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

项目摘要 在世界贸易中心（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， 对以后的健康和发展的影响。与心理影响相反， 早期生活暴露于世界贸易中心（WTC）灾难仍然知之甚少。这是特别 众所周知的健康和疾病的发展起源（DoHAD）概念表明， 在敏感的发育窗口期间发生的暴露可能导致以后的不良健康结果。 生活我们最近已经证明，新生儿和儿童接触化学品（例如，二恶英， 已知与WTC相关的全氟烷基物质（PFAS）经历了不利的健康后果 包括不良的出生结果、血脂水平改变和哮喘。然而，表征世贸中心的整体 确定性--包括心理上的和化学上的确定性--一直具有挑战性，限制了我们的能力， 确定与世卫组织有关的健康影响，这些影响可能随着受影响儿童年龄的增长而出现。在这里，我们雇用 分子实验室技术的进步，使高分辨率的方法来测量 数以千计的外源性化学物质及其对这些暴露的内源性生物反应。这些 强大的代谢组学和代谢组学方法已被用于提高疾病的预后和诊断 以及提供对新生儿、儿童和成人疾病发病机理的深入了解。使用两组WTC- 暴露的新生儿和青年，我们可以1）确定一个外源性的化学签名， 传统的WTC暴露测量，包括基于邻近度的暴露度量和靶向生物标志物 相关的WTC暴露指数（目标1）; 2）确定反映生物学特征的代谢组学特征 对传统的WTC暴露措施和与WTC相关的心理应激源的反应 暴露（目标2）;和3）确定WTC暴露相关的外源性化学特征（目标3a）， 代谢组学特征（Aim 3b）与儿童的不良健康结果相关。如果得到证实， 我们在这两个脆弱的WTC储存的血液中发现了外源性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相关的不良后果 可能会随着暴露的儿童进入成年而出现。

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.