Lifecourse Approach to Developmental Repercussions of Environmental Agents on Metabolic and Respiratory health (LA DREAMERs)

摘要 在人类和动物模型中的科学证据表明，产前，早期生活和潜在的 跨代环境暴露可导致儿童健康缺陷和终身后果 在后代中。特别是，暴露于高环境空气污染，区域和近- 道路污染物和重金属与呼吸和/或代谢健康结果有关 在童年。关于产前暴露对这些结果的影响知之甚少， 对于前几代人的暴露是否会影响呼吸和代谢， 成果-说明科学知识方面的重大差距。研究才刚刚开始理清 使用新的暴露生物标志物、生物介质和创新的 统计方法我们将在一项题为"生命过程方法， 环境因子对代谢和呼吸系统健康的发育抑制作用 梦想家）。"该提案的主要目标是采取跨代生命历程的方法， 研究环境对儿童发展起源的贡献， 成人呼吸和代谢健康。LA DREAMERS将结合来自两个人群的联合收割机8931名受试者- 基于纵向队列的儿童，涵盖了产前到成年早期的暴露期- 环境和社会应激源（MADRES）与儿童健康的孕产妇和发育风险 研究（CHS）队列。该研究提出了以下关键问题：1）产前检查 儿童早期环境暴露改变了儿童和成人的呼吸和代谢 健康？如果是，在整个生命过程中是否存在暴露的关键时期？2)改变的作用是什么 免疫功能的潜在生物学机制？3)更精确的暴露评估 环境空气污染物，通过应用国家时空模型或开发生物标志物， 新生儿干血斑和脐带血可以确定混合物的关键成分？4)做 产前环境暴露诱导跨代表观遗传改变，有助于解释增加 疾病风险？5)创新的统计方法能否解开暴露混合物对多重 健康成果？我们将通过关注环境和环境对健康的影响来解决这些重要问题。 近道路空气污染、金属（As、Pb、Cd、Hg）和新型白蛋白加合物（例如反应性亲电体 例如氧化的多环芳烃和醌类化合物）， 专注于呼吸健康（ECHO焦点领域#1），代谢健康（ECHO焦点领域#2）和统计 方法.通过结合MADRES和CHS，我们在解决环境健康问题方面处于独特的地位。 使用跨代生命过程方法的呼吸和代谢健康问题， 从怀孕到22岁，跨越几代人。

ABSTRACT   Scientific evidence in both humans and animal models suggests that prenatal, early life and potentially transgenerational environmental exposures can result in childhood health deficits and life-long consequences in subsequent generations. In particular, exposures to elevated ambient air pollution, regional and near- roadway pollutants, and heavy metals have been associated with respiratory and/or metabolic health outcomes in childhood. Much less is known about the effects of prenatal exposures on these outcomes, and virtually nothing is known about whether exposures during previous generations can affect respiratory and metabolic outcomes - illustrating critical gaps in scientific knowledge. Studies are just beginning to disentangle the effects of mixtures across the life course using novel biomarkers of exposure, biological mediators and innovative statistical methods. We will address these critical gaps in a new proposal entitled “Life course Approach to Developmental Repercussions of Environmental Agents on MEtabolic and Respiratory health (LA DREAMERs).”The major goal of this proposal is to take a transgenerational life course approach to studying the contribution of the environment to the developmental origins of childhood and emerging adult respiratory and metabolic health. LA DREAMERs will combine 8931 subjects from two population- based longitudinal cohorts of children that cover the prenatal to early adulthood periods of exposure- the Maternal And Developmental Risks from Environmental and Social Stressors (MADRES) and Children's Health Study (CHS) cohorts. The proposed study addresses the following key questions in the field: 1) Do prenatal and early childhood environmental exposures alter childhood and emergent adult respiratory and metabolic health? If so, are there critical periods of exposure across the lifecourse? 2) What is the role of altered immune functions in the underlying biological mechanisms? 3) Will more precise exposure assessment for ambient air pollutants through application of a national spatiotemporal model or development of biomarkers in neonatal dried blood spots and cord blood allow critical components of the mixture to be identified? 4) Do prenatal environmental exposures induce transgenerational epigenetic alterations that help explain increased risk of disease? 5) Can innovative statistical approaches untangle the effects of exposure mixtures on multiple health outcomes? We will address these important questions by focusing on the health effects of ambient and near-roadway air pollution, metals (As, Pb, Cd, Hg), and novel albumin adducts (e.g. reactive electrophiles such as oxidized polyaromatic hydrocarbons and quinones) in a series of three distinct research projects focused on respiratory health (ECHO Focus area #1), metabolic health (ECHO Focus area #2) and statistical methods. By combining MADRES and CHS, we are uniquely positioned to answer environmental health questions pertaining to respiratory and metabolic health using a transgenerational life course approach, spanning from pregnancy through 22 years of age and across generations.