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全世界主要的公共卫生问题。然而，尽管工业工作中普遍暴露于燃烧颗粒和地壳源性颗粒，其浓度比环境环境中与心血管疾病相关的浓度高2-3个数量级，但与暴露于PM相关的职业相关心脏病风险相关的证据很少。我们建议检查大约75,000名暴露于不同成分和浓度的PM2.5中的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，这些工人已经被密切观察了十多年。由于这些正在进行的研究，调查人员掌握了个人社会（如收入、教育、储蓄）和行为（如吸烟、体重指数、胆固醇）风险、工作暴露概况(包括所有相关的物理、化学和心理社会因素（如热量、噪音、压力）、1996年以来的完整健康索赔档案和2007年的NDI结果等无与伦比的信息，并将其完全联系起来。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上的充分合作和支持，提出以下具体目标：目标1：根据PM和化学成分，每年估计每个SEG中细颗粒物（PM2.5）和其他颗粒尺寸分数的浓度。目标2：对一组活跃工人进行长达18年的历史和前瞻性随访，从一系列医疗索赔数据中确定心血管疾病发病率病例，并利用选定的暴露指标（每年平均、每年第95百分位、累积和滞后）估计PM2.5暴露（包括简单PM2.5和成分）与疾病发病率之间的关系。目标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，采用以下方法：将队列随访扩展到死亡率，并将CVD死亡率模型作为终点，而不是发病率，包括不活动和活动的人时间；并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，以处理时间变化的混杂因素，这些混杂因素也可能是因果途径上的中间变量。

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. PUBLIC HEALTH RELEVANCE: Millions of American workers are exposed to fine particulate in the workplaces. Although there is accumulating evidence such exposures may cause cardiovascular disease, fine particulate has not generally been measured in the workplace, nor directly regulated or uncontrolled. Thus, cardiovascular risk remains unknown. This proposal aims to provide such information in a major industrial setting with broad relevance to the US working population.