Recent Insights into the Environmental Determinants of Childhood Asthma.

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.

Improving Asthma Action Plan Completion Rates across Five Divisions in an Academic Children's Hospital.

Introduction: Asthma is the most common chronic disease among children. Asthma Action Plans (AAPs) enable asthma self-management tailored to each patient and should be updated annually. At our institution, providers face challenges in creating reliable processes to consistently complete AAPs for patients with asthma. This project's aim was to increase the percentage of patients across five hospital divisions who have an up-to-date AAP from 80% in May 2021 to 85% by October 1, 2021. Methods: We launched a quality improvement (QI) project using the Model for Improvement, focusing on improving AAP completion rates across five hospital divisions providing ambulatory care for asthma patients. The divisions (Adolescent/Young Adult Medicine, Allergy, Pulmonary, and two Primary Care sites) participated in the QI process using tools to understand the problem context. They implemented a cross-divisional AAP completion competition from June to October 2021. Each month during Action Periods, divisions trialed their interventions using Plan-Do-Study-Act cycles. We held monthly Learning Sessions for divisions to collaborate on successful intervention strategies. Results: Statistical process control chart analysis demonstrated that the overall AAP completion rate increased from a baseline of 80% to 87% with the initiation of the competition. All divisions showed improvement in AAP completion rates during the active intervention period, but sustainment varied. Conclusions: The cross-divisional competition motivated five divisions to improve processes to increase AAP completion rates. This approach effectively fostered engagement and idea sharing to boost performance, and may be considered for other QI projects.

Comparison of Pneumotachometer and Portable Digital Turbine Spirometry for Field-Based Assessment: An Air Quality, Environment, and Respiratory Outcomes in Bronchopulmonary Dysplasia Study.

Introduction: Data on the use of remote spirometry are limited in the pediatric population. We sought to assess the feasibility and accuracy of a digital turbine spirometer, Medical International Research (MIR) Spirobank Smart (MIR, New Berlin, WI, USA), compared with a pneumotachography spirometer, Pneumotrac (Vitalograph Inc., Lenexa, KS, USA), in field-based clinical research. Methods: This is a cross-sectional study of a subgroup of school-aged participants enrolled in the Air quality, Environment, and Respiratory Outcomes in Bronchopulmonary Dysplasia (BPD) study, who performed same-day paired coached baseline spirometry measurements from the Pneumotrac and MIR devices. Proportion of successful tests was estimated for each device and compared using McNemar's test. Correlation between devices forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) was analyzed by Lin's concordance correlation, and Bland-Altman plots were generated. Results: Twenty-one participants with history of BPD completed home spirometry maneuvers on both devices. The mean age of participants was 8.7 years. The mean FEV1 and FVC measurement was 81% predicted and 90.4% predicted, respectively. The proportion of acceptable tests appeared higher using Pneumotrac (81%) than when using MIR (67%), although without evidence of discordance (P = 0.317). Among subjects with successful tests on both devices, Lin's concordance correlation demonstrated moderate agreement (FEV1 r = 0.955, 95% confidence interval [CI]: 0.87-0.98; FVC r = 0.971, CI: 0.91-0.99). The mean difference in FEV1 between Pneumotrac and MIR was 0.079 L (95% limits of agreement were -0.141 to 0.298 L) and FVC was 0.075 L (95% limits of agreement were -0.171 to 0.322 L). These were relatively small and without evidence of systematic or volume-dependent bias. Conclusions: Utilizing turbine spirometers may be a promising and feasible way to perform pulmonary function testing for field research in children.

Defining and Promoting Pediatric Pulmonary Health: Assessing Lung Function and Structure.

Lifelong respiratory health is rooted in the structural and functional development of the respiratory system in early life. Exposures and interventions antenatally through childhood can influence lung development into young adulthood, the life stage with the highest achievable lung function. Because early respiratory health sets the stage for adult lung function trajectories and risk of developing chronic obstructive pulmonary disease, understanding how to promote lung health in children will have far reaching personal and population benefits. To achieve this, it is critical to have accurate and precise measures of structural and functional lung development that track throughout life stages. From this foundation, evaluation of environmental, genetic, metabolic, and immune mechanisms involved in healthy lung development can be investigated. These goals require the involvement of general pediatricians, pediatric subspecialists, patients, and researchers to design and implement studies that are broadly generalizable and applicable to otherwise healthy and chronic disease populations. This National Institutes of Health workshop report details the key gaps and opportunities regarding lung function and structure.

Is chronotype linked with adherence to the Mediterranean diet among adolescents? The EHDLA study.

BACKGROUND: No previous study has evaluated the relationship between chronotype and adherence to the Mediterranean diet among adolescents. The aim of the present study was to assess the association between chronotype and adherence to the Mediterranean diet in a sample of Spanish adolescents aged 12-17 years. METHODS: This study examined secondary data from 820 adolescents (55.5% girls) from the Eating Healthy and Daily Life Activities (EHDLA) study, which included a representative sample of adolescents aged 12-17 years from the Valle de Ricote (Region of Murcia, Spain). Adolescents' chronotype was evaluated with the Morningness/Eveningness Scale in Children. Adherence to the Mediterranean diet was determined through the Mediterranean Diet Quality Index for Children and Teenagers. RESULTS: The proportion of adolescents with an optimal Mediterranean diet was 37.6%. In relation to chronotype, we found that 24.5%, 69.4%, and 6.1% of the adolescents were classified as morning, intermediate, and evening types, respectively. After adjusting for several covariates, both evening- and intermediate-type adolescents showed lower odds of having optimal adherence to the Mediterranean diet (evening-type: odds ratio [OR] = 0.30, confidence interval [CI] 95% 0.12-0.72; intermediate-type: OR = 0.62, CI 95% 0.44-0.87) than morning-type adolescents. CONCLUSIONS: Chronotype could affect adherence to the Mediterranean Diet in adolescents, so it should be a factor to be considered in future studies assessing eating habits. IMPACT: No previous study has evaluated the relationship between chronotype and adherence to the Mediterranean diet among adolescents. Both evening- and intermediate-type adolescents showed lower odds of having optimal Mediterranean diet adherence than morning-type adolescents. These findings may indicate a need to promote eating healthy habits based on a more holistic approach, not only on the total energy expenditure or in specific food groups but also on the chronotype.

Health-Related Qualities of Life in School-Aged Children with Bronchopulmonary Dysplasia.

OBJECTIVE: To determine health-related quality of life (HRQOL) of school-aged children with bronchopulmonary dysplasia (BPD) using the standardized Patient-Reported Outcomes Measurement Information System (PROMIS) assessment tools. STUDY DESIGN: The Indoor Air Quality and Respiratory Morbidity in Children with BPD Study is an ongoing observational study of school-aged children with BPD. HRQOL is assessed at enrollment by 3 PROMIS questionnaires, Parent Proxy Scale-Global Health 7, Parent Proxy Psychological Stress Experiences-Short Form, and the Parent Proxy Profile-Profile-25. PROMIS data were tested for significant deviation from the standardized T-Score references for normative populations of children. RESULTS: Eighty-nine subjects enrolled in the AERO-BPD study had complete outcome data for HRQOL. The mean age was 9 (±2) years and 43% were female. Mean days on respiratory support totaled 96 (±40). Across all domains, school-aged children with BPD reported similar or slightly better outcomes than the reference sample. Statistically significant findings of lower depression (P < .0001), fatigue (P < .0001), and pain (P < .0001) scores were found; there was no difference in psychological stress experiences (P = .87), global health (P = .06), anxiety (P = .08), relationships (P = .80), and mobility (P = .59) domains. CONCLUSIONS: This study demonstrated that children with BPD may have less depression, fatigue, and pain HRQL than the general population. Once validated, these findings may offer reassurance to parents and providers caring for children with BPD.

Effect of radon exposure on asthma morbidity in the School Inner-City Asthma study.

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 (FE 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. FE 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/m3 ) and seasonality predicting log-transformed FE NO, forced expiratory volume in 1 s (FEV1 ) % predicted, forced vital capacity (FVC) % predicted, FEV1 /FVC, and asthma symptom-days was evaluated. RESULTS: Participants with high radon exposure had greater change in FE NO from warm to cold periods compared to low radon exposure (interaction p = 0.0013). Participants with >50th percentile radon exposure experience significant FE NO increase from warm to cold weather ( ß $\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.

Socioeconomic determinants of asthma health.

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.

Air pollution and childhood asthma.

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.

Environment and the development of severe asthma in inner city population.

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.

HEPA filtration intervention in classrooms may improve some students' asthma.

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.

Determinants of lung function across childhood in the Severe Asthma Research Program (SARP) 3.

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 FEV1 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 FEV1 at each assessment for up to 6 years. All models were adjusted for age, predicted FEV1 by Global Lung Function Initiative reference equations, race, sex, and height. Secondary outcomes included postbronchodilator FEV1 and prebronchodilator FEV1/forced vital capacity. RESULTS: A total of 862 spirometry assessments were performed for 188 participants. Factors associated with FEV1 include baseline Feno (B, -49 mL/log2 PPB; 95% CI, -92 to -6), response to a characterizing dose of triamcinolone acetonide (B, -8.4 mL/1% change FEV1 posttriamcinolone; 95% CI, -12.3 to -4.5), and maximal bronchodilator reversibility (B, -27 mL/1% change postbronchodilator FEV1; 95% CI, -37 to -16). Annually assessed time-varying factors of age, obesity, and exacerbation frequency predicted FEV1 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) FEV1 at each successive year. High exacerbation frequency (≥3) 12 to 24 months before assessment was associated with -34 mL (95% CI, -61 to -7) FEV1 at each successive year. CONCLUSIONS: In children with severe and nonsevere asthma, several clinically relevant factors predict FEV1 over time. Boys with recurrent exacerbations are at high risk of lower FEV1 through childhood.

Defining and identifying early-onset lung disease in cystic fibrosis with cumulative clinical characteristics.

BACKGROUND: Because of the heterogeneity in cystic fibrosis (CF) lung disease among young children, a clinical method to identify early-onset lung disease is needed. OBJECTIVE: To develop a CF early-onset lung disease (CFELD) scoring system by utilizing prospectively collected longitudinal data on manifestations in the first 3 years of life. DESIGN: We studied 145 infants born during 2012-2017, diagnosed through newborn screening by age 3 months, and followed to 36 months of age. Cough severity, pulmonary exacerbations (PEx), respiratory cultures, and hospitalizations were collected at each CF center visit (every 1-2 months in infancy and quarterly thereafter). These data were used to construct the CFELD system and to classify lung disease into five categories: asymptomatic, minimal, mild, moderate, and severe. RESULTS: The most frequent manifestation of CF early lung disease was MD-reported PEx episodes, PEx hospitalizations, and positive Pseudomonas aeruginosa cultures. Parent-reported cough severity was correlated with the number of respiratory hospitalizations (r = 0.48, p < 0.0001). The distribution of CFELD categories was 10% asymptomatic, 17% minimal, 29% mild, 33% moderate, and 12% severe. The moderate and severe categories occurred threefold higher in pancreatic insufficient (PI, 49%) versus sufficient subjects (16%), p < 0.0001. In addition to PI, gastrointestinal and nutrition-related hospitalizations, plasma cytokines interleukin (IL)-6 and IL-10, duration of CFTR modulator therapy, and type of health insurance were significant predictors of CFELD scores. CONCLUSION: The CFELD scoring system is novel, allows systematic evaluation of lung disease prognosis early, and may aid in therapeutic decision-making particularly in the initiation of CFTR modulator therapy.

Factors Influencing Classroom Exposures to Fine Particles, Black Carbon, and Nitrogen Dioxide in Inner-City Schools and Their Implications for Indoor Air Quality.

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.

Sex differences in the relationship of sleep-disordered breathing and asthma control among children with severe asthma.

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.

Development and Validation of the Asthma Exacerbation Risk Score Using Claims Data.

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.

Issues affecting young people with asthma through the transition period to adult care.

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.