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Background: Cow's milk allergy is the most common food allergy in young children. In areas outside the United States, milk from other mammals has been studied as a possible and desirable alternative for children with cow's milk allergy. Objectives: We chose to further investigate water buffalo's milk as an alternative for cow's milk allergic children in the United States. Methods: Children with cow's milk allergy were skin prick tested with water buffalo's milk. Additionally, subjects were followed clinically for 1 year after the test to determine how many of the subjects had persistent cow's milk allergy. Results: In total, 30 children, age 8 months to 8 years, were skin prick tested to water buffalo's milk with 73% (22/30) having a positive test. All children with a negative water buffalo's milk skin test also had a negative cow's milk skin test. In follow-up, most (7 of 8) of the children with a negative skin prick test (SPT) to water buffalo's milk were found to have outgrown their cow's milk allergy. In comparison, all of the subjects with a positive skin test to water buffalo's milk had persistent cow's milk allergy. After adjusting for this, we determined that 96% (22/23) of the children with persistent cow's milk allergy were positive on skin testing to water buffalo's milk. Conclusions: In this population, the vast majority of children with persistent cow's milk allergy were positive on skin prick testing to water buffalo's milk. These results indicate that water buffalo's milk is unlikely to be a successful alternative for children with cow's milk allergy. [ABSTRACT FROM AUTHOR]

This review highlights studies from the past 3 years that add to the understanding of the impact of environmental exposures on allergic disease. These include aeroallergens, air quality, prenatal or early life exposures, and occupational exposures. Recent studies focused on the relationship between the environment, the microbiome, and allergic disease as well as new therapeutic options are also reviewed. Lastly, there has been significant recent research that improves our knowledge of the link between health disparities and environmental exposures. These scientific advances have resulted in a better understanding that sets the foundation for current and future research dedicated to improving health outcomes by modifying environmental exposures., (Copyright © 2024. Published by Elsevier Inc.)

Objective: No studies have examined school-nurse visits related to mental health (MH) during the coronavirus disease 2019 (COVID-19) pandemic. We examined changes in the rate of MH-related school-nurse visits before and during the COVID-19 pandemic., Methods: We analyzed school-nurse visit data (n = 3,445,240) for subjects Grade K-12 in US public schools using electronic health record software (SchoolCare, Ramsey, NJ). Data between January 1 and December 31 in 2019 (pre-COVID-19 pandemic) versus January 1 to December 31 in 2020 (during COVID-19 pandemic) were compared. For each year, total visits to a school-nurse were calculated for general MH, anxiety, and self-harm. The exposure was number of school-nurse visits in each time period (2019 vs 2020). The main outcome was change in the rate of general MH, anxiety, and self-harm visits in 2019 versus 2020., Results: There were 2,302,239 total school-nurse visits in 2019 versus 1,143,001 in 2020. During the COVID-19 pandemic, the rate of visits for general MH increased by 30% (4.7-6.1 per 10,000 visits, 95% confidence interval [CI] {18%, 43%}; P < .001), and visits for anxiety increased by 25% (24.8-31 per 10,000 visits, 95% CI [20%,30%]; P < .001). There was no significant difference in self-harm visits across all ages during the COVID-19 pandemic., Conclusions: Our study found a significant increase in the rate of school-nurse visits for MH and anxiety during the COVID-19 pandemic, suggesting the pediatric population is at-risk for increased negative MH-effects associated with the pandemic and highlights a critical role of school-nurses in identifying youth with potential MH-needs., (Copyright © 2022 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Objective: The School Inner-City Asthma Intervention Study 2 (SICAS 2) tested interventions to reduce exposures in classrooms of students with asthma. The objective of this post-hoc analysis was limited to evaluating the effect of high-efficiency particulate (HEPA) filtration interventions on mold levels as quantified using the Environmental Relative Moldiness Index (ERMI) and the possible improvement in the students' asthma, as quantified by spirometry testing., Methods: Pre-intervention dust samples were collected at the beginning of the school year from classrooms and corresponding homes of students with asthma ( n  = 150). Follow-up dust samples were collected in the classrooms at the end of the HEPA or Sham intervention. For each dust sample, ERMI values and the Group 1 and Group 2 mold levels (components of the ERMI metric) were quantified. In addition, each student's lung function was evaluated by spirometry testing, specifically the percentage predicted forced expiratory volume at 1 sec (FEV1%), before and at the end of the intervention., Results: For those students with a higher Group 1 mold level in their pre-intervention classroom than home ( n  = 94), the FEV1% results for those students was significantly ( p  < 0.05) inversely correlated with the Group 1 level in their classrooms. After the HEPA intervention, the average Group 1 and ERMI values were significantly lowered, and the average FEV1% test results significantly increased by an average of 4.22% for students in HEPA compared to Sham classrooms., Conclusions: HEPA intervention in classrooms reduced Group 1 and ERMI values, which corresponded to improvements in the students' FEV1% test results.

Background: Black and Hispanic children living in urban environments in the USA have an excess burden of morbidity and mortality from asthma. Therapies directed at the eosinophilic phenotype reduce asthma exacerbations in adults, but few data are available in children and diverse populations. Furthermore, the molecular mechanisms that underlie exacerbations either being prevented by, or persisting despite, immune-based therapies are not well understood. We aimed to determine whether mepolizumab, added to guidelines-based care, reduced the number of asthma exacerbations during a 52-week period compared with guidelines-based care alone., Methods: This is a randomised, double-blind, placebo-controlled, parallel-group trial done at nine urban medical centres in the USA. Children and adolescents aged 6-17 years, who lived in socioeconomically disadvantaged neighbourhoods and had exacerbation-prone asthma (defined as ≥two exacerbations in the previous year) and blood eosinophils of at least 150 cells per μL were randomly assigned 1:1 to mepolizumab (6-11 years: 40 mg; 12-17 years: 100 mg) or placebo injections once every 4 weeks, plus guideline-based care, for 52 weeks. Randomisation was done using a validated automated system. Participants, investigators, and the research staff who collected outcome measures remained masked to group assignments. The primary outcome was the number of asthma exacerbations that were treated with systemic corticosteroids during 52 weeks in the intention-to-treat population. The mechanisms of treatment response were assessed by study investigators using nasal transcriptomic modular analysis. Safety was assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT03292588., Findings: Between Nov 1, 2017, and Mar 12, 2020, we recruited 585 children and adolescents. We screened 390 individuals, of whom 335 met the inclusion criteria and were enrolled. 290 met the randomisation criteria, were randomly assigned to mepolizumab (n=146) or placebo (n=144), and were included in the intention-to-treat analysis. 248 completed the study. The mean number of asthma exacerbations within the 52-week study period was 0·96 (95% CI 0·78-1·17) with mepolizumab and 1·30 (1·08-1·57) with placebo (rate ratio 0·73; 0·56-0·96; p=0·027). Treatment-emergent adverse events occurred in 42 (29%) of 146 participants in the mepolizumab group versus 16 (11%) of 144 participants in the placebo group. No deaths were attributed to mepolizumab., Interpretation: Phenotype-directed therapy with mepolizumab in urban children with exacerbation-prone eosinophilic asthma reduced the number of exacerbations., Funding: US National Institute of Allergy and Infectious Diseases and GlaxoSmithKline., Competing Interests: Declaration of interests All authors, with the exceptions of PMB, LG, and PJG, report grants from the US National Institutes of Health (NIH)–NIAID during the study. CMV, AC, SW, LG, PJG, and PMB have nothing to disclose outside of the submitted work. LBB reports personal fees from GlaxoSmithKline, Genentech–Novartis, Teva, Boehringer Ingelheim, AstraZeneca, WebMD–Medscape, Merck, DBV Technologies, Circassia, Sanofi–Regeneron, and Vectura, all outside the submitted work. GTO reports personal fees from AstraZeneca and grant funding from Janssen Pharmaceuticals, outside the submitted work. CMD reports personal fees from Horizon Therapeutics and Enzyvant Therapeutics, outside the submitted work. MCA reports personal fees from Sanofi–Regeneron, outside the submitted work. WWB reports personal fees from Boston Scientific, Novartis, GlaxoSmithKline, Genentech, Sanofi–Genzyme, AstraZeneca, Teva, Regeneron, and Elsevier, outside the submitted work. MAG reports an honorarium for and support for travel to the 2017 American Academy of Allergy, Asthma & Immunology meeting during this study and monetary compensation from the American Academy of Pediatrics for her work teaching the biannual Pediatrics board review course: PREP The Course. GKKH reports grants from Adare during the study. DJJ reports personal fees from Novartis, Pfizer, Regeneron, AstraZeneca, Sanofi, and Vifor Pharma; grants and personal fees from GlaxoSmithKline; and grants from NIH–US National Heart, Lung, and Blood Institute (NHLBI), all outside the submitted work. MK reports personal fees from Regeneron, outside the submitted work. RSG reports government employment from the Center for Biologics Evaluation and Research and personal fees from Consulting Massachusetts Medical Society, 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. SJT reports grants from NIH–Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH–NHLBI, and EJF Philanthropies and personal fees from Uptodate, all outside the submitted work. JAP reports provision of study drug for another asthma research study from GlaxoSmithKline and Boehringer Ingelheim and provision of study drug for another asthma research study and for food allergy research studies from Genentech–Novartis, all outside the submitted work. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Atopic dermatitis (AD) and food allergy (FA) may share genetic risk factors. It is unknown whether genetic factors directly cause FA or are mediated through AD, as the dual-allergen hypothesis suggests., Objective: To test the hypothesis that AD mediates the relationship between an IL-4 receptor alpha chain gene (IL4RA) variant, the human IL-4 receptor alpha chain protein-R576 polymorphism, and FA., Methods: A total of 433 children with asthma enrolled in the School Inner-City Asthma Study underwent genotyping for the IL4RA 576 allele. Surveys were administered to determine FA, AD, and associated allergic responses. Mediation analysis was performed adjusting for race and ethnicity, age, sex, and household income. Multivariate models were used to determine the association between genotype and FA severity., Results: AD was reported in 193 (45%) and FA in 80 children (19%). Each risk allele increased odds of AD 1.39-fold ([1.03-1.87], P = .03), and AD increased odds of FA 3.67-fold ([2.05- 6.57], P < .01). There was an indirect effect of genotype, mediated by AD, predicting FA; each risk allele increased the odds of FA by 1.13 (odds ratio [95% CI], Q/R = 1.13 [1.02-1.24], R/R = 1.28 [1.04-1.51]; P < .01). Each risk allele increased the odds of severe FA symptoms 2.68-fold ([1.26-5.71], P = .01)., Conclusions: In a cohort of children with asthma, AD is part of the causal pathway between an IL4RA variant and FA. This variant is associated with increased risk of severe FA reactions. Addressing AD in children with an IL4RA polymorphism may modulate the risk of FA., (Copyright © 2022. Published by Elsevier Inc.)

Background: Little is known about environmental food allergen exposure on school surfaces., Objective: To compare the distribution of major food allergens in floor dust and table wipe samples from elementary schools and dust samples from students' homes., Methods: In this substudy of the School Inner-City Asthma Study-II, 103 table wipe samples and 98 floor dust samples from cafeterias and classrooms in 18 elementary schools were analyzed for milk, peanut, cashew, hazelnut, and egg using a multiplex array. Home kitchen floor and bed dust samples from 90 students were also analyzed., Results: Food allergens were detectable in schools, but at significantly lower levels than in homes (P < .001). In schools, milk and peanut were detected in all table wipe samples; milk and egg were detected in all floor dust samples. Cafeteria table wipe samples contained significantly higher levels of milk, peanut, hazelnut, and egg, compared with classrooms. Cafeteria floor dust samples contained higher levels milk than classrooms. Peanut-restrictive policies did not consistently reduce environmental peanut exposure in schools. Peanut allergen was lower in dust from homes of students with peanut allergy (n = 5) compared with those without peanut allergy (n = 85) (P < .001). Reassuringly, peanut allergen in the schools of peanut-allergic students was not significantly different than in their homes., Conclusion: Food allergens were readily detectable on tables and floors in elementary schools, but at levels lower than in students' homes. For peanut-allergic students, the levels of detectable peanut in their schools were not higher than their homes. The low levels of detectable food allergens in school environments are unlikely to result in severe allergic reactions., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Importance: School and classroom allergens and particles are associated with asthma morbidity, but the benefit of environmental remediation is not known., Objective: To determine whether use of a school-wide integrated pest management (IPM) program or high-efficiency particulate air (HEPA) filter purifiers in the classrooms improve asthma symptoms in students with active asthma., Design, Setting, and Participants: Factorial randomized clinical trial of a school-wide IPM program and HEPA filter purifiers in the classrooms was conducted from 2015 to 2020 (School Inner-City Asthma Intervention Study). There were 236 students with active asthma attending 41 participating urban elementary schools located in the Northeastern US who were randomized to IPM by school and HEPA filter purifiers by classroom. The date of final follow-up was June 20, 2020., Interventions: The school-wide IPM program consisted of application of rodenticide, sealing entry points, trap placement, targeted cleaning, and brief educational handouts for school staff. Infestation was assessed every 3 months, with additional treatments as needed. Control schools received no IPM, cleaning, or education. Classroom portable HEPA filter purifiers were deployed and the filters were changed every 3 months. Control classrooms received sham HEPA filters that looked and sounded like active HEPA filter purifiers. Randomization was done independently (split-plot design), with matching by the number of enrolled students to ensure a nearly exact 1:1 student ratio for each intervention with 118 students randomized to each group. Participants, investigators, and those assessing outcomes were blinded to the interventions., Main Outcomes and Measures: The primary outcome was the number of symptom-days with asthma during a 2-week period. Symptom-days were assessed every 2 months during the 10 months after randomization., Results: Among the 236 students who were randomized (mean age, 8.1 [SD, 2.0] years; 113 [48%] female), all completed the trial. At baseline, the 2-week mean was 2.2 (SD, 3.9) symptom-days with asthma and 98% of the classrooms had detectable levels of mouse allergen. The results were pooled because there was no statistically significant difference between the 2 interventions (P = .18 for interaction). During a 2-week period, the mean was 1.5 symptom-days with asthma after use of the school-wide IPM program vs 1.9 symptom-days after no IPM across the school year (incidence rate ratio, 0.71 [95% CI, 0.38-1.33]), which was not statistically significantly different. During a 2-week period, the mean was 1.6 symptom-days with asthma after use of HEPA filter purifiers in the classrooms vs 1.8 symptom-days after use of sham HEPA filter purifiers across the school year (incidence rate ratio, 1.47 [95% CI, 0.79-2.75]), which was not statistically significantly different. There were no intervention-related adverse events., Conclusions and Relevance: Among children with active asthma, use of a school-wide IPM program or classroom HEPA filter purifiers did not significantly reduce symptom-days with asthma. However, interpretation of the study findings may need to consider allergen levels, particle exposures, and asthma symptoms at baseline., Trial Registration: ClinicalTrials.gov Identifier: NCT02291302.

Background/aims: When conducting clinical trials comparing over-the-counter (OTC) medications, the wide availability of these treatments are a potential challenge to maintaining study integrity. We seek to describe adherence to a study protocol involving widely available OTC medications., Methods: To prospectively evaluate associations between acetaminophen use and asthma in 300 children aged 1-5 years, we conducted a double blind, randomized, controlled trial where parents administered blinded forms of either acetaminophen or ibuprofen as needed to their children over a 48 week period. Written and verbal instructions encouraged the exclusive use of the blinded study medication and discouraged OTC use. Adherence was determined by evaluating the frequency of use of per-protocol blinded study medication compared to off-protocol use of OTC medications., Results: 4195 doses of acetaminophen or ibuprofen were received by children during the study which included 3664 doses (87.3%) of blinded study medication adhering to the protocol and 531 doses (12.7%) of OTC products deviating from the protocol with better adherence among those randomized to ibuprofen as compared to acetaminophen (89.5% vs. 85.5% of doses, p < 0.01). Individually, 227 participants (75.7%) remained fully adherent by not receiving any OTC medications. Pre-study preference for either acetaminophen or ibuprofen by the participants' families was not associated with differential rates of adherence to the blinded medication., Conclusion: This parallel study demonstrated greater than 85% of acetaminophen or ibuprofen doses were blinded study medications adhering to the protocol while less than 15% were OTC deviations from the protocol. This successfully implemented study design provides a template to comparatively evaluate these and other OTC medications., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Asthma is among the most common chronic diseases of children in the United States (US). Mold exposures have been linked to asthma development and exacerbation. In homes, mold exposures have been quantified using the Environmental Relative Moldiness Index (ERMI), and higher home ERMI values have been linked to occupant asthma., Objective: In this analysis of the School Inner-City Asthma Study (SICAS), we aimed to evaluate the ERMI's applicability to measuring mold in schools compared with homes and to examine the prevalence of asthma in relationship to students' demographics and the physical characteristics of school buildings., Methods: Northeastern US schools (n = 32) and homes (n = 33) were selected, and the 36 ERMI molds were quantified in a dust sample from each classroom (n = 114) or home. School building characteristics data were collected from SICAS. Asthma prevalence and student demographics data were obtained from government websites. Linear regression and mixed models were fit to assess the association of the current asthma prevalence and physical characteristics of the school, make-up of the student body, and the ERMI metric., Results: Levels of outdoor group 2 molds were significantly (P < .01) greater in schools compared with homes. The presence of air-conditioning in school buildings correlated significantly (P = .02) with lower asthma prevalence., Conclusion: The prevalence of asthma in student bodies is associated with many factors in schools and homes., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Asthma remains one of the most important challenges to pediatric public health in the US. A large majority of children with persistent and chronic asthma demonstrate aeroallergen sensitization, which remains a pivotal risk factor associated with the development of persistent, progressive asthma throughout life. In individuals with a tendency toward Type 2 inflammation, sensitization and exposure to high concentrations of offending allergens is associated with increased risk for development of, and impairment from, asthma. The cascade of biological responses to allergens is primarily mediated through IgE antibodies and their production is further stimulated by IgE responses to antigen exposure. In addition, circulating IgE impairs innate anti-viral immune responses. The latter effect could magnify the effects of another early life exposure associated with increased risk of the development of asthma - viral infections. Omalizumab binds to circulating IgE and thus ablates antigen signaling through IgE-related mechanisms. Further, it has been shown restore IFN-α response to rhinovirus and to reduce asthma exacerbations during the viral season. We therefore hypothesized that early blockade of IgE and IgE mediated responses with omalizumab would prevent the development and reduce the severity of asthma in those at high risk for developing asthma. Herein, we describe a double-blind, placebo-controlled trial of omalizumab in 2-3 year old children at high risk for development of asthma to prevent the development and reduce the severity of asthma. We describe the rationale, methods, and lessons learned in implementing this potentially transformative trial aimed at prevention of asthma., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Perennial aeroallergen sensitization is associated with greater asthma morbidity and is required for treatment with omalizumab., Objective: To investigate the predictive relationship between the number of aeroallergen sensitizations, total serum IgE, and serum eosinophil count, and response to omalizumab in children and adolescents with asthma treated during the fall season., Methods: This analysis includes inner-city patients with persistent asthma and recent exacerbations aged 6-20 years comprising the placebo- and omalizumab-treated groups in 2 completed randomized clinical trials, the Inner-City Anti-IgE Therapy for Asthma study and the Preventative Omalizumab or Step-Up Therapy for Fall Exacerbations study. Logistic regression modeled the relationship between greater degrees of markers of allergic inflammation and the primary outcome of fall season asthma exacerbations., Results: The analysis included 761 participants who were 62% male and 59% African American with a median age of 10 years. Fall asthma exacerbations were significantly higher in children with greater numbers of aeroallergen-specific sensitizations in the placebo group (odds ratio [OR], 1.33; 95% confidence interval [CI], 1.11-1.60; P < .01), but not in the omalizumab-treated children (OR, 1.08; 95% CI, 0.91-1.28; P = .37), indicating a significant differential effect (P < .01). Likewise, there was a differential effect of omalizumab treatment in children with greater baseline total serum IgE levels (P < .01) or greater baseline serum eosinophil counts (P < .01). Multiple aeroallergen sensitization was the best predictor of response to omalizumab; treated participants sensitized to ≥4 different groups of aeroallergens had a 51% reduction in the odds of a fall exacerbation (OR, 0.49; 95% CI, 0.30-0.81; P < .01)., Conclusions: In preventing fall season asthma exacerbations, treatment with omalizumab was most beneficial in children with a greater degree of allergic inflammation., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Background: Sparse data address the effects of nitrogen dioxide (NO 2 ) exposure in inner-city schools on obese students with asthma., Objective: We sought to evaluate relationships between classroom NO 2 exposure and asthma symptoms and morbidity by body mass index (BMI) category., Methods: The School Inner-City Asthma Study enrolled students aged 4 to 13 years with asthma from 37 inner-city schools. Students had baseline determination of BMI percentile. Asthma symptoms, morbidity, pulmonary inflammation, and lung function were monitored throughout the subsequent academic year. Classroom NO 2 data, linked to enrolled students, were collected twice per year. We determined the relationship between classroom NO 2 levels and asthma outcomes by BMI stratification., Results: A total of 271 predominantly black (35%) or Hispanic students (35%) were included in analyses. Fifty percent were normal weight (5-84th BMI percentile), 15% overweight (≥85-94th BMI percentile), and 35% obese (≥95th BMI percentile). For each 10-parts per billion increase in NO 2 , obese students had a significant increase in the odds of having an asthma symptom day (odds ratio [OR], 1.86; 95% CI, 1.15-3.02) and in days caregiver changed plans (OR, 4.24; 95% CI, 2.33-7.70), which was significantly different than normal weight students who exhibited no relationship between NO 2 exposure and symptom days (OR, 0.90; 95% CI, 0.57-1.42; pairwise interaction P = .03) and change in caregiver plans (OR, 1.37; 95% CI, 0.67-2.82; pairwise interaction P = .02). Relationships between NO 2 levels and lung function and fractional exhaled nitric oxide did not differ by BMI category. If we applied a conservative Holm-Bonferroni correction for 16 comparisons (obese vs normal weight and overweight vs normal weight for 8 outcomes), these findings would not meet statistical significance (all P > .003)., Conclusions: Obese BMI status appears to increase susceptibility to classroom NO 2 exposure effects on asthma symptoms in inner-city children. Environmental interventions targeting indoor school NO 2 levels may improve asthma health for obese children. Although our findings would not remain statistically significant after adjustment for multiple comparisons, the large effect sizes warrant future study of the interaction of obesity and pollution in pediatric asthma., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Traffic proximity has been associated with adverse respiratory health outcomes. Less is known about the combined impact of residential and school exposures on pediatric asthma., Objective: We sought to use spatial analysis methodology to analyze residential and school proximity to major roadways and pediatric asthma morbidity., Methods: The School Inner-City Asthma Study (n = 350) recruited school-aged children with asthma. Each participant's school and home addresses were geocoded, and distances from major roadways were measured to calculate a composite measure accounting for both home and school traffic exposure. Generalized estimating equation models were clustered by subject and adjusted for age, race/ethnicity, sex, income, environmental tobacco smoke, controller medication, upper respiratory tract infections, and seasonality., Results: The majority of participants (62%) attended schools within 100 m from major roadways, and 40% also resided within 100 m of major roadways. In multivariate analyses major roadway proximity was independently associated with increased asthma symptom days. At greater than the threshold of 100 m, children had 29% less odds of a symptom day over the past 2 weeks for each 100-m increase in distance from a major roadway (odds ratio, 0.71; 95% CI, 0.58-0.87; P < .01). Children farther from a major roadway also had significantly less reported health care use (odds ratio, 0.63; 95% CI, 0.47-0.85; P < .01) and were significantly less likely to have poor asthma control (odds ratio, 0.80; 95% CI, 0.69-0.94; P < .01). There was not a meaningful association between distance to a major roadway and lung function outcomes., Conclusions: Proximity to a major roadway, a composite measure of home and school exposure but primarily driven by home exposure, was associated with greater asthma morbidity. More studies are needed to evaluate the independent effect of school distance to a roadway on asthma morbidity., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Objective: To determine research priorities for the management of broken bones of the upper limb in people over 50, which represent the shared priorities of patients, their families, carers and healthcare professionals., Design/setting: A national (UK) research priority setting partnership., Participants: People aged 50 and over who have experienced a fracture of the upper limb, carers involved in their care, family and friends of patients, healthcare professionals involved in the treatment of these patients., Methods: Using a multiphase methodology in partnership with the James Lind Alliance over 15 months (September 2017 to December 2018), a national scoping survey asked respondents to submit their research uncertainties. These were amalgamated into a smaller number of research questions. The existing evidence was searched to ensure that the questions had not already been answered. A second national survey asked respondents to prioritise the research questions. A final shortlist of 25 questions was taken to a multi-stakeholder workshop where a consensus was reached on the top 10 priorities., Results: There were 1898 original uncertainties submitted by 328 respondents to the first survey. These original uncertainties were refined into 51 research questions of which 50 were judged to be true uncertainties following a review of the research evidence. There were 209 respondents to the second (interim prioritisation) survey. The top 10 priorities encompass a broad range of uncertainties in management and rehabilitation of upper limb fractures., Conclusions: The top 10 UK research priorities highlight uncertainties in how we assess outcomes, provide information, achieve pain control, rationalise surgical intervention, optimise rehabilitation and provide psychological support. The breadth of these research areas highlights the value of this methodology. This work should help to steer research in this area for the next 5-10 years and the challenge for researchers now is to refine and deliver answers to these research priorities., Competing Interests: Competing interests: MLC is a member of the NIHR HTA General Board. ZP is funded by the NIHR (Clinician Scientist Award (CS-2018-18-ST2-010)/NIHR Academy)., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Home fungus exposures may be associated with development or worsening of asthma. Little is known about the effects of school/classroom fungus exposures on asthma morbidity in students., Objective: To evaluate the association of school-based fungus exposures on asthma symptoms in both fungus-sensitized and nonsensitized students with asthma., Methods: In this prospective study, 280 children with asthma from 37 inner-city schools were phenotypically characterized at baseline and followed-up for 1 year. Fungal spores were collected by using a Burkard air sampler twice during the school year. Clinical outcomes were evaluated throughout the school year and linked to classroom-specific airborne spore sampling. The primary outcome was days with asthma symptoms per 2-week period., Results: Fungal spores were present in all classroom samples. The geometric mean of the total fungi was 316.9 spores/m 3 and ranged from 15.0 to 59,345.7 spores/m 3 . There was variability in total fungus quantity between schools and classrooms within the same school. Mitospores were the most commonly detected fungal grouping. Investigation of the individual mitospores revealed that exposure to Alternaria was significantly associated with asthma symptom days in students sensitized to Alternaria (OR = 3.61, CI = 1.34-9.76, P = .01), but not in children not sensitized to Alternaria (OR = 1.04, CI = 0.72-1.49, P = .85). Students sensitized to Alternaria and exposed to high levels (≥75th percentile exposure) had 3.2 more symptom days per 2-week period as compared with students sensitized but exposed to lower levels., Conclusion: Children with asthma who are sensitized to Alternaria and exposed to this fungus in their classroom may have significantly more days with asthma symptoms than those who were sensitized and not exposed., Clinical Trial Registration: Clinicaltrials.govNCT01756391., (Copyright © 2019 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

The inner-city is a well-established and well-studied location that includes children at high risk for high asthma prevalence and morbidity. A number of intrinsic and extrinsic risk factors contribute to asthma in inner-city populations. This review seeks to explore these risk factors and evaluate how they contribute to increased asthma morbidity. Previous literature has identified risk factors such as race and ethnicity, prematurity, obesity, and exposure to aeroallergens and pollutants. Environmental and medical interventions aimed at individual risk factors and specific asthma phenotypes have contributed to improved outcomes in the inner-city children with asthma., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Weather and climate change are constant and ever-changing processes that affect allergy and asthma. The purpose of this report is to provide information since the last climate change review with a focus on asthmatic disease. PubMed and Internet searches for topics included climate and weather change, air pollution, particulates, greenhouse gasses, traffic, insect habitat, and mitigation in addition to references contributed by the individual authors. Changes in patterns of outdoor aeroallergens caused by increasing temperatures and amounts of carbon dioxide in the atmosphere are major factors linked to increased duration of pollen seasons, increased pollen production, and possibly increased allergenicity of pollen. Indoor air pollution threats anticipated from climate changes include microbial and mold growth secondary to flooding, resulting in displacement of persons and need for respiratory protection of exposed workers. Air pollution from indoor burning of mosquito repellants is a potential anticipatory result of an increase in habitat regions. Air pollution from fossil fuel burning and traffic-related emissions can alter respiratory defense mechanisms and work synergistically with specific allergens to enhance immunogenicity to worsen asthma in susceptible subjects. Community efforts can significantly reduce air pollution, thereby reducing greenhouse gas emission and improving air quality. The allergist's approach to weather pattern changes should be integrated and anticipatory to protect at-risk patients., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

For food-allergic individuals, the typical exposure to food proteins happens during ingestion; however, individuals may be exposed to foods in other ways. In addition to ingestion reactions, allergic patients may have reactions from cutaneous or mucosal exposures to food proteins, with the classic example being a peanut-allergic child touching a counter with peanut butter and then rubbing their eyes. Similar to hands, saliva can also act as a carrier for food proteins. Finally, there is a wealth of new research regarding the presence of food proteins in the environment, for example, within household floor dust. This review will focus on (1) cross-contact of food proteins and (2) environmental food protein exposures. Cross-contact occurs when one type of food comes into contact with another type of food resulting in the mixture of proteins. For food allergies, cross-contact is important when an allergen is inadvertently transferred to a food/meal that is thought to not contain that specific allergen. We will discuss the current literature regarding the presence of detectable food proteins in different locations, how and if these proteins are transferred or eliminated, and the clinical implications of exposures to food proteins under these different scenarios., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Ambient and home exposure to nitrogen dioxide (NO 2 ) causes asthma symptoms and decreased lung function in children with asthma. Little is known about the health effects of school classroom pollution exposure., Objective: We aimed to determine the effect of indoor classroom NO 2 on lung function and symptoms in inner-city school children with asthma., Methods: Children enrolled in the School Inner-City Asthma Study were followed for 1 academic year. Subjects performed spirometry and had fraction of exhaled nitric oxide values measured twice during the school year at school. Classroom NO 2 was collected by means of passive sampling for 1-week periods twice per year, coinciding with lung function testing. Generalized estimating equation models assessed lung function and symptom relationships with the temporally nearest classroom NO 2 level., Results: The mean NO 2 value was 11.1 ppb (range, 4.3-29.7 ppb). In total, exposure data were available for 296 subjects, 188 of whom had complete spirometric data. At greater than a threshold of 8 ppb of NO 2 and after adjusting for race and season (spirometry standardized by age, height, and sex), NO 2 levels were associated highly with airflow obstruction, such that each 10-ppb increase in NO 2 level was associated with a 5% decrease in FEV 1 /forced vital capacity ratio (β = -0.05; 95% CI, -0.08 to -0.02; P = .01). Percent predicted forced expiratory flow between the 25th and 75th percentile of forced vital capacity was also inversely associated with higher NO 2 exposure (β = -22.8; 95% CI, -36.0 to -9.7; P = .01). There was no significant association of NO 2 levels with percent predicted FEV 1 , fraction of exhaled nitric oxide, or asthma symptoms. Additionally, there was no effect modification of atopy on lung function or symptom outcomes., Conclusion: In children with asthma, indoor classroom NO 2 levels can be associated with increased airflow obstruction., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Asthma exacerbations occur frequently despite the regular use of asthma-controller therapies, such as inhaled glucocorticoids. Clinicians commonly increase the doses of inhaled glucocorticoids at early signs of loss of asthma control. However, data on the safety and efficacy of this strategy in children are limited., Methods: We studied 254 children, 5 to 11 years of age, who had mild-to-moderate persistent asthma and had had at least one asthma exacerbation treated with systemic glucocorticoids in the previous year. Children were treated for 48 weeks with maintenance low-dose inhaled glucocorticoids (fluticasone propionate at a dose of 44 μg per inhalation, two inhalations twice daily) and were randomly assigned to either continue the same dose (low-dose group) or use a quintupled dose (high-dose group; fluticasone at a dose of 220 μg per inhalation, two inhalations twice daily) for 7 days at the early signs of loss of asthma control ("yellow zone"). Treatment was provided in a double-blind fashion. The primary outcome was the rate of severe asthma exacerbations treated with systemic glucocorticoids., Results: The rate of severe asthma exacerbations treated with systemic glucocorticoids did not differ significantly between groups (0.48 exacerbations per year in the high-dose group and 0.37 exacerbations per year in the low-dose group; relative rate, 1.3; 95% confidence interval, 0.8 to 2.1; P=0.30). The time to the first exacerbation, the rate of treatment failure, symptom scores, and albuterol use during yellow-zone episodes did not differ significantly between groups. The total glucocorticoid exposure was 16% higher in the high-dose group than in the low-dose group. The difference in linear growth between the high-dose group and the low-dose group was -0.23 cm per year (P=0.06)., Conclusions: In children with mild-to-moderate persistent asthma treated with daily inhaled glucocorticoids, quintupling the dose at the early signs of loss of asthma control did not reduce the rate of severe asthma exacerbations or improve other asthma outcomes and may be associated with diminished linear growth. (Funded by the National Heart, Lung, and Blood Institute; STICS ClinicalTrials.gov number, NCT02066129 .).

In this review we highlight recent studies that advance the knowledge and understanding of the effects of various environmental factors and associated immune responses in patients with allergic diseases. This review will focus on new literature regarding allergic and immune responses to a variety of environmental factors, including aeroallergens, stinging insects, fungi, pollutants, viral respiratory tract infections, climate change, and microbial exposures., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Asthma is the most common chronic disease of childhood in the United States, causes significant morbidity, particularly in the inner-city, and accounts for billions of dollars in health care utilization. Home environments are established sources of exposure that exacerbate symptoms and home-based interventions are effective. However, elementary school children spend 7 to 12h a day in school, primarily in one classroom. From the observational School Inner-City Asthma Study we learned that student classroom-specific exposures are associated with worsening asthma symptoms and decline in lung function. We now embark on a randomized, blinded, sham-controlled school environmental intervention trial, built on our extensively established school/community partnerships, to determine the efficacy of a school-based intervention to improve asthma control. This factorial school/classroom based environmental intervention will plan to enroll 300 students with asthma from multiple classrooms in 40 northeastern inner-city elementary schools. Schools will be randomized to receive either integrated pest management versus control and classrooms within these schools to receive either air purifiers or sham control. The primary outcome is asthma symptoms during the school year. This study is an unprecedented opportunity to test whether a community of children can benefit from school or classroom environmental interventions. If effective, this will have great impact as an efficient, cost-effective intervention for inner city children with asthma and may have broad public policy implications., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Outdoor air pollution penetrates buildings and contributes to total indoor exposures. We investigated the relationship of indoor to outdoor particulate matter in inner-city school classrooms. The School Inner City Asthma Study investigates the effect of classroom-based environmental exposures on students with asthma in the northeast United States. Mixed effects linear models were used to determine the relationships between indoor PM 2.5 (particulate matter) and black carbon (BC), and their corresponding outdoor concentrations, and to develop a model for predicting exposures to these pollutants. The indoor-outdoor sulfur ratio was used as an infiltration factor of outdoor fine particles. Weeklong concentrations of PM 2.5 and BC in 199 samples from 136 classrooms (30 school buildings) were compared with those measured at a central monitoring site averaged over the same timeframe. Mixed effects regression models found significant random intercept and slope effects, which indicate that: (1) there are important PM 2.5 sources in classrooms; (2) the penetration of outdoor PM 2.5 particles varies by school and (3) the site-specific outside PM 2.5 levels (inferred by the models) differ from those observed at the central monitor site. Similar results were found for BC except for lack of indoor sources. The fitted predictions from the sulfur-adjusted models were moderately predictive of observed indoor pollutant levels (out of sample correlations: PM 2.5 : r 2 =0.68, BC; r 2 =0.61). Our results suggest that PM 2.5 has important classroom sources, which vary by school. Furthermore, using these mixed effects models, classroom exposures can be accurately predicted for dates when central site measures are available but indoor measures are not available.

Background: Children with food allergies spend a large proportion of time in school but characteristics of allergic reactions in schools are not well studied. Some schools self-designate as peanut-free or have peanut-free areas, but the impact of policies on clinical outcomes has not been evaluated., Objective: We sought to determine the effect of peanut-free policies on rates of epinephrine administration for allergic reactions in Massachusetts public schools., Methods: In this retrospective study, we analyzed (1) rates of epinephrine administration in all Massachusetts public schools and (2) Massachusetts public school nurse survey reports of school peanut-free policies from 2006 to 2011 and whether schools self-designated as "peanut-free" based on policies. Rates of epinephrine administration were compared for schools with or without peanut-restrictive policies., Results: The percentage of schools with peanut-restrictive policies did not change significantly in the study time frame. There was variability in policies used by schools self-designated as peanut-free. No policy was associated with complete absence of allergic reactions. Both self-designated peanut-free schools and schools banning peanuts from being served in school or brought from home reported allergic reactions to nuts. Policies restricting peanuts from home, served in schools, or having peanut-free classrooms did not affect epinephrine administration rates. Schools with peanut-free tables, compared to without, had lower rates of epinephrine administration (incidence rate per 10,000 students 0.2 and 0.6, respectively, P = .009)., Conclusions: These data provide a basis for evidence-based school policies for children with food allergies. Further studies are required before decisions can be made regarding peanut-free policies in schools., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)