identification rely on several factors smoking. including whether the APS was trained for that pollen species, morphology CONCLUSIONS: Morphology of AM was changed and M2 AM was complexity, and amount of debris in the background. Identification and strongly affected by smoking. However, these alterations of AM were enumeration using visual machine learning methods in artificial intelli- restored by smoking cessation. These results suggest that smoking gence is a process that improves automatically through experience. It cessation may contribute to inhibition of development in pulmonary requires multiple iterations of repetitive learning to achieve desired disease. accuracy.

Ultrasonic "Mite Killers'' Fail to Decrease Mites Assessment of reduction of the PM 2.5 and 252 in Carpeting 254 fungal spores using AFL Facemask

Jeffrey Miller1; 1New York Medical College and Mission: Allergy, Inc. Nabarun Ghosh1, Constantine Saadeh2, Aubrey Howard, BS1, Jay RATIONALE: Reactivity to house dust mites is a major cause of allergic Vitale, BS3, Prabir Banerjee, MD MS4; 1West Texas A&M University, disease, the treatment of which includes allergen-avoidance. To be of 2Allergy ARTS, Amarillo, 3Air for Life UK, 4R N Tagore Hospital, Cal- possible clinical benefit, any claimed allergen-avoidance measure must cutta, India. actually result in a meaningful decrease of the allergen. Several devices RATIONALE: The current unprecedented situation with the COVID-19 advertised online claim to decrease dust mite survival and numbers by the posed a great challenge to the scientific world, demanding immediate use of ultrasonic sound. One published study claimed clinical benefit from development of technologies to fight with and prevent pathogens, such a device, but no published data demonstrate the ability of these especially in regards to airborne pathogens and surface contaminants. In devices to actually decrease mite numbers or allergen levels. the context of the COVID-19 pandemic, wearing a facemask has become METHODS: I evaluated the effectiveness of two such devices, ‘‘Aramox usual and ubiquitous, in both hospitals and community. Air For Life (UK) Ultrasonic Dust Mite Controller Repeller’’, and ‘‘Newegg Ultrasonic Dust and West Texas A&M University have designed a facemask. Mite Controller Killer Repeller’’. Sections of carpeting were inoculated METHODS: We have been working on the development and assessment with dense cultures of D. pteronyssinus mites. Half were placed a meter of a novel facemask to combat with airborne pathogens and pollutants. A away from an emitting ultrasonic device; the other half were kept in a sepa- partitioned fiberglass chamber (C1,C2) was used to test the AFL MaskÒ in rate room under identical conditions of temperature and humidity. After 3 preventing PM2.5 and microbial spores. We have recorded the number of weeks of exposure of the carpet sections to the ultrasonic devices, mite den- PM2.5 floating inside the chamber C-1 and C-2 by using a Temtop sity was assessed by the ‘‘Mobility Test’’ method of Bischoff, with mites M2000C Monitor. trapped over 3 days on transparent Con-Tact adhesive sheets placed on RESULTS: On using the mask, no particle transmitted into chamber-2 the carpet sections, and then removed and viewed under 20x microscopy. from the chamber-1 indicating protection from Particulate Matters when RESULTS: There was no apparent difference in the number of live mites the AFL MaskÒ is used. These masks are easy to use with comfort. It in the treated vs. the control samples. contains an electric fan for a continuous fresh airflow within the mask. The CONCLUSIONS: Contrary to the claims being made for these devices, air supply system has a constant positive pressure to allow easy breathing these two ultrasonic emitters, used as directed, failed to produce any without a suffocating feeling. The unique design of the air vent prevents the noticeable decrease in mite numbers in a carpet substrate. buildup of condensation inside. CONCLUSIONS: AFL MaskÒ is very efficient in protecting an individ-

ual from airborne pathogens and PM2.5, thereby proving as an efficient PPE available in the market. This mask can provide an internal air supply within the mask and maximum comfort with its ergonomic design and improved filtration technology. J ALLERGY CLIN IMMUNOL Abstracts AB81 VOLUME 147, NUMBER 2

Use of a HEPA filter associated with a decrease Effects of 20,000 EU of Clinical Center Reference 255 in urgent medical visits and hospitalizations for 257 Endotoxin (CCRE) versus placebo on systemic asthma among children living in lower-income and cardiovascular inflammatory responses in New York City apartments mild asthmatics and healthy volunteers

Luis Acosta, MD1, Ray Lopez2, Sergio Galvez2, Regina Dominguez1, Stephen Schworer, MD PhD1, Alan Hinderliter, MD1, Melissa Linda Weiss3, Matthew Perzanowski, PhD1; 1Columbia University, Caughey, PhD2, Carole Robinette1, Kelly Chason, BS3, Allison Mailman School of Public Health, 2Little Sisters of the Assumption Fam- Burbank, MD4, Michelle Hernandez, MD FAAAAI1; 1UNC School of ily Health Service, 3The New York Academy of Medicine. Medicine, 2University of North Carolina and North Carolina State Univer- RATIONALE: The use of High Efficiency Particulate Air (HEPA) filters sity, 3UNC-Chapel Hil, 4University of North Carolina, Chapel Hill. has been shown to reduce asthma exacerbations; however, the efficacy in RATIONALE: Endotoxin is a commonly encountered bioaerosol compo- lower-income urban apartments is less well studied. Secondary analyses of nent of particulate matter (PM), a prevalent indoor and outdoor pollutant. data from an environmental intervention trial was conducted to evaluate PM has been linked to increased cardiovascular morbidity and mortality. whether asthmatic children who were provided a HEPA filter in their This study examines systemic inflammatory effects of inhaled endotoxin homes had a greater improvement in asthma morbidity than those without a and associated alterations in cardiovascular function. HEPA filter. METHODS: Fifteen healthy volunteers participated in a blinded, METHODS: Families living in lower-income communities in New York placebo-controlled crossover study with exposure to inhalation of 20,000 City with an asthmatic child age 7-17 years and report of mold in the home EU Clinical Center Reference Endotoxin (CCRE) or normal saline control. were recruited into a lower-cost home mold and excessive humidity Peripheral and induced sputum neutrophils were obtained at baseline and reduction intervention study. HEPA filters were non-randomly distributed six hours post exposure. Blood pressure, measures of left ventricular to some participants, specifically those reporting unfixed mold or leaks function (ejection fraction (LVEF) and global longitudinal strain and/or cigarette smoke odor in the home. Families were requested to place (LVGLS)), and indices of endothelial function (flow mediated dilation the filter in the room where the asthmatic child spent most of the time. (FMD) and velocity time integral during hyperemia (VTIhyp)) were RESULTS: Comparing children with (n511) versus without (n529) measured before and after treatment. Nonparametric t-tests were used to HEPA filters in their homes, there was a frequency reduction in wheeze compare treated to pre-treatment endpoints. Data sets were compared (36% vs 45%, respectively, P50.73), but a greater decrease in urgent using Pearson correlation. medical visits (73% vs 21%, P50.007) and hospitalizations for asthma RESULTS: In comparison with normal saline, CCRE resulted in signif- (36% vs. 6.9%P50.039). These findings remained statistically significant icant increases in peripheral blood (p50.001) and sputum neutrophils (P<0.05) in models adjusting for age and sex and change in cockroach (p50.01). CCRE caused a decrease in diastolic blood pressure at 3 hours allergen, mouse allergen and report of mold. (3.4mmHg, p50.024) and 24 hours (4mmHg, p50.13) compared to saline. CONCLUSION: While these findings from a secondary analysis in a There were no significant CCRE effects on LVGLS, LVEF, FMD, or relatively small study must be interpreted with caution, they appear to VTIhyp. We found an association between increased peripheral blood support future studies designed to assess the impact HEPA filters in ANC and the absolute value of LVGLS after CCRE at 4 hours (r5 0.721, reducing asthma morbidity in lower-income urban communities. p50.0082) and 24 hours (r50.541, p50.06). CONCLUSIONS: In healthy adults, systemic inflammation after CCRE Annual Comparison of Weed Pollen in Las Vegas inhalation was associated with reduction in diastolic blood pressure. 256 and the Mojave Desert 2017-2019 Systemic neutrophilia increases may be associated with improved left

1 1 1 1 ventricular global longitudinal strain, a finding that deserves additional Joseph Jean , Asma Tahir, MPH , Samin Kamal , Mark Buttner , Dennis study. Bazylinski1, Joram Seggev, MD FAAAAI1; 1University of Nevada Las Vegas. RATIONALE: Weed pollen grains are common allergens in the desert region of Southern Nevada. This study aims to compare annual weed pollen between the Las Vegas Area and a rural site in Jean, Nevada, in the Mojave Desert. METHODS: Air samples were collected using a Burkard spore trap from January 1, 2017, to December 31, 2019, at the National Allergy Bureau site in Las Vegas and a site in Jean. Samples were analyzed via microscopy at 400x magnification. Data were compared using an independent samples t- test. RESULTS: The Las Vegas site had an annual mean of 19, 7, and 10 weed pollen grains/m3 from 2017-2019, respectively. The Jean site had an annual mean of 60, 5, and 15 grains/m3 from 2017-2019, respectively. The Jean site showed significantly higher weed pollen concentration than the Las Vegas site in 2017 (P<_0.001). There was no significant difference between the sites in 2018 (P<0.132) or 2019 (P<0.213). The maximum weed pollen concentration at both sites occurred in 2017; with Las Vegas at 488 grains/ m3 in March and 1745 grains/m3 in April for the Jean site. CONCLUSIONS: Variability between the sites was significant only for 2017, with more weed pollen at the Jean site. The spring of 2017 showed the highest concentrations of weed pollen for both sites. Highest concentrations were observed in spring, an observation unique to this region. There were similar average weed pollen concentrations between the two sites for 2018 and 2019, suggesting that weed pollen in urban environments is similar to the surrounding desert environment. AB82 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Profile of Airborne Pollen in a Recently Placed Depression Scores and TNF-a in Participants of 258 Station In Madrid: Description Of Levels Of 259 a Smoking Cessation Program Pollen In the Last Three Years Kelsey Field, MD1, Cassandra Derella, BS1, Ryan Harris, PhD1, Kathleen Marıa Cervera Garcıa1, Maria Somoza Alvarez, MD2, Ana MarAa~ May, MD FAAAAI1, Martha Tingen, PhD, RN1; 1Medical College of Prieto-Moreno Pfeifer, CME1, Isabel Torres Rojas, CME1, Teresa Alfaya Georgia at Augusta University. Arias3, Diana Perez Alzate, MD4, Elisa Haroun-Diaz1, Maria Vazquez de RATIONALE: Depression is more common in people who smoke, with La Torre5, Francisco RuanoAllergist4, Paula Lopez, MD1, Natalia Blanca depression and smoking being known triggers of inflammation. This pilot study Lopez 1, Francisco Feo Brito3, Gabriela Canto, MD, PhD1; 1Infanta Leo- tests the hypothesis that tobacco cessation will decrease TNF-aand depression. nor University Hospital, 2Allergy Therapeutics Iberica S.L.U., 3General METHODS: Thirty cigarette smokers, 50% female, 71% Caucasian, 20% University Hospital of Ciudad Real, 4Hospital Universitario Infanta Leo- Black, 9% Hispanic and Asian, mean age 3762y, participated in a 3-month nor, 5Hospital Infanta Leonor. (3M) cessation program with 12 month (12M) follow-up. Smoking status RATIONALE: Pollen calendars are practical instruments for allergists. was determined using serum cotinine, a metabolite of nicotine, with a The purpose of this study was to quantify and describe different levels of cutpoint of > 3ng/ml indicating active smoking. The Center for airborne pollen in our working-area (Infanta Leonor U.H, Madrid). Epidemiologic Studies Depression Scale (CES-D) was used to evaluate METHODS: We monitored the pollen in our area (January 2017- depression. Cotinine, CES-D scores, and TNF-a were measured at base- December 2019) with a Hirst-type volumetric collector, according to the line, 3M, and 12M. Mixed factorial 2-way ANOVAs were performed. guidelines of the Aerobiology Committee of the Spanish Academy of RESULTS: Based on serum cotinine, 16 participants were quitters at 3M Asthma and Clinical Immunology. compared to 15 quitters at 12M. TNF-a decreased in both quitters RESULTS: Pollen counts divided by families were as follows: (p50.013) and non-quitters (p50.064), and remained lower at 12M in Cupress/Taxaceae: both quitters and non-quitters (p<0.001). CES-D scores significantly Total (grains/m3): (2017:1,794), (2018:2,989), (2019:3,494) decreased in quitters (p50.046) at 3M, but not in non-quitters (p50.858) Specific pollen (%): (2017:14), (2018:18.20), (2019:26.25) and tended to be lower in both groups at 12M (quitters, p50.152; non- Peak( grains/m3): (2017:395), (2018:541), (2019:259) quitters, p50.080). Five quitters at 3M who became non-quitters by 12M Pollination season: (2017:28/01-19/03), (2018:11/01-2/04), (2019:11/01- also had lower TNF-a (p50.034) and CES-D (p50.169) at 12M. CES-D 5/04) scores were inversely related to cotinine in quitters (r5-0.298; p50.300), Platanus: in contrast to the proportional relationship observed in non-quitters Total: (2017:1,059), (2018:1,613), (2019:1,817) (r50.239; p50.411). Specific pollen: (2017:8), (2018:10.13), (2019:13.65) CONCLUSIONS: Smokers who participate in a 3-month smoking Peak: (2017:135), (2018:231), (2019:314) cessation program exhibit decreases in TNF-a and depression scores Pollination season: (2017:17/03-25/04), (2018:8/04-30/04), (2019:13/03- regardless of final quitting status. Depression can increase in quitters over 13/04) time suggesting a need for continued psychological support. Poaceae: Total: (2017:2,096), (2018:2,318), (2019:1,685) Stability of Cockroach Allergens Versus Non- Specific pollen: (2017:16), (2018:14.5), (2019:12.66) 260 allergens 2017 2018 2019 Peak: ( :117), ( :114), ( :113) 1 2 3 4 2017 2018 2019 Aurora Cabrera , Alexander Foo , Jill Glesner , Sayeh Agah , Lisa Pollination season:( :19/04-3/07), ( :12/05-27/07), ( :14/04- 3 3 2 10/07) Vailes , Sabina Wuenschmann, PhD , Thomas Randall , Anna Pomes, PhD FAAAAI3, Michael Fitzgerald5, Geoffrey Mueller, PhD2; Olea: 1 2 3 4 2017 2018 2019 Duke University, NIEHS, Indoor Biotechnologies, Inc., Indoor Bio- Total: ( :4,932), ( :3,481), ( :1,520) 5 Specific pollen: (2017:37), (2018:22), (2019:11.42) technologies, Professor of Chemistry. Peak: (2017:588), (2018:33), (2019:119) RATIONALE: Recent statistical evidence suggests that allergens are Pollination season:(2017:21/04-25/06)- (2018:27/05-5/07)- (2019:22/05- more stable and more highly expressed than other proteins from an allergen 29/06) source. These factors may influence human exposure and, on a smaller Plantago scale, stability may affect processing by sentinel dendritic cells skewing Total: (2017:1,173), (2018:1,334), (2019:1,441) the immune response toward allergy. Interestingly, for cockroach allergens Specific pollen: (2017:9), (2018:8.4), (2019:10.83) purified from frass, the allergen stabilities were not statistically greater Peak: (2017:87), (2018:103), (2019:154) than their non-allergen counterparts, likely due to the high mean stability of Pollination season:(2017:30/03-14/06), (2018:27/04-18/06), (2019:28/04- the latter. To investigate if this was a statistical sampling anomaly, the 4/06) stability of additional recombinant cockroach allergens was studied. Chenopo/Amarant: METHODS: The stability of 6 recombinant cockroach allergens was Total: (2017:972), (2018:698), (2019:431) measured as a function of guanidinium chloride concentration using HNSB Specific pollen: (2017:7), (2018:4.38), (2019:3.24) and SPROX labeling. Additionally, distant relatives of Bla g 1 (MA Peak: (2017:52), (2018:41), (2019:18) proteins) were compared for their thermal stability using temperature Pollination season: (2017:23/07-19/09), (2018:26/08-26/09) (2019:22/06- dependent circular dichroism as a function of lipid ligand concentration. 10/10) RESULTS: Bla g 1, 4, 6, and 9 showed elevated stabilities compared to the CONCLUSIONS: The frequency of pollen counts has changed in our area mean of non-allergen cockroach proteins. However, the differences in the last year. While Olea was the highest in 2017 and 2018, Cupress/ between allergens and non-allergens was not statistically significant. Taxaceae was predominant in 2019; and in contrast with other areas of Additional MA homologues of Bla g 1 demonstrated similar melting Madrid Weed pollen kept high reactive levels during their flowering temperatures to the latter with no ligand present. However, the stability season. enhancement due to lipid loading was not present or not as great for other These data emphasizes the necessity for close and continuous airborne MA proteins compared to Bla g 1 loaded with lipids. pollen monitoring. CONCLUSIONS: Cockroach allergens are highly stable proteins compared to proteins from other allergen sources. However, compared to non-allergens from cockroaches there is not a significant difference, even with data from additional recombinant allergens. J ALLERGY CLIN IMMUNOL Abstracts AB83 VOLUME 147, NUMBER 2

Applying deep learning to pollen identification Comparative Incidence of Skin Test Reactivity to 261 using metabolic fingerprints 263 Johnson, Timothy, and Bermuda Grasses in San Francisco Les Klimczak1, Cordula Ebner von Eschenbach2, Peter Thompson, PhD3, Jeeroen Buters, PhD4, Geoffrey Mueller, PhD1; 1NIEHS, 2Technical Uni- Christina B. Phan, MD1, Bryce Hoffman, MD1, Andrew Louie1, Julia versity of Munich, 3North Carolina State University, 4ZAUM- Center of Wei2, Peg Strub, MD FAAAAI1; 1Kaiser Permanente, San Francisco, Allergy & Environment. CA, 2Kaiser Permanente, Oakland, CA. RATIONALE: The daily pollen counts are typically measured by visual RATIONALE: Timothy and Bermuda grasses are the mainstay of grass identification by trained experts. Automated visual identification of pollen immunotherapy in Northern California. Recently, Johnson grass (Johnson) grains using deep learning algorithms has been demonstrated. An has become increasingly prevalent. The purpose of this study is to alternative would be to identify the pollens via their metabolite signature, determine the incidence of skin test reactivity to Johnson compared to also known as metabolic fingerprinting. Bermuda grass (Bermuda) and Timothy grass (Timothy) in San Francisco METHODS: Extracts of air-sampled pollen from Munich in 2016 and (SF). 2017 were prepared simultaneously with visual identification for reference. METHODS: A total of 1590 patients had skin prick testing to Johnson, The extracts were lyophilized, rehydrated in 2H buffer, and filtered (3 kDa Timothy, and Bermuda pollen extracts (HollisterStier) from 1/1/2016 to 8/ cutoff) to removed proteins and allergens. NMR spectra of the extracts 14/2020 at Kaiser Permanente SF. Positive cut-off was wheal size >_3mm were acquired. Various machine learning methods and deep learning above negative control. methods were applied to identify the component taxa. RESULTS: Of those tested, 420 (26%) reacted to Johnson with 8.9 mm RESULTS: Categorical prediction algorithms trained for low, medium, average, 703 (44%) reacted to Timothy with 15.2 mm average, and 552 high, and very high pollen count groups achieved accuracies of 74% for the (35%) reacted to Bermuda with 10.2 mm average; 369 (23%) reacted to all tree, 82% for the grass, and 93% for the weed pollen count. Deep learning three grasses. Among Johnson-sensitized patients 95% reacted to Timothy methods using convolutional neural networks (CNN) performed better and 90% to Bermuda; 88% reacted to both. Among Bermuda-sensitized than traditional machine learning using the NMR spectra directly, without patients 88% reacted to Timothy and 68% to Johnson; 67% reacted to both. identification of the metabolites. CNN trained on the NMR spectra were the CONCLUSIONS: This study reveals a high incidence of Johnson grass overall best method in terms of relative error and classification accuracy: sensitization in SF; skin testing and immunotherapy is advisable. Notably, 86% for tree, 89% for grass, and 93% for weed pollen count. we found a very high number of Bermuda (Chloridoideae subfamily) and CONCLUSIONS: This study demonstrates that NMR spectra of air- Johnson (Panicoideae subfamily) sensitized patients also reacted to sampled pollen extracts can be used in an automated fashion to provide Timothy (Pooideae subfamily). Immunotherapy guidelines recommend taxa and type-specific measures of the daily pollen count. This is a proof of treating each subfamily separately. Our results suggest treatment with principal that metabolic fingerprinting, instead of visual identification, may Timothy only may provide sufficient coverage for Bermuda and Johnson in be a viable method to automate pollen identification. SF. Further investigation is needed.

Comparative Incidence of Sensitivity to Oak and Comparative Incidence of Skin Test Reactivity to 262 Alder in San Francisco 264 Russian Thistle, Lambs Quarter and Pigweed in San Francisco Bryce Hoffman, MD1, Christina B. Phan, MD1, Julia Wei2, Peg Strub, MD FAAAAI1; 1Kaiser Permanente, San Francisco, CA, 2Kaiser Perma- Julia Wei1, Bryce Hoffman, MD2, Christina B. Phan, MD2, Peg Strub, nente, Oakland, CA. MD FAAAAI2; 1Kaiser Permanente, Oakland, CA, 2Kaiser Permanente, RATIONALE: Immunotherapy guidelines state that significant cross- San Francisco, CA. reactivity within and between Fagaceae and Betulaceae families enables RATIONALE: Lambs quarter (LQ) is currently used for immunotherapy the selection of one antigen to treat both families. We evaluated skin test at Kaiser Permanente (KP) San Francisco (SF). Russian thistle (thistle) is in reactivity to oak (Fagaceae) and alder (Betulaceae) pollens to optimize the same Chenopodioiddeae subfamily and is thought to provide similar immunotherapy treatment in San Francisco (SF). A secondary goal was to coverage with additional unique antigens. While it is known that cross- analyze the utility of intradermal testing (IDT) for oak and alder. reactivity exists within the Chenopodioiddeae subfamily, it has been sug- METHODS: A total of 1577 patients were tested to oak mix RVW (red, gested that there is also cross-reactivity to pigweed (Atriplex ‘‘saltbush’’ Virginia live, white oak) and red alder pollen extracts (HollisterStier 1:20 genus), another member of the Amaranthaceae family. The purpose of w/v) from 1/1/2016 to 8/14/2020 at Kaiser Permanente SF. All patients this study was to evaluate and compare the incidence of sensitization to underwent skin prick testing (SPT) and 75% of negative patients had IDT thistle, LQ and pigweed in SF. based on provider preference. Positive cut-off for SPT/IDT was wheal size METHODS: A total of 304 patients had skin prick testing to thistle, LQ, >_3 mm above negative control. and rough redroot pigweed pollen extracts (HollisterStier 1:20 w/v) from RESULTS: Of those tested, 410 (26%) reacted to oak with 10 mm average 11/20/2019 to 8/14/2020 at KP SF. Positive cut-off was wheal size >_3mm SPT and 241 (15%) reacted to alder with 9.6 mm average. 211 reacted to above negative control. both oak and alder encompassing 51% of oak-sensitized patients and 88% RESULTS: Of those tested, 89 (29%) reacted to thistle with 8.1 mm of alder-sensitized patients. Only 11/1842 intradermal tests (0.6%) showed average, 38 (13%) reacted to LQ with 7 mm average, and 66 (22%) reacted reactivity and were excluded. to pigweed with 8.2 mm average. 89% of LQ-sensitized patients reacted to CONCLUSIONS: This study shows a higher percentage of alder- thistle; 38% of thistle-sensitized patients reacted to LQ. 76% of pigweed- sensitized patients are sensitized to oak (88%) than oak-sensitized patients sensitized patients reacted to thistle; 56% of thistle-sensitized patients to alder (51%). This is likely due to Aln g 1 homology to Que a 1 in the reacted to pigweed. setting of higher oak prevalence in SF. We conclude that testing and CONCLUSIONS: We conclude that thistle should replace LQ for testing treatment with oak will cover both Fagaceae and Betulaceae families in SF and immunotherapy in SF based on high cross-reactivity and thistle’s and potentially other oak-dominant regions. IDT yielded negligible unique antigens. A high rate of pigweed-sensitive patients reacting to reactivity and should not be routinely performed. thistle was also noted. As pigweed and thistle are more distantly related in the Amaranthaceae family, more research is needed to determine the level of cross-reactivity and its clinical utility. AB84 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Nasal Allergic Symptoms are Highly Asthma Prevalence and Mold Levels in US 265 Reproducible in Cat-Allergic Mild Asthmatics 267 Northeastern Schools in a Naturalistic Exposure Chamber Evin Howard1, Stephen Vesper2, Barbara Gunthrie3, Carter Petty4, Vale- William Yang, MD FAAAAI1, Suzanne Kelly, PhD1, Laura Haya, PhD1, ria Ramden5, Will Sheehan, MD FAAAAI6, Jonathan Gaffin, MD7, Per- Rym Mehri1, Divya Ramesh2, Michelle DeVeaux2, Pretty Meier2, Sumit dita Permaul, MD FAAAAI8, Peggy Lai, MD9, Lisa Bartnikas, MD4, Narula2, Furat Shawki2, Lorah Perlee, PhD3, Gary Herman, MD2, Meagan Amparito Cunningham, MD MPH10, Marissa Hauptman, MD7, Diane OBrien2; 1Red Maple Trials Inc., 2Regeneron Pharmaceuticals, Inc., 3Re- Gold, MD11, Sachin Baxi12, Wanda Phipatanakul, MD MS FAAAAI4; generon Pharmaceuticals Inc. 1Boston Children’s Hospital and Northeastern University, 2Environmental RATIONALE: To evaluate the reproducibility of nasal and ocular allergic Protection Agency, 3Northeastern U, 4Boston Children’s Hospital, 5North- symptoms elicited among cat-allergic mild asthmatics during live cat eastern University, 6Children’s National Medical Center, 7Boston Chil- allergen exposure in a Naturalistic Exposure Chamber (NEC) dren, 8NY Presbyterian Hospital/Weill Cornell Medicine, METHODS: In this prospective, observational study, 30 cat-allergic mild 9Massachusetts General Hospital, 10Harvard University, 11Channing Divi- asthmatics (GINA-1; 43% male, mean age 32 years) underwent two (Day 1 sion of Network Medicine, 12Children. and 28) up to 180-minute cat allergen challenges in a NEC. Total nasal RATIONALE: Asthma is among the most common chronic diseases of symptom score (TNSS) and total ocular symptom score (TOSS) were children in the United States (US). Mold exposures have been linked to measured every 20 mins. Average TNSS and TOSS during NEC exposure asthma development and exacerbation. In homes, mold exposures have were calculated as the AUC divided by time in NEC. Least squares means been quantified using the Environmental Relative Moldiness Index (ERMI) are presented, adjusted for baseline values and NEC cat allergen concen- and higher home ERMI values have been linked to occupant asthma. In this tration. Serum IgE levels for cat dander and Fel d 1 as well as skin prick test analysis of the School Inner-City Asthma Study 2 (SICAS 2), we aimed to (SPT) to cat allergen were measured at screening. evaluate the ERMI’s applicability to measuring mold in schools compared RESULTS: Mean (95% CI) of average TNSS and TOSS on Day 1 were to homes, to assess the relationship between the prevalence of asthma in 3.17 (2.51-3.84) and 0.82 (0.30-1.23), respectively, and 2.6 (1.91-3.39) and schools and mold levels, and to examine the prevalence of asthma in 1.04 (0.38-1.69) on Day 28, respectively. TNSS was highly correlated relationship to students’ demographics and the physical characteristics of within-subjects between the two NEC exposures (r50.73, p<0.0001), school-buildings. TOSS was not (r50.28, p>0.05). Baseline SPT to cat and IgE to cat and Fel METHODS: Northeastern US schools (n532) and homes (n533) were d 1 did not correlate with magnitude of nasal or ocular symptoms (absolute selected and the 36-ERMI molds were quantified in a dust sample from value of Spearman’s r<0.3, p>0.05 for all comparisons). each classroom or home. School building characteristics, student de- CONCLUSIONS: Mean nasal and ocular symptoms of cat-allergic mographics and asthma prevalence data were collected from the SICAS 2 asthmatics, were reproduced in the NEC; however, individual ocular study or obtained from government websites. Linear regression and mixed symptoms were not. NEC is a good model for development of therapies for models were fit to assess the association of current asthma prevalence and cat-specific allergic rhinoconjunctivitis. physical characteristics of the school, make-up of the student body and the ERMI metric. Wind Influence on the Grass Airborne Pollen in RESULTS: Levels of outdoor Group 2 molds were significantly (p<0.01) 266 Bahıa Blanca, Argentina greater in schools compared to homes and higher Group 2 levels in schools

1 1 were linked to higher asthma prevalence for their students. The presence of German Ramon, MD FAAAAI , Laura Barrionuevobiologist , Graciela AC in school buildings correlated significantly (p50.02) with lower Benedetti2, Valeria Duval, Geography PhD2; 1Instituto de Alergia e Inmu- 2 asthma prevalence. nologia del Sur, Universidad Nacional del Sur. CONCLUSION: Higher mold levels in northeastern US schools were RATIONALE: The objective of this work was to identify the influence of associated with an increase in students’ asthma. the wind direction and speed on the airborne grass pollen during the year 2019 in the city of Bahıa Blanca. Its geographical location is by the sea in Forecasting Airborne Pollen for Allergy the southwest of Buenos Aires province. 268 Management for Contiguous United States METHODS: The pollen count was carried out with a Rotorod M 40Ó type impact device. Pollen data are daily and are expressed in pollen grains per Jeremy Hess, MD MPH1, Fiona Lo, PhD1; 1University of Washington. cubic meter of air. The wind data were provided by the Departamento de RATIONALE: Management of pollen allergies can be improved with a Geografıa de la Universidad Nacional del Sur. A descriptive and skillful forecast of pollen concentrations by allowing allergy sufferers to comparative statistical analysis was used. plan and prepare medical therapy and practice exposure avoidance. In the RESULTS: The analysis showed that the predominant wind during 2019 past, pollen forecasts have been limited spatially and temporally in the was from the South, Southeast and Southwest sectors (for 257 days). In the contiguous US. year studied, a maximum gust of 127 km/h was recorded on August 15. The METHODS: Allergenic pollen concentrations are obtained from the maximum number of grass pollen was 36 gr/m3 on November 22. National Allergy Bureau (2003-2018), we focus on the ten most abundant CONCLUSIONS: Historically, the dominant winds come from the North, and allergenic pollen types in the contiguous US. Machine learning Northwest and West with maximum average speeds of 70 km/h. The pollen Random Forest model based on meteorological, vegetation indices, count during the year 2019 was lower compared to other years, for geographic data and google search terms of ‘‘pollen’’ and ‘‘ragweed’’ is example, that a value of 122 gr/m3 registered on November 7, 2018. The used to predict daily pollen concentrations. decrease in the air of Poaceae grains may be due to the wind direction that RESULTS: We forecast pollen 1-14 days in advance throughout the was predominantly from the estuary (southern sector) where there is a contiguous US, in locations that presently do not have pollen observations, scarce population of grass because of the sea. thereby extending the spatial resolution of pollen forecasts. This work represents a substantial improvement over the present forecasting ability. CONCLUSIONS: This model has the potential to forecast pollen concentrations throughout the contiguous US and allows allergy sufferers early warning to prepare and plan medical therapy and exposure avoidance. J ALLERGY CLIN IMMUNOL Abstracts AB85 VOLUME 147, NUMBER 2

Using Hourly Pollen Data to Quantify Relevant The advance in Poaceae pollen seasonality 269 Distance and Response Times of Hay Fever 271 pattern may impact allergy treatment practice Symptoms Following Exposure to Local Pollen Peaks Juliana Camargo1, Sebastian Brill2, Cinthya Souza3, Bruna Sebben3, Theotonio Pauliquevis4, Philip Taylor5, Ricardo Godoi6; 1Federal Univer- Richard Lucas, PhD1, Landon Bunderson2, Dan Dalan, MD3; 1South- sity of Parana, 2Multiphase Chemistry Department, Max Planck Institute west Environmental Institute, 2Pollen Sense, 3Self employed. for Chemistry, 55128, Mainz, Germany, 3Department of Pediatrics, Fed- RATIONALE: Exposure to aeroallergens results in human suffering. This eral University of Parana, Curitiba 80060-240, Brazil, 4Department of study investigated the number of hours following locally reported pollen Environmental Sciences, Federal University of S~ao Paulo, Diadema, peaks and the relevant distance from pollen sampling locations. Brazil, 5Department of Pharmacy and Biomedical Sciences, La Trobe METHODS: We employed an automated pollen sampler (APS) network University, Bundoora, Australia, 6Environmental Engineering Depart- and a mobile application enabling users to self-report when they feel ment, Federal University of Parana, Parana, Brazil. allergenic symptoms. Hourly total pollen counts from the nearest APS RATIONALE: Climate is known to have a significant effect on pollination location were matched with symptom data from anonymized app users, periods of several plants in the northern hemisphere, e.g. Poaceae, which is enabling investigation of response times and relevant distances from APS the main cause of pollen allergy worldwide. This study analyzed whether locations. Relevant distance was determined by evaluating the variance in the seasonal pattern of airborne Poaceae pollen has changed in Curitiba, symptom data as a function of distance, in 10 km increments, from the Southern Brazil nearest APS location. METHODS: For bioaerosol sampling, a Hirst-Burkard-7-day volumetric RESULTS: Hourly pollen data were collected from 90 APS units located spore trap was used. The pollens were stained and identified via light throughout North America and Europe. Symptom data were collected from microscopy. Pollen counts were obtained for 222 days in 2018 and 847 anonymized app users between March 16, 2020 and Aug 17, 2020. compared with those of a previous study performed with the Durham Symptom variance reached a plateau at 40 km. Including only users within palinometer during 1981/82. 40 km from an APS location, the distribution of response times displayed a RESULTS: The Poaceae season started in August and went on to April ( ), clear peak, indicating users felt their worst 3-10 hours following a local corresponding to 90% of all counted Poaceae pollen. The highest daily pollen maxima. The median was 9.5 hours following a total pollen peak. concentration of Poaceae pollen occurred in September 2018 with a The distribution was right-skewed with a kurtosis of -1.43. maximum of , and the lowest counts were observed between May to July ( CONCLUSIONS: Participants in this study exhibited rapid response ). However, the Poaceae season started in September in the year 1981, times over relatively short distance following exposure to elevated levels of peaking in the middle of November, two months later than in 2018. total pollen in the ambient air. Limitations in the availability of pollen data CONCLUSIONS: There is strong evidence for a change in the annual have historically prevented large-scale investigations of response times to cycle of airborne pollen in Curitiba when comparing Poaceae in 2018 to pollen in broad populations. Our data suggest managing personal exposure 1981/82, as the pollination period started and peaked earlier. However, the during peak pollen periods could provide positive outcomes. end of the Poaceae season in April seems to remain consistent. This shift may have been triggered by annual climatic variations, climate change, Airborne pollen analysis during one year in the and/or urbanization, leading to seasonal and perennial symptoms in 270 city of Trelew, Argentina patients allergic to grass pollen.

Gabriel Fueyo1, Laura Barrionuevobiologist2, German Ramon, MD Impact of Climate Change on Tree Pollen Levels FAAAAI3; 1Centro Cardiologico Trelew, 2Instituto de Alergia e Inmuno- 272 in Southern Ontario logia del Sur, 3Instituto de Alergia E Imm. Del Sur. RATIONALE: The city of Trelew is located on the west coast of James Anderson, MLT1, Peter Pityn, PhD2; 1Environmental Allergy As- Argentina Patagonia, with unique geographic characteristics close to the says, 2Oshtech Incorporated. Atlantic Ocean. Since there are no previous studies, a study of air pollen RATIONALE: Scientists have predicted longer, more intense pollen was carried out during 12 months. seasons due to climate change. Our NAB station in SW Ontario, Canada METHODS: Pollen counting was performed with a Rotorod M40 Ó type has reported an opposite trend in ragweed and no measurable changes in impact volumetric device. The data are daily and are expressed in pollen grass pollen. Trees may be subject to the cumulative impacts of grains per cubic meter of air sampled. The pollen classification suggested environmental stressors. by AAAAI/NAB was used. The study period of airborne pollen was carried METHODS: Annual pollen counts of 14 different tree varieties covering out from August 1st 2019 to July 30th 2020. 20 years, from 1998 to 2017, were analyzed. Tree pollen dissemination in RESULTS: Throughout the sampled period, pollen from this area begins in March or early April, with Mulberry typically Chenopodiaceae/Amaranthaceae were found with a total of 2162 grains/ constituting one-quarter of the annual counts. Maple, Juniper, Poplar and m3 of air sampled throughout the period under study, Cupressaceae with Oak each represent about 10% of the counts. We employed anomaly 3804 grains/m3, Fraxinus with 2404 grains/m3, Poaceae with 1294 grains/ detection procedures to identify when tree pollen counts were extraordi- m3 and Populus with 1761 grains/m3. A striking characteristic of this narily high or inordinately low, outside of the expected range. locality is the presence throughout the time of sampling of the RESULTS: Data analysis showed outliers when annual tree pollen levels Chenopodiaceae/Amaranthaceae, and not limited to the months of were either extremely high or low, far beyond the 1st or 99th percentile. The December to March as observed in other cities of Argentina. number of outliers was greater than expected. Distribution of counts was CONCLUSIONS: Considering the most allergogenic species, we can highly skewed at the lower end, often tailing to the right where pollen assume that the most risky periods for tree-sensitive allergy patients are the counts were excessive. months of August to November, patients sensitive to Poaceae during CONCLUSIONS: Climate change may be affecting tree pollen produc- October and November and those sensitive to weeds specifically to tion in an unexpected manner. Years of drought, excess precipitation, Chenopodiaceae / Amaranthaceae, the risk of exposure extends to the pestilence, high temperatures, bitter cold winters, etc., sometimes succes- entire period studied. sively, will have cumulative impacts on tree health. Temporal adjustments to the prevailing seasonal conditions, as well as the cumulative stress, manifest in extreme pollen seasons. The effects of climate change on tree pollen production are complicated and not as well understood as current science has led us to believe. AB86 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Diagnostic accuracy of different commercial preventatively avoiding compared to those with a prior reaction 273 walnut extracts in a paediatric atopic (p50.0025). population CONCLUSIONS: The majority of patients pass low risk almond and hazelnut OFCs. PPV at the 50th percentile for walnut and cashew were Maria Abreu-Ramırez1, Victoria Fuentes-Aparicio1, Cristina Morales- lower than previous studies have suggested. Cabeza2, Alberto Alvarez-Perea 1, Sonsoles Infante, MD2, Carmen Beorle- gui3, Paloma Jaqueti Moreno4, Paula Cabrera-Freitag4; 1Hospital General Proteomic profiling of the inflammatory Universitario Gregorio Maran~on, Madrid, Spain, 2Hospital General Uni- 275 response during oral challenge to peanut ~ 3 4 versitario Gregorio Maranon, Madrid, Spain, Navarre Government, Pe- 1 2 diatric Allergy Unit, Hospital General Universitario Gregorio Maran~on, Nicole Ramsey, MD PhD , Charuta Agashe , Anna Nowak- Wegrzyn, MD, PhD3, Julie Wang, MD FAAAAI4, Scott Sicherer, MD Madrid, Spain. 5 6 1 2 RATIONALE: Walnut is a relevant allergenic food in paediatric popu- FAAAAI , Cecilia Berin, PhD ; Mount Sinai Hospital, Icahn School of Medicine at Mt Sinai, 3NYU Langone Health, 4Icahn School of Med- lation. An accurate diagnosis is essential. The aim of this study was to 5 6 assess the diagnostic capacity of natural and three commercial walnut icine at Mount Sinai, Mt. Sinai School of Medicine, Mount Sinai School extracts to perform skin prick tests (SPT). of Medicine. METHODS: Fifty-one atopic children were included in the study; 39 with RATIONALE: The immune basis of peanut allergy threshold of reactivity a clinical history of walnut allergy and positive specific IgE values to is not fully understood. This study aims to compare cytokine profiles walnut (>_ 0.35 KU/L) and 12 atopic controls tolerating walnut. SPT whit during food challenges for selected patients in the CAFETERIA trial. three commercial walnut extracts (ALKÒ, LetiÒ, RoxallÒ) as well as METHODS: Patients (4-14 years old) who are avoiding peanut and have prick-prick test (PPT) with natural walnut were performed. Wheals >_3mm detectable peanut IgE are being screened for the CAFETERIA trial. Serum were considered positive. samples were collected at baseline and 2 and 4 hours after placebo or The sensitivity and specificity for SPTs with commercial extracts and peanut challenge. Samples were analyzed using the O-link proteomic assay natural walnut, as well as wheal sizes (WS), were analyzed. of 92 inflammation markers. Protein expression was compared between RESULTS: SPTs with ALKÒ, RoxallÒ and LetiÒ walnut extracts as well placebo and peanut challenges, and between those with high ( >443 mg) as natural walnut, showed high sensitivity (100; 100; 97.44; 100) but and low threshold, with FDR adjustment for multiple comparison. moderate to low specificity (75; 41.66; 41.66; 58,33) values with no RESULTS: 27 peanut and 14 placebo challenge samples were analyzed. 5 5 differences between them. CXCL9 (p<0.000001), IL-10 (p 0.000004), and CCL25 (p 0.00003) In walnut allergic patients, the median WS with Roxall’sÒ walnut extract were significantly increased 4h after peanut challenge compared to (9.5mm) was significantly larger than Leti’sÒ (7.5mm; p <0.001) and placebo. CXCL9 is a Th1 chemoattractant, CCL25 promotes T cell gut 5 ALK’sÒ (7.5mm; p <0.001) but similar to those of the PPT (9.5mm; p 5 homing, and IL-10 is a regulatory cytokine. Oncostatin-M (p 0.000001) 5 0.566), while ALK’sÒ and Leti’sÒ WSs were significantly smaller and S100A12 (p 0.000179) were higher in low threshold peanut allergic compared to those of the PPT (p5 0,003; p<0,001). participants. Oncostatin M is associated with mucosal barrier dysfunction, CONCLUSIONS: Commercial walnut extracts from ALKÒ, RoxallÒ and S100A12 is a receptor for advanced glycation end products that can and LetiÒ have a similar diagnostic accuracy. activate mast cells. However, in walnut allergic patients, the WS of the SPT with Roxall’s CONCLUSIONS: We found five inflammatory markers to be dynamically walnut extract is significantly larger than those performed with ALK’s and expressed in the serum of patients during peanut challenge. Markers Leti’s extracts and similar to the PPT. upregulated suggest a compensatory regulatory response and recruitment of T cells to the gut during the reaction. Our results also point to barrier Clinical predictors and outcomes of oral food dysfunction and mast cell amplification loop in highly sensitive patients. 274 challenges illustrate differences among individual tree nuts

Cynhia Hsu1, Meagan Yong1, Jacob Pozin1, Melanie Makhija, MD1, Anne Marie Singh, MD2; 1Northwestern Feinberg School of Medicine, 2University of Wisconsin. RATIONALE: Although allergy to tree nuts is often considered a single entity, there is heterogeneity in patient reactivity and immune response to different tree nuts. We sought to characterize tree nut oral food challenges (OFC) in a pediatric population performed at a single center over a 12-year period and determine differences in OFC outcome to different tree nuts. METHODS: A retrospective chart review was conducted in patients (0- 20 years) who completed an unblinded OFC to any tree nut from 2007- 2019 at Lurie Children’s Hospital. Differences among almond, cashew, hazelnut, and walnut challenges were compared and probability curves were used to estimate positive predictive values (PPV) of sIgE at OFC. RESULTS: 531 tree nut OFCs were included. The mean age at OFC was 7.77 years, 57.5% of patients were male, 66.2% were Caucasian. Overall, 74.0% of children passed their OFC. Of the four most commonly challenged tree nuts (almond, cashew, hazelnut, and walnut), almost all patients passed OFC to almond (97.3%) and hazelnut (87.9%). Pass rates were lower for cashew (65.3%) and walnut (57.0%). Comparing partic- ipants who passed or failed their OFC, we found an association between sIgE at OFC for almond (p 5 0.029), cashew (p 5 0.011), and walnut (p 5 0.0007). The odds of failure were 0.83 times lower for patients who were J ALLERGY CLIN IMMUNOL Abstracts AB87 VOLUME 147, NUMBER 2

Factors associated with tolerating double-blind during purification process, and the identities of the purified minor 276 placebo-controlled food challenge in school- allergens were confirmed by mass spectrometry. aged children CONCLUSIONS: This protocol is a relatively simple and highly reproducible method to purify minor allergens that are very low in Sofianne Gabrielli, MSc1, Bruce Mazer, MD FAAAAI2, Danbing abundance in peanut. Performing the three initial steps is sufficient to Ke, PhD3, Christine McCusker, MD MSc4, Michelle Le, MD1, Lydia separate major allergens from minor allergens, which could be useful in Zhang, MD1, Liane Beaudette, RN1, Duncan Lejtenyi, MSc1, Edmond diagnostic tests, and does not require the special instrumentation necessary Chan, MD FAAAAI5, Ingrid Baerg6, Julia Upton, MD7, Eyal for the cumbersome gradient elution and size exclusion chromatography Grunebaum, MD8, Ann Clarke9, Moshe Ben-Shoshan, MD FAAAAI1; downstream steps which produce pure proteins. 1McGill University Health Centre, 2The McGill University Health Centre, 3McGill University Health Center Research, 4Montreal Children’s Hospi- Panel of Unintended Consequences tal, McGill University Health Centre, 5BC Children, 6BC Children’s Hos- 278 7 8 pital, The Hospital for Sick Children, Hospital for Sick Children, 1 1 9 Daniel Urschel, MD , Jose Calderon, MD , Vivian Hernandez-Trujillo, University of Calgary. 2 1 2 RATIONALE: Positive predictive values of skin prick tests (SPTs) and MD FAAAAI ; Nicklaus Children, Allergy and Immunology Care Cen- specific IgE (sIgE) in children above 6 years old is not currently clear. We ter of So. aimed to assess the percentage of children diagnosed with food allergy RATIONALE: Food Allergy Panels are increasingly accessible. tolerating double-blind placebo-controlled food-challenge (DBPCFC) and Indiscriminate food allergen testing is not sensitive, and has high false- to determine factors associated with tolerating DBPCFC. positive rates. Inaccurate diagnosis of food allergy, and subsequent food METHODS: Children with physician-diagnosed allergy to milk, peanut, avoidance, often results in deleterious physical, psychosocial, and egg and hazelnut were recruited at the Montreal Children’s Hospital, economic effects. Unclear results may lead to inappropriate management British Columbia Children’s Hospital, and the Hospital for Sick Children. of true IgE mediated food allergy. We hypothesized that food allergy panel All patients underwent DBPCFC. Multivariate logistic regression was used orders would be associated with unnecessary food avoidance, as well as to estimate factors associated with tolerating DBPCFC. decreased Epinephrine auto-injector prescriptions in patients with imme- RESULTS: Over 7 years, 145 children were recruited for OIT, 57.2% were diate food reactions. male and the median age was 11.0 years [Interquartile Range (IQR) 8.5, METHODS: We conducted a retrospective chart review of 3600 pediatric 15.0]. DBPCFC to milk, peanut, egg, and hazelnut were conducted in 90 patients’ initial visits in the Nicklaus Children’s Hospital Allergy Clinics. (62.1%), 30 (20.7%), 14 (9.7%) and 11 (7.6%) children, respectively, The number of patients with food panels via serum and/or skin testing, among which, 6.7%, 6.7%, 6.7%, and 54.5% tolerated their respective individual food testing or no testing, diagnosis, history of clinical food challenges (10.3% for all foods). reactions, food avoidance history, and Epinephrine auto-injector pre- SIgE was significantly lower in those that tolerated DBPCFC to peanut (p- scriptions prior to appointment were documented. Patients with prior value50.035) and to milk (p-value50.006). Baseline SPT was signifi- Allergist evaluation or insufficient encounter documentation were cantly lower among those that tolerated DBPCFC to milk (p-val- excluded. 2961 encounters meeting criteria were analyzed. ue50.009). Tolerating DBPCFC was associated with hazelnut [adjusted RESULTS: Food panel patients were more likely to be avoiding foods Odds Ratio (aOR) 1.49 (95% CI, 1.25, 1.77)], lower sIgE values at baseline based on testing without clinical reaction than patients with individual food 2 5 5 5 [aOR 0.99 (95% CI, 0.99, 0.99)] and lower SPTat baseline [aOR 0.98 (95% tests. x (1,N 694) 23.78 p <.00001. Patients with history of immedi- CI, 0.97, 0.99)], while adjusting for sex and age. ate reactions to foods were less likely to have Epinephrine prescriptions if 2 5 5 CONCLUSIONS: It is important to consider a challenge prior to starting evaluated by panel compared to individual testing. x (1,N 280) 7.25 5 OIT in children for those with hazelnut allergy, and those with lower SPT p <.01. size and sIgE levels. CONCLUSIONS: Compared to individualized testing, food panels are associated with unnecessary food avoidance, and decreased Epinephrine Separation from major allergens and co- auto-injector prescriptions for patients with immediate food reactions. 277 purification of two minor allergens in peanut These findings represent the inherent difficulty of integrating food panel extract test results with clinical history, and need for careful interpretation.

Jane McBride, MS1, Soheila Maleki, PhD FAAAAI2, Barry Hurlburt, PhD3; 1USDA Agricultural Research Service, 2USDA-Agricultural Research Service, 3USDA. RATIONALE: Peanut allergies can cause anaphylaxis and even death, with the four major allergens (Ara h 1, 2, 3, and 6) being responsible for serious reactions in the US, while the minor allergens, Ara h 8 and 9, are either associated with minor symptoms of the oral cavity or are generally less recognized by allergic people outside of the Mediterranean, and occasionally cause systemic allergic reactions. A protocol to separate major and minor allergens in extracts for diagnostics like skin prick tests may therefore be desirable. METHODS: Defatted peanut flour was extracted in mildly acidic buffer and subjected to ammonium sulfate precipitation and ion exchange and hydrophobic interaction chromatography. Natural Ara h 8 and 9 were separated from each other by size exclusion chromatography. RESULTS: The steps of extraction in acidic buffer and of passing the extract through an anion exchange column removed the major allergens. Ara h 8 enrichment and isolation were monitored by western blotting AB88 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Characteristics of Reactions that Pass During Applicability of US-based risk stratification for 279 Oral Food Challenges 281 oral food challenges in Chilean pediatric population Katherine Weller, MD1, Jaclyn Bjelac, MD1, Samantha Knox1,Wei Liu1; 1Cleveland Clinic. Florencia Neumann1, Sara Concha1, Josefina Castagnoli1, Arturo RATIONALE: Oral food chasllenge (OFC) remains the gold standard Borzutzky, MD FAAAAI1, Rodrigo Hoyos2; 1Pontificia Universidad Ca- diagnostic procedure for food allergy. Determining when to stop a tolica de Chile, 2Pontificia Universidad Catolica de Chile. challenge due to mild reactions, such as subjective complaints or contact RATIONALE: Oral food challenges (OFC) are the gold standard hives, may be difficult. This study aimed to identify factors associated with diagnostic test for food allergies (FA). Skin prick test and sIgE testing ultimately passing a challenge, instead of failing, in patients that do not accurately predict who will pass an OFC and no risk stratification experienced reaction during OFC. based on those tests has been attempted in Latin American children. METHODS: Retrospective review including children and young adults METHODS: Chart review of patients who underwent OFC at the Allergy who completed OFCs from 2013-2018 at Cleveland Clinic Children’s. and Immunology Clinic at the UC-Christus Health Network between 2017- Demographics, atopic history, culprit food, reaction history, diagnostic 2020. OFCs were ordered using sIgE and skin prick test risk stratification testing, as well as challenge details and outcomes were collected and cutoffs previously published for North American children (Simberloff et at, analyzed. JACI in Practice 2016). RESULTS: A total of 1,269 OFCs of patients 5 months to 21 years were RESULTS: 46 OFCs were performed in 44 patients. Five patients were reviewed. There were 816 OFCs without any documented reaction. 453 allergic to more than one food, 16% had a previous history of anaphylaxis patients had symptoms of a reaction, of which 144 patients (31.7%) to the tested food. Seventy three percent of patients had additional allergic ultimately passed and 309 failed OFC. The patients who reacted but passed conditions, 27% had asthma, 36% had allergic rhinitis and 57% had atopic had lower serum-specific IgE (sIgE) levels compared to failed challenges dermatitis. Atopic dermatitis affected 42% and 83% of patients with egg (1.3 vs 2.5 ku/L, p<0.001). There was no significant difference in co- and peanut allergy, respectively. Median age at OFC was 3 years (6 months morbidities or allergic history between groups. The most common – 14 years), tested foods were peanut (28%), egg (33%), milk (23%), baked symptoms experienced in those who passed were isolated cutaneous egg (18%), lentils (4%), nut (2%) and soy (2%). Reactions to challenge (45.8%) or gastrointestinal (27.8%), most commonly grade 1 (77.1%) or were observed in only 3 patients, 2 to peanut and 1 to milk, none of them grade 2 (18%). Foods most likely to have symptoms then still pass were had a reaction requiring epinephrine. milk (21% of challenges), baked milk (17%), soy (14.1%), egg (11%), CONCLUSIONS: Although food sIgE and skin prick test diagnostic baked egg (11%), and finned fish (11%). cutoffs vary in different populations, risk stratification cut offs provide a CONCLUSIONS: In patients who had symptoms of reaction during OFC, useful tool to minimize the risks of children undergoing an outpatient OFC lower sIgE levels, isolated skin or gastrointestinal symptoms, and and are applicable outside of the population in which they were developed. challenges to milk, baked milk, and soy were associated with a higher likelihood of passing. Outcome of Double-Blind Placebo-Controlled 282 Food Challenges in Shrimp-Sensitized The use of LAD2 cells in the mast cell activation Participants 280 test (MAT): a potential tool for food allergy diagnosis Shirly Jiang, MD1, Divya Kumar, PhD2, Shu Cao2, Jessica Fitzpatrick2, Andrew Long, PharmD3, Margaret Woch2, Jenny Johansson2, Kari Mohammad Farazuddin1, Nicholas Ludka, BS1, James Baker, MD Nadeau, MD PhD FAAAAI4, Sharon Chinthrajah, MD2, Sayantani FAAAAI1; 1University of Michigan. Sindher, MD2; 1Santa Clara Valley Medical Center, 2Stanford University RATIONALE: The diagnosis of allergic disease has traditionally relied on - Sean N. Parker Center for Allergy and Asthma Research, 3Stanford Uni- clinical history, levels of allergen specific IgE, skin prick tests and for food versity, 4Stanford Univ School Medicine. allergy oral food challenge (OFC). This latter test is considered the gold RATIONALE: Shellfish is a major food allergen, of which shrimp is the most standard for diagnosis of food allergy and involves the ingestion of common, with a prevalence of 2.9% in adults and 1.3% in children. Shrimp gradually increasing amounts of food under medical supervision. During allergy diagnosis depends on clinical suspicion, skin prick test (SPT) and/or the test, symptoms can range from hives to severe anaphylaxis and this sIgE, of which positive outcomes result in standard clinical recommendation to imparts stress in the patient and care provider. The basophil activation test strictly avoid the offending agent, however, oral allergy syndrome, due to (BAT) and mast cell activation test (MAT) have been proposed as an house dust mite (HDM) cross reactivity may confound the results. alternative to OFC but has logistic challenges as the cells need to be METHODS: We conducted double-blind placebo-controlled food chal- evaluated within a few hours of harvest. The Laboratory of Allergic lenges (DBPCFCs) in participants with shrimp allergy based on clinical Diseases (LAD2) mast cell line has proven to be a useful tool in the study of history, positive biomarkers to shrimp (SPT wheal >3mm or sIgE > 0.35 mast cell biology, but several papers have indicated it is of lesser value in an IU/mL) as part of screening for clinical trials. assay of food-induced mast cell degranulation. Our objective was to RESULTS: Of 31 participants aged 7 to 53, 17 (54.8%) had asthma, 28 examine LAD2 cells with Ionomycin/human IgE to develop a diagnostic (90.3%) had allergic rhinitis, and 17 (54.8%) had atopic dermatitis. Only tool. 17 (54.8%) had dose limiting reactions, which included pruritus (58.8%), METHODS: We examined increase in intracellular Ca+2 levels, released abdominal pain (35.3%), and cough (23.5%) within two hours of ingestion. TNF-a, b-hexosaminidase and CD107a cell surface expression with There was no significant association between SPT size (median, 5.25mm) ionomycin or anti-IgE on LAD2 cells. and challenge outcome. Greater than 80% of participants had positive dust RESULTS: Ionomycin/IgE stimulation of LAD2 cells resulted increase in mite SPT with no statistical difference in challenge outcome. all the parameters examined. Issues raised by other investigators appeared CONCLUSIONS: Clinical history, positive SPT/sIgE, and HDM co- related to the timing of the assays and cell’s passages. sensitivity were not predictive of challenge outcome and 45% of CONCLUSIONS: Passive sensitization of LAD2 cells with patient serum, participants did not experience dose-limiting symptoms during followed by IgE crosslinking with allergen, could provide a standardized DBPCFCs. Food challenges should be incorporated in outpatient clinical MAT with potential utility in predicting the results of OFC. practice for confirming true shrimp allergy and can avoid unnecessary dietary restriction. Further exploration of variability in allergenic protein among different shrimp species is needed to understand true IgE-mediated shrimp allergy. J ALLERGY CLIN IMMUNOL Abstracts AB89 VOLUME 147, NUMBER 2

Skin Test Reactivity After Food-Induced Predicting Outcomes of Baked Egg and 283 Anaphylaxis: A 5 Year Retrospective Review 284A Baked Milk Oral Food Challenges Using a Ratio of Food-Specific IgE to Total IgE Monica Kraft, MD1, Benjamin Prince, MD MCSI FAAAAI2, Rebecca Scherzer, MD FAAAAI3, Irene Mikhail, MD3, Peter Mustillo, MD Michelle Maciag, MD1, Brittany Esty, MD2, Lisa Bartnikas, MD1, Carter FAAAAI2; 1Nationwide Children’s Hospital/ The Ohio State University, Petty1, Andrew MacGinnitie, MD PhD FAAAAI1, Will Sheehan, MD 2Nationwide Children’s Hospital, 3Nationwide Children. FAAAAI3, Wanda Phipatanakul, MD MS FAAAAI1; 1Boston Children’s RATIONALE: Allergy skin prick testing (SPT) is commonly used in the Hospital, 2Boston Children, 3Children’s National Medical Center. evaluation of food allergy (FA). In cases of anaphylaxis, there is practice RATIONALE: Food-specific IgE (sIgE) and skin prick tests are used to variability regarding the appropriate timing of SPT post reaction. Some risk-stratify patients for oral food challenges (OFCs). More accurate providers test shortly after anaphylaxis, while others defer SPT due to a predictors are needed. potential refractory period and resulting false negative (FN) results, as Our objective was to evaluate the ratio of sIgE to total IgE (tIgE) (the described in venom and perioperative anaphylaxis. ‘‘Ratio’’)as a predictor of outcomes for OFCs to baked egg and baked milk METHODS: A retrospective chart review was performed including and to determine if the Ratio better predicts the outcome of OFCs patients who presented to the emergency department from 2015-2019 for compared with sIgE alone. suspected food-induced allergic reaction/anaphylaxis and were evaluated METHODS: Data from all OFCs to baked (extensively-heated) egg and at a tertiary care pediatric allergy clinic within 30 days of reaction. Patients baked milk from January 2010 until January 2016 were reviewed for pre- without SPT or whose reactions were not consistent with anaphylaxis were challenge sIgE and tIgE, post-challenge outcome, and severity of reaction excluded. SPT wheal size, demographic/allergic information and reaction in failed challenges. The Ratio was calculated for egg white, ovomucoid, details were recorded. FN results were defined as SPT <3 mm to the and milk and assessed as a predictor of OFC outcome with receiver implicated food with subsequent diagnosis of FA by serum specific IgE, operator characteristic (ROC) curves. oral food challenge or repeat SPT. RESULTS: The pre-challenge Ratios of egg white and milk were RESULTS: Of 253 encounters reviewed, 45 patients met inclusion significantly higher in failed challenges as compared to passed challenges, criteria. The presenting allergic reaction included cutaneous (71%), 1.19% vs. 0.71% (p50.02) for baked egg, and 3.68% vs. 0.75% (p50.02) respiratory (60%) and gastrointestinal (49%) symptoms. Thirty-two for baked milk. The Ratio for ovomucoid was not significantly higher in patients (71%) were treated with epinephrine. SPT was performed an failed as compared to passed challenges for baked egg, 0.50% vs. 0.44%, average of 13.3 days (range 2-29) following reaction. Six patients (13%) (p50.47). When assessing ROC curves, the Ratio did not perform had FN SPT, which is higher than published FN rates for the testing device significantly better than sIgE alone in predicting challenge outcome for (0-5.65%). Mean time between reaction and SPT was similar (13.7 days, egg white, 0.62 vs 0.68 (p50.24), ovomucoid 0.54 vs. 0.58 (p50.55), or range 3-29) to the entire cohort. All six received epinephrine. milk 0.73 vs 0.69 (p50.70). CONCLUSIONS: Similar to venom and perioperative anaphylaxis, there CONCLUSIONS: The Ratios for egg white and milk were predictive of may be an increased likelihood of FN SPT if performed within 1 month of outcomes of baked egg and baked milk challenges, respectively; however, food-induced anaphylaxis. the Ratio was not more predictive than sIgE alone.

Alanine scans of IgE-binding to linear epitopes Serum food-specific Immunoglobulin G4 (sIgG4) 284 of Ara h 2 reveal critical amino acids 285 levels decrease after steroid treatment in Eosinophilic Esophagitis (EoE) Nicole Canon, MD1, Catherine Schein, PhD2, Xueni Chen, MD3, Marina Pozzoli3, Vidhya Pathy4, Stephen Dreskin, MD PhD FAAAAI5; 1Univer- Rung-chi Li, DO PhD1, Behnam Keshavarz, PhD1, Jeffrey Wilson, MD sity of Colorado/National Jewish Health, 2University of Texas Medical PhD1, Lisa Workman, BA1, Barrett Barnes, MD1, Bryan Sauer, MD, Branch, 3University of Colorado - Denver, 4Choate Rosemary Hall, 5Uni- MSc1, Thomas Platts-Mills, MD PhD FAAAAI1, Emily McGowan, MD versity of Colorado Denver. PhD FAAAAI2; 1University of Virginia, 2University of Virginia School RATIONALE: Important IgE-binding linear epitopes of Ara h 2 have of Medicin. been described but the core sequences and relative importance of individ- RATIONALE: Recent research has demonstrated higher food sIgG4 levels ual amino acids have not been defined. in patients with EoE. There is little information on whether sIgG4 levels METHODS: Sera were obtained from patients with strong histories of correlate with disease activity. Our objective was to compare food sIgG4 peanut allergy, peanut-specific IgE of >15 kU/L and Ara h 2-specific IgE of levels before and after swallowed steroid treatment in patients with EoE. >5 kU/L. Biotinylated 20mer peptides of 4 known linear epitopes of Ara h 2 METHODS: This was a longitudinal study of adult patients enrolled in the were synthesized and IgE binding was evaluated by ELISA. Truncated prospective UVA EoE Cohort Study. The diagnosis of EoE was made per versions were then synthesized and IgE binding was assessed to define the consensus guidelines. Sera at both pre and post-treatment time points were core sequences of 12-18 amino acids (epitope 1, DRRCQSQLERAN; epitope collected, and individuals were included if they achieved histologic 3, DEDSYERDPYS-Hyp-SQDP; epitope 5, ALQQIMENQSDRLQGRQQ; remission (<15 eos/hpf) with swallowed steroid treatment. Serum sIgG4 and epitope 6, NQSDRLQGRQQEQQFKR). The core sequences were was measured to milk components (Bos d 4, 5, 8), wheat, egg, and soy by printed onto microarrays along with the same sequences with individual ImmunoCAP. Mean sIgG4 levels before and after treatment were amino acids changed sequentially to alanine. IgE binding was measured compared using the Wilcoxon signed-rank test. using a pool of 10 sera and with two individual sera. RESULTS: A total of 12 adult patients with EoE (age 20-57; 58% male) RESULTS: IgE binding to epitopes 1, 3, 5 and 6 revealed consistent loss of were included in these analyses. Two patients were treated with swallowed binding when specific charged, polar, and aromatic amino acids were replaced Flovent, and 10 patients were treated with budesonide. The median with alanine. Glutamines and arginines were particularly important depending treatment interval was 2 months (range 2-13 months). Among these upon the sequence. This was seen with two individual sera and with the serum patients, there was a significant decrease in sIgG4 to milk (p50.001), pool. These findings were also consistent with the presence of these amino wheat (p50.006), and soy (p50.02), but not egg (p50.66) after treatment acids on the surface of Ara h 2 based on the known three-dimensional structure. with swallowed steroids. CONCLUSIONS: Alanine scanning of important epitopes of Ara h 2 CONCLUSIONS: Milk, wheat, and soy sIgG4 levels significantly demonstrated that amino acids characterized by nitrogen containing side decreased after treatment with swallowed steroids. This finding suggests chains contribute disproportionately to IgE binding. These data help that IgG4 levels correlate with disease activity. Whether IgG4 is involved in understand the molecular basis of IgE-allergen interactions. the pathogenesis of EoE, however, is unknown and warrants further study. AB90 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Itch and Swallow – Atopic Dermatitis is Not Outcomes in Pediatric vs. Adult Eosinophilic 286 Associated With an Increased Rate of 288 Esophagitis Fibroses, Food Impaction and Stricture in Patients with Eosinophilic Esophagitis. Susan Schuval, MD FAAAAI1, Deborah Boktor, MD2, Michelle Sheyman, MD2, Hector Alcala, PhD, MPH, CPH3, Michelle Aparna Daley1, Pooja Jhaveri, MD1, Erik Lehman, MS2; 1Penn State Tobin, MD1, Alexandra Guillaume, MD2; 1Stony Brook Children’s Hospi- Health Milton S. Hershey Medical Center, 2Penn State University. tal, 2Stony Brook University Hospital, 3Stony Brook University. RATIONALE: We hypothesized atopic dermatitis is associated with RATIONALE: Eosinophilic esophagitis (EoE) is a chronic disorder of increased severity of eosinophilic esophagitis (EoE), defined as an children and adults. Complications include strictures, food impactions, increased rate of food impaction, esophageal stricture, or subepithelial narrow-caliber esophagus, and perforation. We retrospectively compared fibrosis on biopsy in pediatric patients. outcomes of EoE in children vs. adults at a tertiary care medical center. METHODS: We performed a retrospective chart review of patients with a METHODS: EoE patients were identified via ICD-9/10 codes in the diagnosis of EoE seen at our clinic between January 1, 2016 and June 30, electronic medical record. EMR charts were retrospectively reviewed to 2019. Of 273 charts surveyed, 196 patients were excluded, and 77 with determine duration of follow-up, complications, and to determine whether confirmed EoE were included. clinical or histologic resolution of EoE (defined as <5 eos/hpf) had occurred. RESULTS: Atopic dermatitis was found in 16 (21%) patients. Sub- Patients not seen for > 1 year were classified as ‘‘lost to follow-up.’’ epithelial fibrosis on esophageal biopsy was found in 32 (42%) patients, RESULTS: We identified 177 EoE patients, including 41 children (< 21 while food impaction was present in 13 (17%) patients, micro-abscesses years) and 136 adults (> 21 years). Pediatric patients had been followed for found in 31 (40%) patients and esophageal strictures in 1 patient (1.36%). a median duration of 33.0 months, compared with 28.9 month follow-up in Of 16 patients with EoE and atopic dermatitis, sub-epithelial fibrosis was adults, (p50.45). Forty-two adults (31%) had food impactions vs.1 child found in 4 (25%, p-value 0.119) patients while food impaction was found (2.4%), (p<0.001); strictures occurred in 17 adults (12.6%), vs. 1 child in 1 patient (6.25%, p-value 0.288). We found a statistically significant (2.4%), (p50.078). Histologic remission occurred in 17 children (50%), increased median eosinophil count on initial biopsy of the proximal compared with 26 adults (19.2%), (p50.004). Clinical remission was seen esophagus in patients with concomitant atopic dermatitis (60 vs. 20, p- in 18 children (43.9%), compared with 41 adults (30.4%), (p50.108). value 0.011). There was also a statistically significant elevated median Sixteen pediatric patients (39.0%) and 97 adult patients (71.9%) were lost eosinophil count on initial biopsy regardless of location (proximal, mid- or to follow-up, (p<0.001). distal esophagus), in patients with concomitant atopic dermatitis (65 vs. 40, CONCLUSIONS: Food impactions occur more often in adults with EoE, p-value 0.005). compared with children. Histologic remission is seen more often in pediatric CONCLUSIONS: While concomitant atopic dermatitis was not found to than adult EoE but clinical remission rates do not differ significantly. Many confer a higher degree of severity of EoE, elevated eosinophil counts on children and adults with EoE are lost to follow-up. Pediatric and adult biopsy may require a more tailored management approach to achieve gastroenterologists need to develop more effective strategies to keep EoE remission of disease. Further study is required, including success of patients engaged in care to prevent longterm complications. treatments in this population.

Characterization of Adults with Eosinophilic 287 Esophagitis in British Columbia, Canada

Bei Yuan (Ethan) Zhang1, Lianne Soller, PhD2, Vishal Avinashi, MD2, Edmond Chan, MD FAAAAI2, Hin Hin Ko1; 1University of British Columbia, 2BC Children. RATIONALE: Eosinophilic esophagitis (EoE) is a complex, clinicopath- ologic disease that affects both children and adults. There is a lack of data on the experience of Canadian adults with EoE. METHODS: We performed a retrospective review of all adult (>_ 18 years) patients with EoE from a gastroenterology clinic at a tertiary care center in Vancouver, BC, Canada. We evaluated patient demographics, comorbid atopic conditions, family history, endoscopic findings, and treatments. RESULTS: Of the 45 patients with biopsy-proven EoE, 36 (80.0%) were male and 9 (20.0%) were female. 44 (97.8%) self-identified as white and 1 (2.2%) identified as East Asian. Mean age was 35.9 years (95% CI: 31.8 – 40.0). 27 (60.0%) patients had concurrent atopic disease while 15 (33.3%) had a family history of atopy. Patients most commonly reported dysphagia (75.6%) and food impaction (26.7%) and presented with elevated eosinophils in the proximal (26.8/hpf) and distal (35.9/hpf) esophagus. 43 (95.6%) were on medical interventions, 2 (4.4%) on dietary restrictions, and 14 (31.1%) on both. Of those on medical interventions, 30 (69.8%) used proton pump inhibitors (PPIs), 17 (39.5%) used fluticasone, and 5 (11.6%) were on oral viscous budesonide. CONCLUSIONS: Our cohort of EoE patients was predominantly Caucasian men. The majority of patients had allergic predisposition with concurrent atopic disease or a family history of atopy. Unlike children, adults presented with a narrower spectrum of symptoms. Adults were managed with predominantly PPIs. Future work will focus on reasons for major differences in management in Canadian children versus adults. J ALLERGY CLIN IMMUNOL Abstracts AB91 VOLUME 147, NUMBER 2

Increased Prevalence of Eosinophilic Esophagitis pain, heartburn, regurgitation, and vomiting (score range: 5–25). Higher 289 (EoE) in Children with Inflammatory Bowel EoE-IQ/EoE-SQ-Frequency scores indicate greater impact on HRQoL/ Disease (IBD) symptom burden. Proportion of patients reporting dysphagia improvement on the Patient Global Impression of Change (PGIC) was evaluated. Ryan Eid1, Christina Mounzer2, Michael Mendoza, MD2, Jeremy RESULTS: At baseline, mean EoE-IQ was 2.0/2.4 and mean EoE-SQ- Middleton, MD1, Barrett Barnes, MD2, Emily McGowan, MD PhD Frequency 10.1/11.5 in dupilumab/placebo groups, respectively. At Week 24, FAAAAI3; 1University of Virginia, 2The University of Virginia, 3Univer- LS mean change from baseline difference for dupilumab versus placebo was sity of Virginia School of Medicin. 20.4(95% CI:20.6,20.1;nominal P50.008) for EoE-IQ and RATIONALE: Patients with IBD are at increased risk for developing 21.7(22.9,20.5;nominal P50.005) for EoE-SQ-Frequency. At Week 24, EoE, but little is known about the clinical characteristics or risk factors for 40.5% versus 7.7% (nominal P<0.001) of dupilumab versus placebo patients developing EoE in this population. The objective of this study was to assess reported dysphagia as ‘‘very much better’’ compared with baseline on the the prevalence of EoE in patients with IBD and compare characteristics PGIC; 26.2% versus 10.3%(nominal P50.074) reported ‘‘moderately better’’. between patients with both IBD/EoE and EoE alone. CONCLUSIONS: Weekly dupilumab improved disease-specific HRQoL METHODS: ICD-10 codes identified pediatric patients with IBD seen at and reduced symptom burden in adolescent/adult EoE patients. the University of Virginia between October 2015 and June 2020. Charts were reviewed to identify those with esophageal eosinophilia (EE, >_15 eos/ Efficacy And Safety Of Budesonide Oral hpf). IBD/EoE was defined as patients who developed EE after their 291 Suspension In A Pediatric Population: Pooled diagnosis of IBD and had esophageal symptoms. These IBD/EoE patients Data From A Phase 2 And Phase 3 Trial In were matched 6:1 to patients with EoE alone. We compared demographic Patients With Eosinophilic Esophagitis and clinical characteristics of these populations. All analysis was 1 2 3 conducted using Stata15.1(College Station,TX). Sandeep Gupta , Vincent Mukkada ,EvanDellon,MD,Benjamin Gold, MD4, Margaret Collins, MD5, David Katzka, MD6, Gary Falk, MD, RESULTS: A total of 464 children were identified with IBD, and 326(70.2%) 7 8 8 8 had an esophagogastroduodenoscopy. Thirteen children(2.8%) developed EE MS , Lan. Lan, PhD , Nirav Desai, MD , James Williams, MD , Ikuo Hir- ano, MD9; 1Indiana University School of Medicine, Riley Hospital for Chil- after IBD, and 7(1.5%) also had esophageal symptoms (IBD/EoE). On 2 6 dren at Indiana University Health, Cincinnati Children’s Hospital Medical average, patients developed EoE 17.5 6.9 months after IBD. Patients with 3 4 5 Center, University of North Carolina at Chapel Hill, Children’s Center IBD/EoE were less likely to present with dysphagia(p .03) and more likely to 5 5 for Digestive Healthcare, LLC, GI Care for Kids, Cincinnati Children’s Hos- present with weight loss(p 0.02) than children with EoE alone. All 7 children 6 with IBD/EoE received anti-TNF medications at the time of EoE diagnosis. pital Medical Center, University of Cincinnati College of Medicine, Mayo Clinic, 7University of Pennsylvania Perelman School of Medicine, 8Shire, a CONCLUSIONS: In this retrospective study, we found a high prevalence 9 of EoE among children with IBD. The use of anti-TNF medications Takeda company, Northwestern University Feinberg School of Medicine. preceded the development of EoE in the patients with underlying IBD. RATIONALE: To evaluate efficacy and safety of budesonide oral suspension Whether this represents a shared immunologic pathway or a consequence (BOS) in pediatric patients with eosinophilic esophagitis (EoE). of anti-TNF therapy warrants further study. METHODS: We used pooled data from two 12-week, randomized, double-blind, placebo-controlled trials of BOS 2.0 mg b.i.d. (phase 2 [MPI Dupilumab Improves Health-Related Quality of 101-06/NCT01642212] and phase 3 [ORBIT1/SHP621-301/ 290 Life (HRQoL) and Reduces Symptom Burden in NCT02605837]) in patients aged 11–17 years with EoE and dysphagia. Patients with Eosinophilic Esophagitis (EoE): Peak eosinophil counts, the Dysphagia Symptom Questionnaire (DSQ) and Results From Part A of a Randomized, Placebo- EoE Endoscopic Reference Score (EREFS) assessed histologic, symp- Controlled Three-Part Phase 3 Study tomatic and endoscopic outcomes, respectively. RESULTS: Overall, 76 patients received >_ 1 dose of study drug (BOS 2.0 Evan Dellon, MD1, Marc Rothenberg, MD PhD FAAAAI2, Ikuo mg b.i.d. [n 5 45] or placebo [n 5 31]). Significantly more BOS- than Hirano, MD3, Mirna Chehade, MD MPH4, Albert J. Bredenoord5, Jona- placebo-treated patients had histologic responses (<_ 6 eosinophils/high- than Spergel, MD, PhD6, Qiong Zhao7, Bethany Beazley7, Isabelle Guil- power field [eos/hpf], 46.7% vs 6.5%; < 15 eos/hpf, 53.3% vs 9.7%; <_ 1 lemin8, Leda Mannent, MD8, Elizabeth Laws8, Nikhil Amin, MD7, Brad eos/hpf, 42.2% vs 0.0%; all, p<0.001) after 12 weeks of therapy. More Shumel, MD7, Jennifer Maloney7, Siddhesh Kamat7; 1University of North BOS- than placebo-treated patients had symptom responses (>_ 30% reduc- Carolina School of Medicine, 2Cincinnati Children’s Hospital Medical tion in DSQ score: 68.9% vs 58.1%; p 5 0.314) after 12 weeks of therapy. Center and University of Cincinnati College of Medicine, 3Northwestern Significantly more BOS- than placebo-treated patients had a combined University Feinberg School of Medicine, 4Mount Sinai Center for Eosin- response (<_ 6 eos/hpf and >_ 30% reduction in DSQ score: 31.1% vs ophilic Disorders, Icahn School of Medicine at Mount Sinai, 5Amsterdam 3.2%; p 5 0.003) after 12 weeks of therapy. BOS-treated patients had University Medical Center, 6Children’s Hospital of Philadelphia, 7Regen- significantly greater reductions in least-squares mean EREFS (24.1 vs eron Pharmaceuticals, Inc., 8Sanofi. 22.1; p 5 0.021) from baseline to week 12 than placebo. BOS was gener- RATIONALE: Dupilumab, a fully human mAb, blocks the shared receptor ally well tolerated, with no significant differences in adverse events versus component for interleukin-4/interleukin-13. Part A of a 3-part, phase 3 study placebo. (NCT03633617) evaluated the efficacy/safety of weekly dupilumab 300mg CONCLUSIONS: BOS significantly improved histologic, endoscopic versus placebo in adolescent/adult EoE patients. Co-primary endpoints, and combined (histologic and symptomatic) outcomes in pediatric patients proportion of patients achieving peak esophageal intraepithelial eosinophil with EoE versus placebo. count <_6eos/hpf, and change from baseline in Dysphagia Symptom Questionnaire score at Week 24, were achieved and dupilumab was well tolerated. This analysis assesses dupilumab’s effect versus placebo on HRQoL and symptom burden at Week 24 (secondary/exploratory endpoints). METHODS: 81 patients (dupilumab542; placebo539) were enrolled. HRQoL was assessed by 11-item EoE Impact Questionnaire (EoE-IQ), measuring emotional, social, productivity, and sleep-related impacts of EoE (score range: 1–5). Symptom burden was assessed by 5-item EoE Symptom Questionnaire (EoE-SQ-Frequency), measuring frequency of EoE symp- toms other than dysphagia/swallowing pain, including chest pain, stomach AB92 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Endotype and Phenotype Relationships in was no significant difference in healthcare utilizations, oral corticosteroid 292 Children With Eosinophilic Esophagitis Treated bursts, or ACT scores. With Diet Elimination CONCLUSIONS: EoE, when active, is associated with lower lung function and more severe asthma in children. Prospective cohort studies Melissa Watts1, Rethavathi Janarthanam, PhD2, Ming Wang, MD3, Kai- with larger well-characterized populations are needed to confirm this tlin Keeley, BS2, Joshua Wechsler, MD4; 1Northwestern University, 2Ann relationship. and Robert H. Lurie Children’s Hospital, 3Ann and Robert H Lurie Chil- dren’s Hospital, 4Ann & Robert H. Lurie Children’s Hospital. Integrative analysis of eosinophilic esophagitis RATIONALE: Eosinophilic esophagitis (EoE) is an antigen mediated 294 genome-wide association study single- inflammatory disease. Dietary removal of specific foods is effective nucleotide polymorphisms therapy. The EoE transcriptome is well described, however changes with 1 1 1 diet elimination treatment are unclear. We examined transcriptome- Melanie Ruffner, MD PhD , Margaret Carroll , Michele Meline , Kathleen Sullivan, MD, PhD1, Zhe Zhang1, Jonathan Spergel, MD, associated endotype-phenotype relationships in an EoE cohort treated 1 1 1 with elimination diet (ED). PhD , Patrick Sleiman, PhD ; Children’s Hospital of Philadelphia. METHODS: We identified patients who underwent ED treatment with RATIONALE: Eosinophilic esophagitis (EoE) is a multifactorial, com- identification of one or more food triggers of inflammation. RNA was plex allergic disorder of the esophagus. GWAS have identified potential isolated from FFPE specimens and total RNA-SEQ was performed. causal loci, however overall these are associated with modest increases in Samples with DV200>530% were used. We performed principal disease risk. This study integrates gene expression and epigenetic data with component analysis (PCA), differential expression (DE) and pathway GWAS to more completely characterize the molecular basis of EoE. (DAVID) analysis of pre-ED, and paired pre/post-ED specimens. METHODS: 936 subjects with EoE of European ancestry and 4312 Comparisons were made to a public RNA-SEQ dataset of EoE vs. control. matched population controls were assessed using data from previously Clinical characteristics of pre-ED were compared among principal published GWAS. Single nucleotide polymorphisms (SNPs) with p<0.05 components (PC) 1-5. were analyzed using i-GSEA-4GWAS to uncover potential polygenic ef- RESULTS: Forty-one pre-DE specimens were sequenced; 33 had paired fects contributing to disease susceptibility. SNP were mapped to gene post-DE specimens. Among paired specimens, the top DE genes were loci and compared to esophageal and air-liquid interface mRNA and pro- ALOX15, LRRC31, CCL26, TNFAIP6, SLC26A4, POSTN, ANO1, and tein expression data. NTRK1. 558 genes were DE (logFC cutoff: 1, adjusted p-value<0.05), of RESULTS: Analysis of GWAS SNP data implicates several common which 177 were found in the EoE-control dataset. 381 genes were uniquely pathways, including cell-cell adhesion as top enriched pathway. EoE SNPs DE in the ED cohort. Pathway analysis showed immune activation was have high degree of overlap with transcripts highly expressed in primary common between cohorts while the EoE-control cohort had prominent an- esophageal cells (OR: 58.7 [44.3, 77.9]) and esophageal-specific proteins tigen presentation, and the ED cohort had cell adhesion/proliferation and (OR: 172.2 [113.7, 258.6], fisher’s exact test, p<0.001). Further, compar- collagen trimming. Among the pre-ED specimens, we found high PC1 ison of EoE SNP with gene expression of IL-13-treated esophageal air associated with dysphagia, while high PC2 associated with eosinophil liquid interface results in 696 differentially expressed transcripts at loci count, and low PC5 associated with the number of food triggers of with EoE SNP. eosinophilia. CONCLUSIONS: We observe a high degree of overlap in epithelial cell- CONCLUSIONS: This study illustrates endotype-phenotype differences specific transcripts and proteins in SNPs from EoE GWAS. These results that exist among children with EoE treated with dietary elimination. shed light on the complex mechanisms underlying EoE and highlight potential target disease pathways. Active Eosinophilic Esophagitis is Associated 293 with Increased Asthma Severity and Lower Lung Function in Children with Comorbid Asthma

Karyn Parsons1, Katharine Guarnieri, MD2, Dawit Tadesse, PhD2,Md Monir Hossain, MSc, PhD2, Vincent Mukkada2, Marc Rothenberg, MD PhD FAAAAI2, Theresa Guilbert, MD, MS2, Sandy Durrani, MD2; 1Wa- satch Pediatrics, 2Cincinnati Children’s Hospital Medical Center/Univer- sity of Cincinnati College of Medicine. RATIONALE: Eosinophilic esophagitis (EoE) is an important comorbid condition in childhood asthma but the effect of active versus inactive EoE on asthma severity and control has not been addressed. METHODS: Retrospective chart review was conducted on children aged 0 to 18 years evaluated at Cincinnati Children’s Hospital Medical Center Asthma Center between 2009 and 2015. Sixty-two patients with both endoscopy-proven EoE and physician-diagnosed asthma were identified. Features of EoE, including disease activity defined by >15 eosinophils per high-powered field, and asthma measures, including spirometry, asthma control test (ACT) scores, and severity defined by inhaled corticosteroid dose, were collected and analyzed. RESULTS: EoE was present in 62 of 3071 subjects with asthma (2.0%). Active EoE was associated with lower forced expiratory volume in 1 second (FEV1) (b5-6.15; p50.014) and FEV1/forced vital capacity (FVC) (b5-3.37; p50.0208) when compared to children with inactive EoE (adjusted for age, sex, and race). Active EoE was associated with more severe asthma (persistent versus intermittent; b51.81; p50.002). There J ALLERGY CLIN IMMUNOL Abstracts AB93 VOLUME 147, NUMBER 2

Transgenic expression of secreted/active IL-33 SD: 12.6; Mblack: 47.7, SD: 12.9, p50.002). Adjusting for current child 295 results in type 2 immune responses and age, gender, multiple FAs, and annual household income, this effect was eosinophilic esophagitis not significant (Beta: 3.5; p50.4). We did not find a significant interaction between race and income. Alfred Doyle, PhD1, Mia Masuda, BS1, Huijun Luo, PhD1, Rish Pai, MD, CONCLUSIONS: Mean HEI scores in this food-allergic, multiracial PhD1, Takao Kobayashi, PhD1, Koji Iijima, PhD1, Matthew Rank, MD sample were comparable to that reported in the general US pediatric FAAAAI1, Hirohito Kita, MD1; 1Mayo Clinic Arizona. population. Although a trend in lower diet quality among Black compared RATIONALE: EoE is an increasingly common inflammatory condition of to White children was identified, ongoing diet assessment may elucidate the esophagus, however, the underlying immunologic mechanisms remain nutritional differences in this cohort. poorly understood. The epithelium-derived cytokine IL-33 is associated with type 2 responses and is elevated in esophageal biopsies from EoE The Racial and Ethnic Makeup of Food Allergy subjects. We hypothesized that overexpression of secreted and active IL-33 297 Immunotherapy Trials by the esophageal epithelium would result in innate and adaptive immune Lauren Davidson1, Bridgette Jones, MD FAAAAI2; 1University of Mis- responses associated with type 2 inflammation representative of human 2 disease. souri-Kansas City School of Medicine, Children. ; METHODS: We generated a novel mouse model in which a secreted/ RATIONALE: Food allergies are diagnosed in 8% of children and active form of IL-33 is overexpressed in the esophagus (i.e. EoE33) by African American children are disproportionately impacted by food combining the IL-2 secretory signal peptide with an active IL-33 fragment allergy compared to Caucasian children. Pivotal trials have demonstrated gene sequence. The Epstein-Barr virus promoter (ED-L2) was used to efficacy of food allergen immunotherapy. Black and African American drive expression of the IL-33 fusion gene from the esophageal epithelium. participants are generally under-represented in therapeutic trials. We IL-33 expression, eosinophilia, type 2 cytokines, and food-specific aimed to determine the racial/ethnic distribution of participants included antibody levels were assessed by RT-PCR, immunohistochemistry, and/ in food allergy immunotherapy trials. or ELISA. Th2 T cells were assessed by flow cytometry. Histopathologic METHODS: We conducted a review of the literature regarding food findings were characterized using an adaptation of the EoE Histologic allergen immunotherapy within PubMed.gov, ClinicalTrials.gov, and other Scoring System (EoEHSS). Weight data was collected to assess for failure sources, using an appropriate keyword search. We identified 191 articles to thrive. meeting initial search criteria, of which 135 were classified as human clin- RESULTS: Expression of secreted/active IL-33 by the esophageal ical trials. We noted the number of trials reporting race/ethnicity data and epithelium resulted in increased median EoEHSS scores (0.56 vs. 0, the distribution of racial/ethnic groups. p<0.05), eos/hpf (129 vs. 0, p<0.05), type 2 cytokines, Th2 T cells, and RESULTS: Racial demographics were reported in only 12% (16/135) of wheat-specific IgG1 relative to wild type. Esophageal hyperplasia, fibrosis, trials (13/16 conducted in the U.S.). The following racial/ethnic distribu- and failure to thrive were observed (EoE33 vs wild type mean weight at 5 tion was observed among combined trials reporting race/ethnicity: White/ 5 5 weeks 11.8g vs 18.0g, p<0.01). Caucasian (n 1366) 81.70%, Asian (n 128) 7.66%, Multiple Races/ 5 5 CONCLUSIONS: Expression of secreted/active IL-33 from the esoph- Other (n 108) 6.46%, Black/African American (n 47) 2.81%, Hispanic/ 5 5 ageal epithelium generated a mouse model with type 2 immune responses Latino (n 21) 1.26%, and Native American or Pacific Islander (n 2) and pathologic findings characteristic of EoE. 0.12%. CONCLUSIONS: Racial/ethnic demographics were not reported for Differences in Diet Quality Among Food-Allergic most trials, and Caucasian/white participants were over-represented within 296 Black and White Children trials reporting race/ethnicity in relation to the U.S. general and food allergy population. African American and Hispanic participants were Eileen Vincent1, Jialing Jiang1, Jamie Fierstein, PhD1, Alexandria Bo- severely under-represented in these pivotal trials. Food allergen immuno- zen1, Isabel Galic1, Pamela Newmark1, Christopher Warren, PhD1, Lucy therapy trials do not represent the general population or food allergy Bilaver, PhD MS MA1, Jacqueline Pongracic, MD FAAAAI2, Annika population. Efforts are needed to make sure trials are inclusive and Chura3, Amal Assa’ad, MD FAAAAI3, Aame Andy-Nweye4, Susan representative. Fox, PA4, Mahboobeh Mahdavinia, MD PhD FAAAAI4, Mary Tobin, MD FAAAAI4, Adam Robinson5, Amaziah Coleman, MD5, Hem- ant Sharma, MD, MHS5, Andrea Pappalardo, MD FAAAAI6, Ruchi Gupta, MD MPH1; 1Northwestern University Feinberg School of Medi- cine, 2Ann & Robert H. Lurie Children’s Hospital of Chicago, 3Cincinnati Children’s Hospital Medical Center, 4Rush University Medical Center, 5Children’s National Hospital, 6University of Illinois Hospital & Health. RATIONALE: Disparities in food allergy (FA) are emerging. Yet, racial differences in dietary quality among children with FA are unclear. METHODS: Black and White children (0-12 years old) with a diagnosed FAwere enrolled into a prospective, multi-site, cohort study. Demographic data collected merged with dietary assessment data gleaned from the Automated Self-Administered 24-hour Dietary Assessment Survey. Healthy Eating Index (HEI) scores were calculated using one 24-hour diet recall. Univariable statistics described demographics and mean HEI scores ranging from 0 to 100 (1005superior diet quality). Two-sided independent t-tests were used to compare mean HEI scores across groups. Multivariable linear regression evaluated significant predictors of mean HEI scores. Cross-product terms of income by race were evaluated. RESULTS: Among 157 children with a baseline diet data, the majority were white (77.1%) male (62.8%), and 5-12 years of age (60.5%). HEI scores ranged from 21.8 to 82.2; the mean was 53.4 (SD: 12.6). There were significant racial differences with respect to mean HEI scores (Mwhite: 55.1, AB94 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Symptoms of Allergic Reactions to Food via Sunflower Seed Allergy: A Case Series 298 Breastmilk in Infants and Likelihood to 299 Develop Tolerance Celine Galleani1, M. C. Dieguez1, J. F. Crespo1; 112 de Octubre Hospital. Abigail Lang1, Shrey Patel2, Karen Rychlik, MS3, Deanna Caruso4, Xiao- RATIONALE: We sought to investigate the clinical and immunologic bin Wang, MD MPH ScD5, Jacqueline Pongracic, MD FAAAAI6, Rajesh features of adult patients sensitized to sunflower seed. Kumar, MD FAAAAI6; 1Lurie Children’s Hospital, 2University of Illinois METHODS: A retrospective case series study of 117 consecutive patients at Urbana-Champaign, 3Biostatistics Research Core, Stanley Manne Chil- (median age 32 yr) having positive sunflower seed-specific IgE was dren’s Research Institute, 4University of North Carolina at Chapel Hill, performed. Patients underwent skin tests and detection of specific IgE and 5Johns Hopkins University, 6Ann & Robert H. Lurie Children. if indicated, oral food challenges. RATIONALE: We sought to determine if clinical reactivity to food RESULTS: Clinical allergy to sunflower seed was recognized in 28 allergens via breastfeeding was associated with decreased likelihood of patients (24%). Most had a history of atopic disease (26 patients; 93%) and future tolerance. nuts (21 patients; 75%) and Rosaceae fruits (15 patients; 54%) reactions. METHODS: Subjects identified from the Chicago Food Allergy Study The onset of the symptoms occurred mostly in adulthood (23 patients; (2005-2011) were categorized by reactions to maternally ingested foods 82%). Fourteen patients (50%) suffered anaphylaxis, graded as moderate via breastfeeding (50/898 peanut-allergic, 69/620 egg-allergic, and 153/ (13 patients) and severe (1 patient). Anaphylaxis most frequent symptoms 589 milk-allergic had reactions attributable to breastmilk). Data regarding were cutaneous and respiratory (12 patients; 86%), and 10 patients (71%) reactions and allergen exposure were collected by maternal report and oral required emergency department visits. There was significant difference in food challenge (OFC) results. The primary outcome was tolerance (passed skin test wheal size (median: 9 vs. 6 mm; p 5 0,006) and sunflower seed- OFC or consumption of previously implicated food). Secondary outcomes IgE level (median: 2.16 vs. 0.69 kUA/L; p 5 0.001) between patients with included severe reactions (anaphylaxis and/or cardiovascular/lower respi- proved clinical allergy and those who tolerated its ingestion. Skin testing ratory symptoms) and multiple food allergies. Univariate chi-square reactivity to Artemisia pollen was found to be more frequent in clinical analyses assessed for association between variables, followed by logistic allergic patients (71% vs. 22%, p 5 0.021). No differences were found on regression modeling. LTP or other pollens sensitization rates. RESULTS: Of the 50 subjects with peanut-associated symptoms with CONCLUSIONS: Half of the patients with actual clinical allergy to breastfeeding, none gained tolerance. There were no significant associa- sunflower seed experienced anaphylaxis. The size of skin testing, sun- tions between breastfeeding symptoms and persistent allergy for egg and flower seed-IgE level, and reactivity to Artemisia pollen seems to be milk (egg: OR 0.46, 95% CI 0.21-1.01, p50.053; milk: OR 1.13, 95% CI associated with clinical reactivity. To our knowledge, this is the largest 0.70-1.81, p50.614). All subjects with egg-associated symptoms while series of sunflower seed sensitization. breastfeeding had multiple food allergies (n569), but milk- and peanut- allergic subjects were not more likely to have multiple food allergies (milk: OR 1.89, 95% CI 0.88-4.02, p50.10; peanut: OR 2.36, 95% CI 0.72-7.76, p50.16). There were no significant associations between breastfeeding symptoms and subsequent reaction severity. CONCLUSIONS: Infants with symptoms of peanut allergy during breastfeeding may be less likely to gain tolerance. Infants reactive to egg via breastmilk exposure may be more likely to have multiple food allergies. Symptomatic food allergy via breastfeeding was not associated with later severe reactions. J ALLERGY CLIN IMMUNOL Abstracts AB95 VOLUME 147, NUMBER 2

Prevalence of Food Allergy Diagnosis in Characteristics of Adult-Onset Food Allergy 300 Moderate-Severe Atopic Dermatitis Pediatric 302 Patients Referred to Allergy and/or Dermatology Subspecialty Clinics Amanda McIntyre, MD1, Gayatri Patel, MD2, Joshua Wechsler, MD3, Anne Marie Singh, MD4; 1University of Wisconsin School of Medicine Jennifer Li, MD1, Lisa Arkin, MD1, Anne Marie Singh, MD1; 1Univer- and Public Health, Madison, WI, 2Northwestern Feinberg School of Med- sity of Wisconsin-Madison. icine, Chicago, IL, 3Ann & Robert H. Lurie Children’s Hospital, North- RATIONALE: Prevalence of food allergy (FA) and atopic dermatitis western Feinberg School of Medicine, Chicago, IL, 4Northwestern (AD) have increased. However, the updated prevalence of FA among AD Feinberg School of Medicine, Chicago, IL, University of Wisconsin patients and how they present is not well characterized. School of Medicine and Public Health, Madison, WI. METHODS: In a retrospective chart review, 314 children with AD RATIONALE: Despite multiple studies examining food allergy preva- referred to allergy and/or dermatology were identified. 136 children with lence and diagnosis in children, the available data on adult food allergy is moderate-severe AD were enrolled. Moderate AD was determined by the limited. We sought to identify demographic characteristics and triggers of subspecialist or requirement of consistent daily use of topical steroid. adult-onset food allergy. Severe AD was determined by the subspecialist. Atopic disease history, METHODS: A cross-sectional survey was distributed to adult patients in allergy testing and food allergy diagnosis were reviewed. IgE-mediated FA the Northwestern University health care system, who had an ICD-9/ICD- was diagnosed by a pediatric allergist-immunologist, with evidence of 10 code for food allergy. Subjects were asked to recall information about sensitization and history of immediate reaction to food. their food allergy triggers, testing, and diagnosis. Patient charts were RESULTS: Among 136 patients with moderate-severe AD, 52% were reviewed to determine what confirmatory testing was performed. diagnosed with IgE-mediated FA, 17% were sensitized without immediate RESULTS: 159 adults with self-reported onset of first food allergy at 18 reaction, and 31% were not diagnosed with FA. 53% saw allergy only, 5% years or older completed the survey. There were an average of 1.9 food saw dermatology only, and 42% saw both subspecialties. 52% (54/104) of allergies per participant. Among all the food allergies reported, the average moderate AD patients and 53% (17/32) of severe AD patients had FA age of new food allergy onset was 34 +/- 13 years. The majority of the (p>0.05). Among patients with chief complaint of AD only, 39% (32/82) patients in this study were female (78%) and white (72%). The most were diagnosed with FA. Patients with FA were more likely to be aged < 1 common food allergies reported were shellfish (22%), tree nut (21%), and year (59% vs 32%, p50.03), evaluated by both subspecialists (81% vs wheat (19%). 105 patients (66%) reported being seen by an allergist for 59%, p50.05), and less likely to have a family history of atopic disease (69 their food allergy. Of those who saw a Northwestern allergist (81 patients), vs 88%, p50.05). Peanut (38%) and egg (28%) were the most common 50 patients had confirmatory testing documented. The most common food triggers, and food allergy testing decreased over time (88% before testing performed was skin prick testing (40 patients), followed by serum 2016 vs 64%, p50.03). IgE (6 patients), and oral challenge (4 patients). CONCLUSIONS: FA remains common in children with moderate-severe CONCLUSIONS: Patients with adult-onset food allergy reported typical AD, particularly if less than 1 year old. food triggers. However, almost one-third of patients with a self-reported food allergy did not see a provider for their symptoms. Patients who report Evaluation of comorbid atopic diseases in food allergy should be encouraged to seek a formal evaluation by an pediatric patients with multiple IgE-mediated 301 allergist. food allergies

Mosopefoluwa Lanlokun1, Merritt Fajt, MD FAAAAI2; 1University of Pittsburgh Medical Center, Children’s Hospital of Pittsburgh, 2University of Pittsburgh Medical Center. RATIONALE: Risk factors for severe food allergic reactions include comorbid asthma and prior food reactions. Up to 70% of pediatric food- allergic patients have multiple food allergies (MFA) (Wang, 2010). We hypothesize that children with MFA are more likely to have comorbid atopic diseases than children with a single food allergy (SFA). METHODS: The EMR of pediatric patients evaluated at the Allergy clinic from January 2009-January 2019 for food allergy based on ICD9/10 codes, clinical history, and allergy testing were retrospectively reviewed. Subjects were categorized as SFA or MFA, and the groups were compared by demographics, atopic comorbidities, and family history of atopic diseases using Chi-Square analysis via JMP statistical software (Cary, NC). RESULTS: In 20 children with IgE-mediated food allergy, 13 (65%) had MFA. Children with MFA were older than those with SFA (median 6 vs. 3 years, p50.03), but did not differ by race or sex. Children with MFA tended to have a higher prevalence of asthma than SFA (54% vs. 14%, p50.08). There were no differences in the prevalence of allergic rhinitis, eczema, eosinophilic esophagitis, or family history of atopy (all p-values > 0.16). Children with MFA were more likely to have been evaluated in the ED for food reactions vs. SFA (38% vs. 0, p50.05). CONCLUSIONS: In this small retrospective study, children with MFA were older, more likely to have asthma and seek emergency care. Given the increased risk of severe food allergic reactions in patients with asthma, this reiterates the importance of strict asthma control in patients with MFA. AB96 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Disparities of GERD treatment and limpet, while 25% also showed allergy to crustacean and the other 25% had 303 Gastroenterology Care in Black Children with allergy to different seafood groups. Food Allergy in FORWARD Cohort Skin prick test (SPT) to common inhalant were positive to Dermatophagoides pteronyssinus, Dermatophagoides farinae and Blomia Mary Tobin, MD FAAAAI1, Jamie Fierstein, PhD2, Jialing Jiang3, Aame tropicalis. SPT also were positive to Thyreophagus putrescentiae and Andy-Nweye4, Susan Fox, PA5, Mahboobeh Mahdavinia, MD PhD Lepidoglyphus in the most of cases. SPT to seafood and prick by prick FAAAAI4, Andrea Pappalardo, MD FAAAAI6, Annika Chura7, Amal test (PPT) to raw and boiled limpet were performed and were positive in Assa’ad, MD FAAAAI8, Adam Robinson9, Hemant Sharma, MD, most cases. MHS9, Amaziah Coleman, MD9, Lucy Bilaver, PhD MS MA2, Christo- CONCLUSIONS: Limpet sensitization has been confirmed in patients pher Warren, PhD10, Pamela Newmark2, Alexandria Bozen3, Jacqueline with severe respiratory reactions. Pongracic, MD FAAAAI11, Ruchi Gupta, MD MPH12; 1University Con- In vivo cross reactivity among different groups of seafood has been found sultants in Asthma and Allergy, 2Northwestern University, 3Northwestern in the current investigated sample, although it stands out the percentage of University Feinberg School, 4Rush University Medical Center, 5Univ. monosensitive patients. Consultants in Allergy and Immunol, 6University of Illinois Hospital & We need to do more studies about allergens that explain rhinoconjunctivitis Health, 7Cincinnati Children, 8Cincinnati Children’s Hospital Medical due to dust mites allergy and seafood allergy. Center, 9Children, 10University of Southern California, 11Ann & Robert H. Lurie Children, 12Northwestern Medicine. Clinical Characterization of Chilean Patients RATIONALE: Previous studies link gastroesophageal reflux (GERD) and 305 with Food Protein-Induced Enterocolitis food allergy (FA), but racial differences are unclear. This study assesses the Syndrome relationship between race, GERD, FA type, asthma, eczema, and 1 1 1 1 gastroenterology consultation. Francisca Moya , Barbara Cid , Ivana Ormazabal , Josefina Cortes , ~ 1 1 2 1 METHODS: We analyzed intake and 6 month follow-up surveys for Enzo Munoz , Arturo Borzutzky, MD FAAAAI , Rodrigo Hoyos ; Pon- 2 FORWARD, a multicenter prospective study of Black and White food tificia Universidad Catolica de Chile, Pontificia Universidad Catolica de allergic children aged 0-12 years. We evaluated potential links between Chile. race, GERD, associated conditions and specific types of FA. Univariable RATIONALE: There are no studies that describe food protein-induced statistics described demographics and GERD-related variables including enterocolitis syndrome (FPIES) in Latin American children. GERD prevalence and treatment. Chi square tests of independence METHODS: Retrospective chart review of pediatric patients diagnosed determined associations between categorical variab with FPIES seen at Allergy and Immunology Clinics of the UC-Christus RESULTS: There were 654 food allergic children in the current analyses, Health Network (Santiago, Chile) between 2012-2020. and 126 (19.3%) reported GERD. (Black, 15%, n537; White, 21.2%, RESULTS: 60 FPIES patients were included, 53% were male. 55% and n589). White children (83.2%) received more treatment for GERD than 48% of patients had acute FPIES (aFPIES) and chronic FPIES (cFPIES), Black children (56.8%; p50.002). Black children were more likely to have respectively; 3% had an overlapping phenotype. Median age at onset of co-existing eczema and GERD (97.2%) vs. eczema without GERD (80.7%, symptoms was 6 months for aFPIES and 3 months for cFPIES. 39% of p50.015). White children with GERD were likely to have coexisting milk patients with aFPIES and 48% with cFPIES had additional allergic allergy (p<0.001) or egg allergy (p50.02). Black children with GERD had diseases, while 48% of those with aFPIES and 55% with cFPIES had shellfish allergy (43.2%), versus Black children with shellfish allergy family history of allergic diseases. 30% of aFPIES patients and 17% of without GERD (29.8% ) (p>0.05). Six months follow-up, Black children cFPIES patients reacted to a single food. 33% and 59% of patients with with GERD were less likely to be followed by a gastroenterology physician aFPIES and cFPIES, respectively, reacted to >3 foods. 18% had symptoms (Black, 5.6%; White, 30.4%; p50.03). of FPIES during exclusive breastfeeding. Cow’s milk (45%), vegetables CONCLUSIONS: GERD was reported in 19% of food-allergic children, (squash, carrots, among others; 39%), grains (27%), legumes (peas, green similar to the general population, without racial differences. The associ- beans, among others; 24%), and fish (24%) were the most common triggers ation between GERD and FA reveals racial differences in associated of aFPIES. The most common triggers of cFPIES were cow’s milk (72%), conditions, food allergens, and gastroenterology care. We will further grains (41%), soy (38%), vegetables (34%) and chicken (34%). Although explore these associations as we finalize recruitment of the FORWARD no patient had history of immediate food reactions, allergic sensitization cohort. was demonstrated in 9% of patients with aFPIES and 17% of those with cFPIES by sIgE or skin prick test. Clinical profile of limpet allergy: a preliminary CONCLUSIONS: The frequency of food triggers of FPIES in our 304 report population differ from reports in developed countries. A significant number of patients presented symptoms during breastfeeding. Elena Mederos Luis1, Cristina Alava Cruz1, Ruperto Gonzalez Perez, MD PhD1, Victor Matheu, MD, PhD1, Inmaculada Sanchez Ma- chin1, Paloma Poza Guedes, MD PhD2; 1Hospital universitario de Cana- rias, 2Hospital Universitario de Canarias, Tene. RATIONALE: Limpets belong to gastropod species, one of the eight classes of Mollusca phylum. Limpets are eaten in some areas of Spain and Japan and only a few cases of limpet allergy have been reported. METHODS: We selected patients with symptoms after the ingestion of limpets seeking urgent medical assistance. Skin prick test (SPT) to common inhalant, storage mites and seafood and prick by prick test (PPT) to raw and boiled limpet were performed. RESULTS: We selected 26 patients, 18 females and 8 males, with ages between 9 to 47, with histories of rhinoconjunctivits and asthma in 45% of cases and only rhinoconjunctivitis in 55% of them; who present breathlessness, wheezing and cough up to 3 hours after the ingestion of limpets. In some cases, urticaria, angioedema and rhinoconjunctivitis were also presented. Approximately, 50% of them showed a single allergy to J ALLERGY CLIN IMMUNOL Abstracts AB97 VOLUME 147, NUMBER 2

Impact of Socio-economic Status on IgE- Characteristics of Fish and Shellfish Allergy – 306 mediated Food Allergy in Egyptian Children 308 Single Center Experience

Ahmed Elmazaly1, Maged Refaat, MD FAAAAI1, Amal Assa’ad, MD Irina Dawson, MD1, Maria Chitty-Lopez, MD2, Panida Sriaroon, MD FAAAAI2, Mohamed Farris1, Osama Abdel-latif1, Manar Farouk1; 1Ain FAAAAI2; 1Allergy Partners of Fredericksburg, 2University of South Shams University, 2Cincinnati Children’s Hospital Medical Center. Florida. RATIONALE: Egyptian children have different socio-economic statuses KEYWORDS: Fish; food allergy; hypersensitivity; seafood; shrimp (SES). We examined differences between two groups of children from high BACKGROUND: Fish and shellfish are top food allergens in the United (H) and low (L) SES with food allergy (FA). States. We aim to evaluate the characteristics of seafood allergic patients. METHODS: We administered a questionnaire to caregivers of children up METHODS: Retrospective analysis was performed on clinical and to 12 years of age with FA from two groups of 25 seen at allergists’ private laboratory findings in fish- and shellfish-allergic patients at the offices (H-SES) and a public hospital (L-SES). University of South Florida Allergy/Immunology Clinic between 2008 RESULTS: L-SES and H-SES had similar male predominance, age of and 2020. Data reviewed included age of reaction, clinical symptoms weaning, and having only one FA (68% and 64%) (11 (IQR 7–15) and 12 (IQR including anaphylaxis, history of atopic conditions, and serum-specific IgE 10-12) months) (64% and 92%), respectively, and in the symptom being (sIgE) levels. T-test analysis compared numerical variables. cutaneous (100% and 84%) and gastrointestinal (52% and 48%), being severe RESULTS: There were 82 patients with clinical reaction and confirmed (48% and 44%) and in emergency room care (40% and 28%). There were IgE-mediated sensitization to shellfish only (53, 64.6%), fish only (28, statistically significant differences in L-SES group being older (134.4 68.64 34.1%), and both (1, 1.2%). Shrimp (75%), crab (20%), and lobster (13%) months) than H-SES (91.44 626.64 months), born vaginally (76% vs 64%) were the most common shellfish allergies. Age of initial reaction to and having milk allergy (60% vs 16%), respectively, and in H-SES group shellfish was significantly higher than to fish (11.7 vs 4.5 years, compared to L-SES having egg as the commonest allergen (56% vs 36%), respectively, p<0.05). Overall, reactions involved cutaneous (86.6%), being on dietary elimination (52% vs 12%) and on sublingual immunotherapy respiratory (19.5%), and ocular/nasal (11%) symptoms, with anaphylaxis (44% vs 36%), in earlier symptom onset, earlier age at diagnosis and higher reported in 17% of subjects. sIgE levels were elevated in most shellfish- IgE (18 (IQR 12–24) vs 96 (48–96) months), (36 (IQR 24–48) vs 96 (IQR 48– and fish-allergic patients (median 28.7 vs 26.2 kU/L) but did not differ in 102) months), (421 (IQR 237–504) vs 214 (IQR 124–319) IU/dl), respectively. those with or without history of anaphylaxis. Allergic rhinitis, eczema, and No children were prescribed epinephrine auto-injector. asthma were present in most seafood allergic patients (82.9%, 57.3%, and CONCLUSIONS: FA presents and is managed differently among 51.2% respectively). Egyptian children based on SES, highlighting disparities and suggesting CONCLUSIONS: Most shellfish and fish allergies occur separately and environmental factors play a role. begin in later childhood. Elevated sIgE levels correlate with clinical history but not the severity of reaction including anaphylaxis. Which Aspects Of Atopic Dermatitis Predict 307 Peanut Allergy In Infancy? Frequency and Spectrum of Food Allergy Among 309 Adult Patients with Allergic Rhinitis Related to Mansi Kotwal1, Michael Pistiner, MD MMSc2, Wayne Shreffler, MD Cross Sensitizations PhD FAAAAI3, Robert Wood, MD4, Joan Dunlop, MD5, Jennifer Dantzer, MD6, Mihaela Plesa6, Daria Szelag, PNP7, Roger Peng6, Alkis Andrej Kurchenko1, Vladyslav Tsaryk1, Sergej Yuriev1, Lawrence Du- Togias, MD FAAAAI8, Corinne Keet, MD MS PhD9; 1Johns Hopkins buske, MD FAAAAI2; 1Bogomolets National Medical University, Kyiv, Medical Center, 2MassGeneral Hospital for Children, Harva, 3Massachu- Ukraine, 2George Washington University School of Medicine, Washing- setts General Hospital / Harvard, 4Johns Hopkins University School Med- ton, DC, USA, Immunology Research Institute of New England, Gardner, icine, 5Johns Hopkins Hospital, 6Johns Hopkins, 7Johns Hopkins MA, USA. University, 8NIAID/NIH, 9John Hopkins Hospital. RATIONALE: Manifestations of food allergies in adult patients are often RATIONALE: Although severity of atopic dermatitis (AD) in infancy associated with cross-allergic reactions between plant pollen, animal strongly predicts peanut allergy (PA) development, whether specific epidermis and food. Clinical manifestations can range from mild elements of severity confer independent risk of PA is unknown. symptoms of oral allergy syndrome to urticaria, angioedema, and in METHODS: Infants 4-11 months with moderate-severe AD in a pro- some cases anaphylaxis. spective study of children with no history of peanut exposure, reaction or METHODS: The aim of this study was to identify the frequency and PA testing were assessed for PA by oral food challenge or SPT (>10mm). spectrum of food sensitization among patients with allergic rhinitis using Logistic regression was used to assess the association between PA and (a) ALEX-test molecular immunoassay assessing 175 patients. Scoring Atopic Dermatitis (SCORAD) intensity score (IS), (b) body RESULTS: The most common allergens were: peanuts – Ara h 8.9 – 35 surface area (BSA) (c) involvement of ‘‘exposed’’ skin (head, face, neck patients (20%); milk – 19 (11%) with cow Bos d8 – 4, Bos d 9 (epithelium) and hands) and (d) subjective SCORAD elements in ’’crude’’ (adjusted for – 5, Bos d 10 (meat) – 9, Bos d 11 (milk) – 1; eggs – 7 (4%), with chicken age, sex and race) and ‘‘adjusted’’ (additionally adjusted for objective Gald1–5,Gald2–1,Gald3–2,Gald(meat) – 1. Cross-allergic SCORAD [oSCORAD]) models. reactions were noted between birch pollen and fruits (apples, peaches). RESULTS: 195 subjects were included (mean/max: oSCORAD 20.8/83, Clinically, food allergies to milk were seen in only one patient who was BSA 35.4/100, IS 3.9/18, sleep score 0.83/10, irritability score 0.97/10; 63% allergic to milk casein with concomitant atopic dermatitis, while other AD in exposed areas). All elements of SCORAD were associated with PA in patients had cross-allergic reactions between animal epidermis and serum crude analyses (BSA: OR 1.02, 95% CI:1.01-1.04, IS: OR 1.16, 95% CI:1.04- meat albumin. Egg allergy had clinical manifestations in only two patients 1.29 , sleep: OR 1.37, 95% CI:1.15-1.65, irritability: OR 1.32, 95% CI:1.12- in the form of recurrent angioedema. One patient had cross-allergic 1.55) but only the sleep and irritability elements of the subjective SCORAD reactions between egg conalbumin and beef. were independent of the oSCORAD (sleep: OR 1.29, 95% CI:1.05-1.57, CONCLUSIONS: Many patients have latent food sensitization that irritability: OR 1.24, 95% CI:1.03-1.49). AD in exposed areas was not requires further monitoring, assessing cross reactivities which may guide associated with PA in crude or analyses adjusted for oSCORAD (OR 1.65, food elimination therapy before employing immunotherapy. 95% CI:0.71-3.87 and OR 1.21, 95% CI:0.49-2.96, respectively). CONCLUSIONS: All measures of AD severity in the SCORAD are predictive of AD, with no element dominating the prediction. AD should be evaluated holistically to predict PA risk. AB98 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2021

Cross-reactivity Between Tree pollen, Food and (n594), early introduction was more common among White children 310 Latex Allergens (49.3%) than Black children (16.0%), p50.01. CONCLUSIONS: Regardless of race, the majority of children with PA Viktoriia Rodinkova, PhD1, Valentyna Chopyak2, Serhii Yuriev3, Taras had a history of eczema. Additionally, Black children were less likely than Gutor2, Olga Kaminska1, Lawrence Dubuske, MD FAAAAI4; 1National White children to be introduced to peanut products early. These are Pirogov Memorial Medical University, Vinnytsya, Ukraine, 2Danylo Ha- important considerations for current PA prevention guideline lytsky Lviv National Medical University, Lviv, Ukraine, 3Bohomolets Na- implementation. tional Medical University, Kyiv, Ukraine, 4George Washington University School of Medicine, Washington, DC, USA, Immunology Research Insti- "A sweet revenge": Pineapple-related adverse tute of New England, Gardner, MA, USA. 312 food reactions RATIONALE: Precision allergy molecular diagnostics allows assessment Zaimat Beiro1, Mina Dimovaresearch associate1, Ves Dimov, MD1; of cross-reactivity between pollen and food allergens using multiplex 1 measurement arrays. Cleveland Clinic Florida. METHODS: Data from 8016 ALEX tests performed in different regions RATIONALE: Pineapple has been implicated in array of adverse of Ukraine in 2017-2019 were assessed in patients from 1 to 78 years reactions, including uncomfortable mucosal irritation, oral allergy syn- old.Correlation analysis was performed by the Spearman method. drome (OAS), and even anaphylaxis. Mucosal irritation could be due RESULTS: Cross-reactions were mostly seen with Betulaceae pollen combination of acidic pH and enzymatic activity of bromelain. groups. Sensitization to Alnus, Betula and Corylus pollen alone expressed METHODS: Retrospective chart review of 15 patients with pineapple- cross-reactivity to other pollen types in 55-60 % of cases. 51 % of pateints related adverse food reactions at a tertiary center allergy clinic. Data sensitive to Bet v 2 profilin were sensitized to olive pollen profilin Ole e 2 parameters included description and timing of reactions, allergy test and of date palm profilin Pho d 2. 51-53 % of patients were sensitized to results, history of other allergic conditions. Statistical analysis such as PR-10 Bet v 1 of Betula pollen and Ara h 8 peanut allergen. 52 to 60 % mean, mode, median, standard deviation were used to interpret the data. of patients were sensitized to birch and alder pollen PR-10 allergens and RESULTS: Female gender was prevalent among the 15 patients in the to Mal d 1 of apple from the same group. Cross-reaction between alder study, with 13 females and 2 males, median age 47 years. Reactions and celery PR-10 allergens (Aln g 1 and Api g 1) was 50 %. 50 % of patients described were: mucosal Irritation, OAS, and anaphylaxis. Mucosal reacted to profilins of birch and latex (Bet v 2 and Hev b 8). Irritation was the most common presentation, reported in 8 patients, CONCLUSIONS: Pollen-targeted allergen-specific immunotherapy may followed by 4 patients with OAS, 2 with anaphylaxis, and 1 with possibly impact pollen-food oral allergy syndromes based upon allergen nonspecified intolerance. 50% of patients (7), experienced symptoms cross-reactivity within minutes of ingestion. 53% of patients (8) decided to proceed with IgE-testing for pineapple: 3 had positive sIgE for pineapple, 4 had negative History of Eczema Among Black and White sIgE, 1 had a negative skin test. 11 patients had a history of allergic rhinitis, 311 Peanut Allergic Children asthma (4), atopic dermatitis (4), seafood allergy (4). CONCLUSIONS: In pineapple-related adverse food reactions, IgE-based Jialing Jiang1, Jamie Fierstein, PhD1, Lucy Bilaver, PhD MS MA1, Alex- allergy tests can guide clinical decision. Allergic rhinitis was a significant andria Bozen1, Isabel Galic1, Pamela Newmark1, Christopher comorbidity, underlying the need to test for both inhalant and food Warren, PhD1, Audrey Brewer, MD2, Jacqueline Pongracic, MD allergens to evaluate for OAS. Allergy tests and ingestion challenges can FAAAAI2, Annika Chura3, Amal Assa’ad, MD FAAAAI3, Aame Andy- distinguish between IgE-mediated and non-IgE-mediated reactions, and Nweye4, Susan Fox, PA4, Mahboobeh Mahdavinia, MD PhD FAAAAI4, guide prescribing patterns of relatively expensive treatments such as Mary Tobin, MD FAAAAI4, Adam Robinson5, Amaziah epinephrine autoinjectors. Coleman, MD5, Hemant Sharma, MD, MHS5, Andrea Pappalardo, MD FAAAAI6, Ruchi Gupta, MD MPH1; 1Northwestern University Feinberg School of Medicine, 2Ann & Robert H. Lurie Children’s Hospital of Chi- cago, 3Cincinnati Children’s Hospital Medical Center, 4Rush University Medical Center, 5Children’s National Hospital, 6University of Illinois Hospital & Health. RATIONALE: Eczema is a risk factor for peanut allergy (PA) develop- ment. Racial differences in eczema and food allergy outcomes exist. This study aims to explore potential racial differences in eczema history among peanut allergic children. METHODS: Black and White children (0-12 years old) with a diagnosed food allergy were enrolled into FORWARD, a prospective, multi-site, cohort study. Parent-proxy responses were obtained for the intake and 12 month follow-up survey. Surveys included questions on timing of dietary introduction of peanut, current food allergies, and eczema related out- comes. Pearson X2 tests were used to compare differences by race. RESULTS: Responses for the 12 month follow-up survey were received for 183 peanut allergic children (n5 46 Black, 137 White). Of the 183, 153 had eczema. Among Black children with PA, 89.1% reported ever having eczema vs 81.8% of White children. For medications during the first year of life, 59.5% used topical prescription medication to control eczema while 16.3% received antibiotics for skin infection related to eczema. No statistically significant differences in race were observed. However, among children with PAwho ever had eczema, only 38 (24.8%) introduced peanut early (before 1 year of age). Among those that were ever introduced peanut