Healthy Worker Effect, Occupational Exposure to PM and Cardiopulmonary Mortality

描述(由申请人提供)：这项修订建议的目标是研究长期定量接触金属加工液(MWF)与心肺死亡率之间的关系。MWF是油和化学添加剂的复杂混合物，广泛用于工业环境中，用于冷却和润滑金属加工操作。油基MWF含有多环芳烃和金属，这些成分也存在于与交通相关的空气污染的细颗粒物(PM2.5)中，PM2.5是一种公认的心血管危险。此外，职业性接触MWF的浓度很高--比环境空气污染高出数量级--进一步支持了相关假设。这项建议建立在我们最近在密歇根州接触MWF的汽车工人的队列研究中应用g-估计来控制健康工人幸存者效应(HWSE)的基础上；这是这种因果方法在职业研究中的首次应用。自我们上次提交报告以来报告的基于g-估计的新结果表明，暴露于油基MWF的时间显著增加了因缺血性心脏病和慢性阻塞性肺疾病而导致的死亡风险。这两种关系只有在对HWSE进行调整后才能检测到。我们现在建议将g-估计框架从二元暴露扩展到浓度-通过利用现有的MWF大小分数颗粒质量(PM)(mg/m~3)的定量测量。全美汽车工人联合会-通用汽车队列研究是一项丰富的资源，因为它的规模(近40,000名受试者)、多样性、60年的生命状态跟踪期以及接触石油和水基MWF的定量指标(PM3.5和PM3.5-9.8)。利用现有的样品，我们将使用常见的分析技术，通过PM3.5和PM3.5-9.8的颗粒大小比例，将MWF与空气污染和香烟烟雾的物理化学成分进行比较。这些化学结果将补充流行病学研究结果。MWF没有具体的健康标准；它们只受到未受其他监管的颗粒物的通用暴露限值的限制。2010年4月，美国汽车工人联合会再次向OSHA请愿，要求根据哮喘、过敏性肺炎和癌症制定MWF标准，强调了这一申请的重要性和及时性。该提案解决了关于职业暴露于小颗粒物，特别是MWF的心肺健康风险方面的一个严重知识缺口。随着绿色制造业的发展，例如节能型汽车、轻轨车辆和风力涡轮机系统，接触MWF的工人数量可能会增加。鉴于广泛的工业接触和这些慢性病的高发病率，即使死亡率略有上升，也意味着相当大的职业负担。 公共卫生相关性：拟议研究的目标是检查长期定量暴露于金属加工液(MWF)的心血管和慢性阻塞性肺疾病死亡率与长期接触金属加工液(MWF)的关系，并对UAW-GM汽车工人队列进行超过60年的随访。这项建议基于最近的研究结果，这些发现表明，暴露在油基连续MWF中的时间显著增加了因缺血性心脏病和COPD而死亡的风险，但只有在对健康的工人幸存者效应进行调整后才会这样做。我们将充分利用现有的MWF(可吸入颗粒物、胸部颗粒物和总颗粒物)的量化指标，将g-估算框架从接触时间扩展到浓度。结果将有助于在整个制造业中预防接触金属加工液的工人的心肺疾病。

DESCRIPTION (provided by applicant): The goal of this revised proposal is to examine the relation between long-term quantitative exposure to metalworking fluids (MWF) and cardiopulmonary mortality. MWF are complex mixtures of oils and chemical additives widely used in industrial settings to cool and lubricate metal machining operations. Oil-based MWF contain polyaromatic hydrocarbons and metals, constituents also present in the fine particulate mass (PM2.5) of traffic-related air pollution, a well established cardiovascular hazard. Moreover, occupational exposure to MWF occurs at high concentrations - orders of magnitude higher than ambient air pollution - providing further support for the hypotheses of interest. The proposal builds on our recent application of g-estimation to control for healthy worker survivor effect (HWSE) in a cohort study of Michigan autoworkers exposed to MWF; the first implementation of this causal method in an occupational study. New results based on g-estimation reported since our previous submission suggest that duration of exposure to oil-based MWF significantly increases the risk of mortality due to both ischemic heart disease and chronic obstructive pulmonary disease. Both relationships were only detected after adjustment for HWSE. We now propose to extend the g-estimation framework from binary exposure to concentration - by taking advantage of existing quantitative measures of size fractionated particle mass (PM) of MWF (mg/m3). The United Autoworkers - General Motors cohort study is a rich resource due to its size (almost 40,000 subjects), diversity, 60 year vital status follow-up period, and quantitative metrics of exposure to oil-and water-based MWF (PM3.5 and PM3.5-9.8). Using available samples, we will compare the physicochemical composition of MWF with air pollution and cigarette smoke - by particle size fractions of PM3.5 and PM3.5-9.8 - using common analytic techniques. These chemical results will complement the epidemiologic findings. There is no specific health standard for MWF; they are subject only to generic exposure limits for particles not otherwise regulated. In April 2010, the United Autoworkers again petitioned OSHA for a MWF standard on the basis of asthma, hypersensitivity pneumonitis and cancer, underscoring the significance and timeliness of this application. The proposal addresses a critical gap in knowledge about the cardiopulmonary health risks of occupational exposures to small particles in general, and to MWF in particular. With the growth of the green manufacturing sector, e.g., fuel efficient automobiles, light rail cars and wind turbine systems, the number of workers exposed to MWF will likely increase. Given widespread industrial exposure combined with the high incidence of these chronic diseases, even a modestly elevated mortality rate ratio would imply a substantial occupational burden. PUBLIC HEALTH RELEVANCE: The goal of the proposed research is to examine cardiovascular and chronic obstructive pulmonary disease mortality in relation to long-term quantitative exposure to metalworking fluids (MWF) in a heavily exposed UAW-GM autoworker cohort with over 60 years of follow-up. The proposal builds on recent findings suggesting that duration of exposure to oil-based straight MWF significantly increases the risk of mortality due to both ischemic heart disease and COPD, but only after adjustment for healthy worker survivor effect. We will extend the g-estimation framework from duration of exposure to concentration by taking full advantage of existing quantitative measures of MWF (respirable, thoracic and total particulate matter). Results will contribute to the prevention of cardiopulmonary diseases in workers exposed to metal working fluids throughout the manufacturing sector.