Air pollution exposure and COPD in the Framingham Heart Study

描述（由申请人提供）：空气污染已被发现会引发慢性阻塞性肺疾病（COPD）恶化和死亡，但目前尚不清楚美国的慢性室外空气污染是否会导致COPD的发展。在美国，四分之一的慢性阻塞性肺病患者从未吸烟，但除了吸烟外，其他暴露因素在慢性阻塞性肺病发病机制中的作用知之甚少。很少有研究能够反复测量肺活量并检查多次暴露，包括细颗粒物成分，以了解哪些暴露对肺功能最有害。该项目的目的是确定暴露于环境污染物（来自交通，发电厂和工业过程）对患有和非COPD受试者肺功能的急性影响，其次，使用最先进的暴露评估工具，确定慢性暴露于空气污染是否会增加患临床或亚临床COPD的风险。我们将在弗雷明汉心脏研究的后代和第三代队列的7000多名受试者中调查这些问题，从1995年到现在，我们对他们进行了反复的肺量测定，对近3000名受试者进行了定量胸部CT，以及我们小组最近开发的详细的地理编码暴露评估数据。我们假设短期暴露于空气污染物（细颗粒物、黑碳、臭氧、氮氧化物、硫酸盐和金属）的升高会损害肺功能，通过肺量测定和DLCO调整吸烟后。我们进一步假设，长期暴露于细颗粒物（使用卫星模型）、黑碳（使用区域温度-空间模型）和交通（使用住所到主要道路的距离和住所周围的交通密度）将与(1)肺活量测量中增加的气流阻塞和(2)定量CT测量的低衰减面积百分比（肺气肿测量）和壁面厚度（气道疾病测量）增加有关。作为研究培训计划的一部分，主要研究者将完成

DESCRIPTION (provided by applicant): Air pollution has been found to trigger chronic obstructive pulmonary disease (COPD) exacerbations and deaths, but it is unknown whether chronic outdoor air pollution in the U.S. contributes to the development of COPD. One in four patients in the U.S. with COPD has never smoked, yet little is known about the role of exposures other than smoking in COPD pathogenesis. Few studies have been able to measure spirometry repeatedly and examine multiple exposures, including constituents of fine particulate matter, to understand which exposures are most harmful to lung function. The purpose of this project is to identify the acute effects of exposure to ambient pollutants (from traffic, power plants and industrial processes) on lung function in subjects with and without COPD and secondly to determine, using state-of-the art exposure assessment tools, if chronic exposures to air pollution increase risk of developing clinical or subclinical COPD. We will investigate these questions in the more than 7,000 subjects of the Framingham Heart Study's Offspring and Third Generation cohorts, who have been followed from 1995 to the present with repeated spirometry, a quantitative chest CT in a subset of nearly 3,000 subjects, and detailed geocoded exposure assessment data recently developed by our group. We hypothesize that elevations in short-term exposure to air pollutants (fine particulate matter, black carbon, ozone, nitrogen oxides, sulfates and metals) will impair lung function by spirometry and DLCO after adjustment for smoking. We further hypothesize that long-term exposure to fine particulate matter (using a satellite model), black carbon (using a regional tempero-spatial model) and traffic (using distance from residence to major roadway and traffic density around residence) will be associated with (1) increased airflow obstruction on spirometry and (2) increased percentage of low attenuation area (a measure of emphysema) and wall area thickness (a measure of airways disease) measured by quantitative CT. As part of the research training program, the principle investigator will complete a Master of Public Health with a concentration in Quantitative Methods in order to master the needed skills in epidemiology and biostatistics to complete this work. This research project will be performed under the guidance of a well-established investigator in epidemiology and air pollution health effects research and with advice from experts in environmental obstructive lung disease and quantitative CT analysis.