Exposomic Approach to Identifying WTC Exposures and Effects in Survivor Youth.

项目总结 在世贸中心(WTC)附近生活、工作或上学的孕妇和儿童 2001年9月11日经历了各种心理和化学暴露，具有潜在的不良影响。 对以后的健康和发展的影响。与心理影响相比，身体健康的影响 早年接触世界贸易中心(WTC)灾难的人仍然知之甚少。这是特别的 重要的是众所周知的健康和疾病的发育起源(DOHaD)概念表明 发生在敏感发育窗口的暴露可能会在以后导致不利的健康后果 生活。我们最近证明，新生儿和儿童暴露在化学品(例如，二恶英、 已知与WTC有关的全氟烷基物质(PFAS)对健康造成不良后果 包括不良生育结局、血脂水平改变和哮喘。然而，将WTC的总体特征 暴露--包括心理和化学暴露--一直具有挑战性，限制了我们 确定与WTC相关的健康影响，这些影响可能会随着受影响的儿童年龄的增长而出现。在这里，我们雇佣了 分子实验室技术的进步，使高分辨率方法能够测量 数以千计的外源化学物质及其对这些暴露的内源性生物反应。这些 强大的暴露组学和代谢组学方法已被用于提高疾病预后和诊断 以及提供对新生儿、儿童和成人疾病发病机制的洞察。使用WTC的两个队列- 接触过的新生儿和年轻人，我们可以1)识别与以下物质有关的外源化学特征 传统的WTC暴露措施，包括基于接近程度的暴露指标和靶向生物标志物 相关的WTC暴露指数(目标1)；2)确定反映生物的代谢特征 对常规WTC暴露措施和与WTC相关的心理应激源的反应 暴露(目标2)；以及3)确定WTC暴露是否与外源化学特征有关(目标3a)和 代谢组学特征(目标3b)与儿童的不良健康后果有关。如果得到确认， 我们在这两个脆弱的WTC储存的血液中发现了外源化学和代谢组学特征- 暴露人群将提供独特的指纹，可用于预测与WTC相关的不良结果 这可能会随着接触病毒的儿童进入成年期而出现。

PROJECT SUMMARY Pregnant women and children who lived, worked or attended school near the World Trade Center (WTC) on September 11, 2001 experienced a variety of psychological and chemical exposures with potential adverse consequences for later health and development. In contrast to psychological effects, physical health effects of early life exposure to the World Trade Center (WTC) disaster remain poorly understood. This is particularly important as the well-known developmental origins of health and disease (DoHAD) concept indicates that exposures occurring during sensitive developmental windows may lead to adverse health outcomes in later life. We have recently demonstrated that neonates and children exposed to chemicals (e.g., dioxins, perfluoroalkylsubstances (PFAS)) known to be associated with WTC experience adverse health outcomes including adverse birth outcomes, altered lipid levels, and asthma. However, characterizing the totality of WTC exposure—including both psychologicial and chemical exposures—has been challenging, limiting our ability to identify WTC-related health effects, which are likely to emerge as exposed children age. Here, we employ advances in molecular laboratory technology, which have enabled high-resolution methods to measure thousands of exogenous chemicals and their endogenous biological responses to these exposures. These powerful exposomic and metabolomic approaches have been used to enhance disease prognosis and diagnosis as well as provide insight into disease pathogenesis in neonates, children and adults. Using two cohorts of WTC- exposed neonates and youth, we can 1) identify an exogenous chemical signature that is associated with conventional WTC exposure measures including proximity-based exposure metrics and targeted biomarkers associated WTC exposure indices (Aim 1); 2) identify a metabolomic signature that reflects the biological response to both conventional WTC exposure measures and psychological stressors associated with WTC exposure (Aim 2); and 3) determine if WTC-exposure related exogenous chemical signatures (Aim 3a) and metabolomic signatures (Aim 3b) are associated with adverse health outcomes in children. If confirmed, the exogenous chemical and metabolomic signatures we identify in blood stored from these two vulnerable WTC- exposed populations will provide unique fingerprints that can be used to predict adverse WTC-related outcomes that may emerge as exposed children age into adulthood.