Background Integrated pest management (IPM) is thought to improve asthma symptoms through reduced mouse allergen exposure. Whether IPM acts through changes in mouse-associated microbes remains unknown. Objectives To examine the effects of school-based IPM on the classroom microbiome, and to determine the association between intervention microbiome signatures and student asthma morbidity. Methods In this ancillary study based on a randomized placebo-controlled clinical trial of school IPM and classroom high efficiency air purifiers (ClinicalTrials.gov NCT02291302), we performed deep metagenomics sequencing of longitudinally collected dust samples from 208 classrooms in 41 schools of 236 children with active, physician-diagnosed asthma with prospective follow-up of asthma severity during the school year. We assessed the effect of the interventions on classroom microbial communities in intention-to-treat analyses. Sparse Partial Least Squares models were used to identify microbial signatures of the interventions and the association between these microbial signatures and asthma morbidity was assessed using mixed effects models, controlling for covariates including mouse allergen exposure. Results IPM significantly altered classroom bacterial and phage community structure and increased bacterial, archaeal, and fungal diversity. A classroom microbiome signature of IPM was identified (AUC=0.84) and was associated with lower odds of any asthma symptom days in the past two weeks (OR 0.47, 95% CI [0.22, 0.97], p=0.043) and lower Composite Asthma Severity Index (β -0.92, 95% CI [-1.51, -0.33], p=0.002), adjusting for mouse allergen levels and student characteristics. Conclusion IPM-associated changes in the classroom microbiome are associated with lower asthma morbidity independent of mouse allergen exposure.

BACKGROUND:Respiratory viral infections are common and can trigger asthma exacerbations in children. The roles of the nasal microbiome and phageome (viruses that infect microbes) are not well understood. OBJECTIVE:We sought to characterize the epidemiology of respiratory viral infections and the interplay between the nasal microbiome, phageome, and viral infections in school-age children with asthma. METHODS:We performed metagenomic sequencing and quantitative RT-PCR detection of respiratory viruses on 375 nasal samples from 227 school-age children with asthma collected routinely 3 times over a year. Surveys on parent-reported cold and asthma symptoms were administered routinely every 2 months. We evaluated multikingdom changes to the nasal microbiome during infection. A sparse partial least-squares discriminant analysis model identified microbial signatures associated with prospective viral infection risk. RESULTS:Respiratory viruses were identified in 124 (33%) samples, with rhinovirus being the most prevalent. Cold and asthma symptoms within the previous 14 days had a sensitivity of 79% and 59%, respectively, for quantitative RT-PCR-confirmed infection. Respiratory viral infection increased asthma symptoms and was accompanied by loss of nasal bacterial diversity and a reproducible bloom of pathobionts with no change in the mycobiome or phageome. A baseline bacteriome-dominated profile was protective (adjusted odds ratio, 0.41 [95% CI, 0.25-0.67]; P < .001), whereas phageome profiles increased risk (adjusted odds ratio, 3.74 [95% CI, 1.85-7.55]; P < .001) of viral infection. Specific phages inversely correlated with Staphylococcus epidermidis abundance, the most protective commensal against infection risk. CONCLUSIONS:The nasal microbiome and phageome exert opposing influences on respiratory viral infection risk, highlighting their potential roles in modulating susceptibility to viral infections.

Importance:The magnitude of school respiratory virus exposure and the effectiveness of environmental mitigation measures remain unclear. Objective:To evaluate whether portable high-efficiency particulate air (HEPA) purifiers are associated with reduced respiratory virus exposure in elementary school classrooms. Design, Setting, and Participants:This ad hoc secondary analysis was performed between July 2023 and September 2024 and used data from a cluster-randomized, placebo-controlled trial (School Inner-City Asthma Intervention Study) of HEPA purifiers conducted from September 2015 to June 2020. A total of 200 classrooms from 39 public schools in Northeastern US were enrolled and randomized. Interventions:Classrooms were randomized 1:1 to receive either active HEPA purifiers or visually identical sham HEPA units (4 per classroom). School staff and investigators were blinded to intervention assignments. Main Outcomes and Measures:The primary outcome was high viral exposure, identified by K-means clustering of individual viral concentrations. Secondary outcomes included viral diversity (defined as number of detected virus types) and individual viral concentrations. Week-long bioaerosol samples were collected 3 times during 1 school year, and concentrations of 19 respiratory viruses were quantified by digital droplet polymerase chain reaction. Results:Of the 200 enrolled classrooms (91 in the sham purifier group and 109 in the HEPA purifier group) analyzed, the median (IQR) class size was 19 (18-20) and the median (IQR) grade was 3 (2-5). A total of 532 bioaerosol samples were collected; viruses were detected in 524 samples (98.5%), with a median (IQR) of 3 (2-5) viruses per classroom. Rhinovirus was most prevalent (476 [89.5%]), while respiratory syncytial virus A and B (66 [12.4%] and 127 [23.9%]) as well as influenza A and B (94 [17.7%] and 76 [14.3%]) were also detected. High viral exposure was present in 118 samples (22.2%). The HEPA purifier intervention was not associated with lower odds of high viral exposure (odds ratio [OR], 0.50; 95% CI, 0.08-3.25; P = .46) but did correspond to a modest reduction in viral diversity (β = -1.02; 95% CI, -1.68 to -0.35; P = .003). Elastic net regression identified relative humidity, grade, winter season, and coarse particulate matter as the environmental risk factors for viral exposure. Conclusions and Relevance:In this secondary analysis, HEPA purifiers were not associated with a reduction in high viral exposure but were associated with a modest decrease in viral diversity. Multicomponent interventions may be needed to mitigate respiratory viral exposures in schools.

Background: The cost-effectiveness of school environmental remediation in asthma is not known. The School Inner City Asthma Intervention Study (SICAS2) was a randomized controlled trial that assessed school integrated pest management (IPM) and classroom high efficiency particulate air (HEPA) filtration on asthma morbidity in urban schools. Objective: The objective was to evaluate the cost-effectiveness of SICAS2. Methods: We conducted a cost-effectiveness analysis from a societal perspective that compared four interventions: IPM, HEPA, IPM + HEPA, and no intervention. Quality-adjusted life years (QALY) were derived from the EuroQol-5 Dimension-Youth and EuroQol-5 Dimension-3 levels instruments. Total costs (2021 U.S. dollars) included intervention cost, cost of caregiver productivity impacted by child school absenteeism, and health-care utilization costs (e.g., emergency department visits). The evaluation period was based on a mean follow-up time of 166 days. Sensitivity analyses were performed by using cost estimates 50% above and below initial cost benchmarks. Results: A total of 154 SICAS2 participants were included. Intervention costs per student were $12.21 (IPM + HEPA), $7.27 (IPM), and $4.94 (HEPA). Sequential analyses revealed that IPM + HEPA was the most cost-effective option, with an incremental cost-effectiveness ratio of $19,667 per QALY. Sensitivity analyses demonstrated stability, with variability in probability estimates not exceeding 10%. Conclusion: IPM + HEPA demonstrated good value to society, which reflected the low cost and the economic impact of missed school days. This intervention may have a pronounced benefit for historically minoritized and marginalized children in urban schools who are disproportionately exposed to air pollution and indoor allergens. The SICAS2 intervention may offer a cost-effective tool to target proximal causes of disparities even in the most resource-limited schools.

Introduction: Schools are a major source of viral transmission. Quantifying airborne viral exposures in classrooms and the impact of indoor air quality on exposures are unknown. In this study, we employed multiplexed droplet digital polymerase chain reaction (ddPCR) to comprehensively quantify airborne respiratory viral pathogens in elementary school classrooms and to investigate how easily measurable indoor air quality metrics can be a surrogate for viral exposure. Method: In an ancillary study based on the School Inner City Asthma Intervention Study (SICAS-2: ClinicalTrials.govNCT02291302), week-long bioaerosol samples were collected using 5 uM PTFE filters at 3 L/min from elementary school classrooms during the school years spanning 2015-2019. Simultaneously, other indoor air quality measures including gravimetric measures of fine (PM2.5) and coarse particulate matter (PM10) and sensor-based measurements of carbon dioxide (CO2), temperature, and relative humidity were obtained. We utilized multiplex ddPCR panels to quantify 19 common respiratory viruses (viral copies/m3). K- means clustering analysis based on concentrations of all viruses was used to binarize samples into high vs. low global virus exposure clusters which served as the primary outcome. The secondary outcome was viral diversity, or number of viruses detected per class. To identify built environment and sensor-based measures of indoor air quality predictive of viral exposure and diversity, variable selection was performed using random forest models. Subsequently, the five most influential variables were used in a multivariate generalized additive mixed effects models adjusting for repeated measures and season. Results: A total of 347 air samples were collected from 202 elementary school classrooms. The median number of viral pathogens detected in each bioaerosol sample was 3 [interquartile range 2 – 5, range 0-13]. PM10 levels > 7 ug/m3 was the most highly associated with increased risk of high viral exposure (OR = 3.16 [95% CI 1.04 – 9.59]. High air exchange rate was found to be inversely associated (OR = 0.34 [95% CI 0.13 – 0.91]) (Figure 1A). High PM10 was also associated with high viral diversity while class grade was inversely associated (Figure 1B). Conclusions: PM10 was highly associated with increased viral exposure in classrooms. Increased air exchange rate was protective against high viral exposure. Low-cost sensor-based measures of PM10 are already being used to monitor indoor air quality and may serve as a surrogate marker for monitoring indoor viral exposure in schools.

OBJECTIVE:Sleep Disordered Breathing (SDB) is both prevalent and under-recognized in pediatric minority populations. Recognition of SDB is often triggered by symptoms of caregiver-reported snoring. However, the validity and utility of caregiver reports likely vary across populations. Our objective is to assess the association between caregiver-reported snoring and objectively recorded snoring in a low-income urban community and explore factors associated with agreement between objective and subjective snoring. METHODS:169 6 to 12 year old participants underwent at-home sleep studies with a WatchPAT device as part of the Environmental Assessment of Sleep in Youth (EASY) cohort study. Differences in subjective snoring, objective snoring, and concordance between subjective and objective snoring based on socioeconomic and clinical characteristics were assessed. RESULTS:The sample had a high proportion of non-white (78.9 %) and low income (39.6 %) children. Caregivers reported snoring for 20.7 % of the children and snoring was measured objectively for 21.9 %. Of those with objective snoring, only 29.7 % were identified as snorers by caregiver report (sensitivity: 0.30; specificity: 0.82). Primary Spanish language and co-sleeping were associated with increased caregiver reported snoring, and allergy was associated with increased objective snoring. Older child age and normal range BMI percentile were associated with higher concordance between caregiver and objective snoring. CONCLUSIONS:Among a community-based, predominantly minority sample, caregiver-reported snoring resulted in under-estimation of prevalence of objectively assessed snoring. Reliance on caregiver report may poorly identify children with snoring or SDB in clinical practice.

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:The mechanisms by which genetic and environmental factors interact to promote asthma remain unclear. Both the IL-4 receptor alpha chain R576 (IL-4RαR576) variant and Notch4 license asthmatic lung inflammation by allergens and ambient pollutant particles by subverting lung regulatory T (Treg ) cells in an IL-6-dependent manner.OBJECTIVE:We examined the interaction between IL-4RαR576 and Notch4 in promoting asthmatic inflammation.METHODS:Peripheral blood mononuclear cells (PBMCs) of asthmatics were analyzed for T helper type 2 cytokine production and Notch4 expression on Treg cells as a function of IL4RR576 allele. The capacity of IL-4RαR576 to upregulate Notch4 expression on Treg cells to promote severe allergic airway inflammation was further analyzed in genetic mouse models.RESULTS:Asthmatics carrying the IL4RR576 allele had increased Notch4 expression on their circulating Treg cells as a function of disease severity and serum IL-6. Mice harboring the Il4raR576 allele exhibited increased Notch4-dependent allergic airway inflammation that was inhibited upon Treg cell-specific Notch4 deletion or treatment with an anti-Notch4 antibody. Signaling via IL-4RαR576 upregulated the expression in lung Treg cells of Notch4 and its downstream mediators Yap1 and beta-catenin, leading to exacerbated lung inflammation. This upregulation was dependent on growth factor receptor-bound protein 2 (GRB2) and IL-6 receptor.CONCLUSION:These results identify an IL-4RαR576-regulated GRB2-IL-6-Notch4 circuit that promotes asthma severity by subverting lung Treg cell function.

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. (C) 2022 Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology

Asthma is the most common disease of childhood, with a disproportionate burden in inner-city populations.1 Within inner-city homes, specific aeroallergen exposures, particularly mouse and cockroach, have been associated with asthma morbidity.2,3 Inner-city schools have also been shown to be a significant source of allergen exposure contributing to asthma morbidity.4 The first School Inner-City Asthma Study (SICAS 1), occurring between 2008 and 2013, revealed an association between exposure to mouse allergen in schools and worsening asthma symptoms, independent of sensitization status or home environmental exposure.

BACKGROUND:School classrooms, where students spend the majority of their time during the day, are the second most important indoor microenvironment for children. OBJECTIVE:We investigated factors influencing classroom exposures to fine particulate matter (PM2.5), black carbon (BC), and nitrogen dioxide (NO2) in urban schools in the northeast United States. METHODS:Over the period of 10 y (2008-2013; 2015-2019) measurements were conducted in 309 classrooms of 74 inner-city schools during fall, winter, and spring of the academic period. The data were analyzed using adaptive mixed-effects least absolute shrinkage and selection operator (LASSO) regression models. The LASSO variables included meteorological-, school-, and classroom-based covariates. RESULTS:LASSO identified 10, 10, and 11 significant factors (p<0.05) that were associated with indoor PM2.5, BC, and NO2 exposures, respectively. The overall variability explained by these models was R2=0.679, 0.687, and 0.621 for PM2.5, BC, and NO2, respectively. Of the model's explained variability, outdoor air pollution was the most important predictor, accounting for 53.9%, 63.4%, and 34.1% of the indoor PM2.5, BC, and NO2 concentrations. School-based predictors included furnace servicing, presence of a basement, annual income, building type, building year of construction, number of classrooms, number of students, and type of ventilation that, in combination, explained 18.6%, 26.1%, and 34.2% of PM2.5, BC, and NO2 levels, whereas classroom-based predictors included classroom floor level, classroom proximity to cafeteria, number of windows, frequency of cleaning, and windows facing the bus area and jointly explained 24.0%, 4.2%, and 29.3% of PM2.5, BC, and NO2 concentrations, respectively. DISCUSSION:The adaptive LASSO technique identified significant regional-, school-, and classroom-based factors influencing classroom air pollutant levels and provided robust estimates that could potentially inform targeted interventions aiming at improving children's health and well-being during their early years of development. https://doi.org/10.1289/EHP10007.

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 characterifrom 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. (C) 2020 American Academy of Allergy, Asthma & Immunology

Patient-reported outcomes (PROs) better capture the impact of disease on quality of life, allowing providers and researchers to more fully gauge response to treatment, but are subjective and are impacted by language barriers, cognition, and literacy level. Integrating PRO measures with objective data, such as pedometry, can guide understanding of how disease and interventions impact patient health outcomes. Children ages 8-17 with partly or uncontrolled asthma wore pedometers to track step counts for 4 weeks. Each week, volunteers completed PROMIS Pediatric measures addressing health-related quality of life domains: Asthma Impact, Depressive Symptoms, Anxiety, Peer Relationships, and Mobility. Bivariate analyses and linear mixed regression modeling were performed to examine the association between average daily step count and PROs. 105 children were enrolled from 2 sites. Younger children (ages 8-11) took more average daily steps than older children (ages 12-17). During weeks 1-2, lower daily step count was associated with higher self-reported asthma impact (wk 1: r= -0.30, p=0.01; wk 2: r=-0.28, p=0.01) and lower self-reported mobility (wk 1: r=0.30, p=0.01; wk 2: r=0.35, p=0.002), with no significant relationships to other PROs studied. This association remained significant after controlling for asthma severity and other demographic factors. Average daily step count dropped significantly during weeks 3-4, along with reduced adherence to wearing the pedometer. Wearable technology to track activity shows promise to complement but not replace PROs in asthma care, though strategies that promote consistent use of these devices are crucial.

BACKGROUND: Whether concomitant home exposures modify the effectiveness of mouse allergen reduction among mouse-sensitized children with asthma is unknown. OBJECTIVE: To determine whether a lower baseline home mouse allergen level, lower particulate matter 10 mu or less (PM10), and the absence of sensitization and exposure to other indoor allergens are associated with greater improvements in asthma associated with mouse allergen reduction. METHODS: A secondary analysis of a randomized clinical trial of a home mouse allergen intervention was performed to examine the effect of 3 indoor factors on the relationship between mouse allergen reduction and a range of asthma outcomes. RESULTS: Participants (N = 297) were predominantly minority (78% African American, 22% Hispanic) and publicly insured (88%). Higher baseline mouse allergen levels were associated with a greater response to mouse allergen reduction for several symptom and exacerbation outcomes. Lower indoor PM10 levels were associated with a greater response to mouse allergen reduction for several symptom outcomes, but not exacerbation outcomes. Overall, sensitization and exposure to other indoor allergens did not appear to modify the effect of mouse allergen reduction. CONCLUSIONS: In this population of predominantly low-income children with persistent asthma and mouse sensitization, mouse allergen reduction was associated with improvements in asthma, especially among those with high baseline mouse allergen exposure. Lower indoor PM10 was associated with greater improvements in asthma symptoms. (C) 2021 American Academy of Allergy, Asthma & Immunology

Aim: To confirm the presence of extracellular vesicles (EVs) in cell-free saliva (CFS) of children with asthma and describe the isolated EV population. Methods: A pooled sample of CFS EVs isolated from 180 participants using ExoQuick-TC was examined in downstream analyses. Transmission electron microscopy (TEM) was used to confirm the presence of EVs. Nanoparticle tracking analysis (NTA) and single particle interferometric reflectance imaging sensing (SP-IRIS) with fluorescence were used for sizing, counting, and phenotyping of EVs. Capillary immunoassays were used for protein quantitation. Results: TEM confirmed the presence of EVs of diverse sizes, indicating the prep contained a heterogeneous population of EVs. Capillary immunoassays confirmed the presence of EV-associated proteins (CD9, CD63, CD81, ICAM-1, and ANXA5) and indicated limited cellular contamination. As others have also reported, there were discrepancies in the EV sizing and enumeration across platforms. Fluorescent NTA detected particles with a mode diameter of similar to 90 nm, whereas SP-IRIS reported sizes of similar to 55- 60 nm that more closely approximated the TEM results. Consistent with protein immunoassay results, SP-IRIS with fluorescence showed that the majority of these EVs were CD9- and CD63-positive, with little expression of CD81. Conclusion: EVs from CFS can be isolated using a high-throughput method that can be scaled to large epidemiological studies. To our knowledge, we are the first to characterize CFS EVs from patients with asthma. The use of CFS EVs as potential novel biomarkers in asthma warrants further investigation and opens a new avenue of research for future studies.

Exposure to mouse allergen is associated with increased asthma morbidity in children.1-3 Reduction in exposure is associated with improvements in asthma.4,5 In the Mouse Allergen and Asthma Intervention Trial (MAAIT), a dose–response relation was found between reduction in mouse allergen and improvement in asthma outcomes regardless of the intervention implemented.4 Achieving a clinically meaningful reduction in mouse allergen levels can be challenging. Ideally, environmental interventions could be tailored to optimize chances for success.

INTRODUCTION:Almost half of all school-age children with bronchopulmonary dysplasia (BPD) have asthma-like symptoms and more suffer from lung function deficits. While air pollution and indoor respiratory irritants are known to affect high-risk populations of children, few studies have objectively evaluated environmental contributions to long-term respiratory morbidity in this population. This study aimed to examine the role of indoor environmental exposures on respiratory morbidity in children with BPD. METHODS AND ANALYSIS:The Air quality, Environment and Respiratory Ouctomes in BPD (AERO-BPD) study is a prospective, single-centre observational study that will enrol a unique cohort of 240 children with BPD and carefully characterise participants and their indoor home environmental exposures. Measures of indoor air quality constituents will assess the relationship of nitrogen dioxide (NO2), particulate matter (PM2.5), nitric oxide (NO), temperature and humidity, as well as dust concentrations of allergens, with concurrently measured respiratory symptoms and lung function.Adaptations to the research protocol due to the SARS-CoV-2 pandemic included remote home environment and participant assessments. ETHICS AND DISSEMINATION:Study protocol was approved by the Boston Children's Hospital Committee on Clinical Investigation. Dissemination will be in the form of peer-reviewed publications and participant information products. TRIAL REGISTRATION NUMBER:NCT04107701.

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-a 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.

The COVID-19 pandemic produced unprecedented disruption to many social determinants of health. We sought to explore the initial impact of the COVID-19 emergency on asthma control and health in school-age children and their families. We remotely surveyed the parents of children attending elementary school in a city in the Northeast, about their experiences from February-July 2020. We recorded demographic information about the children and their family members, COVID-19 associated illness and testing, asthma control, and socioeconomic factors related to health. The online survey was completed by 120 families. Seventy-four households (66.7%) had ≥1 adult working outside the home during the state of emergency. Two children (1.7%) had documented illness with SARS-CoV-2. Documented or suspected COVID-19-related illness was reported in ≥1 family member in 9.9% of households. Thirty-six children (30%) had asthma. During the initial period of the COVID-19 emergency, parents generally perceived their children's asthma as well-controlled (52.8%) or completely-controlled (41.7%). Most families reported good adherence to asthma medications (76%), though some (11.1%) expressed reluctance to access medical care during the outbreak. Nearly all children were offered online education during school closures. Many families reported that technical and/or logistical barriers limited participation. Notable proportions of families reported working outside the home and experiencing COVID-19-related illness during the first 4 months of the pandemic. Despite significant disruption to daily life, the situation tended to enhance protective factors on asthma control. Further studies are needed to better guide management of pediatric asthma and evaluate socioeconomic changes occurring during the COVID-19 emergency.

ImportanceSchool and classroom allergens and particles are associated with asthma morbidity, but the benefit of environmental remediation is not known.ObjectiveTo 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 ParticipantsFactorial 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.InterventionsThe 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 MeasuresThe 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.ResultsAmong 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 RelevanceAmong 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 RegistrationClinicalTrials.gov Identifier: NCT02291302.