Occupational Exposure to PM2.5 and Cardiovascular Disease(CVD)

描述(由申请人提供)：与空气污染中的颗粒物(PM)相关的心血管疾病(CVD)风险增加已成为美国和世界范围内的一个主要公共卫生问题。然而，尽管接触燃烧和地壳来源的颗粒物在工业工作中很普遍，其浓度比周围环境中与CVD有关的浓度高出2-3个数量级，但与PM接触有关的职业性心脏病风险的证据很少。我们建议调查暴露在不同成分和浓度的PM2.5中的大约75,000名工人的心血管疾病发病率和死亡率，作为PI在一家大型铝业公司正在进行的研究的一部分，他们已经被密切观察了十多年。作为这些正在进行的研究的结果，调查人员掌握了关于个人社会(如收入、教育、储蓄)和行为(如吸烟、体重指数、胆固醇)风险的无与伦比的信息，包括所有相关的物理、化学和心理社会因素(如高温、噪音、紧张)的工作暴露概况，自1996年以来的完整健康索赔文件，以及截至2007年的NDI结果。利用这些数据和我们丰富的工作经验，以及公司在研究这一关键问题方面的充分合作和支持，提出了以下具体目标：目标1：每年估计PM和化学成分在员工队伍中每个SEG中的细颗粒物(PM2.5)和其他颗粒物尺寸分数的浓度。目的2：在一群积极工作的工人中，从一系列医疗索赔数据中确定心血管疾病发病率的病例，并使用选定的暴露指标(年平均、每年第95个百分位数、累积和滞后)来估计PM2.5暴露(包括简单的PM2.5和成分)与疾病发生率之间的关系。目的3：为了解决健康工人幸存者效应可能导致低估效应的潜在偏差，应用以下方法：扩大对死亡率的队列随访，将心血管疾病死亡率建模为终点，而不是发病率，包括不活跃和活跃的人-时间；应用嵌套结构模型来估计发病率和死亡率结果的因果剂量-反应参数，以处理时变的混杂因素，这些混杂因素也可能是因果路径上的中间变量。

DESCRIPTION (provided by applicant): Increased risk of cardiovascular disease (CVD) related to particulate matter (PM) in air pollution has become a major public health concern in the US and worldwide. However, while exposure to particles of combustion and crustal origin are prevalent in industrial work, in concentrations up to 2-3 orders of magnitude higher than those associated with CVD in the ambient environment, evidence regarding occupational-related heart disease risk associated with PM exposure is scant. We propose to examine CVD incidence and mortality in a cohort of approximately 75,000 workers exposed to PM2.5 of varying composition and concentration, who has been under intense observation for over a decade as part of the PI's ongoing studies at a major Aluminum Company. As a consequence of these ongoing studies, the investigators have in-hand and fully linked unparalleled information on individual social (e.g. income, education, savings) and behavior (e.g. smoking, BMI, cholesterol) risks, work exposure profiles including all physical, chemical and psycho-social factors of relevance (e.g. heat, noise, strain), complete health claims files since 1996, and NDI results through 2007. Availing this trove of data and our extensive experience working with it, as well as the full cooperation and support of the Company to study this critical problem, the following Specific Aims are proposed: Aim 1: Estimate the concentration of fine (PM2.5) and other particulate size fractions in each SEG in the workforce year by year for both PM and by chemical composition. Aim 2: In a cohort of active workers, followed historically and prospectively for up to 18 years, identify cases of CVD incidence derived from serial medical claims data, and estimate the relationship between PM2.5 exposure (both simple PM2.5 and by composition) and disease incidence utilizing selected exposure metrics- annual average each year, 95th percentile in each year, cumulative, and lagged. Aim 3: To address potential bias due to healthy worker survivor effects that can lead to underestimates of effects, apply the following approaches: extend follow-up of the cohort to mortality and model CVD mortality as end-points, rather than incidence, including inactive as well as active person-time; and applying nested structural models to estimate causal dose-response parameters for both incidence and mortality outcomes to handle time varying confounders that may also be intermediate variables on the causal pathway.