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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.)

Background: Certain environmental allergen exposures are more common in disadvantaged communities and may contribute to differences in susceptibility to upper respiratory infections (URIs)., Objectives: We examined associations between indoor allergens and: (1) URI; (2) URI + cold symptoms; (3) URI + cold symptoms + pulmonary eosinophilic inflammation (fraction of exhaled nitric oxide ≥20 ppb); and (4) URI + cold symptoms + reduced lung function (percent predicted forced expiratory volume in 1 second of <80%)., Methods: We used data from the Environmental Control as Add-on Therapy for Childhood Asthma (ECATCh) study. Allergen concentrations were measured in air (mouse) and settled dust (mouse, cockroach, dog, and cat). URI was determined by testing nasal mucus for upper respiratory viruses. We evaluated associations between allergen concentrations and URI-associated outcomes accounting for age, sex, study month, season, health insurance, and household size., Results: Ninety participants (92% Black, 92% public insurance) with 192 observations were included; 52 (27%) of observations were positive for URI. A doubling in cockroach allergen concentration increased the odds of a URI with cold symptoms by 18% (odds ratio [OR] = 1.18, 95% confidence interval [CI], 0.99-1.40), the odds of a URI + cold symptoms + pulmonary eosinophilic inflammation by 31% (OR = 1.31, 95% CI, 1.10-1.57), and the odds of a URI + cold symptoms + reduced lung function by 45% (OR = 1.45, 95% CI, 1.13-1.85). Mouse allergen concentrations were positively associated with all outcomes. Associations were suggestively stronger among children sensitized to pest allergens., Conclusions: Cockroach and mouse, but not dog or cat, allergen exposure may predispose children with asthma to URIs with colds and lower respiratory outcomes., Competing Interests: Disclosure statement Supported by core funds of the Dell Medical School at the University of Texas at Austin (to D.B. and P.J.R.) and the US Environmental Protection Agency (assistance agreement 83615201 to M.C.M.). Research was also supported by the National Institutes of Health (NIH) (grants K24AI114769, R01ES023447, and R01ES026170 to E.C.M., grant P50ES018176 to M.C.M., grant U01AI125290 to C.A.K., grant K01OD019918 to M.F.D., and grant KL2 TR002646 to D.B.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Previous studies have linked prenatal acetaminophen use to increased asthma risk in children. However, none have explored this association while differentiating between asthma cases with and without other allergic conditions or by employing objective biomarkers to assess acetaminophen exposure., Objective: To evaluate whether the detection of acetaminophen biomarkers in cord blood is associated with the subgroups of asthma both with and without allergic comorbidities in children., Methods: Acetaminophen biomarkers, including unchanged acetaminophen and acetaminophen glucuronide, were measured in neonatal cord blood samples from the Boston Birth Cohort. Asthma subgroups were defined on the basis of physician diagnoses of asthma and other allergic conditions (atopic dermatitis and allergic rhinitis). Multinomial regressions were used to evaluate the associations between acetaminophen biomarkers and asthma subgroups, adjusting for multiple confounders, including potential indications for maternal acetaminophen use such as maternal fever., Results: The study included 142 children with asthma and at least 1 other allergic condition, 55 children with asthma but no other allergic condition, and 613 children free of asthma. Detection of acetaminophen in cord blood, reflecting maternal exposure to acetaminophen shortly before delivery, was associated with 3.73 times the odds of developing asthma without allergic comorbidities (95% CI: 1.79-7.80, P = .0004). In contrast, the detection of acetaminophen in cord blood was not associated with an elevated risk of asthma with allergic comorbidities. Analysis of acetaminophen glucuronide yielded consistent results., Conclusion: In a prospective birth cohort, cord blood acetaminophen biomarkers were associated with an increased risk of childhood asthma without allergic comorbidities, but were not associated with childhood asthma with allergic comorbidities., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

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: Prior studies of peanut sublingual immunotherapy (SLIT) have suggested a potential advantage with younger age at treatment initiation., Objective: We studied the safety and efficacy of SLIT for peanut allergy in 1- to 4-year-old children., Methods: Peanut-allergic 1- to 4-year-old children were randomized to receive 4 mg peanut SLIT versus placebo. Desensitization was assessed by double-blind, placebo-controlled food challenge (DBPCFC) after 36 months of treatment. Participants desensitized to at least 443 mg peanut protein discontinued therapy for 3 months and then underwent DBPCFC to assess for remission. Biomarkers were measured at baseline and longitudinally during treatment., Results: Fifty participants (25 peanut SLIT, 25 placebo) with a median age of 2.4 years were enrolled across 2 sites. The primary end point of desensitization was met with actively treated versus placebo participants having a significantly greater median cumulative tolerated dose (4443 mg vs 143 mg), higher likelihood of passing the month 36 DBPCFC (60% vs 0), and higher likelihood of demonstrating remission (48% vs 0). The highest rate of desensitization and remission was seen in 1- to 2-year-olds, followed by 2- to 3-year-olds and 3- to 4-year-olds. Longitudinal changes in peanut skin prick testing, peanut-specific IgG 4 , and peanut-specific IgG 4 /IgE ratio were seen in peanut SLIT but not placebo participants. Oropharyngeal itching was more commonly reported by peanut SLIT than placebo participants. Skin, gastrointestinal, upper respiratory, lower respiratory, and multisystem adverse events were similar between treatment groups., Conclusion: Peanut SLIT safely induces desensitization and remission in 1- to 4-year-old children, with improved outcomes seen with younger age at initiation., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Studies on the efficacy of peanut sublingual immunotherapy (SLIT) are limited. The durability of desensitization after SLIT has not been well described., Objective: We sought to evaluate the efficacy and safety of 4-mg peanut SLIT and persistence of desensitization after SLIT discontinuation., Methods: Challenge-proven peanut-allergic 1- to 11-year-old children were treated with open-label 4-mg peanut SLIT for 48 months. Desensitization after peanut SLIT was assessed by a 5000-mg double-blind, placebo-controlled food challenge (DBPCFC). A novel randomly assigned avoidance period of 1 to 17 weeks was followed by the DBPCFC. Skin prick test results immunoglobulin levels, basophil activation test results, T H 1, T H 2, and IL-10 cytokines were measured longitudinally. Safety was assessed through patient-reported home diaries., Results: Fifty-four participants were enrolled and 47 (87%) completed peanut SLIT and the 48-month DBPCFC per protocol. The mean successfully consumed dose (SCD) during the DBPCFC increased from 48 to 2723 mg of peanut protein after SLIT (P < .0001), with 70% achieving clinically significant desensitization (SCD > 800 mg) and 36% achieving full desensitization (SCD = 5000 mg). Modeled median time to loss of clinically significant desensitization was 22 weeks. Peanut skin prick test; peanut-specific IgE, IgG4, and IgG4/IgE ratio; and peanut-stimulated basophil activation test, IL-4, IL-5, IL-13, IFN-γ, and IL-10 changed significantly compared with baseline, with changes seen as early as 6 months. Median rate of reaction per dose was 0.5%, with transient oropharyngeal itching being the most common, and there were no dosing symptoms requiring epinephrine., Conclusions: In this open-label, prospective study, peanut SLIT was safe and induced clinically significant desensitization in most of the children, lasting more than 17 weeks after discontinuation of therapy., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Importance: Structural racism has been implicated in the disproportionally high asthma morbidity experienced by children living in disadvantaged, urban neighborhoods. Current approaches designed to reduce asthma triggers have modest impact., Objective: To examine whether participation in a housing mobility program that provided housing vouchers and assistance moving to low-poverty neighborhoods was associated with reduced asthma morbidity among children and to explore potential mediating factors., Design, Setting, and Participants: Cohort study of 123 children aged 5 to 17 years with persistent asthma whose families participated in the Baltimore Regional Housing Partnership housing mobility program from 2016 to 2020. Children were matched to 115 children enrolled in the Urban Environment and Childhood Asthma (URECA) birth cohort using propensity scores., Exposure: Moving to a low-poverty neighborhood., Main Outcomes: Caregiver-reported asthma exacerbations and symptoms., Results: Among 123 children enrolled in the program, median age was 8.4 years, 58 (47.2%) were female, and 120 (97.6%) were Black. Prior to moving, 89 of 110 children (81%) lived in a high-poverty census tract (>20% of families below the poverty line); after moving, only 1 of 106 children with after-move data (0.9%) lived in a high-poverty tract. Among this cohort, 15.1% (SD, 35.8) had at least 1 exacerbation per 3-month period prior to moving vs 8.5% (SD, 28.0) after moving, an adjusted difference of -6.8 percentage points (95% CI, -11.9% to -1.7%; P = .009). Maximum symptom days in the past 2 weeks were 5.1 (SD, 5.0) before moving and 2.7 (SD, 3.8) after moving, an adjusted difference of -2.37 days (95% CI, -3.14 to -1.59; P < .001). Results remained significant in propensity score-matched analyses with URECA data. Measures of stress, including social cohesion, neighborhood safety, and urban stress, all improved with moving and were estimated to mediate between 29% and 35% of the association between moving and asthma exacerbations., Conclusions and Relevance: Children with asthma whose families participated in a program that helped them move into low-poverty neighborhoods experienced significant improvements in asthma symptom days and exacerbations. This study adds to the limited evidence suggesting that programs to counter housing discrimination can reduce childhood asthma morbidity.

Background: Per- and polyfluoroalkyl substances (PFAS) are a class of chemicals widely used in manufacturing and are highly resistant to degradation, so they accumulate in the environment. Serum concentrations of these so-called forever chemicals have been associated with impairment of innate and adaptive immune responses. The relationship between serum PFAS levels and asthma morbidity has not been studied., Objective: We tested the association between serum PFAS concentration and asthma exacerbations., Methods: We performed secondary analysis of data from the National Health and Nutrition Examination Survey (NHANES, 2003-18). We fit multivariable logistic regression models to estimate odds ratios and 95% CIs for asthma exacerbation in the prior 12 months, given serum concentrations of PFAS. Models were adjusted for relevant covariates., Results: Of 1101 participants with self-reported current asthma and available serum PFAS data, we observed that higher serum perfluorooctanoic and perfluorodecanoic acids were associated with greater odds of asthma attacks in the previous 12 months (respectively, adjusted odds ratio 1.16, 95% CI 1.01, 1.33; and adjusted odds ratio 1.21, 95% CI 1.03, 1.43). After stratification by age, the association between perfluorooctanoic acid and asthma attacks was significant in the 12-18-year-old group only (adjusted odds ratio 1.56, 95% CI 1.06, 2.31). No significant relationships were observed between PFAS and asthma-related emergency department visits. After correction for multiple comparison testing, none of the associations reached the threshold of significance., Conclusion: The role of these bioaccumulative forever chemicals in susceptibility to asthma attacks warrants further examination in longitudinal studies. (J Allergy Clin Immunol Global 2023;2:100078.)., Competing Interests: Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest.

Background: Multiple mAbs are currently approved for the treatment of asthma. However, there is limited evidence on their comparative effectiveness., Objective: Our aim was to compare the effectiveness of omalizumab, mepolizumab, and dupilumab in individuals with moderate-to-severe asthma., Methods: We emulated a hypothetical randomized trial using electronic health records from a large US-based academic health care system. Participants aged 18 years or older with baseline IgE levels between 30 and 700 IU/mL and peripheral eosinophil counts of at least 150 cells/μL were eligible for study inclusion. The study period extended from March 2016 to August 2021. Outcomes included the incidence of asthma-related exacerbations and change in baseline FEV 1 value over 12 months of follow-up., Results: In all, 68 individuals receiving dupilumab, 68 receiving omalizumab, and 65 receiving mepolizumab met the inclusion criteria. Over 12 months of follow-up, 31 exacerbations occurred over 68 person years (0.46 exacerbations per person year) in the dupilumab group, 63 over 68 person years (0.93 per person year) in the omalizumab group, and 86 over 65 person years (1.32 per person year) in the mepolizumab group (adjusted incidence rate ratios: dupilumab vs mepolizumab, 0.28 [95% CI = 0.09-0.84]; dupilumab vs omalizumab, 0.36 [95% CI = 0.12-1.09]; and omalizumab vs mepolizumab, 0.78 [95% CI = 0.32-1.91]). The differences in the change in FEV 1 comparing patients who received the different biologics were as follows: 0.11 L (95% CI = -0.003 to 0.222 L) for dupilumab versus mepolizumab, 0.082 L (95% CI -0.040 to 0.204 L) for dupilumab versus omalizumab, and 0.026 L (95% CI -0.083 to 0.140 L) for omalizumab versus mepolizumab., Conclusions: Among patients with asthma and eosinophil counts of at least 150 cells/μL and IgE levels of 30 to 700 kU/L, dupilumab was associated with greater improvements in exacerbation and FEV 1 value than omalizumab and mepolizumab., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Air trapping is an obstructive phenotype that has been associated with more severe and unstable asthma in children. Air trapping has been defined using pre- and postbronchodilator spirometry. The causes of air trapping are not completely understood. It is possible that environmental exposures could be implicated in air trapping in children with asthma., Objective: We investigated the association between indoor exposures and air trapping in urban children with asthma., Methods: Children with asthma aged 5 to 17 years living in Baltimore and enrolled onto the Environmental Control as Add-on Therapy for Childhood Asthma study were evaluated for air trapping using spirometry. Aeroallergen sensitization was assessed at baseline, and spirometry was performed at 0, 3, and 6 months. Air trapping was defined as an FVC z score of less than -1.64 or a change in FVC with bronchodilation of ≥10% predicted. Logistic normal random effects models were used to evaluate associations of air trapping and indoor exposures., Results: Airborne and bedroom floor mouse allergen concentrations were associated with air trapping but not airflow limitation (odds ratio 1.19, 95% confidence interval 1.02-1.37, P = .02 per 2-fold increase in airborne mouse allergen; odds ratio 1.23, 95% confidence interval 1.07-1.41, P = .003 per 2-fold increase in bedroom floor mouse allergen). Other indoor exposures (cockroach, cat, dog, dust mite, particulate matter, and nicotine) were not associated with air trapping or airflow limitation., Conclusion: Mouse allergen exposure, but not other indoor exposure, was associated with air trapping in urban children with asthma., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Objective: To determine if the addition of home environmental control strategies (ECSs) to controller medication titration reduces asthma controller medication requirements and in-home allergen concentrations among children with persistent asthma in Baltimore City., Methods: 155 children ages 5-17 with allergen-sensitized asthma were enrolled in a 6-month randomized clinical trial of multifaceted, individually-tailored ECS plus asthma controller medication titration compared to controller medication titration alone. Participants had to meet criteria for persistent asthma and have had an exacerbation in the previous 18 months. Allergen sensitization (mouse, cockroach, cat, dog, dust mite) was assessed at baseline and home dust allergen concentrations were measured at baseline, 3 and 6 months. ECS was delivered 3-4 times over the trial. Asthma controller medication was titrated using a guidelines-based algorithm at baseline, 2, 4, and 6 months. The primary outcome was controller medication treatment step at 6 months (0-6, as-needed albuterol to high-dose ICS + LABA)., Results: The population was predominately Black (90%), on public insurance (93%), and male (61%). The mean age was 10.1 years (SD 3.3). More than 70% were sensitized to a rodent, >50% to cockroach, and 70% were polysensitized. At 6 months, there were no differences in either treatment step (3.8 [SD 1.4] vs. 3.7 [SD 1.5]) or allergen concentrations between groups., Conclusion: Among this predominantly low-income, Black pediatric asthma population, the addition of ECS to controller medication titration reduced neither indoor allergen concentrations nor controller medication requirements compared to controller medication titration alone.

Objective: To inform readers of the current and forthcoming skin barrier interventions that have clinically relevant implications in the prevention of allergic sensitization and atopic diseases., Data Sources: Peer-reviewed journal articles indexed on PubMed and clinical trials referenced on clinicaltrials.gov were analyzed., Study Selections: Literature searches from PubMed and clinicaltrials.gov were performed using combinations of the following search terms: prevention, allergy, atopy, skin, cutaneous, microbiome, microbiota, Staphylococcus aureus, atopic dermatitis, eczema, food allergy, and asthma., Results: The skin barrier represents an entry point for allergic sensitization and T H 2-mediated allergic disorders. Results from clinical trials designed to improve microbiome complexity and reduce S aureus colonization, provide skin barrier enhancement, and deliver epicutaneous immunotherapy are summarized and discussed in the context of primary, secondary, and tertiary prevention of allergic disease., Conclusion: The skin barrier is a promising target for prevention of allergic disease, though clinical trial results thus far have been mixed, at best., (Copyright © 2022. Published by Elsevier Inc.)

Research into food allergy continues to rapidly evolve, accompanying and driving real changes in the clinical approach to these diseases. The past year has seen the rollout of the first treatment approved for active management of food allergy, more data on alternative methods of treatment, the continued evolution of strategies for prevention of food allergy, a renewed interest in phenotyping food allergy subtypes, and, importantly, key new insights into the pathophysiology of food allergy. We expect that in the coming years, the therapies that are in preclinical or early clinical evaluation now will make their way to the clinic, finally allowing the possibility of safe and effective treatments for food allergy., (Copyright © 2022. Published by Elsevier Inc.)

Background: Vancomycin, the most common antimicrobial used in US hospitals, can cause diverse adverse reactions, including hypersensitivity reactions (HSRs). Yet, little is known about vancomycin reactions documented in electronic health records., Objective: To describe vancomycin HSR epidemiology from electronic health record allergy data., Methods: This was a cross-sectional study of patients with 1 or more encounter from 2017 to 2019 and an electronic health record vancomycin drug allergy label (DAL) in 2 US health care systems. We determined prevalence and trends of vancomycin DALs and assessed active DALs by HSR phenotype determined from structured (coded) and unstructured (free-text) data using natural language processing. We investigated demographic associations with documentation of vancomycin red man syndrome (RMS)., Results: Among 4,490,618 patients, 14,426 (0.3%) had a vancomycin DAL with 18,761 documented reactions (2,248 [12.0%] free-text). Quarterly mean vancomycin DALs added were 253 ± 12 and deleted were 12 ± 2. Of 18,761 vancomycin HSRs, 7,903 (42.1%) were immediate phenotypes and 3,881 (20.7%) were delayed phenotypes. Common HSRs were rash (32% of HSRs) and RMS (16% of HSRs). Anaphylaxis was coded in 6% cases of HSRs. Drug reaction eosinophilia and systemic symptoms syndrome was the most common coded vancomycin severe cutaneous adverse reaction. RMS documentation was more likely for males (odds ratio, 1.30; 95% CI, 1.17-1.44) and less likely for blacks (odds ratio, 0.59; 95% CI, 0.47-0.75)., Conclusions: Vancomycin causes diverse adverse reactions, including common (eg, RMS) and severe (eg, drug reaction eosinophilia and systemic symptoms syndrome) reactions entered as DAL free-text. Anaphylaxis comprised 6% of documented vancomycin HSRs, although true vancomycin IgE-mediated reactions are exceedingly rare. Improving vancomycin DAL documentation requires more coded entry options, including a coded entry for RMS., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Traditional measures of socioeconomic status (SES) are associated with asthma morbidity, but their specific contributions are unclear. Increased exposure to indoor allergens among low SES children is an important consideration. Material hardship, a concept describing poor access to basic goods and services, may explain the relationship between low SES and indoor allergen exposure, and thereby, the increased risk of asthma morbidity. We sought to (i) describe the specific hardships experienced by low-Income, urban, minority children with asthma and indoor allergen sensitization and (ii) determine if material hardship is associated with indoor allergen exposure in this population. We conducted a cross-sectional analysis of children undergoing the baseline assessment for a clinical trial of home environmental modification. Participants were scored in five domains of material hardship. Domain scores were assigned based on caregiver responses to a questionnaire and were summed to generate a total material hardship score. Linear regression was used to examine the relationship between material hardship scores and bedroom floor concentrations of five common indoor allergens. Participants experienced high levels of material hardship in each of the five domains, with 33% not having access to a car, 35% not being able to pay utility bills, and 28% not being able to pay rent in the past year. Each one-point increase in material hardship was associated with an increase in cockroach allergen of 16.2% (95% CI 9.4%, 24.6%) and an increase in mouse allergen of 9.4% (95% CI 1.0%, 18.5%). After adjusting for traditional measures of SES, including household income, health insurance type, caregiver education, and caregiver employment status, the association between material hardship and cockroach allergen, but not mouse allergen, remained. These data suggest that a significant proportion of families of low-income, minority children with asthma may experience material hardship, and that they may be at greater risk of cockroach allergen exposure than their peers with similar income, but without material hardship.

Background: Studies on the association between folate/folic acid exposure and the development of allergic disease have yielded inconsistent results, which may be due, in part, to lack of data distinguishing folate from folic acid exposure., Objective: To examine the association between total folate, 5-methyltetrahydrofolate (5-MTHF), and unmetabolized folic acid (UMFA) concentrations at birth and in early childhood and the development of food sensitization (FS) and food allergy (FA)., Methods: A nested case control study was performed in the Boston Birth Cohort (BBC). Total folate, 5-MTHF, and UMFA were measured at birth and in early childhood. Based on food-specific IgE (sIgE) levels, diet, and clinical history, children were classified as FS (sIgE ≥0.35 kU/L), FA, or non-FS/FA (controls). Folate concentrations were divided into quartiles, and multiple logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs)., Results: Of a total of 1394 children, 507 children with FS and 78 with FA were identified. Although mean total folate concentrations at birth were lower among those who developed FA (30.2 vs 35.3 nmol/L; P = .02), mean concentrations of the synthetic folic acid derivative, UMFA, were higher (1.7 vs 1.3 nmol/L, P = .001). Higher quartiles of UMFA at birth were associated more strongly with FA (OR 8.50; 95% CI 1.7-42.8; test for trend P = .001). Neither early childhood concentrations of 5-MTHF nor UMFA were associated with the development of FS or FA., Conclusion: Among children in the BBC, higher concentrations of UMFA at birth were associated with the development of FA, which may be due to increased exposure to synthetic folic acid in utero or underlying genetic differences in synthetic folic acid metabolism., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Rationale: Diabetes and metabolic syndrome have been associated with worsened asthma control. Metformin improves insulin resistance and metabolic function. Experimental studies suggest that metformin may improve pathologic features of asthma, but evidence of clinical benefit is limited. Objectives: To determine if treatment with metformin in a cohort of individuals with asthma and diabetes is associated with lower risk of asthma exacerbation. Methods: A 6-year retrospective cohort of individuals over age 18 with asthma and diabetes was assembled from a national administrative claims database. New users of metformin were matched to nonusers by propensity score on the basis of demographic, comorbidity, and medication-use characteristics. An exacerbation was defined as an asthma-related hospitalization, emergency department visit, or filling of a systemic corticosteroid prescription within 14 days of an asthma-related ambulatory visit. Cox proportional hazards estimated the change in hazard of asthma exacerbation associated with metformin initiation. Results: In a cohort of 23,920 individuals with asthma and diabetes, metformin initiation was associated with lower hazard of asthma exacerbation (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.86-0.98), driven by lower hazards of asthma-related emergency department visits (HR, 0.81; 95% CI, 0.74-0.88) and hospitalization (HR, 0.67; 95% CI, 0.50-0.91), without differences in corticosteroid use (HR, 0.96; 95% CI, 0.86-1.03). Conclusions: In an administrative cohort of individuals with asthma and diabetes, metformin initiation was associated with a lower hazard of asthma-related emergency department visits and hospitalizations. These findings suggest a possible benefit of metformin in more severe asthma exacerbations. Investigation within cohorts with more detailed participant characterization is necessary.

Background: The prevalence of IgE-mediated food allergy (FA) is increasing worldwide, but the underlying mechanisms are poorly understood., Objective: We sought to examine the role of maternal lipidomic profiles in risk of FA development in offspring and to investigate the potential modification effects by timing of first solid-food introduction., Methods: This report included 1068 mother-child dyads from the Boston Birth Cohort. Maternal lipid metabolites in plasma were assessed by using liquid chromatography tandem mass spectrometry. Food sensitization (FS) was defined as a specific IgE level of 0.35 kU/L or greater to any of the 8 common food allergens determined by using ImmunoCAP. FA was defined based on FS, clinical symptoms, and food avoidance. Logistic regression was applied to analyze associations between maternal metabolites and risk of FS and FA in offspring and to explore potential effect modifications., Results: Of the 1068 children, 411 had FS, and 132 had FA. Among the 209 metabolites, maternal triacylglycerols (TAGs) of shorter carbon chains and fewer double bonds were associated with greater risk of FA, whereas TAGs of longer carbon chains and more double bonds were significantly associated with lower risk of FA in offspring. These associations were stronger in children with delayed solid-food introduction (≥7 months of age) than those with earlier solid-food introduction (P = .010 for interaction between the maternal TAG score and timing of solid-food introduction). No significant association was found for FS., Conclusion: This is the first study to demonstrate a link between maternal TAGs and risk of FA in offspring and potential risk modification by timing of solid-food introduction., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Background: Metabolic dysfunction may contribute to worsened asthma in obesity. The relationship between prediabetes and diabetes, metabolic conditions more common in obesity, and asthma outcomes is not well characterized., Objective: We sought to determine the association between prediabetes/diabetes and asthma exacerbations in an obese asthma cohort., Methods: A retrospective cohort of US obese adults with asthma, aged 18-64, was created from a claims-based health services database spanning 2010 to 2015. Individuals with a hemoglobin A1c (HbA1c) measurement were identified, categorized as within normal (<5.6%), prediabetes (5.7% to 6.4%), and diabetes (≥6.5%) ranges. Exacerbations, defined as asthma-related hospitalization, emergency department visit, or corticosteroid prescription ±14 days of an asthma-related outpatient visit, were ascertained. Associations were fit with zero-inflated negative binomial models, adjusted for age, sex, region, smoking, medication use, and comorbidities., Results: A total of 5722 individuals were identified. Higher HgbA1c was associated with higher asthma exacerbation rates. In the fully adjusted model, compared with individuals with normal HbA1c, those in the prediabetes range had a 27% higher rate (95% confidence interval [CI], 5% to 52%), and those in the diabetes range had a 33% higher rate (95% CI, 2% to 73%)., Conclusions: Prediabetes and diabetes were associated with higher rates of asthma exacerbation among obese adults with asthma. Results support evidence that insulin resistance and metabolic syndrome, metabolic features common in prediabetes/diabetes, can influence asthma morbidity., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Rationale: In developing countries, poor and rural areas have a high burden of chronic obstructive pulmonary disease (COPD), and environmental pollutants and indoor burning of biomass have been implicated as potential causal exposures. Less is known about the prevalence of COPD in the United States with respect to urban-rural distribution, poverty, and factors that uniquely contribute to COPD among never-smokers., Objectives: To understand the impact of urban-rural status, poverty, and other community factors on COPD prevalence nationwide and among never-smokers., Methods: We studied a nationally representative sample of adults in the National Health Interview Survey 2012-2015, with data linkage between neighborhood data from the U.S. Census's American Community Survey and the National Center for Health Statistics Urban-Rural Classification Scheme. The main outcome was COPD prevalence., Measurements and Main Results: The prevalence of COPD in poor, rural areas was almost twice that in the overall population (15.4% vs. 8.4%). In adjusted models, rural residence (odds ratio [OR], 1.23; P < 0.001) and census-level poverty (OR, 1.12; P = 0.012) were both associated with COPD prevalence, as were indicators of household wealth. Among never-smokers, rural residence was also associated with COPD (OR, 1.34; P < 0.001), as was neighborhood use of coal for heating (OR, 1.09; P < 0.001)., Conclusions: In a nationally representative sample, rural residence and poverty were risk factors for COPD, even among never-smokers. The use of coal for heating was also a risk factor for COPD among never-smokers. Future disparities research to elucidate contributors to COPD development in poor and rural areas, including assessments of heating sources and environmental pollutants, is needed.

Peanut allergy affects 1% to 3% of the Western world, usually begins in early childhood, is rarely outgrown, and has no currently approved treatment. The identification and application of prevention strategies is therefore essential. In 2015, the Learning Early About Peanuts study findings found that early consumption of peanut protein was effective in preventing peanut allergy in high-risk children as compared with peanut avoidance. These findings resulted in changes to allergy prevention guidelines and policy across the world. There are country-specific variations to guidelines, but, within these variations, feeding peanut to children in infancy is a common theme. There are numerous logistical challenges surrounding the implementation of contemporary guidelines at a population level. In the United States, guidelines advise according to risk level with prescreening recommended for high-risk children (mod/severe eczema, egg allergy). Even though high-risk children represent the minority of the childhood population, there are still significant challenges associated with identifying and screening such infants. The need for conducting allergy testing before first giving peanut protein to high-risk infants is debated; although adopting this approach promotes safety, it is financially and logistically challenging. Clinical trials that explore the real-life application of these guidelines are needed as is an assessment of guidelines (Australia, for example) that do not adopt the approach of screening., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

This review highlights research and policy advances in food allergy that were published in 2017 in the Journal and beyond. In 2017, many important studies on the treatment of food allergy were published, bringing us ever closer to a standardized treatment for food allergy. Other important advancements included research into other management strategies, including thresholds for avoidance, management of food allergies in schools, and development of new guidelines for prevention of food allergy. There were several important epidemiologic studies helping us understand the phenotypes of allergic disease, and new hypotheses were proposed for how best to prevent food allergy. Finally, there was a welcome increased attention to non-IgE-mediated food allergies., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Clinical trials of baked milk (BM) introduction have demonstrated accelerated resolution of milk allergy., Objective: Long-term data regarding real-world introduction of BM are lacking. We sought to characterize our experience of BM introduction., Methods: We performed a retrospective chart review of consecutive BM oral food challenges performed in our clinic from 2009 to 2014, with a minimum follow-up of 24 months., Results: Of the 206 patients challenged, 99 (48%) passed and 187 were sent home with detailed instructions to incorporate BM into their diets. After a median of 49 months of follow-up, 43% of the 187 had progressed to direct milk, 20% to less-cooked forms of milk, 10% remained ingesting BM, and 28% were strictly avoiding milk. Higher milk IgE levels were associated with decreased odds of passing a BM challenge and advancing to less-cooked forms of milk. Predictors of progressing to less-cooked forms of milk were passing the challenge and younger age. There were 79 reported milk reactions involving 68 patients (33% of total) during follow-up. Of these, 78% were classified as mild, 14% severe, and 6 patients developed eosinophilic esophagitis. Of 11 severe reactions, 4 were accidental exposures, 3 were planned escalations, and 4 occurred with previously tolerated doses., Conclusions: The majority of patients who underwent a BM challenge, including those who failed their challenge, were able to progress to direct or less-cooked forms of milk. However, adverse reactions were common, and even a successful BM challenge does not guarantee future tolerance of BM or preclude later reactions, even to previously tolerated doses., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Rationale: Short- and long-term fine particulate matter (particulate matter ≤2.5 μm in aerodynamic diameter [PM 2.5 ]) pollution is associated with asthma development and morbidity, but there are few data on the effects of long-term exposure to coarse PM (PM 10-2.5 ) on respiratory health., Objectives: To understand the relationship between long-term fine and coarse PM exposure and asthma prevalence and morbidity among children., Methods: A semiparametric regression model that incorporated PM 2.5 and PM 10 monitor data and geographic characteristics was developed to predict 2-year average PM 2.5 and PM 10-2.5 exposure during the period 2009 to 2010 at the zip-code tabulation area level. Data from 7,810,025 children aged 5 to 20 years enrolled in Medicaid from 2009 to 2010 were used in a log-linear regression model with predicted PM levels to estimate the association between PM exposure and asthma prevalence and morbidity, adjusting for race/ethnicity, sex, age, area-level urbanicity, poverty, education, and unmeasured spatial confounding., Measurements and Main Results: Exposure to coarse PM was associated with increased asthma diagnosis prevalence (rate ratio [RR] for 1-μg/m 3 increase in coarse PM level, 1.006; 95% confidence interval [CI], 1.001-1.011), hospitalizations (RR, 1.023; 95% CI, 1.003-1.042), and emergency department visits (RR, 1.017; 95% CI, 1.001-1.033) when adjusting for fine PM. Fine PM exposure was more strongly associated with increased asthma prevalence and morbidity than coarse PM. The estimates remained elevated across different levels of spatial confounding adjustment., Conclusions: Among children enrolled in Medicaid, exposure to higher average coarse PM levels is associated with increased asthma prevalence and morbidity. These results suggest the need for direct monitoring of coarse PM and reconsideration of limits on long-term average coarse PM pollution levels.

Although there is no FDA approved therapy for food allergy, over the past decades, several routes of immunotherapy have been investigated for food allergy. Thus far, these therapies have shown variable levels of efficacy at desensitizing to foods, with oral immunotherapy (OIT) far more successful than sublingual immunotherapy (SLIT) or epicutaneous immunotherapy (EPIT). However, desensitization tends to be temporary, and safety remains a major concern with OIT. Moreover, although it seems logical that desensitization will result in fewer reactions, it is not clear whether OIT or other immunotherapies are associated with an overall lower or higher risk of reactions over the long term. Eosinophilic esophagitis is a known complication of OIT, and may also be a risk with SLIT and possibly EPIT, although it has not been reported in the relatively few patients treated thus far. Adjuvants such as omalizumab or probiotics may improve the safety and/or efficacy of immunotherapy for food allergy, but more research is needed. In the future, biomarkers may identify subsets of patients who are better candidates for specific treatments. As therapies become commercially available, patients and providers will need to consider whether the benefits justify the risks and burdens of these treatments., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Understanding the epidemiology of food allergy is complicated by the difficulty of identifying it on a large scale. The prevalence of food allergy is higher in younger age groups and decreases with age. Allergy to peanut and egg seems to be more common in Northern Europe, the United States, Canada and Australia compared with Southern Europe, Eastern Europe and Asia, whereas shellfish and fish allergies may be more common in Asia. The rate of transient unrecognized food allergy may be high and variable recognition of food allergy may explain some of the differences seen in food allergy prevalence., (Copyright © 2017 Elsevier Inc. All rights reserved.)