Taxi Particulate Matter Study (TIPS)

A.摘要 美国大约有24万名出租车/豪华轿车司机(1)。纽约市有4.2万名出租车司机，其中84%是移民(2)。纽约市的出租车司机工作时间很长(10-12小时/天轮班，~6天/周)，经常在交通繁忙的情况下工作。暴露于高水平的可吸入颗粒物(PM)与入院人数增加、肺癌风险和死亡率以及呼吸系统和心肺死亡率密切相关(3-9)。两项研究表明，在调整吸烟因素后，职业司机的肺癌患病率较高，这表明与PM暴露有关(10，11)。在对哈佛六大城市的重新分析中 研究发现，PM2.5暴露每增加10pg/m^，调整后的全因死亡率增加14%(95%CI：7，22)，肺癌死亡率增加37%(95%CI：7，75)(12)。一项长达26年的前瞻性研究发现，在从不吸烟的人中，PM2.5(PM&lt；2.5 PM)暴露每增加10 pg/m^，肺癌死亡率就会增加15-27%。出租车颗粒物研究(TIPS)是一项针对纽约市高危出租车司机的社区参与的T1-T4翻译研究。TIPS将解决以下关键研究问题：1)通过比较司机和司机提名的非出租车司机同行对照组，过量接触PM与生理和生化标志物不利变化的程度；2)出租车内HEPA过滤干预对减少随机接受HEPA干预的出租车司机与随机进入对照组的出租车司机减少PM暴露和相关生物标记物水平的影响。 参与的出租车司机将按1：1的比例随机分为控制条件或 HEPA滤器干预条件。第三个由司机提名的匹配同行参照组将作为非出租车司机的控制组。 目的1-确定出租车司机在车内过量PM暴露的大小分布、质量浓度和化学成分(在轮班和在家测量)，并与匹配的非司机同行参考组进行比较；评估过量PM暴露是否与肺癌中间生理和生化标记物的变化有关。便携式监测器将被用来测量PM，迷你气体计将被用来测量黑碳、柴油尾气的标志和一种已知的致癌物质(13)。还将使用有机化合物筛选方法，通过气相色谱/质谱仪(GC/MS)鉴定大气气溶胶中的有机化合物；还将分析金属。生理和生化标记物将包括促炎/抗炎细胞因子、呼出的亚硝酸盐/硝酸盐(氧化应激指标)以及与癌症和/或炎症相关的表观遗传变化。有数据表明，呼气冷凝液和支气管肺泡灌洗液中炎性细胞因子和呼出的亚硝酸盐/硝酸盐水平升高与肺癌有关(14-16)。特定基因的表观遗传甲基化与肺癌有关，可以比临床诊断早三年(17，18)。假设1-纽约市的出租车司机在轮班期间暴露于车辆中PM水平的升高，并与细胞因子水平升高、呼出的亚硝酸盐/硝酸盐增加以及特定基因的甲基化有关，所有这些都可能与肺相关和/或预测肺 癌症风险(与匹配的同龄人参考组和工作前/工作后的自己进行比较)。 目的2-使用随机对照设计来评估定向干预措施，即安装便携式汽车高效颗粒物(HEPA)过滤器(以去除PM和挥发性有机化合物)是否导致出租车司机减少车内PM暴露和相关的生理和生化标志物。假设2-安装一个小型、便携、低成本(200英镑)、易于使用的汽车HEPA过滤器将减少车载PM暴露以及相关的司机生理和生化风险标记物。 目标3-通过社区参与的风险教育计划，在个人和系统层面传播目标1和目标2的结果。将制定一项关于职业风险、PM暴露、相关健康风险以及降低这些风险的方法的风险教育计划。研究结果将通过纽约一个国家倡议、纽约出租车工人联盟以及学术出版物和演示文稿在机场发布。假设3-关于PM风险的数据和降低风险的干预措施，可以通过社区参与的风险教育计划有效地传播。

A. Abstract There are approximately 240,000 U.S. taxi/limousine drivers in the U.S.(1). New York City (NYC) is home to 42,000 taxi drivers, 84% of whom are immigrants (2). NYC taxi drivers work long hours (10-12 h/d shifts, ~6d/wk), often in heavy traffic (2). Exposure to high levels of respirable particulate matter (PM) is closely linked to increased hospital admissions, lung cancer risk and mortality, and respiratory and cardiopulmonary mortality (3-9). Two studies have demonstrated high lung cancer prevalence among professional drivers, after adjusting for smoking, suggesting an association with PM exposure (10, 11). In a reanalysis ofthe Harvard Six Cities Study, each 10 pg/m^ increase in PM2.5 exposure was associated with an adjusted increased risk of all-cause mortality of 14% (95% Cl: 7, 22), and with a 37% (95% Cl: 7, 75) increase in lung cancer mortality (12). A 26- year prospective study found that each 10 pg/m^ increase in PM2.5 (PM <2.5 pm) exposure is associated with a 15-27% increase in lung cancer mortality among never-smokers (3). Taxi Particulate matter Study (TIPS) is a community-engaged T1-T4 translational research study for at-risk taxi drivers in NYC. TIPS will address the following key research questions: 1) the extent to which excess PM exposure is associated with adverse changes in physiologic and biochemical markers, by comparing drivers with a driver nominated non-taxi-driver peer comparison group; 2) the effect of an In-taxi HEPA filtration intervention on decreasing PM exposure and associated biomarker levels among taxi drivers randomized to the HEPA intervention in comparison with taxi drivers randomized to a control group. Participating taxi drivers will be randomized with a 1:1 ratio into either the control condition or the HEPA filter intervention condition. A third, driver-nominated matched peer reference group will serve as non-taxi-driver controls. Aim 1 - To determine in-vehicle excess PM exposure, including size distribution, mass concentration, and chemical composition among taxi drivers (measured during work shifts and at home) compared to a matched non-driver peer reference group; and to assess whether excess PM exposure is associated with changes in intermediate physiologic and biochemical markers of lung cancer. Portable monitors will be used to measure PM, and a mini-aethalometer to measure black carbon, a marker of diesel exhaust, and a known carcinogen (13). An organic compound screening method will also be used to identify organic compounds in atmospheric aerosols with gas chromatography/mass spectrometry (GC/MS); metals will also be analyzed. Physiologic and biochemical markers will include pro/anti-inflammatory cytokines, exhaled nitrite/nitrate (indicators of oxidative stress), and epigenetic changes associated with cancer and/or inflammation. There are data showing that increased levels of inflammatory cytokines and exhaled nitrite/nitrate in exhaled breath condensate and bronchoalveolar lavage fluid are associated with lung cancer (14-16). Epigenetic methylation of specific genes has been associated with lung cancer, and can precede clinical diagnosis by up to three years (17, 18). Hypothesis 1 - Taxi drivers in NYC are exposed to elevated PM levels in their vehicles during work shifts, and have associated elevated cytokine levels, increased exhaled nitrite/nitrate, and methylation of specific genes, all of which are likely to be associated with and/or predictive of lung cancer risk (compared to a matched peer reference group and to themselves before/after work). Aim 2 - To use a randomized controlled design to assess if a targeted intervention, installation of a portable car high-efficiency particulate air (HEPA) filter (to remove PM and volatile organic compounds), results in a reduction of in-vehicle PM exposure and associated physiologic and biochemical markers among taxi drivers. Hypothesis 2 - Installation of a small, portable, low-cost (<$200), easy to use, car HEPA filter will result in a reduction of in-vehicle PM exposure and associated physiologic and biochemical markers of risk among drivers. Aim 3 - To disseminate results of Aims 1 and 2 at the individual and systems level through community engaged risk education programs. A risk education program will be developed on occupational risks, exposure to PM, associated health risks, and methods to reduce these risks. Study results will be disseminated at airport holding lots, through the One NYC One Nation initiative, through the New York Taxi Workers' Alliance, and through academic publications and presentations. Hypothesis 3 - Data about PM risks, and risk-reducing interventions, can be effectively disseminated through community-engaged risk education programs.