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球的主要公共卫生问题。然而，虽然暴露于燃烧和地壳来源的颗粒在工业工作中很普遍，其浓度比周围环境中与CVD相关的浓度高2-3个数量级，但与PM暴露相关的职业相关心脏病风险的证据很少。我们建议在一个约75，000名暴露于不同成分和浓度的PM2.5的工人队列中检查CVD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，他们已经接受了十多年的密切观察。由于这些正在进行的研究，调查人员掌握了关于个人社会的无与伦比的信息，（例如收入、教育、储蓄）和行为（如吸烟、体重指数、胆固醇）风险、工作暴露情况，包括所有相关的物理、化学和心理社会因素（如热、噪音、应变）、自1996年以来的完整健康声明文件以及2007年的NDI结果。根据这些数据和我们在这方面的丰富经验，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：每年估算每个SEG中PM和化学成分的细颗粒（PM2.5）和其他颗粒尺寸分数的浓度。 目标二：在一组活跃的工人中，历史和前瞻性地跟踪长达18年，识别来自连续医疗索赔数据的CVD发病率病例，并利用选定的暴露指标（每年的年平均值，每年的第95百分位数，累积和滞后）估计PM2.5暴露（简单PM2.5和成分）与疾病发病率之间的关系。 目标3：为了解决由于健康工人幸存者效应可能导致低估效应的潜在偏倚，应用以下方法：将队列随访扩展到死亡率，并将CVD死亡率作为终点，而不是发病率，包括非活动和活动的人-时间;并应用嵌套结构模型来估计因果剂量-发病率和死亡率结局的响应参数，以处理随时间变化的混杂因素，这些混杂因素也可能是因果通路上的中间变量。 公共卫生相关性：数百万美国工人暴露在工作场所的细颗粒物中。虽然有越来越多的证据表明，这种暴露可能会导致心血管疾病，但细颗粒物通常没有在工作场所进行测量，也没有直接受到管制或不受管制。因此，心血管风险仍然未知。该提案旨在提供与美国劳动人口广泛相关的主要工业环境中的此类信息。

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.