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Background: Cockroach allergy contributes to morbidity among urban children with asthma. Few trials address the effect of subcutaneous immunotherapy (SCIT) with cockroach allergen among these at-risk children., Objectives: We sought to determine whether nasal allergen challenge (NAC) responses to cockroach allergen would improve following 1 year of SCIT., Methods: Urban children with asthma, who were cockroach-sensitized and reactive on NAC, participated in a year-long randomized double-blind placebo-controlled SCIT trial using German cockroach extract. The primary endpoint was the change in mean Total Nasal Symptom Score (TNSS) during NAC after 12 months of SCIT. Changes in nasal transcriptomic responses during NAC, skin prick test wheal size, serum allergen-specific antibody production, and T-cell responses to cockroach allergen were assessed., Results: Changes in mean NAC TNSS did not differ between SCIT-assigned (n = 28) versus placebo-assigned (n = 29) participants (P = .63). Nasal transcriptomic responses correlated with TNSS, but a treatment effect was not observed. Cockroach serum-specific IgE decreased to a similar extent in both groups, while decreased cockroach skin prick test wheal size was greater among SCIT participants (P = .04). A 200-fold increase in cockroach serum-specific IgG 4 was observed among subjects receiving SCIT (P < .001) but was unchanged in the placebo group. T-cell IL-4 responses following cockroach allergen stimulation decreased to a greater extent among SCIT versus placebo (P = .002), while no effect was observed for IL-10 or IFN-γ., Conclusions: A year of SCIT failed to alter NAC TNSS and nasal transcriptome responses to cockroach allergen challenge despite systemic effects on allergen-specific skin tests, induction of serum-specific IgG 4 serum production and down-modulation of allergen-stimulated T-cell responses., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Peanut Oral Immunotherapy (POIT) holds promise for remission of peanut allergy, though treatment is protracted and successful in only a subset of patients. Because the gut microbiome is linked to food allergy, we sought to identify fecal microbial predictors of POIT efficacy and to develop mechanistic insights into treatment response. Longitudinal functional analysis of the fecal microbiome of children (n=79) undergoing POIT in a first double-blind, placebo-controlled clinical trial, identified five microbial-derived bile acids enriched in fecal samples prior to POIT initiation that predicted treatment efficacy (AUC 0.71). Failure to induce disease remission was associated with a distinct fecal microbiome with enhanced capacity for bile acid deconjugation, amino acid metabolism, and increased peanut peptide degradation in vitro . Thus, microbiome mechanisms of POIT failure appear to include depletion of immunomodulatory secondary bile and amino acids and the antigenic peanut peptides necessary to promote peanut allergy desensitization and remission.

Background: A randomized trial demonstrated consumption of peanut from infancy to age 5 years prevented the development of peanut allergy. An extension of that trial demonstrated the effect persisted after 1 year of peanut avoidance. This follow-up trial examined the durability of peanut tolerance at age 144 months after years of ad libitum peanut consumption., Methods: Participants from a randomized peanut consumption trial were assessed for peanut allergy following an extended period of eating or avoiding peanuts as desired. The primary end point was the rate of peanut allergy at age 144 months., Results: We enrolled 508 of the original 640 participants (79.4%); 497 had complete primary end point data. At age 144 months, peanut allergy remained significantly more prevalent in participants in the original peanut avoidance group than in the original peanut consumption group (15.4% [38 of 246 participants] vs. 4.4% [11 of 251 participants]; P<0.001). Participants in both groups reported avoiding peanuts for prolonged periods of time between 72 and 144 months. Participants at 144 months in the peanut consumption group had levels of Ara h2-specific immunoglobulin E (a peanut allergen associated with anaphylaxis) of 0.03 ± 3.42 kU/l and levels of peanut-specific immunoglobulin G4 of 535.5 ± 4.98 μg/l, whereas participants in the peanut avoidance group had levels of Ara h2-specific immunoglobulin E of 0.06 ± 11.21 kU/l and levels of peanut-specific immunoglobulin G4 of 209.3 ± 3.84 μg/l. Adverse events were uncommon, and the majority were related to the food challenge., Conclusions: Peanut consumption, starting in infancy and continuing to age 5 years, provided lasting tolerance to peanut into adolescence irrespective of subsequent peanut consumption, demonstrating that long-term prevention and tolerance can be achieved in food allergy. (Funded by the National Institute of Allergy and Infectious Diseases and others; ITN070AD, ClinicalTrials.gov number, NCT03546413.).

Background: Food allergies are common and are associated with substantial morbidity; the only approved treatment is oral immunotherapy for peanut allergy., Methods: In this trial, we assessed whether omalizumab, a monoclonal anti-IgE antibody, would be effective and safe as monotherapy in patients with multiple food allergies. Persons 1 to 55 years of age who were allergic to peanuts and at least two other trial-specified foods (cashew, milk, egg, walnut, wheat, and hazelnut) were screened. Inclusion required a reaction to a food challenge of 100 mg or less of peanut protein and 300 mg or less of the two other foods. Participants were randomly assigned, in a 2:1 ratio, to receive omalizumab or placebo administered subcutaneously (with the dose based on weight and IgE levels) every 2 to 4 weeks for 16 to 20 weeks, after which the challenges were repeated. The primary end point was ingestion of peanut protein in a single dose of 600 mg or more without dose-limiting symptoms. The three key secondary end points were the consumption of cashew, of milk, and of egg in single doses of at least 1000 mg each without dose-limiting symptoms. The first 60 participants (59 of whom were children or adolescents) who completed this first stage were enrolled in a 24-week open-label extension., Results: Of the 462 persons who were screened, 180 underwent randomization. The analysis population consisted of the 177 children and adolescents (1 to 17 years of age). A total of 79 of the 118 participants (67%) receiving omalizumab met the primary end-point criteria, as compared with 4 of the 59 participants (7%) receiving placebo (P<0.001). Results for the key secondary end points were consistent with those of the primary end point (cashew, 41% vs. 3%; milk, 66% vs. 10%; egg, 67% vs. 0%; P<0.001 for all comparisons). Safety end points did not differ between the groups, aside from more injection-site reactions in the omalizumab group., Conclusions: In persons as young as 1 year of age with multiple food allergies, omalizumab treatment for 16 weeks was superior to placebo in increasing the reaction threshold for peanut and other common food allergens. (Funded by the National Institute of Allergy and Infectious Diseases and others; ClinicalTrials.gov number, NCT03881696.)., (Copyright © 2024 Massachusetts Medical Society.)

Background: The Learning Early About Peanut Allergy (LEAP) study team developed a protocol-specific algorithm using dietary history, peanut-specific IgE, and skin prick test (SPT) to determine peanut allergy status if the oral food challenge (OFC) could not be administered or did not provide a determinant result., Objective: To investigate how well the algorithm determined allergy status in LEAP; to develop a new prediction model to determine peanut allergy status when OFC results are not available in LEAP Trio, a follow-up study of LEAP participants and their families; and to compare the new prediction model with the algorithm., Methods: The algorithm was developed for the LEAP protocol before the analysis of the primary outcome. Subsequently, a prediction model was developed using logistic regression., Results: Using the protocol-specified algorithm, 73% (453/617) of allergy determinations matched the OFC, 0.6% (4/617) were mismatched, and 26% (160/617) participants were nonevaluable. The prediction model included SPT, peanut-specific IgE, Ara h 1, Ara h 2, and Ara h 3. The model inaccurately predicted 1 of 266 participants as allergic who were not allergic by OFC and 8 of 57 participants as not allergic who were allergic by OFC. The overall error rate was 9 of 323 (2.8%) with an area under the curve of 0.99. The prediction model additionally performed well in an external validation cohort., Conclusion: The prediction model performed with high sensitivity and accuracy, eliminated the problem of nonevaluable outcomes, and can be used to estimate peanut allergy status in the LEAP Trio study when OFC is not available., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Despite similar clinical symptoms, peanut-allergic (PA) individuals may respond quite differently to the same therapeutic interventions., Objective: This study aimed to determine whether inherent qualities of cell response at baseline could influence response to peanut oral immunotherapy (PnOIT)., Methods: We first performed ex vivo T-cell profiling on peanut-reactive CD154 + CD137 + T (pTeff) cells from 90 challenge-confirmed PA individuals. We developed a gating strategy for unbiased assessment of the phenotypic distribution of rare pTeff cells across different memory CD4 + T-cell subsets to define patient immunotype. In longitudinal samples of 29 PA participants enrolled onto the IMPACT trial of PnOIT, we determined whether patient immunotype at baseline could influence response to PnOIT., Results: Our data emphasize the heterogeneity of pTeff cell responses in PA participants with 2 mutually exclusive phenotypic entities (CCR6 - CRT H 2 + and CCR6 + CRT H 2 - ). Our findings lead us to propose that peanut allergy can be classified broadly into at least 2 discrete subtypes, termed immunotypes, with distinct immunologic and clinical characteristics that are based on the proportion of T H 2A pTeff cells. PnOIT induced elimination of T H 2A pTeff cells in the context of the IMPACT clinical trial. Only 1 PA patient with a low level of T H 2A pTeff cells at baseline experienced long-lasting benefit of remission after PnOIT discontinuation., Conclusion: Dividing PA patients according to their individual peanut-specific T-cell profile may facilitate patient stratification in clinical settings by identifying which immunotypes might respond best to different therapies., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Asthma prevalence and severity have markedly increased with urbanisation, and children in low-income urban centres have among the greatest asthma morbidity. Outdoor air pollution has been associated with adverse respiratory effects in children with asthma. However, the mechanisms by which air pollution exposure exacerbates asthma, and how these mechanisms compare with exacerbations induced by respiratory viruses, are poorly understood. We aimed to investigate the associations between regional air pollutant concentrations, respiratory illnesses, lung function, and upper airway transcriptional signatures in children with asthma, with particular focus on asthma exacerbations occurring in the absence of respiratory virus., Methods: We performed a retrospective analysis of data from the MUPPITS1 cohort and validated our findings in the ICATA cohort. The MUPPITS1 cohort recruited 208 children aged 6-17 years living in urban areas across nine US cities with exacerbation-prone asthma between Oct 7, 2015, and Oct 18, 2016, and monitored them during reported respiratory illnesses. The last MUPPITS1 study visit occurred on Jan 6, 2017. The ICATA cohort recruited 419 participants aged 6-20 years with persistent allergic asthma living in urban sites across eight US cities between Oct 23, 2006, and March 25, 2008, and the last study visit occurred on Dec 30, 2009. We included participants from the MUPPITS1 cohort who reported a respiratory illness at some point during the follow-up and participants from the ICATA cohort who had nasal samples collected during respiratory illness or at a scheduled visit. We used air quality index values and air pollutant concentrations for PM 2·5 , PM 10 , O 3 , NO 2 , SO 2 , CO, and Pb from the US Environmental Protection Agency spanning the years of both cohorts, and matched values and concentrations to each illness for each participant. We investigated the associations between regional air pollutant concentrations and respiratory illnesses and asthma exacerbations, pulmonary function, and upper airway transcriptional signatures by use of a combination of generalised additive models, case crossover analyses, and generalised linear mixed-effects models., Findings: Of the 208 participants from the MUPPITS1 cohort and 419 participants from the ICATA cohort, 168 participants in the MUPPITS1 cohort (98 male participants and 70 female participants) and 189 participants in the ICATA cohort (115 male participants and 74 female participants) were included in our analysis. We identified that increased air quality index values, driven predominantly by increased PM 2·5 and O 3 concentrations, were significantly associated with asthma exacerbations and decreases in pulmonary function that occurred in the absence of a provoking viral infection. Moreover, individual pollutants were significantly associated with altered gene expression in coordinated inflammatory pathways, including PM 2·5 with increased epithelial induction of tissue kallikreins, mucus hypersecretion, and barrier functions and O 3 with increased type-2 inflammation., Interpretation: Our findings suggest that air pollution is an important independent risk factor for asthma exacerbations in children living in urban areas and is potentially linked to exacerbations through specific inflammatory pathways in the airway. Further investigation of these potential mechanistic pathways could inform asthma prevention and management approaches., Funding: National Institutes of Health, National Institute of Allergy and Infectious Diseases., Competing Interests: Declaration of interests MCA, MK, GTO, RCM, EW, PL, AC, MAG, RSG, AHL, SL-D, JAP, CMK, GKKH, EMZ, SJT, LBB, WWB, JEG, and DJJ report grants from the US National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases, and Division of Allergy, Immunology, and Transplantation during the conduct of study. MCA reports personal fees for consulting from Regeneron, outside the submitted work. AHL reports personal fees from Phadia ThermoFisher as consulting honoraria; grants and non-financial support from ResMed–Propeller Health; non-financial support from Revenio; grants and personal fees from Avillion; and personal fees from Labcorp, all outside the submitted work. SL-D reports funding from the National Heart, Lung, and Blood Institute (NHLBI) and the Robert Wood Johnson Foundation. JAP reports provisions of study drug for other asthma studies from GlaxoSmithKline, Boehringer Ingelheim, and Genentech–Novartis. CMK reports royalties from UpToDate. SJT reports grant meetings to support the CAUSE network from NIH–NIAID, payment for episode on biologics in asthma care from Medscape, and personal fees from UpToDate, all outside the submitted work. LBB reports personal fees from GlaxoSmithKline, Genentech–Novartis, Teva, AstraZeneca, WebMD–Medscape, DBV Technologies, Sanofi–Regeneron, OM Pharma, Kinaset, Vertex, and the American Board of Allergy and Immunology; non-financial support from the American Academy of Allergy Asthma and Immunology; and royalties from Elsevier, all outside the submitted work. WWB reports personal fees from Novartis, GlaxoSmithKline, Genentech, Sanofi, AstraZeneca, Regeneron, and Elsevier, outside the submitted work. JEG reports personal fees and stock options from Meissa Vaccines, personal fees from AstraZeneca and Ena Therapeutics, and a patent on methods for production of rhinoviruses. DJJ reports personal fees from Novartis, Avillion, Pfizer, AstraZeneca, and Sanofi; grants and personal fees from GlaxoSmithKline and Regeneron; and grants from NIH–NHLBI, all outside the submitted work. LMW, SMS, PJG, and AT declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Thymic stromal lymphopoietin (TSLP) has been shown to play a central role in the initiation and persistence of allergic responses., Objective: We evaluated whether tezepelumab, a human monoclonal anti-TSLP antibody, improved the efficacy of subcutaneous allergen immunotherapy (SCIT) and promoted the development of tolerance in patients with allergic rhinitis., Methods: We conducted a double-blind parallel design trial in patients with cat allergy. A total of 121 patients were randomized to receive either intravenous tezepelumab plus subcutaneous cat SCIT, cat SCIT alone, tezepelumab alone, or placebo for 52 weeks, followed by 52 weeks of observation. Nasal allergen challenge (NAC), skin testing, and blood and nasal samples were obtained throughout the study., Results: At week 52, the NAC-induced total nasal symptom scores (TNSS) (calculated as area under the curve [AUC 0-1h ] and as peak score [Peak 0-1h ] during the first hour after NAC) were significantly reduced in patients receiving tezepelumab/SCIT compared to SCIT alone. At week 104, one year after stopping treatment, the primary end point TNSS AUC 0-1h was not significantly different in the tezepelumab/SCIT group compared to SCIT alone, while TNSS Peak 0-1h was significantly lower in those receiving combination treatment versus SCIT. Transcriptomic analysis of nasal epithelial samples demonstrated that treatment with the combination of SCIT/tezepelumab, but neither monotherapy, caused persistent downregulation of a gene network related to type 2 inflammation that was associated with improvement in NAC responses., Conclusions: Inhibition of TSLP augments the efficacy of SCIT during therapy and may promote tolerance after a 1-year course of treatment. (ClinicalTrials.gov NCT02237196)., (Copyright © 2022. Published by Elsevier Inc.)

Purpose: Over the past two decades, the involvement of a Pharmacist Scientist in clinical settings has improved patient safety, decreased medication errors, and enabled successful conduct of clinical trials and faster product development [1-5]. The impact of an oversight by a Pharmacist Scientist on clinical trial performance and execution in terms of Pharmacy and Investigational Product (IP)-related deviations has not been evaluated by a sponsor., Methods: This was a retrospective observational study conducted by the Division of Allergy, Immunology and Transplantation (DAIT), National Institute of Allergy and Infectious Diseases (NIAID). We assessed the association of the number of Pharmacy and Investigational Product (IP)-related deviations with Pharmacist oversight and use of DAIT Pharmacy/ Pharmaceutical services in two groups: Intervention Group (IG) and the Control Group (CG)., Results: We evaluated monitoring data from 116 studies conducted between 2006 through 2020. Forty-one eligible clinical trials were included and analyzed: 13 trials were in the IG with Pharmacist oversight and use of Pharmacy Services; 28 trials were in the CG with no Pharmacist oversight and zero to partial use DAIT Pharmacy/ Pharmaceutical Services. The evaluation revealed the expected risk of having a pharmacy and IP-related deviations were 2.94 times higher (95% CI 1.28, 6.67, = 0.01) in trials not having Pharmacist oversight and zero to partial use of Pharmaceutical/ Pharmacy Program services. This significant finding was associated with having Pharmacist oversight when adjusting for study size (# of sites and patients needed), anticipated study duration, design complexity, and whether recruitment was completed or not., Conclusion: We found a statistically significant association between Pharmacist Scientist involvement and oversight from protocol development to study execution and a reduction in Pharmacy and IP-related deviations., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)

There is mounting evidence that environmental exposures can result in effects on health that can be transmitted across generations, without the need for a direct exposure to the original factor, for example, the effect of grandparental smoking on grandchildren. Hence, an individual's health should be investigated with the knowledge of cross-generational influences. Epigenetic factors are molecular factors or processes that regulate genome activity and may impact cross-generational effects. Epigenetic transgenerational inheritance has been demonstrated in plants and animals, but the presence and extent of this process in humans are currently being investigated. Experimental data in animals support transmission of asthma risk across generations from a single exposure to the deleterious factor and suggest that the nature of this transmission is in part due to changes in DNA methylation, the most studied epigenetic process. The association of father's prepuberty exposure with offspring risk of asthma and lung function deficit may also be mediated by epigenetic processes. Multi-generational birth cohorts are ideal to investigate the presence and impact of transfer of disease susceptibility across generations and underlying mechanisms. However, multi-generational studies require recruitment and assessment of participants over several decades. Investigation of adult multi-generation cohorts is less resource intensive but run the risk of recall bias. Statistical analysis is challenging given varying degrees of longitudinal and hierarchical data but path analyses, structural equation modelling and multilevel modelling can be employed, and directed networks addressing longitudinal effects deserve exploration as an effort to study causal pathways., (© 2022 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Background: Seasonal variation in respiratory illnesses and exacerbations in pediatric populations with asthma is well described, though whether upper airway microbes play season-specific roles in these events is unknown., Objective: We hypothesized that nasal microbiota composition is seasonally dynamic and that discrete microbe-host interactions modify risk of asthma exacerbation in a season-specific manner., Methods: Repeated nasal samples from children with exacerbation-prone asthma collected during periods of respiratory health (baseline; n = 181 samples) or first captured respiratory illness (n = 97) across all seasons, underwent bacterial (16S ribosomal RNA gene) and fungal (internal transcribed spacer region 2) biomarker sequencing. Virus detection was performed by multiplex PCR. Paired nasal transcriptome data were examined for seasonal dynamics and integrative analyses., Results: Upper airway bacterial and fungal microbiota and rhinovirus detection exhibited significant seasonal dynamics. In seasonally adjusted analysis, variation in both baseline and respiratory illness microbiota related to subsequent exacerbation. Specifically, in the fall, when respiratory illness and exacerbation events were most frequent, several Moraxella and Haemophilus members were enriched both in virus-positive respiratory illnesses and those that progressed to exacerbations. The abundance of 2 discrete bacterial networks, characteristically comprising either Streptococcus or Staphylococcus, exhibited opposing interactions with an exacerbation-associated SMAD3 nasal epithelial transcriptional module to significantly increase the odds of subsequent exacerbation (odds ratio = 14.7, 95% confidence interval = 1.50-144, P = .02; odds ratio = 39.17, 95% confidence interval = 2.44-626, P = .008, respectively)., Conclusions: Upper airway microbiomes covary with season and with seasonal trends in respiratory illnesses and asthma exacerbations. Seasonally adjusted analyses reveal specific bacteria-host interactions that significantly increase risk of asthma exacerbation in these children., (Copyright © 2022. Published by Elsevier Inc.)

Background: For young children with peanut allergy, dietary avoidance is the current standard of care. We aimed to assess whether peanut oral immunotherapy can induce desensitisation (an increased allergic reaction threshold while on therapy) or remission (a state of non-responsiveness after discontinuation of immunotherapy) in this population., Methods: We did a randomised, double-blind, placebo-controlled study in five US academic medical centres. Eligible participants were children aged 12 to younger than 48 months who were reactive to 500 mg or less of peanut protein during a double-blind, placebo-controlled food challenge (DBPCFC). Participants were randomly assigned by use of a computer, in a 2:1 allocation ratio, to receive peanut oral immunotherapy or placebo for 134 weeks (2000 mg peanut protein per day) followed by 26 weeks of avoidance, with participants and study staff and investigators masked to group treatment assignment. The primary outcome was desensitisation at the end of treatment (week 134), and remission after avoidance (week 160), as the key secondary outcome, were assessed by DBPCFC to 5000 mg in the intention-to-treat population. Safety and immunological parameters were assessed in the same population. This trial is registered on ClinicalTrials.gov, NCT03345160., Findings: Between Aug 13, 2013, and Oct 1, 2015, 146 children, with a median age of 39·3 months (IQR 30·8-44·7), were randomly assigned to receive peanut oral immunotherapy (96 participants) or placebo (50 participants). At week 134, 68 (71%, 95% CI 61-80) of 96 participants who received peanut oral immunotherapy compared with one (2%, 0·05-11) of 50 who received placebo met the primary outcome of desensitisation (risk difference [RD] 69%, 95% CI 59-79; p<0·0001). The median cumulative tolerated dose during the week 134 DBPCFC was 5005 mg (IQR 3755-5005) for peanut oral immunotherapy versus 5 mg (0-105) for placebo (p<0·0001). After avoidance, 20 (21%, 95% CI 13-30) of 96 participants receiving peanut oral immunotherapy compared with one (2%, 0·05-11) of 50 receiving placebo met remission criteria (RD 19%, 95% CI 10-28; p=0·0021). The median cumulative tolerated dose during the week 160 DBPCFC was 755 mg (IQR 0-2755) for peanut oral immunotherapy and 0 mg (0-55) for placebo (p<0·0001). A significant proportion of participants receiving peanut oral immunotherapy who passed the 5000 mg DBPCFC at week 134 could no longer tolerate 5000 mg at week 160 (p<0·001). The participant receiving placebo who was desensitised at week 134 also achieved remission at week 160. Compared with placebo, peanut oral immunotherapy decreased peanut-specific and Ara h2-specific IgE, skin prick test, and basophil activation, and increased peanut-specific and Ara h2-specific IgG4 at weeks 134 and 160. By use of multivariable regression analysis of participants receiving peanut oral immunotherapy, younger age and lower baseline peanut-specific IgE was predictive of remission. Most participants (98% with peanut oral immunotherapy vs 80% with placebo) had at least one oral immunotherapy dosing reaction, predominantly mild to moderate and occurring more frequently in participants receiving peanut oral immunotherapy. 35 oral immunotherapy dosing events with moderate symptoms were treated with epinephrine in 21 participants receiving peanut oral immunotherapy., Interpretation: In children with a peanut allergy, initiation of peanut oral immunotherapy before age 4 years was associated with an increase in both desensitisation and remission. Development of remission correlated with immunological biomarkers. The outcomes suggest a window of opportunity at a young age for intervention to induce remission of peanut allergy., Funding: National Institute of Allergy and Infectious Disease, Immune Tolerance Network., Competing Interests: Declaration of interests SMJ reports grants from NIH-NIAID, Food Allergy Research & Education (FARE), Aimmune Therapeutic, DBV Technologies, Astellas, Sanofi, Regeneron, and Genentech; and personal fees from FARE, EMMES Corporation, and Aimmune Therapeutics. EHK reports personal fees from DBV Technologies, Aimmune Therapeutics, AllerGenis, Ukko, Vibrant America, Allakos, Kenota Health, and Duke Clinical Research Institute; and grants from FARE and the Wallace Research Foundation. KCN reports grants from NIAID, National Heart, Lung, and Blood Institute, National Institute of Environmental Health Sciences, and FARE; other fees from World Allergy Organization and Cour Pharma; other support from Before Brands, Alladapt, Latitude, IgGenix, Immune Tolerance Network (ITN), and NIH clinical research centres; and pending patent applications for inhibition of allergic reaction to peanut allergen using an IL-33 inhibitor (62/647,389), special oral formula for decreasing food allergy risk and treatment for food allergy (62/119,014), basophil activation based diagnostic allergy test (S10-392), granulocyte-based methods for detecting and monitoring immune system disorders (12/686,121), methods and assays for detecting and quantifying pure subpopulations of white blood cells in immune system disorders (12/610,940), mixed allergen compositions and methods for using the same (10/064,936), and microfluidic device and diagnostic methods for allergy testing based on detection of basophil activation (62/767,444). AN-W reports grants from NIH-NIAID, DBV Technologies, Astellas Pharma, and FARE; and grants and personal fees from Nestlé and Nutricia. RAW reports grants from NIAID, Aimmune, Astellas, DBV Technologies, Genentech, Regeneron, and Sanofi; and personal fees from UpToDate. HAS receives funding to his institution for grants from NIH-NIAID; consulting fees from DBV Technologies, N-Fold Therapeutics, and Siolta; and stock options from DBV Technologies and N-Fold Therapeutics. AMS reports grants from NIAID-ITN, FARE, Aimmune, DBV Technologies, Astellas, Sanofi, Regeneron, and Genentech; and personal fees from DBV Technologies. JW reports grants from NIAID and personal fees from DBV Technologies, ALK Abello, Genentech, and UpToDate. SBS reports grants from NIAID, Regeneron, DBV Technologies, Aimmune, Novartis, and Sanofi; and personal fees from AstraZeneca. MK reports grants from NIH and Department of Defence. JJ reports grants from NIAID. KS reports grants from NIH-NIAID. DCB reports grants from NIH-NIAID. HC reports grants from NIH-NIAID. DL reports grants from NIH-NIAID. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The prevalence of food allergy (FA) is increasing in some areas of the globe, highlighting the need for better strategies for prevention, diagnosis, and therapy. In the last few decades, we have made great strides in understanding the causes and mechanisms underlying FAs, prompting guideline updates. Earlier guidelines recommended avoidance of common food allergens during pregnancy and lactation and delaying the introduction of allergenic foods in children aged between 1 and 3 years. Recent guidelines for allergy prevention recommend consumption of a healthy and diverse diet without eliminating or increasing the consumption of allergenic foods during pregnancy or breast-feeding. Early introduction of allergenic foods is recommended by most guidelines for allergy prevention after a period of exclusive breast-feedng (6 months [World Health Organization] or 4 months [European Academy of Allergy and Clinical Immunology]). New diagnostics for FA have been developed with varied availability of these tests in different countries. Finally, the first oral immunotherapy drug for FA was approved by the US Food and Drug Administration and European Medicines Agency in 2020. In this review, we will address the global prevalence of FA, our current understanding of the causes of FA, and the latest guidelines for preventing, diagnosing, and treating FA. We will also discuss similarities and differences between FA guidelines., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)