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

环境因素对代谢和呼吸系统健康的发育影响的生命全程方法（LA DREAMERs）

• 批准号: 10469376
• 负责人: Theresa M Bastain
• 金额: $ 555.26万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-21 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10469376
• 关键词: 6 year old; Address; Adult; Affect; Age-Years; Air Pollutants; Air Pollution; Albumins; Animal Model; Area; Aromatic Polycyclic Hydrocarbons; Arsenic; Asthma; Behavioral; Biological; Biological Markers; Blood; Body Composition; Body mass index; Chemicals; Child; Child Health; Childhood; Childhood Asthma; Cohort Studies; DNA Methylation; Data; Development; Disease; Environment; Environmental Exposure; Environmental Health; Environmental Risk Factor; Epigenetic Process; Evaluation; Exposure to; Generations; Goals; Health; Heavy Metals; Human; Investigation; Knowledge; Lead; Life; Life Cycle Stages; Longitudinal cohort; Malnutrition; Maternal Exposure; Mediator of activation protein; Metabolic; Metal exposure; Metals; Methods; Modeling; Molecular; Mothers; Natural Immunity; Neonatal; Obesity; Outcome; Oxides; Pathway interactions; Population; Positioning Attribute; Pregnancy; Quinones; Research; Research Project Grants; Risk; Role; Series; Serum Albumin; Smoke; Smoking; Spottings; Statistical Methods; Time; Tobacco smoke; Umbilical Cord Blood; adduct; ambient air pollution; biomarker development; cohort; critical period; cytokine; disorder risk; early childhood; early life exposure; emerging adult; emerging adulthood; environmental agent; environmental stressor; epidemiologic data; human model; immune function; improved; innovation; novel; novel marker; obesity development; obesity in children; pollutant; population based; prenatal; prenatal environmental exposure; prenatal exposure; programs; pulmonary function; respiratory; respiratory health; social; social stressor; spatiotemporal; virtual

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.

抽象的   人类和动物模型中的科学证据表明，产前，早期和潜在的证据 跨代环境暴露会导致儿童健康缺陷和终身后果 在后代。特别是，暴露于升高的环境空气污染，区域和接近 - 道路污染物和重金属与呼吸道和/或代谢健康结果有关 在童年时期。关于产前暴露对这些结果的影响，实际上是了解的，实际上是 关于前几代的暴露是否会影响呼吸和代谢，尚无任何了解 结果 - 说明科学知识中的关键差距。研究刚刚开始消除效果 使用新型的曝光，生物介质和创新的生物标志物在整个生活课程中的混合物 统计方法。我们将在题为“生命课程方法的新提案中解决这些关键差距 环境因素对代谢和呼吸健康的发展影响（LA） 梦想家）。 研究环境对儿童和新兴的发展起源的贡献 成人呼吸和代谢健康。洛杉矶梦想家将结合来自两个人口的8931名受试者 基于涵盖产前到成年初期的儿童的纵向人群 - 环境和社会压力源（MADRES）和儿童健康的孕产妇和发展风险 研究（CHS）队列。拟议的研究解决了现场的以下关键问题：1）做产前 和幼儿环境暴露改变了童年和新兴的成人呼吸和代谢 健康？如果是这样，整个生命过程中是否存在关键的接触时期？ 2）改变的作用是什么 潜在生物学机制中的免疫功能？ 3）将更精确的暴露评估 环境空气污染物通过应用国家空间时间模型或生物标志物的发展 新生儿干血点和脐带血可以鉴定混合物的关键成分？ 4）做 产前环境暴露会引起变革性的表观遗传学改变，以解释增加 疾病的风险？ 5）创新的统计方法可以解开暴露混合物对多种的影响 健康结果？我们将通过关注环境的健康影响和 近路空气污染，金属（AS，PB，CD，HG）和新型白蛋白加合物（例如，反应性电泳 在一系列三个不同的研究项目中，例如氧化的多芳烃和奎因酮） 专注于呼吸健康（ECHO焦点区域＃1），代谢健康（Echo Focus＃2）和统计 方法。通过将Madres和CHS相结合，我们可以独特地回答环境健康 使用变革型生活课程方法，与呼吸和代谢健康有关的问题， 从怀孕到22岁，跨越几代人。