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

摘要 在过去的十年中，婴儿发育和环境研究的前两个阶段 证明产前暴露于内分泌干扰物(EDCs)、邻苯二甲酸盐和双酚， 影响性二态生殖发育(肛门距离)和神经发育 (内化/外化行为)通过荷尔蒙紊乱在婴儿期和儿童期早期的结果。 潮汐III：青少年呼吸道健康中的内分泌干扰、激素和性别差异进一步推动了这一点 研究确定青少年呼吸道健康中特定性别的结果。儿童时期呼吸道健康受损 从青春期开始，从男性占优势转变为女性占优势。因此，发病率和 呼吸道疾病的经济负担和肺功能下降对女性的影响不成比例。新兴 有证据表明，接触邻苯二甲酸盐和双酚可能会对特定性别的呼吸道健康产生影响， 部分是通过性激素的激素作用。男性和女性性激素分泌的差异性 女性在青春期可能会影响呼吸道功能的性别差异。在《潮汐3》中，我们建议 对500名青少年进行了两次新的研究访问(年龄分别为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种尿样类固醇代谢物的靶向小组，以及呼吸道 评估(喘息问卷、沙丁胺醇肺活量测定、呼出一氧化氮分数)。我们的首要目标是 评估产前和青春期内分泌细胞与呼吸道结局的纵向相关性： 1秒用力呼气量(FEV1)与用力肺活量(FVC)之比，用力呼气流量 (FEF25-75)、部分呼出的一氧化氮(FeNO)和目前的青春期哮喘。第二个目标是 评价围产期和青春期血清性类固醇激素与呼吸道结局的关系 青春期。第三个目标将确定产前内皮细胞与性激素的关系。 激素和尿类固醇代谢物，最终的探索目标将评估激素和激素 代谢物作为内分泌细胞和呼吸道结果之间的中介。使用有针对性的尿路类固醇 代谢物方法将使识别与性激素合成有关的新代谢物成为可能 受EDC的影响。这项研究将直接解决来自国家医学科学院和 美国国立卫生研究院将性别作为生物变量进行检查。这些发现将提高我们对 生理性别差异。我们的多点纵向研究将确定影响生物的可修改因素 呼吸道健康中的性别差异可能导致新的临床预测工具和政策的开发 旨在减少EDC的风险敞口。

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.