Environmental Determinants of Asthma Exacerbation in Children

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Asthma exacerbations are a public health problem that disproportionately affects urban and minority low-income children. Multiple factors contribute to poor asthma outcomes including 1) exposure to environmental asthma triggers that worsen symptoms and lead to exacerbations, and 2) viral infections. We hypothesize that respiratory viruses and multiple respirable environmental exposures both independently and interactively provoke airway epithelial and immune responses in children with asthma that lead to asthma exacerbations and exacerbation- related outcomes. To test this hypothesis, we propose the following aims: Aim 1: Investigate how individual and composite asthma-relevant environmental exposures (viruses, allergens, tobacco smoke, nitrogen dioxide, ozone, particulate matter, molds, endotoxin) contribute to asthma exacerbations and related outcomes (lung dysfunction, airway inflammation, severity, control) in urban children with exacerbation-prone asthma. Aim 2: Determine if individual and composite environmental exposures are associated with differences in airway epithelial and immune responses (bronchial and nasal) with Project 2, PI: Seibold. Aim 3: Determine which airway biological responses to environmental exposures mediate exposure-exacerbation relationships. Our proposal seeks to improve scientific knowledge about the environmental determinants of asthma exacerbations by seasonally measuring and tracking environmental exposures that are known to worsen asthma, and gaining insights to the mechanisms by which they exert their effects. As a result of the synergy with the other PPG components and Cores, we will be able to study the relationship of environment exposures to exacerbations and exacerbation-related outcomes (Clinical Core and Biostatistics, Bioinformatics and Environmental Sampling Core), and to respiratory viruses and airway responses (Project 2). By achieving the proposed aims, this knowledge will lead to a better understanding of exposure susceptibility, better prediction of exacerbations, and multiple targets for environmental and therapeutic interventions. Ultimately, the goal is to prevent asthma exacerbations, which could lead to lower healthcare costs, reduced health disparities, and better quality of life.