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

摘要 在过去的十年中，婴儿发展和环境研究（TIDES）的前两个阶段 证明产前接触内分泌干扰化学品（EDCs），邻苯二甲酸盐和双酚， 影响性二型生殖（肛门生殖器距离）和神经发育的发展 （内化/外化行为）的结果在婴儿期和幼儿期通过激素中断。 潮汐三：内分泌干扰，激素，和青少年气道健康的性别差异进一步这一点 研究以确定青少年气道健康的性别特异性结果。儿童气道健康受损 从青春期开始由男性主导转变为女性主导因此，发病率和 呼吸道疾病和肺功能下降的经济负担对女性的影响尤为严重。新兴 有证据表明，邻苯二甲酸酯和双酚的暴露可能会对性别特异性气道健康产生影响， 部分是通过性类固醇激素的作用。男性和女性性类固醇激素的差异 青春期的女性可能影响气道功能的性别差异。在潮汐III中，我们建议 在500名青少年中进行两次新的研究访视（12岁和14岁），以评估尿邻苯二甲酸盐， 双酚、血清性类固醇激素、29种尿类固醇代谢物的靶向组和气道 评估（喘鸣问卷、沙丁胺醇肺功能测定、呼出气一氧化氮分数）。我们的首要目标是 评估产前和青少年内分泌干扰物与气道结果之间的纵向联系： 一秒用力呼气量（FEV 1）与用力肺活量（FVC）的比值，用力呼气流量 （FEF 25 -75）、呼出气一氧化氮分数（FENO）和青春期哮喘。第二个目标将 评估产前和青春期血清性类固醇激素与气道结果之间的关系， 青春期第三个目标是确定产前内分泌干扰物与性类固醇之间的关系 激素和尿类固醇代谢物，最终的探索性目标将评估激素和激素 代谢物作为内分泌干扰物和气道结果之间的介质。使用有针对性的尿类固醇 代谢物的方法将能够鉴定参与性类固醇合成的新代谢物， 受EDCs影响。这项研究将直接解决国家医学科学院和 美国国立卫生研究院研究性别作为一个生物变量。研究结果将提高我们对 生理性别差异我们的多中心纵向研究将确定影响生物学的可改变因素， 气道健康的性别差异可能导致新的临床预测工具和政策的发展 旨在减少EDC暴露。

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.