Prenatal PM2.5 and programming of respiratory outcomes: Placental biomarkers and effect modification by stress

产前 PM2.5 和呼吸系统结局的规划：胎盘生物标志物和压力的影响修正

• 批准号: 9223449
• 负责人: Alison G Lee
• 金额: $ 18.99万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-03-01 至 2022-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9223449
• 关键词: 3 year old; Address; Age; Air Pollutants; Air Pollution; Asthma; Award; Biological; Biological Markers; Birth; Caliber; Cardiovascular Diseases; Cell Differentiation process; Cell physiology; Child; Child health care; Childhood; Chronic; Code; Coupled; DNA; DNA Methylation; DNA copy number; Data; Databases; Development; Dose; Environment; Environmental Exposure; Environmental Health; Epigenetic Process; Event; Exposure to; Fetus; Frequencies; Funding; Future; Genes; Goals; Health; Joints; Knowledge; Lead; Length; Life; Link; Literature; Longitudinal cohort study; Low Income Population; Low income; Lung; Lung diseases; Maternal-Fetal Exchange; Measures; Mediating; Mediation; Mentors; Methods; Methylation; Mitochondria; Mitochondrial DNA; Mitochondrial Proteins; Modeling; Modification; Molecular; Morbidity - disease rate; Mothers; Neurocognitive; Nuclear; Obesity; Oscillometry; Outcome; Oxidative Stress; Particulate Matter; Pathway interactions; Perinatal; Phenotype; Physicians; Placenta; Play; Population; Predisposition; Pregnancy; Prevention strategy; Process; Prospective Studies; Prospective cohort; Protein Region; Proteins; Psychosocial Stress; Reactive Oxygen Species; Research; Research Design; Resistance; Resources; Respiratory physiology; Risk; Risk Factors; Role; Scientist; Signal Transduction; Site; Statistical Methods; Stress; Tissues; Toxicant exposure; Training; Umbilical Cord Blood; Wheezing; ambient air pollution; career; cohort; cost effective; early childhood; early life exposure; epigenetic marker; epigenome; fetal; fetal programming; in utero; indexing; interest; maternal stress; modifiable risk; molecular marker; novel; oxidative damage; postnatal; prenatal; prenatal environmental exposure; prenatal exposure; prenatal stress; programs; respiratory; respiratory health; response; secondary analysis; skills; social; spatiotemporal; statistics; telomere

Project Summary I am a physician-scientist with a primary research interest in the programming of respiratory diseases by prenatal/early-life environmental exposures, such as air pollution and maternal stress, with particular interest in the programming mechanisms at the maternal-fetal interface, i.e., the placenta. With research linking ambient air pollution to childhood respiratory disease, the goal of this proposal is to add to the growing research linking urban air pollutants, stress, and respiratory development by identifying sensitive windows of exposure and identifying novel mitochondrial and telomere biomarkers through which in utero exposures may be operating to impact future respiratory development. Through formal coursework and expert mentoring, this award will enable me to develop the knowledge and skills necessary to become an independent transdisciplinary environmental health scientist and achieve my long-term career goals: to establish a competitive and successfully funded program to study the cumulative effects of environmental exposures (e.g., air pollution/stress) on the programming of biological mechanisms related to chronic childhood conditions. While this award focuses on respiratory outcomes, it is worth noting that the knowledge and skills obtained will be broadly applicable to a range of child health outcomes given the large number of childhood conditions with mitochondrial and telomere underpinnings (e.g., asthma, obesity, cardiovascular disease, neurocognitive outcomes). Specifically, I will 1) obtain training in air pollution and stress assessment in the context of a longitudinal cohort study design; 2) receive training and guidance in selecting and interpreting mitochondrial and telomere analyses; and 3) undergo extensive training in advanced quantitative methods (e.g. non-linear distributed lag models) to understand dose-response and temporal relationships between air pollution and health. The proposed study will be the first to investigate windows of vulnerability to prenatal ambient air pollution exposure on child respiratory development and to investigate mitochondrial and telomere biomarkers in a target tissue (e.g. placenta) with respect to prenatal environmental exposures (e.g. ambient air pollution and stress) and early respiratory phenotypes. We will use daily air pollution exposures derived from a validated spatio-temporal modeling approach coupled with distributed lag methods to identify sensitive windows of air pollution exposure on respiratory phenotype. We will use state-of-art analyses of placental mitochondrial and telomere biomarkers that: 1) have been shown to be altered by environmental exposures; and 2) reflect cumulative oxidative damage over gestation. This study is also highly cost effective as we will leverage the resources of an existing well-phenotyped urban and ethnically-mixed pregnancy cohort [Perinatal Environmental and Development Study (PEDS)] with extant environmental exposure (air pollution and stress), covariate, and epigenome data.

项目摘要 我是一名医生，科学家，主要研究兴趣是呼吸系统疾病的规划， 产前/生命早期环境暴露，如空气污染和母亲压力，特别关注 母胎界面的编程机制，即，胎盘研究表明， 空气污染对儿童呼吸道疾病的影响，这项建议的目标是增加日益增长的研究联系 城市空气污染物，压力和呼吸系统的发展，通过确定敏感的窗口暴露， 确定新的线粒体和端粒生物标志物，通过这些生物标志物，子宫内暴露可能起作用， 影响未来呼吸系统发育。 通过正式的课程和专家指导，这个奖项将使我能够发展知识， 和必要的技能，成为一个独立的跨学科的环境健康科学家，并实现 我的长期职业目标：建立一个有竞争力和成功资助的计划，以研究累积 环境暴露的影响（例如，空气污染/压力）对生物机制规划的影响 与慢性儿童疾病有关。虽然该奖项侧重于呼吸结果，但值得注意的是， 所获得的知识和技能将广泛适用于一系列儿童健康成果， 大量具有线粒体和端粒基础的儿童疾病（例如，哮喘，肥胖， 心血管疾病、神经认知结果）。具体来说，我将1）接受空气污染方面的培训， 在纵向队列研究设计的背景下进行压力评估; 2）接受培训和指导， 选择和解释线粒体和端粒分析;和3）接受高级培训 定量方法（如非线性分布滞后模型），以了解剂量反应和时间 空气污染与健康的关系。 这项拟议中的研究将是第一个调查胎儿对产前环境空气的脆弱性的窗口 污染暴露对儿童呼吸发育的影响，并研究线粒体和端粒生物标志物 与产前环境暴露（例如环境空气污染）有关的靶组织（例如胎盘）中 和应激）和早期呼吸表型。我们将使用从经验证的 与分布式滞后方法相结合的时空建模方法，以识别空气的敏感窗口 污染暴露对呼吸表型的影响。我们将使用最先进的胎盘线粒体分析， 端粒生物标志物：1）已被证明是由环境暴露改变;和2）反映 妊娠期累积氧化损伤。这项研究也具有很高的成本效益，因为我们将利用 现有的良好表型的城市和种族混合妊娠队列的资源[围产期 环境与发展研究]与现有的环境暴露（空气污染和压力）， 协变量和表观基因组数据。