TIDES III: Endocrine Disruption, Hormones, and Sex Differences in Adolescent Airway Health

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ABSTRACT Over the past decade, the first two phases of The Infant Development and Environment Study (TIDES) demonstrated that prenatal exposure to endocrine disrupting chemicals (EDCs), phthalates and bisphenols, influences the development of sexually dimorphic reproductive (anogenital distance) and neurodevelopmental (internalizing/externalizing behavior) outcomes in infancy and early childhood through hormonal disruption. TIDES III: Endocrine Disruption, Hormones, and Sex Differences in Adolescent Airway Health furthers this research to determine sex-specific outcomes in adolescent airway health. Impaired airway health in childhood shifts from male to female predominance, beginning in adolescence. Consequently, the morbidity and economic burden of airway disease and reduced lung function disproportionately affects females. Emerging evidence suggests exposures to phthalates and bisphenols may program sex-specific airway health impacts, in part, through sex steroid hormonal action. Differential sex steroid hormone production among males and females through adolescence may influence sex differences in airway function. In TIDES III, we propose to conduct two new study visits (ages 12 and 14 years) in 500 adolescents to assess urinary phthalates, bisphenols, serum sex steroid hormones, a targeted panel of 29 urine steroid metabolites, and airway assessment (wheeze questionnaire, spirometry with albuterol, fractional exhaled nitric oxide). Our first aim will evaluate longitudinal associations between prenatal and adolescent EDCs in relation to airway outcomes: the ratio of forced expiratory volume in one second (FEV1) over forced vital capacity (FVC), forced expiratory flow (FEF25-75), fractional exhaled nitric oxide (FENO) and current asthma during adolescence. The second aim will evaluate associations between prenatal and adolescent serum sex steroid hormones and airway outcomes in adolescence. The third aim will determine relationships between prenatal EDCs in relation to sex steroid hormones and urinary steroid metabolites, and a final exploratory aim will evaluate hormones and hormone metabolites as mediators between EDCs and airway outcomes. Employing a targeted urinary steroid metabolite approach will enable identification of novel metabolites involved in sex steroid synthesis that may be affected by EDCs. This study will directly address imperatives from The National Academy of Medicine and the National Institutes of Health to examine sex as a biological variable. Findings will improve our understanding of biological sex disparities. Our multi-site, longitudinal study will identify modifiable factors affecting biological sex differences in airway health that could lead to the development of novel clinical predictive tools and policies that aim to reduce EDC exposures.