Environmental Predictors of Treatment Responsiveness for Pediatric Acute Asthma Exacerbations

PROJECT SUMMARY Acute exacerbations are the primary cause of morbidity and mortality among children with asthma. Current treatment for acute asthma exacerbations in the pediatric emergency department (ED) follows a “one-size-fits- all” approach, including inhaled bronchodilators and systemic corticosteroids. However, treatment response to initial protocolized therapies is variable and unpredictable presenting a significant management challenge for ED clinicians. The factors driving the heterogeneity in ED treatment response are poorly understood, which has impeded accurate prediction of treatment response, development of effective therapeutics, and advances in ED asthma management. Thus, there is a critical need to better characterize the factors driving treatment response to inform precise ED treatment strategies for asthma exacerbations. We have found that almost all ED asthma exacerbations are associated with a respiratory virus and that specific viral species influence ED treatment response. However, the role of nonviral causes of asthma exacerbations, such as outdoor air pollution and environmental allergens, are less understood. These critical environmental factors are strongly associated with asthma exacerbation occurrence and severity, but their impact on treatment response remains unknown. This R03 application proposes a proof-of-principle study to investigate the role of outdoor air pollution and environmental allergens in driving treatment response in children with asthma exacerbations in the ED. Leveraging robust clinical data and banked biosamples, we will determine the association between outdoor air pollutant exposure (Aim 1) and aeroallergen sensitization (Aim 2) and acute asthma exacerbation treatment responsiveness in the ED. This work builds on the PI’s K23 findings and will provide critical preliminary data for a multicenter R01 application aimed at validation of a comprehensive clinical prediction rule incorporating environmental, biologic, and physiologic predictors to differentiate ED treatment responsiveness early in the ED course. An effective prediction rule will improve outcomes by guiding clinical decisions and facilitating timely and appropriate therapeutic interventions and disposition decisions. This work represents a paradigm shift in the ED by moving from a “one-size-fits-all” to a personalized, phenotype- directed approach for the management of asthma exacerbations.