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

潮汐 III：内分泌干扰、激素和青少年气道健康的性别差异

• 批准号: 10684016
• 负责人: Sheela Sathyanarayana
• 金额: $ 125.64万
• 依托单位: SEATTLE CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-05-01 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10684016
• 关键词: Academy; Address; Adolescence; Adolescent; Adolescent Development; Affect; Age; Airway Disease; Albuterol; Allergic; Asthma; Attenuated; Behavioral; Biological; Biology; Chemical Exposure; Chemicals; Childhood; Data; Development; Economic Burden; Endocrine Disruptors; Endocrine disruption; Environment; Estrogens; Exhalation; Exposure to; Female; Forced expiratory volume function; Gonadal Steroid Hormones; Homeostasis; Hormonal; Hormones; Infant; Infant Development; Inflammation; Longitudinal Studies; Measures; Mediating; Mediator; Medicine; Modification; Morbidity - disease rate; Nitric Oxide; Outcome; Pathway interactions; Phase; Phenols; Play; Policies; Positioning Attribute; Pregnancy; Preventive care; Production; Pulmonary Inflammation; Questionnaires; Research; Risk; Role; Serum; Sex Differences; Site; Spirometry; Steroid biosynthesis; Steroids; Testing; Testosterone; Time; United States National Institutes of Health; Urine; Visit; Vital capacity; Wheezing; airway inflammation; androgenic; anogenital distance; biological sex; clinical predictors; cohort; diagnostic tool; early childhood; estrogen disruption; estrogenic; externalizing behavior; health management; improved; infancy; injured airway; insight; lung health; male; novel; phthalates; predictive tools; prenatal; prenatal exposure; programs; pulmonary function; reproductive; respiratory health; sex; sex disparity; sexual dimorphism; steroid hormone; urinary

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.

抽象的 在过去的十年中，婴儿发育与环境研究（TIDES）的前两个阶段 证明产前接触内分泌干扰化学物质（EDC）、邻苯二甲酸盐和双酚， 影响性二态性生殖（肛门生殖器距离）和神经发育的发育 （内化/外化行为）通过荷尔蒙干扰导致婴儿期和幼儿期的结果。 潮汐 III：青少年气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 确定青少年气道健康中性别特异性结果的研究。儿童期气道健康受损 从青春期开始，男性主导转向女性主导。因此，发病率和 气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，接触邻苯二甲酸盐和双酚可能会对特定性别的气道健康产生影响， 部分是通过性类固醇激素的作用。男性和女性之间性类固醇激素产生的差异 女性在青春期可能会影响气道功能的性别差异。在 TIDES III 中，我们建议 对 500 名青少年进行两项新的研究访问（12 岁和 14 岁），以评估尿中邻苯二甲酸盐的含量， 双酚、血清性类固醇激素、29 种尿液类固醇代谢物的目标组和气道 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 评估产前和青少年 EDC 与气道结果之间的纵向关联： 一秒用力呼气量 (FEV1) 与用力肺活量 (FVC) 之比，用力呼气流量 (FEF25-75)、呼出一氧化氮分数 (FENO) 和青春期当前的哮喘。第二个目标将 评估产前和青少年血清性类固醇激素与气道结局之间的关联 青春期。第三个目标是确定产前 EDC 与性类固醇之间的关系 激素和尿类固醇代谢物，最终的探索目标是评估激素和激素 代谢物作为 EDC 和气道结果之间的中介。使用靶向尿类固醇 代谢物方法将能够鉴定参与性类固醇合成的新代谢物，这些代谢物可能是 受 EDC 影响。这项研究将直接解决美国国家医学院和 美国国立卫生研究院将性别作为一个生物变量进行检查。研究结果将加深我们对 生理上的性别差异。我们的多地点纵向研究将确定影响生物的可改变因素 气道健康的性别差异可能导致新型临床预测工具和政策的开发 旨在减少 EDC 暴露。

项目成果

Pregnancy intention and phthalate metabolites among pregnant women in The Infant Development and Environment Study cohort.

• DOI: 10.1111/ppe.12674
• 发表时间: 2020-11
• 期刊: Paediatric and perinatal epidemiology
• 影响因子: 2.8
• 作者: Lyden GR;Barrett ES;Sathyanarayana S;Bush NR;Swan SH;Nguyen RHN
• 通讯作者: Nguyen RHN

Anogenital distance and penile width measurements in The Infant Development and the Environment Study (TIDES): methods and predictors.

• DOI: 10.1016/j.jpurol.2014.11.018
• 发表时间: 2015-04
• 期刊: JOURNAL OF PEDIATRIC UROLOGY
• 影响因子: 2
• 作者: Sathyanarayana, Sheela;Grady, Richard;Redmon, J. B.;Ivicek, Kristy;Barrett, Emily;Janssen, Sarah;Nguyen, Ruby;Swan, Shanna H.
• 通讯作者: Swan, Shanna H.

Prenatal sex hormones and behavioral outcomes in children.

• DOI: 10.1016/j.psyneuen.2019.104547
• 发表时间: 2020-03
• 期刊: Psychoneuroendocrinology
• 影响因子: 3.7
• 作者: Day DB;Collett BR;Barrett ES;Bush NR;Swan SH;Wang C;Sathyanarayana S;TIDES Study team
• 通讯作者: TIDES Study team

First Trimester Phthalate Exposure and Infant Birth Weight in the Infant Development and Environment Study.

• DOI: 10.3390/ijerph13100945
• 发表时间: 2016-09-23
• 期刊: International journal of environmental research and public health
• 作者: Sathyanarayana S;Barrett E;Nguyen R;Redmon B;Haaland W;Swan SH
• 通讯作者: Swan SH

Phthalate mixtures in pregnancy, autistic traits, and adverse childhood behavioral outcomes.

• DOI: 10.1016/j.envint.2020.106330
• 发表时间: 2021-03
• 期刊: ENVIRONMENT INTERNATIONAL
• 影响因子: 11.8
• 作者: Day, Drew B.;Collett, Brent R.;Barrett, Emily S.;Bush, Nicole R.;Swan, Shanna H.;Nguyen, Ruby H. N.;Szpiro, Adam A.;Sathyanarayana, Sheela
• 通讯作者: Sathyanarayana, Sheela