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

空气污染暴露与儿童健康：反事实框架中的调解和互动

基本信息

批准号：
9894798
负责人：
Andreas Neophytou
金额：
$ 24.9万
依托单位：
COLORADO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-03-15 至 2023-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9894798
关键词：
Accounting Address African American Air Pollutants Air Pollution American Area Aromatic Polycyclic Hydrocarbons Asthma Award Behavioral Genetics Biological Biological Markers Child Child Health Childhood Chronic Chronic Disease Collaborations Complex Data Data Set Death Rate Development Diabetes Mellitus Disease Education Environmental Epidemiology Environmental Exposure Environmental Health Environmental Risk Factor Epidemiologic Methods Epidemiology Epigenetic Process European Exposure to FOXP3 gene Future GALA Genetic Glucose Glycosylated hemoglobin A Goals Growth Health Immune System Diseases Immune system Impairment Income Individual Inflammation Inflammatory Intervention Latino Life Link Literature Lung diseases Machine Learning Measures Mediating Mediation Mediator of activation protein Mentors Metabolic Metabolic syndrome Methodology Methods Minority Modification Neighborhoods Obesity Outcome Oxidative Stress Pathway interactions Pollution Population Poverty Predisposition Prevalence Process Puerto Rican Randomized Regulatory T-Lymphocyte Reporting Research Research Personnel Research Training Respiratory physiology Risk Risk Estimate Risk Factors Socioeconomic Factors Subgroup Time Training Underrepresented Populations Vulnerable Populations adverse outcome analog base career cytokine disorder risk early life exposure epidemiologic data epidemiology study ethnic difference experience exposure pathway health disparity interest minority children pollutant public health intervention pulmonary function racial and ethnic social social disparities social epidemiology social factors social vulnerability tool

项目摘要

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.

项目摘要 /摘要暴露于空气污染是哮喘的确定危险因素，肺功能降低以及炎症和氧化过程又与肥胖和糖尿病有关。这些不利结果的风险从童年初开始，有据可查的种族/种族差异和社会差异使少数群体儿童特别容易受到伤害，但这些人群在文献中的人数不足。真正的分析代表性效应估计值应考虑广泛的遗传，社会和环境因素，从暴露于疾病的生物学途径，考虑因果介体和相互作用。调解和相互作用分析还可以帮助确定一个估计效应的可运输能力人口到另一个。但是，中介分析中目标参数的估计和可解释性是诸如中介结果相互作用，非线性和暴露引起的问题之类的问题变得复杂混杂，无法使用传统回归方法解决。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，以最能降低总体风险感兴趣的人群。我将利用高级流行病学方法，最大化内部有效性和目标估计的效率。我将扩展现有方法，以估计存在的效果时间变化的暴露和协变量以及暴露引起的调解人结果混淆（估计自然直接和自然直接的随机干预类似物的估计间接效应）无法通过传统的回归方法来解决。提出的方法适合评估连续暴露的潜在干预措施，这尤其是在环境流行病学领域有益。在本提案的目标1和2中，我将使用这些建议评估空气污染暴露对哮喘风险，总肺的直接，间接和总影响的方法功能和代谢综合征，在反事实框架内。我非常适合执行提议基于1）我过去在环境健康和高级方法和反事实上的经验方法2）我组装的跨学科指导团队和3）独特的研究该提案中数据集提供的机会主要由少数民族儿童组成。这项建议的研究将使我能够量化特别脆弱人群中空气污染暴露的介导作用。我会由世界一流的导师团队建议，扩大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程序的方法（例如，机器学习和因果推理的有效估计量参数）在环境流行病学研究中；表观遗传学和外卵形因素作为潜在的修饰符或效力介体；以及与环境暴露有关的健康差异和社会因素。这拟议的研究和培训将使我能够成为干预领域的独立职业环境流行病学的评估和因果推断。