Air pollution exposures and children's health: mediation and interaction in a counterfactual framework

项目摘要/摘要 暴露在空气污染中是哮喘、肺功能减退和炎症的既定危险因素 以及氧化过程，这反过来又与肥胖和糖尿病有关。这些不良后果的风险 从小就开始，有充分记录的种族/民族差异和社会差异使少数族裔 儿童特别容易受到伤害，但这些群体在文学作品中的代表性不足。True的分析 代表性效应评估应考虑广泛的遗传、社会和环境因素， 暴露于疾病的生物途径，考虑因果媒介和相互作用。 中介和交互作用分析还可以帮助确定估计结果的可传递性 人口转移到另一个国家。然而，中介分析中目标参数的估计和可解释性是 因中介-结果交互、非线性和暴露诱导等问题而变得复杂 混淆，这不能用传统的回归方法来解决。我的长期职业目标 评估对环境健康风险因素的最佳干预措施，以最大限度地降低 感兴趣的人群。我将利用先进的流行病学方法，最大化内部有效性和 目标估计的效率。我将详述现有的在以下情况下估计影响的方法 时变暴露和协变量以及暴露诱导的介体结果混杂 受控直接效应和自然直接和随机干预类似物的估计 间接影响)，这是传统回归方法无法解决的问题。建议的方法 将适用于评估对持续暴露的潜在干预措施，这将特别 有益于环境流行病学领域。在本提案的目标1和目标2中，我将使用以下建议 方法评估空气污染暴露对哮喘风险的直接、间接和总体影响，整个肺 功能和代谢综合症，在反事实的框架内。我非常适合执行建议的 研究基于1)我过去在环境健康方面的经验以及先进的方法和反事实 方法2)我组建的特殊的跨学科指导团队和3)独特的研究 提案中的数据集提供了机会，主要由少数族裔儿童组成。这项拟议的研究 将使我能够量化空气污染暴露在特别脆弱的人群中的中介影响。这就做 得到世界级导师团队的建议，以扩展我在整合高级流行病学方面的专业知识 具有因果推理应用的方法(例如，机器学习和因果推理的有效估计器 参数)在环境流行病学研究中；表观遗传和暴露因素作为潜在的修饰物 或影响因素；与环境暴露有关的健康差距和社会因素。这个 拟议的研究和培训将使我能够建立一个独立的职业生涯，成为干预领域的领导者 环境流行病学中的评估和因果推断。

Project Summary / Abstract Exposure to air pollution is an established risk factor for asthma, reduced lung function as well as inflammatory and oxidative processes which are in turn linked with obesity and diabetes. Risk for these adverse outcomes begins early in childhood and well-documented racial/ethnic differences and social disparities render minority children especially vulnerable, yet these populations are underrepresented in the literature. Analysis for truly representative effect estimates should consider a wide array of genetic, social and environmental factors, biologic pathways from exposure to disease, with consideration for causal mediators and interactions. Mediation and interaction analysis can also aid in determining the transportability of estimated effects from one population to another. However, estimation and interpretability of target parameters in mediation analysis is complicated by issues such as mediator-outcome interactions, non-linearities, and exposure-induced confounding, which cannot be addressed using traditional regression approaches. My long-term career goals are to assess optimal interventions on environmental health risk factors that best reduce overall risk in populations of interest. I will utilize advanced epidemiologic methods maximinzing internal validity and efficiency of estimation of target. I will expand on existing methods for estimation of effects in the presence of time varying exposures and covariates as well as exposure-induced mediator outcome confounding (estimation of controlled direct effects and the randomized intervention analogues for the natural direct and indirect effects) which cannot be addressed with traditional regression approaches. The proposed methodology will be suitable for assessment of potential interventions on continuous exposures, which will be especially beneficial in the area of environmental epidemiology. In Aims 1 & 2 of this proposal I will use these proposed methods to assess direct, indirect and total effects of air pollution exposures on risk of asthma, overall lung function and metabolic syndrome, within a counterfactual framework. I am well suited to perform the proposed research based on 1) my past experience in environmental health and advanced methods and counterfactual approaches 2) the exceprional interdisciplinary mentoring team I have assembled and 3) the unique research opportunity offered by the datasets in the proposal, comprised largely of minority children. This proposed study will enable me to quantify mediated effects of air pollution exposures in especially vulnerable populations. I will be advised by a world-class team of mentors to expand my expertise in integrating advanced epidemiologic methods with causal inference applications (e.g., machine learning and efficient estimators of causal inference parameters) in environmental epidemiological studies; epigenetic and exposomic factors as potential modifiers or mediators of effect; and health disparities and social factors associated with environmental exposures. The proposed research and training will enable me to establish an independent career as a leader in intervention assessment and causal inference in environmental epidemiology.