Asthma treatment response modified by fine particulate matter, nitrogen dioxide, and ozone among Black children: A reanalysis of the AsthmaNet Best African American Response to Asthma Drugs trial

Background: Asthma morbidity significantly affects children of all racial backgrounds; however, Black children experience a greater disease burden than children from other racial groups. Despite the known influence of air pollution on asthma outcomes, its role in the efficacy of asthma treatments remains underexplored. Objective: We sought to examine how exposure to particulate matter <2.5 μm (PM2.5), nitrogen dioxide (NO2), and ozone (O3) influenced treatment outcomes in the National Institutes of Health AsthmaNet Best African American Response to Asthma Drugs trial. Methods: The trial randomized 224 Black children to 4 asthma treatments consisting of an inhaled corticosteroid (ICS) and long-acting β-agonist (LABA) administered in a randomized crossover fashion. Treatment efficacy was assessed by the frequency of asthma exacerbations, percent predicted FEV1, and annualized asthma control days. Residential exposures to PM2.5, NO2, and O3 were estimated using a validated spatiotemporal model. Mixed-effects models were used to evaluate the interaction between pollution exposure and treatment efficacy, adjusting for age, household triggers, and trial site. Results: PM2.5, NO2, and O3 exposures ranged substantially across participants from 2.28 to 15.3 μg/m³, 2.34 to 63.7 ppm, and 2.57 to 23.7 ppb, respectively. NO2 and PM2.5 exposures were not associated with increased exacerbations post-treatment (P for interaction = .15 and .08, respectively). However, NO2 exposure significantly modified the effect of high-dose ICS+LABA therapy on lung function. Children with below median NO2 exposures while receiving ICS+LABA therapy had a reduction of 5.86 (95% CI 1.16, 10.56) in percent predicted FEV1 compared with children with above median NO2 exposures. Conclusion: Residential high NO2 exposure may significantly attenuate the efficacy of ICS+LABA therapy on lung function in Black children. These findings suggest the need to consider environmental factors in clinical trials and asthma management strategies.