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BACKGROUND No approved treatment for peanut allergy exists for children younger than 4 years of age, and the efficacy and safety of epicutaneous immunotherapy with a peanut patch in toddlers with peanut allergy are unknown. METHODS We conducted this phase 3, multicenter, double-blind, randomized, placebo-controlled trial involving children 1 to 3 years of age with peanut allergy confirmed by a double-blind, placebo-controlled food challenge. Patients who had an eliciting dose (the dose necessary to elicit an allergic reaction) of 300 mg or less of peanut protein were assigned in a 2:1 ratio to receive epicutaneous immunotherapy delivered by means of a peanut patch (intervention group) or to receive placebo administered daily for 12 months. The primary end point was a treatment response as measured by the eliciting dose of peanut protein at 12 months. Safety was assessed according to the occurrence of adverse events during the use of the peanut patch or placebo. RESULTS Of the 362 patients who underwent randomization, 84.8% completed the trial. The primary efficacy end point result was observed in 67.0% of children in the intervention group as compared with 33.5% of those in the placebo group (risk difference, 33.4 percentage points; 95% confidence interval, 22.4 to 44.5; P<0.001). Adverse events that occurred during the use of the intervention or placebo, irrespective of relatedness, were observed in 100% of the patients in the intervention group and 99.2% in the placebo group. Serious adverse events occurred in 8.6% of the patients in the intervention group and 2.5% of those in the placebo group; anaphylaxis occurred in 7.8% and 3.4%, respectively. Serious treatment-related adverse events occurred in 0.4% of patients in the intervention group and none in the placebo group. Treatment-related anaphylaxis occurred in 1.6% in the intervention group and none in the placebo group. CONCLUSIONS In this trial involving children 1 to 3 years of age with peanut allergy, epicutaneous immunotherapy for 12 months was superior to placebo in desensitizing children to peanuts and increasing the peanut dose that triggered allergic symptoms. (Funded by DBV Technologies; EPITOPE ClinicalTrials.gov number, NCT03211247. opens in new tab.) [ABSTRACT FROM AUTHOR]

In February 2024, omalizumab was approved by the U.S. Food and Drug Administration for the treatment of food allergy, based on data from the landmark phase 3 clinical trial, Omalizumab as Monotherapy and as Adjunct Therapy in Children and Adults (OUtMATCH). In this Rostrum, OUtMATCH investigators share their perspectives on the trial results, the implications for translation into daily practice, and on remaining gaps in the field. The study met its primary and key secondary end points, demonstrating a large effect size in multiallergen desensitization compared with placebo; yet there were some participants who did not respond, and the percentage of responders tolerating all 3 food allergens was lower than that for single foods. Clinicians are likely to have many questions about appropriate patient selection, monitoring for treatment responsiveness, and how to manage off-label considerations such as dietary incorporation or cotreatment with oral immunotherapy. Additional research is needed to answer these remaining questions and ensure that the translation of omalizumab in real-world practice leads to high-quality outcomes., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

The fact that genetic and environmental factors could trigger disruption of the epithelial barrier and subsequently initiate a T H 2 inflammatory cascade conversely proposes that protecting the same barrier and promoting adequate interactions with other organs, such as the gut, may be crucial for lowering the risk and preventing atopic diseases, particularly, food allergies. In this review, we provide an overview of structural characteristics that support the epithelial barrier hypothesis in patients with atopic dermatitis, including the most relevant filaggrin gene mutations, the recent discovery of the role of the transient receptor potential vanilloid 1, and the role involvement of the microbiome in healthy and damaged skin. We present experimental and human studies that support the mechanisms of allergen penetration, particularly the dual allergen exposure and the outside-in, inside-out, and outside-inside-outside hypotheses. We discuss classic skin-targeted therapies for food allergy prevention, including moisturizers, steroids, and topical calcineurin inhibitors, along with pioneering trials proposed to change their current use (Prevention of Allergy via Cutaneous Intervention and Stopping Eczema and ALlergy). We provide an overview of the novel therapies that enhance the skin barrier, such as probiotics and prebiotics topical application, read-through drugs, direct and indirect FLG replacement, and interleukin and janus kinases inhibitors. Last, we discuss the newer strategies for preventing and treating food allergies in the form of epicutaneous immunotherapy and the experimental use of single-dose of adeno-associated virus vector gene immunotherapy., Competing Interests: Disclosures Dr Ciaccio receives research grant support from the National Institutes of Health (NIH), Food Allergy Research & Education (FARE), and Paul and Mary Yovovich and has served as a medical consultant/advisor for Genentech, Novartis, Siolta, Clostrabio, and FARE. Dr Chinthrajah reports receiving grants from National Institute of Allergy and Infectious Diseases (NIAID), CoFAR, Regeneron, Stanford Maternal and Child Health Research Institute, and FARE and is an advisory board member at Alladapt Therapeutics, Novartis, Genentech, Allergenis, Intrommune Therapeutics, and IgGenix. Dr Chan reports receiving grant from NIAID and NIH. Prof Leung reports receiving grants from Genentech, Incyte Corporation, and Sanofi-Genzyme; nonfinancial support from Aslan Pharmaceuticals; and personal fees from Leo Pharmaceuticals. Dr Marshall reports receiving research grant support from NIH. Prof Nadeau reports receiving grants from NIAID; National Heart, Lung, and Blood Institute (NHLBI); National Institute of Environmental Health Sciences (NIEHS); and FARE; receiving stock options from IgGenix, Seed Health, ClostraBio, Cour, and Alladapt; serving as an advisor at Cour Pharma; serving as a consultant for Excellergy, Red tree ventures, Before Brands, Alladapt, Cour, Latitude, Regeneron, and IgGenix; serving as a co-founder of Before Brands, Alladapt, Latitude, and IgGenix; serving as National Scientific Committee member at Immune Tolerance Network (ITN) and NIH clinical research centers; and having patents including, “Mixed allergen composition and methods for using the same,” “Granulocyte-based methods for detecting and monitoring immune system disorders,” and “Methods and Assays for Detecting and Quantifying Pure Subpopulations of White Blood Cells in Immune System Disorders.” Dr Radulovic reports receiving grant from NIAID and NIH. Prof Lack reports receiving grant from NIAID/NIH; having personal fees and stock options from DBV Technologies; having stock options from Mission MightyMe; and serving as a scientific consultant/advisor for Novartis, Sanofi-Genzyme, Regeneron, ALK-Abello, Reckitt Mead Johnson, and Lurie Children's Hospital. Dr Sindher receives research grant support from NIH, FARE, CoFAR, DBV, AIMMUNE, and Regeneron and has served as an advisor for Genentech. Prof Brough reports receiving grant from NIAID and NIH and receiving speaker honoraria from DBV Technologies, GlaxoSmithKline, and Sanofi. The remaining authors have no conflicts of interest to report., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Disclosures Dr Marshall reports research grant support from National Institutes of Health (NIH). Dr Leung reports grants from Genentech, Incyte Corporation, and Sanofi-Genzyme, nonfinancial support from Aslan Pharmaceuticals, and personal fees from Leo Pharmaceuticals. Professor Lack reports grant from National Institute of Allergy and Infectious Diseases (NIAID)/NIH, personal fees and stock options from DBV Technologies, and stock options from Mission MightyMe; and has served as a scientific consultant/advisor for Novartis, Sanofi-Genzyme, Regeneron, ALK-Abello, Reckitt Mead Johnson, and Lurie Children's Hospital. Dr Sindher receives research grant support from NIH, Food Allergy Research & Education (FARE), CoFAR, DBV, AIMMUNE and Regeneron and has served as an advisor for Genentech. Dr Ciaccio receives research grant support from the NIH, FARE, and Paul and Mary Yovovich and has served as a medical consultant/advisor for Genentech, Novartis, Siolta, Clostrabio, and FARE. Dr Chan reports grant from NIAID/NIH. Professor Nadeau reports grants from NIAID, National Heart, Lung, and Blood Institute, National Institute of Environmental Health Sciences, and FARE; stock options from IgGenix, Seed Health, ClostraBio, Cour, Alladapt; advisor at Cour Pharma; consultant for Excellergy, Red Tree Ventures, Before Brands, Alladapt, Cour, Latitude, Regeneron, and IgGenix; cofounder of Before Brands, Alladapt, Latitude, and IgGenix; National Scientific Committee member at Immune Tolerance Network, and NIH clinical research centers; and patents include “Mixed allergen com-position and methods for using the same,” “Granulocyte-based methods for detecting and monitoring immune system disorders,” and “Methods and Assays for Detecting and Quantifying Pure Subpopulations of White Blood Cells in Immune System Disorders.” Professor Brough reports grant from NIAID/NIH and speaker honoraria from DBV Technologies, GSK, and Sanofi.

Background: Cashew nuts often cause strong allergic reactions, which are even more severe than those of peanuts. Ana o 1 (vicilin), Ana o 2 (legumin), and Ana o 3 (2S albumin) are major cashew allergens. Cosensitization to all 3 nonhomologous cashew nut allergens has been observed. We hypothesize that this might be due to IgE cross-reactivity., Methods: IgE cross-inhibitions were performed with Ana o 1-3 using serum samples from cashew nut-allergic patients. The related hazelnut allergens Cor a 11, 9, and 14 were used as controls. For comparison, IgE cross-reactivity between the hazelnut allergens was investigated using serum samples from hazelnut-allergic patients., Results: The median percentages of cross-inhibition between Ana o 1, 2, and 3 were 84%-99%. In comparison, the median cross- inhibition values between hazelnut allergens were 33%-62%. The IC50 values revealed the highest IgE affinity to be to Ana o 3 and Cor a 14. Hazelnut legumin Cor a 9 inhibited IgE binding to Ana o 1, 2, and 3, with median percentages of 75%, 56%, and 48%, respectively. No cross-reactivity was observed between allergenic vicilins or between 2S albumins from cashew and hazelnut. Potentially cross-reactive peptides of Ana o 3 identified in silico overlapped with previously reported IgE epitopes of all 3 allergens., Conclusion: IgE with high affinity to Ana o 3 that cross-reacts with the other 2 major nonhomologous cashew nut allergens might be responsible for the high allergenic potency of cashew nut. These cross-reactive IgE types comprise the major fraction of specific IgE in cashew-allergic patients and might be responsible for cross-reactivity between unrelated tree nuts.

Although dysregulated stress biology is becoming increasingly recognized as a key driver of lifelong disparities in chronic disease, we presently have no validated biomarkers of toxic stress physiology; no biological, behavioral, or cognitive treatments specifically focused on normalizing toxic stress processes; and no agreed-upon guidelines for treating stress in the clinic or evaluating the efficacy of interventions that seek to reduce toxic stress and improve human functioning. We address these critical issues by (a) systematically describing key systems and mechanisms that are dysregulated by stress; (b) summarizing indicators, biomarkers, and instruments for assessing stress response systems; and (c) highlighting therapeutic approaches that can be used to normalize stress-related biopsychosocial functioning. We also present a novel multidisciplinary Stress Phenotyping Framework that can bring stress researchers and clinicians one step closer to realizing the goal of using precision medicine-based approaches to prevent and treat stress-associated health problems.

Background: Eosinophilic esophagitis (EoE) is a chronic immune-mediated inflammatory disease characterized by eosinophil inflammation of the esophagus. It has been described as a component of the Allergic March and is often seen with other atopic diseases. Some atopic diseases, including asthma, are known to be heterogenous with endotypes that guide treatment. Similarly, we propose that EoE is a heterogenous disease with varying phenotypes and endotypes that might impact response to therapy., Methods: A single-center retrospective review of pediatric patients ≤18 years of age diagnosed with EoE was conducted. All gastrointestinal clinic visits and esophagogastroduodenoscopies (EGD) from disease presentation through the first three years after diagnosis were reviewed. Histologic remission rate and therapies utilized [proton pump inhibitor (PPI), topical steroid, dietary elimination] were assessed., Results: One hundred and thirty-seven patients were included, 80% of whom had at least one concurrent atopic condition at diagnosis, with food allergies being the most common (57%) followed by eczema (34%), and asthma (29%). The remission rate of the overall cohort was 65%, and by concurrent allergy, comorbid pollen food syndrome and eczema had the highest remission rates at 100% and 81%, respectively followed by asthma (62%), food allergies (62%), seasonal allergic rhinitis (60%), and history of anaphylaxis (56%). Kaplan-Meier curves for each atopic condition show that patients with eczema and pollen food syndrome achieve histologic remission faster than those without. All treatment modalities were more successful in patients with eczema than those without, and PPI was most effective treatment at inducing remission., Conclusions: In a real-world pediatric cohort, 80% of patients with EoE had an underlying atopic condition. Patients with eczema and pollen food syndrome had a swifter response and were more likely to achieve histologic remission than patients with other atopic conditions. This study suggests that EoE, like other allergic diseases, may have heterogenous phenotypes that could affect response to treatment. There is currently a knowledge gap in classifying EoE based on endotypes and phenotypes at diagnosis and correlating responses to various treatment modalities., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Sessions, Purington, Wang, McGhee, Sindher, Goyal and Khavari.)

Purpose of Review: With increasing prevalence of peanut allergy (PA) globally and the greater risk of potential reactions occurring due to the leading role of nuts in food products, PA has become a significant public health concern over the past decade, affecting up to 5 million of the US adult population. This review details updates and advances in prevalence, diagnosis, and immunotherapies that have occurred over the past year., Recent Findings: Therapeutic and diagnostic advances remain at the forefront of research and have continued to push the food allergy (FA) field forward to provide a promising role in the detection and treatment of PA. The FA field has researched significant advances in peanut immunotherapy, biomarker diagnosis, and quality of life (QoL) improvement., Summary: Given the burden and consequences for individuals with PA, these advances delivered in clinical practice can significantly improve the QoL of individuals with PA and their caregivers. Ongoing studies will continue to investigate long-term outcome measures of desensitisation and effective management plans tailored to the families' needs., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

The incidence and prevalence of food allergy (FA) is increasing. While several studies have established the safety and efficacy of early introduction of single allergens in infants for the prevention of FA, the exact dose, frequency, and number of allergens that can be safely introduced to infants, particularly in those at high or low risk of atopy, are still unclear. This 1-year pilot study evaluated the safety of the early introduction of single foods (milk, egg, or peanut) vs. two foods (milk/egg, egg/peanut, milk/peanut) vs. multiple foods (milk/egg/peanut/cashew/almond/shrimp/walnut/wheat/salmon/hazelnut at low, medium, or high doses) vs. no early introduction in 180 infants between 4-6 months of age. At the end of the study, they were evaluated for plasma biomarkers associated with food reactivity via standardized blood tests. Two to four years after the start of the study, participants were evaluated by standardized food challenges. The serving sizes for the single, double, and low dose mixtures were 300 mg total protein per day. The serving sizes for the medium and high dose mixtures were 900 mg and 3000 mg total protein, respectively. Equal parts of each protein were used for double or mixture foods. All infants were breastfed until at least six months of age. The results demonstrate that infants at either high or low risk for atopy were able to tolerate the early introduction of multiple allergenic foods with no increases in any safety issues, including eczema, FA, or food protein induced enterocolitis. The mixtures of foods at either low, medium, or high doses demonstrated trends for improvement in food challenge reactivity and plasma biomarkers compared to single and double food introductions. The results of this study suggest that the early introduction of foods, particularly simultaneous mixtures of many allergenic foods, may be safe and efficacious for preventing FA and can occur safely. These results need to be confirmed by larger randomized controlled studies.

Background: Food allergy (FA) is a growing global problem that can affect patients' health-related quality of life (HRQoL) owing to increased anxiety as well as social and economic restrictions. Interventions such as oral food challenges (OFCs) and oral immunotherapy (OIT) have been shown to improve HRQoL. However, meta-analyses and systematic synthesis of these data are lacking., Objective: To review and quantitatively synthesize potential benefits of interventions (OIT and OFC) systematically to address FA to a variety of foods., Methods: We conducted a systematic search through PubMed and Cochrane Medical Library databases and performed a meta-analysis focusing on studies assessing changes in HRQoL after OIT and/or OFCs in FA participants and caregivers from 2010 to July 2020. Random effects model and I 2 statistics were used to assess overall intervention effects and heterogeneity across studies., Results: We included 13 publications in this meta-analysis (OIT = 7; OFCs = 6). Mean change in HRQoL scores after OIT and OFCs was -1.25 (P < .001) and -0.78 (P = .052), with a significant I 2 of 87% (P < .001) and 90% (P < .001), respectively. Five OIT studies found significant improvements in HRQoL in the OIT group compared with the placebo group, with an overall standardized mean difference of -0.56 (P = .007; I 2  = 42%, P = .099)., Conclusions: This meta-analysis showed that in FA patients, both OIT and OFCs are associated with an improvement in HRQoL. Well-designed and long-term HRQoL studies are necessary to ascertain sustained benefits of OIT and OFCs., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Food allergy (FA) is a growing public health problem with personal, social, nutritional, and economic consequences. In the United States, it is estimated that 8% of children and 10.8% of adults have food allergies. Allergies to peanuts are particularly worrisome as unlike allergies to other allergenic foods, such as milk and egg, which are commonly outgrown by 5 or 10 years of age, 80% of peanut allergies persist into adulthood. The first drug for peanut allergy, Palforzia, was approved by the US Food and Drug Administration (FDA) in January 2020. For other food allergies, the current standard of care for the management of FA is suboptimal and is limited to dietary elimination of the offending allergen, vigilance against accidental ingestion, and treatment of allergic reactions with antihistamines and epinephrine. However, dietary avoidance can be challenging, and it is estimated that approximately 40% of patients with food allergies report at least one food allergy-related emergency department in their lifetime. Reactions, even from minimal exposures, can be life-threatening. Oral immunotherapy (OIT) has been the best researched therapeutic approach for treating FA over the last decade, with clinical trials investigating its efficacy, safety, and ability to improve participants' quality of life (QoL). A number of studies and meta-analyses have shown that OIT treatment is effective in raising the threshold of reactivity to peanuts and other foods in addition to producing a measurable serum immune response to such therapy. Although OIT-related adverse events (AEs) are common during treatment, serious reactions are rare. In fact, while the majority of patients experience AEs related to dosing, most continue daily dosing in hopes of achieving protection against the culprit food. Moreover, the majority of participants report improvement of QoL after OIT and are positive about undergoing OIT. These results show patients' commitment to OIT and their optimism regarding the benefits of treatment. As a first step in therapeutic options to protect from reactions to unintentional ingestion of allergenic foods, and importantly, to address the many psychosocial aspects of living with FA, OIT shows promise. Future research will focus on identifying optimal OIT regimens that maintain protection after therapy and allow for regular food consumption without allergic symptoms. Education and informed shared decision making between patients and providers are essential in optimizing current therapy regimens., Competing Interests: Dr. Nadeau reports grants from National Institute of Allergy and Infectious Diseases (NIAID), Food Allergy Research & Education (FARE), End Allergies Together (EAT), Allergenis, and Ukko Pharma; Grant awardee at NIAID, National Institute of Environmental Health Sciences (NIEHS), National Heart, Lung, and Blood Institute (NHLBI), and the Environmental Protection Agency (EPA); involved in Clinical trials with Regeneron, Genentech, AImmune Therapeutics, DBV Technologies, AnaptysBio, Adare Pharmaceuticals, and Stallergenes-Greer; Research Sponsorship by Novartis, Sanofi, Astellas, Nestle; Data and Safety Monitoring Board member at Novartis and NHLBI; Cofounded Before Brands, Alladapt, ForTra, and Iggenix; Chief Intellectual Office at FARE, Director of the World Health Organization (WAO) Center of Excellence at Stanford, Personal fees from Regeneron, Astrazeneca, ImmuneWorks, and Cour Pharmaceuticals; Consultant and Advisory Board Member at Ukko, Before Brands, Alladapt, IgGenix, Probio, Vedanta, Centecor, Seed, Novartis, NHBLI, EPA, National Scientific Committee of ITN and NIH Programs, US patents (patent numbers 62/647,389; 62/119,014; 12/610,940, 12/686,121, 10/064,936, 62/767,444; application numbers S10-392); Dr. Chinthrajah receives grant support from CoFAR NIAID, Aimmune, DBV Technologies, Astellas, AnaptysBio, Novartis, and Regeneron, and is a scientific advisory board member for Alladapt Immunotherapeutics; Dr. Sayantani Sindher receives grant support from Aimmune, DBV Technologies, and Regeneron; all other authors declare no conflict of interest., (© 2020 The Authors.)

With the rising prevalence, food allergies have become a significant health burden that affects 6% to 13% of the global population. Although oral immunotherapy (OIT) has been promising for food allergies, this therapy has limitations, including high rates of adverse reactions and long treatment periods. Biologics may address these limitations by increasing the safety and tolerability of OIT and decreasing treatment periods. The use of biologics and vaccines are actively being explored as monotherapy as well as adjunctive therapy in combination with allergen specific OIT. A number of biologics that target key molecules known to be involved in food allergy are under investigation, including anti-immunoglobulin E therapy (omalizumab), anti-interleukin (IL) 4 receptor a (dupilumab), anti-IL-5 (mepolizumab and reslizumab), and anti-IL-5R (benralizumab), anti-IL-33 (etokimab), and peanut DNA plasmid vaccines. In the era of precision medicine, the future of food allergy looks promising, and biologics will provide treatment as well as further insights into the molecular mechanisms associated with food allergy., Competing Interests: The authors have no conflicts of interest to declare pertaining to this article, (Copyright © 2020, The Author(s). Published by OceanSide Publications, Inc., U.S.A.)

Background: Double-blind placebo-controlled food challenges (DBPCFCs) remain the gold standard for the diagnosis of food allergy; however, challenges require significant time and resources and place the patient at an increased risk for severe allergic adverse events. There have been continued efforts to identify alternative diagnostic methods to replace or minimize the need for oral food challenges (OFCs) in the diagnosis of food allergy. Methods: Data was extracted for all IRB-approved, Stanford-initiated clinical protocols involving standardized screening OFCs to a cumulative dose of 500 mg protein to any of 11 food allergens in participants with elevated skin prick test (SPT) and/or specific IgE (sIgE) values to the challenged food across 7 sites. Baseline population characteristics, biomarkers, and challenge outcomes were analyzed to develop diagnostic criteria predictive of positive OFCs across multiple allergens in our multi-allergic cohorts. Results: A total of 1247 OFCs completed by 427 participants were analyzed in this cohort. Eighty-five percent of all OFCs had positive challenges. A history of atopic dermatitis and multiple food allergies were significantly associated with a higher risk of positive OFCs. The majority of food-specific SPT, sIgE, and sIgE/total IgE (tIgE) thresholds calculated from cumulative tolerated dose (CTD)-dependent receiver operator curves (ROC) had high discrimination of OFC outcome (area under the curves > 0.75). Participants with values above the thresholds were more likely to have positive challenges. Conclusions: This is the first study, to our knowledge, to not only adjust for tolerated allergen dose in predicting OFC outcome, but to also use this method to establish biomarker thresholds. The presented findings suggest that readily obtainable biomarker values and patient demographics may be of use in the prediction of OFC outcome and food allergy. In the subset of patients with SPT or sIgE values above the thresholds, values appear highly predictive of a positive OFC and true food allergy. While these values are relatively high, they may serve as an appropriate substitute for food challenges in clinical and research settings.

Background: Food allergy prevalence has continued to rise over the past decade. While studies have reported threshold doses for multiple foods, large-scale multi-food allergen studies are lacking. Our goal was to identify threshold dose distributions and predictors of severe reactions during blinded oral food challenges (OFCs) in multi-food allergic patients. Methods: A retrospective chart review was performed on all Stanford-initiated clinical protocols involving standardized screening OFCs to any of 11 food allergens at 7 sites. Interval-censoring survival analysis was used to calculate eliciting dose (ED) curves for each food. Changes in severity and ED were also analyzed among participants who had repeated challenges to the same food. Results: Of 428 participants, 410 (96%) had at least one positive challenge (1445 standardized OFCs with 1054 total positive challenges). Participants undergoing peanut challenges had the highest ED 50 (29.9 mg), while those challenged with egg or pistachio had the lowest (7.07 or 1.7 mg, respectively). The most common adverse event was skin related (54%), followed by gastrointestinal (GI) events (33%). A history of asthma was associated with a significantly higher risk of a severe reaction (hazard ratio [HR]: 2.37, 95% confidence interval [CI]: 1.36, 4.13). Higher values of allergen-specific IgE (sIgE) and sIgE to total IgE ratio (sIgEr) were also associated with higher risk of a severe reaction (1.49 [1.19, 1.85] and 1.84 [1.30, 2.59], respectively). Participants undergoing cashew, peanut, pecan, sesame, and walnut challenges had more severe reactions as ED increased. In participants who underwent repeat challenges, the ED did not change ( p = 0.66), but reactions were more severe ( p = 0.02). Conclusions: Participants with a history of asthma, high sIgEr, and/or high values of sIgE were found to be at higher risk for severe reactions during food challenges. These findings may help to optimize food challenge dosing schemes in multi-food allergic, atopic patients, specifically at lower doses where the majority of reactions occur. Trials Registration Number: ClinicalTrials. gov number NCT03539692; https://clinicaltrials.gov/ct2/show/NCT03539692.

Food allergies continue to increase in prevalence. Standard care is a strict elimination diet, but life-threatening reactions still occur. Allergen immunotherapy has the most potential in treating food allergy. Subcutaneous immunotherapy has not been adopted into food allergy therapy. Oral immunotherapy has a high rate of adverse reactions. Sublingual immunotherapy (SLIT) uses the tolerogenic environment of the oral mucosa and epicutaneous immunotherapy (EPIT) uses the immune cells of the epidermis to transport antigens to afferent lymph nodes to activate immune responses. SLIT and EPIT can successfully desensitize patients. More research is needed to define optimal doses and administration protocols., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The incidence of asthma morbidity and mortality is highest among minority inner-city populations. Among New York City's five boroughs, the Bronx has the highest rate of asthma-related hospitalizations and mortality. Outdoor air pollutants have been associated with increased asthma-related ED visits (AREDV) in this borough., Objective: To better understand the contribution of pollen and mold to asthma severity in the Bronx., Methods: The numbers of daily adult and pediatric AREDV and asthma-related hospitalizations (ARH) from 2001 to 2008 were obtained from two Bronx hospitals. AREDV and ARH data were acquired retrospectively through the Clinical Looking Glass data analysis software. Daily counts for tree, grass and weed pollen and mold spore counts from March 2001 to October 2008 were obtained from the Armonk counting station. All data were statistically analyzed and graphed as daily values., Results: There were a total of 42 065 AREDV and 10 132 ARH at both Bronx hospitals. There were spring and winter peaks of increased AREDV. Tree pollen counts significantly correlated with total AREDV (rho = 0.3639, p < 0.001), and pediatric (rho = 0.33, p < 0.001) and adult AREDV (rho = 0.28, p < 0.001). ARH positively correlated with tree pollen counts (Spearman rho = 0.2389, p < 0.001)., Conclusions: There exists a significant association between spring AREDV and ARH and tree pollen concentrations in a highly urbanized area such as the Bronx. Early anticipation of spring pollen peaks based on ongoing surveillance could potentially guide clinical practice and minimize asthma-related ED visits in the Bronx.