Multiple long-term environmental exposures and incidence of asthma

ABSTRACT Asthma is a disease of the respiratory tract that results in reversible narrowing of airways, leading to symptoms ranging from wheezing and dyspnea to death. The US Centers for Disease Control estimate that over 26 million Americans live with asthma. Incidence of asthma is more prevalent in boys in childhood, but is more prevalent in women in adulthood, and there are wide disparities in asthma incidence by race/ethnicity, socioeconomic status, and exposures to environmental factors. A growing body of evidence has suggested that individual environmental exposures (e.g. air pollution) are associated with asthma incidence, however, other environmental factors are understudied. Furthermore, most studies have only examined the health effects associated with one environmental exposure at a time, or only in one stage of the life course (e.g. prenatal). In reality, individuals are exposed to multiple exposures simultaneously. However, without rigorous approaches to estimate the health effects associated with multiple exposures across decades, the environment-related health burden will likely be underestimated, especially as these interconnections may be changing due to climate change. Using the vast resources of the nationwide prospective Nurses’ Health Studies (NHS, NHSII, NHS3), Health Professionals’ Follow-Up Study (HPFS) and the Growing Up Today Studies (GUTS), we are in a unique position to study the complex associations of multiple long-term environmental exposures on incidence of asthma. GUTS participants can be followed from the prenatal period through young adulthood, while all other cohorts can be followed throughout adulthood. Using the addresses of each participant during follow-up, we are able to append information on multiple chemical stressors (air pollution, traffic), physical stressors (temperature, humidity, ultraviolet radiation), features of the built and natural environment (greenness, blue space, walkability) to more than 300,000 participants for decades. Plasma metabolomics in adulthood are available for over 20,000 participants. These data will be used to explore biological pathways that may underlie the associations with the environmental exposures. We will assess the following specific aims: (1) Determine how multiple long-term environmental exposures are associated with incident asthma; (2) Identify demographic (e.g., age, sex, race/ethnicity), behavioral, and social environmental characteristics that modify the associations of multiple environmental exposures with incident asthma; (3) Explore how features of the plasma metabolome may mediate the impact of the multiple environmental exposures in adulthood on incidence of asthma. Our findings will provide valuable information on the role of modifiable exposures on risk of asthma, how multiple exposures interact, and factors that impact resiliency.