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Background: In the United States, Black and Latino children with asthma are more likely than White children with asthma to require emergency department visits or hospitalizations because of an asthma exacerbation. Although many cite patient-level socioeconomic status and access to health care as primary drivers of disparities, there is an emerging focus on a major root cause of disparities-systemic racism. Current conceptual models of asthma disparities depict the historical and current effects of systemic racism as the foundation for unequal exposures to social determinants of health, environmental exposures, epigenetic factors, and differential healthcare access and quality. These ultimately lead to biologic changes over the life course resulting in asthma morbidity and mortality. Methods: At the 2022 American Thoracic Society International Conference, a diverse panel of experts was assembled to identify gaps and opportunities to address systemic racism in childhood asthma research. Panelists found that to examine and address the impacts of systemic racism on children with asthma, researchers and medical systems that support biomedical research will need to 1 ) address the current gaps in our understanding of how to conceptualize and characterize the impacts of systemic racism on child health, 2 ) design research studies that leverage diverse disciplines and engage the communities affected by systemic racism in identifying and designing studies to evaluate interventions that address the racialized system that contributes to disparities in asthma health outcomes, and 3 ) address funding mechanisms and institutional research practices that will be needed to promote antiracism practices in research and its dissemination. Results: A thorough literature review and expert opinion discussion demonstrated that there are few studies in childhood asthma that identify systemic racism as a root cause of many of the disparities seen in children with asthma. Community engagement and participation in research studies is essential to design interventions to address the racialized system in which patients and families live. Dissemination and implementation studies with an equity lens will provide the multilevel evaluations required to understand the impacts of interventions to address systemic racism and the downstream impacts. To address the impacts of systemic racism and childhood asthma, there needs to be increased training for research teams, funding for studies addressing research that evaluates the impacts of racism, funding for diverse and multidisciplinary research teams including community members, and institutional and financial support of advocating for policy changes based on study findings. Conclusions: Innovative study design, new tools to identify the impacts of systemic racism, community engagement, and improved infrastructure and funding are all needed to support research that will address impacts of systemic racism on childhood asthma outcomes.

Background: The burden of pediatric asthma and other allergic diseases is not evenly distributed among United States populations., Objective: To determine whether urinary biomarkers are associated with asthma morbidity, and if associations vary by child race, ethnicity and sex., Methods: This study includes n = 152 children with physician-diagnosed asthma who participated in the School Inner-City Asthma Intervention Study (SICAS-2). Metabolites of phenol, paraben, polycyclic aromatic hydrocarbons, and phthalate analytes were analyzed from urine samples collected at baseline. Asthma symptom days over the past 2 weeks were dichotomized to no asthma symptom days or any asthma symptom days. Cross-sectional regression models were adjusted for age, sex, number of colds, household income, prescription control, race and ethnicity, body mass index (BMI) percentile, and smoke exposure. Weighted quantile sum regression was used to analyze each chemical class and a total mixture effect, controlling for the same covariates. Analyses were conducted with the assistance of the National Institute of Environmental Health Sciences Children's Health Exposure Analysis Resource (CHEAR)., Results: Participants were mostly Hispanic/Latino and low income with an average age of 7.83 years and the average maximum asthma symptom days over the past two weeks of 2.13 (standard deviation: 3.56). The maximum concentrations indicate extreme values for several chemicals, including bisphenol-3, 2,5-dichlorophenol, propyl and methyl parabens, triclosan, methyl paraben and cotinine. We found a significant interaction effect and differing contributions of analytes for children with allergen sensitivity versus those that did not. For stratified analyses assessing effect modification by child race and ethnicity, weighted quantile sum interaction models showed reduced odds of asthma symptoms to a greater magnitude in children of other races and ethnicities compared to Black, Non-Hispanic children., Conclusions: Preliminary analyses of the association between environmental chemical exposure and asthma symptoms among inner-city children revealed an inverse association, which may be due to personal care and medication use and can be understood further in future analyses. Beneficial effects were detected for most of the chemicals., (Copyright © 2024. Published by Elsevier GmbH.)

Purpose of Review: Ubiquitous environmental exposures, including ambient air pollutants, are linked to the development and severity of childhood asthma. Advances in our understanding of these links have increasingly led to clinical interventions to reduce asthma morbidity., Recent Findings: We review recent work untangling the complex relationship between air pollutants, including particulate matter, nitrogen dioxide, and ozone and asthma, such as vulnerable windows of pediatric exposure and their interaction with other factors influencing asthma development and severity. These have led to interventions to reduce air pollutant levels in children's homes and schools. We also highlight emerging environmental exposures increasingly associated with childhood asthma. Growing evidence supports the present threat of climate change to children with asthma. Environmental factors play a large role in the pathogenesis and persistence of pediatric asthma; in turn, this poses an opportunity to intervene to change the course of disease early in life., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Radon may have a role in obstructive lung disease outside its known carcinogenicity. Little is known about radon's effects on asthma morbidity., Objective: To determine the effect of radon on fractional exhaled nitric oxide (F E NO), asthma symptom-days, and lung function in inner-city asthmatic school children., Methods: Two hundred ninety-nine school-aged asthmatic children enrolled in the School Inner-City Asthma Study (SICAS-1) were followed. One and two-month averaged radon was assessed using a spatiotemporal model predicting zip code-specific monthly exposures. F E NO and spirometry were measured twice during the academic year. Asthma symptoms were assessed four times during the academic year. The interaction between indoor radon exposure (Bq/m 3 ) and seasonality predicting log-transformed F E NO, forced expiratory volume in 1 s (FEV 1 ) % predicted, forced vital capacity (FVC) % predicted, FEV 1 /FVC, and asthma symptom-days was evaluated., Results: Participants with high radon exposure had greater change in F E NO from warm to cold periods compared to low radon exposure (interaction p = 0.0013). Participants with >50th percentile radon exposure experience significant F E NO increase from warm to cold weather ( β $\beta $  = 0.29 [95% confidence interval [CI]: 0.04-0.54], p = 0.0240). We report a positive association between radon 1-month moving average (incidence rate ratio [IRR] = 1.01, p = 0.0273) and 2-month moving average (IRR = 1.01, p = 0.0286) with maximum asthma symptom-days (n = 299, obs = 1167)., Conclusions: In asthmatic children, radon may be associated with increased asthma morbidity, suggesting radon may be a modifiable environmental risk factor for airway inflammation., (© 2023 Wiley Periodicals LLC.)

Purpose of Review: The current review provides an assessment of the recent pediatric literature evaluating socioeconomic drivers of asthma incidence and morbidity. The review addresses the specific social determinants of health related to housing, indoor and outdoor environmental exposures, healthcare access and quality, and the impact of systematic racism., Recent Findings: Many social risk factors are associated with adverse asthma outcomes. Children living in low-income, urban neighborhoods have greater exposure to both indoor and outdoor hazards, including molds, mice, second-hand smoke, chemicals, and air pollutants, all of which are associated with adverse asthma outcomes. Providing asthma education in the community - via telehealth, school-based health centers, or peer mentors - are all effective methods for improving medication adherence and asthma outcomes. The racially segregated neighborhoods created by the racist 'redlining' policies implemented decades ago, persist today as hotspots of poverty, poor housing conditions, and adverse asthma outcomes., Summary: Routine screening for social determinants of health in clinical settings is important to identify the social risk factors of pediatric patients with asthma. Interventions targeting social risk factors can improve pediatric asthma outcomes, but more studies are needed related to social risk interventions., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: Higher asthma prevalence and morbidity are seen in inner-city areas, disproportionately affecting low-income families living in substandard housing. Children within these families experience more frequent asthma exacerbations, acute care and emergency department visits, and hospitalizations, thus characterizing severe asthma. In this review, we assess recent published literature focused on indoor and outdoor exposures that contribute to the development and morbidity of asthma., Recent Findings: Many urban environmental exposures contribute to asthma burden, including tobacco/e-cigarette smoke, pest allergens, molds, and possibly synthetic chemicals such as phthalates and bisphenol A, radon, and volatile organic compounds. Individuals living in inner-city areas also experience higher levels of air pollutants and ambient heat, further perpetuating asthma incidence and severity., Summary: This article summarizes the latest advances and provides direction for future research on risk factors, interventions, and public policy to help alleviate the burden of asthma due to urban environment exposures., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: Asthma is the most common chronic disease of childhood. Environmental exposures, such as allergens and pollutants, are ubiquitous factors associated with asthma development and asthma morbidity. In this review, we highlight the most recent studies relevant to childhood asthma risk, onset, and exacerbation related to air pollution exposure., Recent Findings: In this article, we review current research that has been published between 2021 and 2022, demonstrating the effects of early-life exposure to key air pollutants (e.g., particulate matter (PM), nitrogen dioxide (NO 2 ), sulfur dioxide (SO 2 ) and ground-level ozone (O 3 ), environmental tobacco smoke, radon, and volatile organic compounds (VOC) on respiratory health., Summary: Air pollution continues to be a global burden with serious consequences related to respiratory health. Interventions aimed at reducing air pollution in the environment must be achieved in an effort to improve asthma outcomes and pediatric health., (Copyright © 2022 Wolters Kluwer Health, 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: Children with asthma are at risk for low lung function extending into adulthood, but understanding of clinical predictors is incomplete., Objective: We sought to determine phenotypic factors associated with FEV 1 throughout childhood in the Severe Asthma Research Program 3 pediatric cohort., Methods: Lung function was measured at baseline and annually. Multivariate linear mixed-effects models were constructed to assess the effect of baseline and time-varying predictors of prebronchodilator FEV 1 at each assessment for up to 6 years. All models were adjusted for age, predicted FEV 1 by Global Lung Function Initiative reference equations, race, sex, and height. Secondary outcomes included postbronchodilator FEV 1 and prebronchodilator FEV 1 /forced vital capacity., Results: A total of 862 spirometry assessments were performed for 188 participants. Factors associated with FEV 1 include baseline Feno (B, -49 mL/log 2 PPB; 95% CI, -92 to -6), response to a characterizing dose of triamcinolone acetonide (B, -8.4 mL/1% change FEV 1 posttriamcinolone; 95% CI, -12.3 to -4.5), and maximal bronchodilator reversibility (B, -27 mL/1% change postbronchodilator FEV 1 ; 95% CI, -37 to -16). Annually assessed time-varying factors of age, obesity, and exacerbation frequency predicted FEV 1 over time. Notably, there was a significant age and sex interaction. Among girls, there was no exacerbation effect. For boys, however, moderate (1-2) exacerbation frequency in the previous 12 months was associated with -20 mL (95% CI, -39 to -2) FEV 1 at each successive year. High exacerbation frequency (≥3) 12 to 24 months before assessment was associated with -34 mL (95% CI, -61 to -7) FEV 1 at each successive year., Conclusions: In children with severe and nonsevere asthma, several clinically relevant factors predict FEV 1 over time. Boys with recurrent exacerbations are at high risk of lower FEV 1 through childhood., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Objective: Children with severe asthma are underrepresented in studies of the relationship of sleep-disordered breathing (SDB) and asthma and little is known about sex differences of these relationships. We sought to determine the relationship of SDB with asthma control and lung function among boys and girls within a pediatric severe asthma cohort., Methods: Patients attending clinic visits at the Boston Children's Hospital Pediatric Severe Asthma Program completed the Pediatric Sleep Questionnaire (PSQ), Asthma Control Test (ACT) and Spirometry. The prevalence of SDB was defined as a PSQ score >0.33. We analyzed the association between PSQ score and both ACT score and spirometry values in mixed effect models, testing interactions for age and sex., Results: Among 37 subjects, mean age was 11.8 years (4.4) and 23 (62.2%) were male, the prevalence of SDB was 43.2% (16/37). Including all 80 observations, there was a moderate negative correlation between PSQ and ACT scores (r=-0.46, p  < 0.001). Multivariable linear regression models revealed a significant sex interaction with PSQ on asthma control ( p  = 0.003), such that for each 0.10 point increase in PSQ there was a 1.88 point decrease in ACT score for females but only 0.21 point decrease in ACT score for males. A positive PSQ screen was associated with a 9.44 point (CI 5.54, 13.34, p  < 0.001) lower ACT score for females and a 3.22 point (CI 0.56, 5.88, p  = 0.02) lower score for males., Conclusions: SDB is common among children with severe asthma. Among children with severe asthma, SDB in girls portends to significantly worse asthma control than boys., Supplemental data for this article is available online at https://doi.org/10.1080/02770903.2021.1897838.

Asthma is among the most common medical conditions affecting children and young people, with adolescence a recognised period of increased risk, overrepresented in analyses examining recent increasing asthma mortality rates. Asthma may change significantly during this period and management also occurs in the context of patients seeking increased autonomy and self-governance whilst navigating increasing academic and social demands. A number of disease factors can destabilise asthma during adolescence including: increased rates of anaphylaxis, anxiety, depression, obesity, and, in females, an emerging resistance to corticosteroids and the pro-inflammatory effects of oestrogen. Patient factors such as smoking, vaping, poor symptom recognition, treatment non-adherence and variable engagement with health services contribute to difficult to treat asthma. Significant deficiencies in the current approach to transition have been identified by a recent EAACI task force, and subsequent asthma-specific recommendations, published in 2020 provide an important framework moving forward. As with other chronic conditions, effective transition programmes plan ahead, engage with adolescents and their families to identify the patients' management priorities and the current challenges they are experiencing with treatment. Transition needs may vary significantly across asthma patients and for more complex asthma may include dedicated transition clinics involving multidisciplinary care requiring input including, amongst others, allergy and immunology, psychological medicine, respiratory physicians and scientists and nurse specialists. Across different global regions, barriers to treatment may vary but need to be elicited and an individualised approach taken to optimising asthma care which is sustainable within the local adult healthcare system., (Copyright © 2021. Published by Elsevier Ltd.)

Asthma is a heterogeneous disease, with multiple underlying inflammatory pathways and structural airway abnormalities that impact disease persistence and severity. Recent progress has been made in developing targeted asthma therapeutics, especially for subjects with eosinophilic asthma. However, there is an unmet need for new approaches to treat patients with severe and exacerbation-prone asthma, who contribute disproportionately to disease burden. Extensive deep phenotyping has revealed the heterogeneous nature of severe asthma and identified distinct disease subtypes. A current challenge in the field is to translate new and emerging knowledge about different pathobiologic mechanisms in asthma into patient-specific therapies, with the ultimate goal of modifying the natural history of disease. Here, we describe the Precision Interventions for Severe and/or Exacerbation-Prone Asthma (PrecISE) Network, a groundbreaking collaborative effort of asthma researchers and biostatisticians from around the United States. The PrecISE Network was designed to conduct phase II/proof-of-concept clinical trials of precision interventions in the population with severe asthma, and is supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health. Using an innovative adaptive platform trial design, the PrecISE Network will evaluate up to 6 interventions simultaneously in biomarker-defined subgroups of subjects. We review the development and organizational structure of the PrecISE Network, and choice of interventions being studied. We hope that the PrecISE Network will enhance our understanding of asthma subtypes and accelerate the development of therapeutics for severe asthma., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: The Hospital Asthma Severity Score (HASS) was developed to communicate inpatient asthma severity between providers. The purpose of this prospective study was to validate the HASS against the Pediatric Respiratory Assessment Measure (PRAM) and spirometry for assessment of inpatient asthma exacerbation severity in patients 2-18 years old, at a single point-in-time., Methods: This study was registered with clinicaltrials.gov (NCT02782065). Children admitted to a tertiary care, free-standing children's hospital were assessed for asthma severity using the HASS, PRAM, and pulmonary function by spirometry. Inter-rater agreement of HASS and PRAM scores was assessed between two blinded clinician raters. Spirometry results were obtained by a certified pulmonary laboratory technician and correlated with HASS and PRAM scores., Results: The sample included 58 subjects. Allowing for a one-point difference in continuous HASS and PRAM scores, inter-rater agreement was 79% for the HASS and 60% for the PRAM. When the scores were categorized as mild, moderate, and severe, inter-rater agreement was 62% for the HASS and 93% for the PRAM ( p < .0001). Additionally, intra-rater agreement between HASS and PRAM severity categories was 71% for Rater 1 and 64% for Rater 2. A weak correlation was noted between both the HASS and FEV 1 (r = -0.31; p  = 0.11), and PRAM and FEV 1 (r = -0.30; p  = 0.11) for the 29 subjects with acceptable spirometry results., Conclusions: The HASS and PRAM have acceptable inter-rater and intra-rater agreement. These results support validation of the HASS for managing hospitalized patients during asthma exacerbations.

Assessment of asthma comorbidities, conditions that adversely affect the pathobiology of asthma or impair its response to therapies, is a fundamental step in the evaluation and management of patients with difficult-to-treat asthma. Identifying and effectively treating asthma comorbidities, such as obesity, obstructive sleep apnea, and chronic sinusitis with nasal polyps, may improve asthma control and reduce exacerbations. In addition, identifying comorbid T2 inflammatory conditions may help guide optimal selection of biologic therapies. Here, we describe common comorbid conditions found in adult and pediatric difficult-to-control asthma, discuss evidence for the association with asthma morbidity and treatment benefit, and provide information on how and when to assess comorbidities., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Objective: Pediatric asthma is a costly and complex disease with proven interventions to prevent exacerbations. Finding the patients at highest risk of exacerbations is paramount given limited resources. Insurance claims identify all outpatient, inpatient, emergency, pharmacy, and diagnostic services. The objective was to develop a risk score indicating the likelihood of asthma exacerbation within the next year based on prior utilization., Methods: A retrospective analysis of insurance claims for patients 2 to 18 years in a network in Massachusetts with 3 years of continuous enrollment in a commercial plan. Thirty-six potential predictors of exacerbation in the third year were assessed with a stepwise regression. Retained predictors were weighted relative to their contribution to asthma exacerbation risk and summed to create the Asthma Exacerbation Risk (AER) score., Results: In a cohort of 28,196 patients, there were 10 predictors associated with the outcome of having an asthma exacerbation in the next year that depend on age, meeting the Healthcare Effectiveness Data and Information Set persistent asthma criteria, fill patterns of asthma medications and oral steroids, counts of nonexacerbation outpatient visits, an exacerbation in the last 6 months, and whether spirometry was performed. The AER score is calculated monthly from a claims database to identify potential patients for an asthma home-visiting program., Conclusions: The AER score assigns a risk of exacerbation within the next 12 months using claims data to identify patients in need of preventive services., (Copyright © 2021 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Background: Inner-city children are disproportionately affected by asthma and sleep-disordered breathing (SDB). However, little is known about the association of SDB symptoms with asthma morbidity in this vulnerable population., Objective: Assess the relationship between snoring frequency and asthma morbidity., Methods: This study was part of the School Inner-City Asthma Study, a longitudinal prospective cohort study of children with persistent asthma who attended schools in the Northeast United States from 2008 to 2013. Participants had baseline assessments of asthma symptoms, snoring, and allergy status. Caregivers completed quarterly surveys for 12 months on symptoms of asthma, snoring, and health care outcomes. Snoring frequency (non-, rare-, sometimes-, habitual-snoring) and its relationship with asthma symptoms and asthma morbidity were assessed by mixed-effects models., Results: There were 1186 observations from 339 subjects. Mean age was 7.9 years; roughly half were male, and most were of minority race. Half were overweight or obese, and 65.5% had atopy. At initial snoring assessment, 24.8% reported habitual snoring, but report of snoring frequency varied over the study period. Multivariate analyses revealed increased odds of maximum asthma symptom days for habitual snoring compared with nonsnoring (1.58; 95% CI, 1.19-2.10; P < .002) and all other snoring categories. Habitual snoring was associated with greater odds of health care utilization (incidence rate ratio, 1.72; 95% CI, 1.10-2.69; P = .02) and worse asthma control (odds ratio, 1.49; 95% CI, 1.05-2.11; P = .03) compared with nonsnoring., Conclusions: Snoring is common among inner-city school-age children with asthma, and habitual snoring is associated with increased asthma symptom burden and health care utilization., (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.

Rationale: It is unclear why select patients with moderate-to-severe asthma continue to lose lung function despite therapy. We hypothesized that participants with the smallest responses to parenteral corticosteroids have the greatest risk of undergoing a severe decline in lung function. Objectives: To evaluate corticosteroid-response phenotypes as longitudinal predictors of lung decline. Methods: Adults within the NHLBI SARP III (Severe Asthma Research Program III) who had undergone a course of intramuscular triamcinolone at baseline and at ≥2 annual follow-up visits were evaluated. Longitudinal slopes were calculated for each participant's post-bronchodilator FEV 1 % predicted. Categories of participant FEV 1 slope were defined: severe decline, >2% loss/yr; mild decline, >0.5-2.0% loss/yr; no change, 0.5% loss/yr to <1% gain/yr; and improvement, ≥1% gain/yr. Regression models were used to develop predictors of severe decline. Measurements and Main Results: Of 396 participants, 78 had severe decline, 91 had mild decline, 114 had no change, and 113 showed improvement. The triamcinolone-induced difference in the post-bronchodilator FEV 1 % predicted (derived by baseline subtraction) was related to the 4-year change in lung function or slope category in univariable models ( P  < 0.001). For each 5% decrement in the triamcinolone-induced difference the FEV1% predicted, there was a 50% increase in the odds of being in the severe decline group (odds ratio, 1.5; 95% confidence interval, 1.3-1.8), when adjusted for baseline FEV 1 , exacerbation history, blood eosinophils and body mass index. Conclusions: Failure to improve the post-bronchodilator FEV 1 after a challenge with parenteral corticosteroids is an evoked biomarker for patients at risk for a severe decline in lung function.

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.)

Objectives: Psychological comorbidities have been associated with asthma in adults and children, but have not been studied in a population of children with severe asthma. The aim of this study was to test the hypothesis that symptoms of anxiety or depression are highly prevalent in pediatric severe asthma and negatively effects asthma control., Methods: Longitudinal assessments of anxiety or depression symptoms (Patient Health Questionnaire-4 [PHQ-4]), asthma control (Asthma Control Test [ACT]), and lung function were performed in a single-center pediatric severe asthma clinic. Participant data were collected during routine clinical care. Primary outcomes were ACT and forced expiratory volume in 1 s per forced vital capacity (FEV1/FVC)., Results: Among 43 subjects (with total 93 observations), 58.1% reported at least one anxious or depressive symptom and 18.6% had a PHQ-4 more than 2, the threshold for an abnormal test result. After adjusting for age, sex, race, and asthma medication step, there was a significant reduction in ACT for girls with PHQ-4 more than 2 (adjusted mean [SE] ACT for PHQ-4 > 2: 13.64 [0.59], ACT for PHQ-4 ≤ 2: 20.64 [1.25], p = .02) but not boys. Moreover, there was a significant differential effect of mental health impairment for girls than boys. ACT for girls with PHQ more than 2: 13.64 (0.59) compared with boys with PHQ-4 more than 2: 17.82 (0.95), adjusted mean difference ACT by sex = 4.18 points; 95% confidence interval, 0.63-7.73; p = .033. In adjusted models, there was no association between PHQ-4 more than 2 and FEV1/FVC., Conclusions: Symptoms of anxiety and depression are common. In children with severe asthma, a PHQ-4 score more than 2 is associated with worse asthma symptom control in girls, but not boys., (© 2020 Wiley Periodicals LLC.)

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: 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.)

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.)

Corticosteroids are the most effective treatment for asthma; inhaled corticosteroids (ICSs) are the first-line treatment for children and adults with persistent symptoms. ICSs are associated with significant improvements in lung function. The anti-inflammatory effects of corticosteroids are mediated by both genomic and nongenomic factors. Variation in the response to corticosteroids has been observed. Patient characteristics, biomarkers, and genetic features may be used to predict response to ICSs. The existence of multiple mechanisms underlying glucocorticoid insensitivity raises the possibility that this might indeed reflect different diseases with a common phenotype., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The diagnosis of asthma in children under five years has been controversial due to changing concepts of what true asthma is in this age group. Previous diagnostic algorithms that used clinical indices to predict the persistence of asthma symptoms or phenotypes based on asthma triggers do not predict which children will benefit from asthma medication. A pragmatic approach to asthma diagnosis in this age group is based on identifying signs and symptoms of reversible airflow obstruction and documenting their response to asthma medication. Hopefully, this approach will provide clearer guidance to clinicians and improve asthma morbidity in these young children., (Copyright © 2018 Elsevier Ltd. 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: Although pre-puberty asthma is more prevalent in males, after puberty through middle-age, asthma is more prevalent in females. The surge of sex hormones with puberty might explain this gender switch., Methods: To examine the effects of sex hormones on lung function and symptoms with puberty, Tanner stage was assessed in 187 children 6-18 years of age (59% severe) enrolled in the NIH/NHLBI Severe Asthma Research Program (SARP). The effects of circulating sex hormones (n = 68; testosterone, dehydroepiandrosterone sulfate (DHEA-S), estrogen, and progesterone) on lung function and 4 week symptom control (ACQ6) in cross-section were tested by linear regression., Results: From pre-/early to late puberty, lung function did not change significantly but ACQ6 scores improved in males with severe asthma. By contrast females had lower post-BD FEV 1 % and FVC% and worse ACQ6 scores with late puberty assessed by breast development. In males log DHEA-S levels, which increased by Tanner stage, associated positively with pre- and post-BD FEV 1 %, pre-BD FVC %, and negatively (improved) with ACQ6. Patients treated with high-dose inhaled corticosteroids had similar levels of circulating DHEA-S. In females, estradiol levels increased by Tanner stage, and associated negatively with pre-BD FEV 1 % and FVC %., Conclusions: These results support beneficial effects of androgens on lung function and symptom control and weak deleterious effects of estradiol on lung function in children with asthma. Longitudinal data are necessary to confirm these cross-sectional findings and to further elucidate hormonal mechanisms informing sex differences in asthma features with puberty., Trial Registration: ClinicalTrials.gov registration number: NCT01748175 .

Severe asthma accounts for only a small proportion of the children with asthma but a disproportionately high amount of resource utilization and morbidity. It is a heterogeneous entity and requires a step-wise, evidence-based approach to evaluation and management by pediatric subspecialists. The first step is to confirm the diagnosis by eliciting confirmatory history and objective evidence of asthma and excluding possible masquerading diagnoses. The next step is to differentiate difficult-to-treat asthma, asthma that can be controlled with appropriate management, from asthma that requires the highest level of therapy to maintain control or remains uncontrolled despite management optimization. Evaluation of difficult-to-treat asthma includes an assessment of medication delivery, the home environment, and, if possible, the school and other frequented locations, the psychosocial situation, and comorbid conditions. Once identified, aggressive management of issues related to poor adherence and drug delivery, remediation of environmental triggers, and treatment of comorbid conditions is necessary to characterize the degree of control that can be achieved with standard therapies. For the small proportion of patients whose disease remains poorly controlled with these interventions, the clinician may assess steroid responsiveness and determine the inflammatory pattern and eligibility for biologic therapies. Management of severe asthma refractory to traditional therapies involves considering the various biologic and other newly approved treatments as well as emerging therapies based on the individual patient characteristics.

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 .).

Background: The effect of age on asthma severity is poorly understood., Objectives: The objective of this study was to compare the baseline features of severe and nonsevere asthma in the Severe Asthma Research Program (SARP) III cohort, and examine in cross section the effects of age on those features., Methods: SARP III is a National Institutes of Health/National Heart Lung Blood Institute multisite 3-year cohort study conducted to investigate mechanisms of severe asthma. The sample included 188 children (111 severe, 77 nonsevere) and 526 adults (313 severe, 213 nonsevere) characterized for demographic features, symptoms, health care utilization, lung function, and inflammatory markers compared by age and severity., Results: Compared with children with nonsevere asthma, children with severe asthma had more symptoms and more historical exacerbations, but no difference in body weight, post-bronchodilator lung function, or inflammatory markers. After childhood, and increasing with age, the cohort had a higher proportion of women, less allergen sensitization, and overall fewer blood eosinophils. Enrollment of participants with severe asthma was highest in middle-aged adults, who were older, more obese, with greater airflow limitation and higher blood eosinophils, but less allergen sensitization than adults with nonsevere asthma., Conclusions: The phenotypic features of asthma differ by severity and with advancing age. With advancing age, patients with severe asthma are more obese, have greater airflow limitation, less allergen sensitization, and variable type 2 inflammation. Novel mechanisms besides type 2 inflammatory pathways may inform the severe asthma phenotype with advancing age., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Despite available and effective tools for asthma self-assessment (Asthma Control Test, ACT) and self-management (Asthma Action Plan, AAP), they are underutilized in outpatient specialty clinics. We evaluated the impact of a patient-centered checklist, the Asthma Passport, on improving ACT and AAP utilization in clinic., Methods: This was a randomized, interventional quality-improvement project in which the Asthma Passport was distributed to 120 pediatric asthma patients over the duration of 16 weeks. The passport's checklist consisted of tasks to be completed by the patient/family, including completion of the ACT and AAP. We compared rates of completion of the ACT and AAP for those who received the passport versus the control group, and assessed patient/caregiver and provider satisfaction., Results: Based on electronic medical record data from 222 participants, the ACT completion rate was not significantly different between the passport and control groups, however, the AAP completion rate was significantly greater than control (30.0% vs. 17.7%, p = 0.04). When per-protocol analysis was limited to groups who completed and returned their passports, ACT and AAP completion rates were significantly greater than control (73.8% vs. 44.1% (p = 0.002) and 35.7% vs. 17.7% (p = 0.04), respectively). Nearly all participants reported high satisfaction with care, and surveyed providers viewed the passport favorably., Conclusions: A patient-centered checklist significantly improved the completion rate of the AAP. For patient's who completed and returned the asthma passport, the ACT completion rate was also improved. Participants and providers reported high satisfaction with the checklist, suggesting that it can effectively promote asthma self-management and self-assessment without burdening clinicians or clinic workflow.

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.)

Rationale: Phenotypic distinctions between severe asthma (SA) and nonsevere asthma (NONSA) may be confounded by differential adherence or incorrect use of corticosteroids., Objectives: To determine if there are persistent phenotypic distinctions between SA (as defined by 2014 American Thoracic Society/European Respiratory Society guidelines) and NONSA after intramuscular triamcinolone acetonide (TA), and to identify predictors of a corticosteroid response in these populations., Methods: A total of 526 adults age 18 years and older (315 SA) and 188 children age 6 to less than 18 years (107 SA) in the NHLBI Severe Asthma Research Program III were characterized before and 3 weeks after TA. The primary outcome for corticosteroid response was defined as greater than or equal to 10-point improvement in percent predicted FEV 1 ., Measurements and Main Results: Adult asthma groups exhibited a small but significant mean FEV 1 % predicted improvement after TA (SA group mean difference, 3.4%; 95% confidence interval, 2.2-4.7%; P = 0.001), whereas children did not. Adult SA continued to manifest lower FEV 1 and worse asthma control as compared with NONSA after TA. In children, after TA only prebronchodilator FEV 1 distinguished SA from NONSA. A total of 21% of adults with SA and 20% of children with SA achieved greater than or equal to 10% improvement after TA. Baseline bronchodilator response and fractional exhaled nitric oxide had good sensitivity and specificity for predicting response in all groups except children with NONSA., Conclusions: One in five patients with SA exhibit greater than or equal to 10% improvement in FEV 1 with parenteral corticosteroid. Those likely to respond had greater bronchodilator responsiveness and fractional exhaled nitric oxide levels. In adults, differences in airflow obstruction and symptoms between SA and NONSA persist after parenteral corticosteroids, suggesting a component of corticosteroid nonresponsive pathobiology in adults with SA that may differ in children. Clinical trial registered with www.clinicaltrials.gov (NCT 01606826).

Importance: Home aeroallergen exposure is associated with increased asthma morbidity in children, yet little is known about the contribution of school aeroallergen exposures to such morbidity., Objective: To evaluate the effect of school-specific aeroallergen exposures on asthma morbidity among students, adjusting for home exposures., Design, Setting, and Participants: The School Inner-City Asthma Study was a prospective cohort study evaluating 284 students aged 4 to 13 years with asthma who were enrolled from 37 inner-city elementary schools in the northeastern United States between March 1, 2008, and August 31, 2013. Enrolled students underwent baseline clinical evaluations before the school year started and were then observed clinically for 1 year. During that same school year, classroom and home dust samples linked to the students were collected and analyzed for common indoor aeroallergens. Associations between school aeroallergen exposure and asthma outcomes during the school year were assessed, adjusting for home exposures., Exposures: Indoor aeroallergens, including rat, mouse, cockroach, cat, dog, and dust mites, measured in dust samples collected from inner-city schools., Main Outcomes and Measures: The primary outcome was maximum days in the past 2 weeks with asthma symptoms. Secondary outcomes included well-established markers of asthma morbidity, including asthma-associated health care use and lung function, measured by forced expiratory volume in 1 second., Results: Among 284 students (median age, 8 years [interquartile range, 6-9 years]; 148 boys and 136 girls), exposure to mouse allergen was detected in 441 (99.5%) of 443 school dust samples, cat allergen in 420 samples (94.8%), and dog allergen in 366 samples (82.6%). Levels of mouse allergen in schools were significantly higher than in students' homes (median settled dust level, 0.90 vs 0.14 µg/g; P < .001). Exposure to higher levels of mouse allergen in school (comparing 75th with 25th percentile) was associated with increased odds of having an asthma symptom day (odds ratio, 1.27; 95% CI, 1.05-1.54; P = .02) and 4.0 percentage points lower predicted forced expiratory volume in 1 second (95% CI, -6.6 to -1.5; P = .002). This effect was independent of allergic sensitization. None of the other indoor aeroallergens were associated with worsening asthma outcomes., Conclusions and Relevance: In this study of inner-city students with asthma, exposure to mouse allergen in schools was associated with increased asthma symptoms and decreased lung function. These findings demonstrate that the school environment is an important contributor to childhood asthma morbidity. Future school-based environmental interventions may be beneficial for this important public health problem.

Background: Home-based interventions to improve indoor air quality have demonstrated benefits for asthma morbidity, yet little is known about the effect of environmental interventions in the school setting., Objective: We piloted the feasibility and effectiveness of a classroom-based air cleaner intervention to reduce particulate pollutants in classrooms of children with asthma., Methods: In this pilot randomized controlled trial, we assessed the effect of air cleaners on indoor air particulate pollutant concentrations in 18 classrooms (9 control, 9 intervention) in 3 urban elementary schools. We enrolled 25 children with asthma (13 control, 12 intervention) aged 6 to 10 years. Classroom air pollutant measurements and spirometry were completed once before and twice after randomization. Asthma symptoms were surveyed every 3 months., Results: Baseline classroom levels of fine particulate matter (particulate matter with diameter of <2.5 μm [PM 2.5 ]) and black carbon (BC) were 6.3 and 0.41 μg/m 3 , respectively. When comparing the intervention to the control group, classroom PM 2.5 levels were reduced by 49% and 42% and BC levels were reduced by 58% and 55% in the first and second follow-up periods, respectively (P < .05 for all comparisons). When comparing the children randomized to intervention and control classrooms, there was a modest improvement in peak flow, but no significant changes in forced expiratory volume in 1 second (FEV 1 ) and asthma symptoms., Conclusions: In this pilot study, a classroom-based air cleaner intervention led to significant reductions in PM 2.5 and BC. Future large-scale studies should comprehensively evaluate the effect of school-based environmental interventions on pediatric asthma morbidity., (Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Phenotypic presentations in young children with asthma are varied and might contribute to differential responses to asthma controller medications., Methods: The Individualized Therapy for Asthma in Toddlers study was a multicenter, randomized, double-blind, double-dummy clinical trial in children aged 12 to 59 months (n = 300) with asthma necessitating treatment with daily controller (Step 2) therapy. Participants completed a 2- to 8-week run-in period followed by 3 crossover periods with daily inhaled corticosteroids (ICSs), daily leukotriene receptor antagonists, and as-needed ICS treatment coadministered with albuterol. The primary outcome was differential response to asthma medication based on a composite measure of asthma control. The primary analysis involved 2 stages: determination of differential response and assessment of whether 3 prespecified features (aeroallergen sensitization, previous exacerbations, and sex) predicted a differential response., Results: Seventy-four percent (170/230) of children with analyzable data had a differential response to the 3 treatment strategies. Within differential responders, the probability of best response was highest for a daily ICS and was predicted by aeroallergen sensitization but not exacerbation history or sex. The probability of best response to daily ICS was further increased in children with both aeroallergen sensitization and blood eosinophil counts of 300/μL or greater. In these children daily ICS use was associated with more asthma control days and fewer exacerbations compared with the other treatments., Conclusions: In young children with asthma necessitating Step 2 treatment, phenotyping with aeroallergen sensitization and blood eosinophil counts is useful for guiding treatment selection and identifies children with a high exacerbation probability for whom treatment with a daily ICS is beneficial despite possible risks of growth suppression., (Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Competing Interests: All authors declare no potential conflicts of interest related to this work.