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.