Responses to Drastic Changes in Air Pollution: Reversibility and Susceptibility

描述（由申请人提供）：在2008年北京奥运会和残奥会（2008年7月25日至9月17日）期间，将采取前所未有的行动，确保世界上污染最严重的地区之一的环境空气质量得到实质性改善。细颗粒物（PM2.5）的目标比奥运会前的每立方米减少约70%。该研究将利用这一独特的机会来测试以下假设：(1)在当地居民中测量的肺部和全身炎症、血管内皮功能障碍、血液凝固、自主神经功能障碍和氧化应激的生物标志物将随着空气污染的大幅减少而发生显著变化。此外，在奥运会结束后放松空气污染控制后，这些生物标志物将恢复到奥运会前的水平。(2)在整个研究期间，PM2.5、超细颗粒物和某些PM成分将各自与特定的生物标志物相关联。(3)受试者对污染物暴露变化的反应取决于其与所测生物标志物或pm诱导氧化应激机制直接相关的分子通路的遗传多态性。拟议的小组研究将在50名男性和50名女性中进行，他们是健康的、不吸烟的住院医生，在同一家医院工作和居住，空气污染物和生物标志物将被测量。具体而言，我们将：(1)在三个研究期间（奥运会前、奥运会期间和奥运会后）连续或每天测量PM成分和共污染物；(2)在每个受试者中测量一系列反映肺部和全身炎症、内皮功能障碍、凝血、自主神经功能障碍和氧化应激的生物标志物，每周期两次（总共6次）；(3)分析各受试者候选基因多态性；(4)对上述假设进行统计分析。流行病学证据强烈表明，急性和慢性心肺疾病和事件与暴露于空气污染，特别是PM2.5有关。然而，这些结果的具体机制仍然不明确；机械研究非常有限，而且很大程度上局限于基于实验室的暴露，可能无法反映现实情况。通过扩展PM成分测量套件，同时测量多种生物标志物和途径相关基因，并检查生物标志物反应的大范围时间框架（从数小时到数天到数周），这项现实世界的研究是对PM效应的几个重要假设机制的全面调查。它还将提供宝贵的数据，以改进对减少空气污染对公众健康影响的评估。

DESCRIPTION (provided by applicant): Unprecedented actions will be taken during the 2008 Beijing Olympics and Paralympics (July 25 - September 17, 2008) to ensure that ambient air quality in one of the world's most polluted regions will be substantially improved. The targeted reduction in fine particulate matter (PM2.5) is ~70% from a pre-Olympics level of >100 5g/m3. The proposed study will take advantage of this unique opportunity to test the following hypotheses: (1) Biomarkers of lung and systemic inflammation, vascular endothelial dysfunction, blood coagulation, autonomic dysfunction, and oxidative stress measured in local residents will change significantly in response to this substantial air pollution reduction. Further, these biomarkers will return to pre-Olympic levels following relaxation of air pollution controls when the Olympics are over. (2) PM2.5, ultrafine particles, and certain PM constituents will each be associated with specific biomarkers across the whole study period. (3) Subjects' responses to changes in pollutant exposure will vary depending on their inherited polymorphisms for molecular pathways related either directly to the biomarkers measured or to mechanisms of PM-induced oxidative stress. The proposed panel study will be carried out in 50 male and 50 female, healthy, non-smoking medical residents, who work and reside in the same hospital facility where both air pollutants and biomarkers will be measured. Specifically, we will: (1) measure PM constituents and co-pollutants on a continuous or daily basis throughout the three study periods (pre-Olympics, during-Olympics, and post- Olympics); (2) measure a suite of biomarkers reflecting lung and systemic inflammation, endothelial dysfunction, blood coagulation, autonomic dysfunction, and oxidative stress, in each subject twice per period (6 times total); (3) analyze candidate gene polymorphisms in each subject; and (4) perform statistical analyses to test the above hypotheses. Epidemiological evidence strongly suggests that acute and chronic cardio-respiratory diseases and events are related to exposure to air pollution especially PM2.5. However, specific mechanisms for these outcomes remain ill-defined; and mechanistic studies have been very limited and largely confined to laboratory-based exposures that may not reflect real-life conditions. By expanding the suite of PM constituent measures, measuring multiple biomarkers and pathway-related genes simultaneously, and examining a wide range of time frames (from hours to days to a few weeks) for biomarker responses, this real-world study is a comprehensive investigation of several prominently hypothesized mechanisms of PM effects. It will also provide invaluable data to improve the assessment of public health impacts of air pollution reduction.