Responses to Drastic Changes in Air Pollution: Reversibility and Susceptibility

对空气污染急剧变化的反应：可逆性和敏感性

• 批准号: 7387939
• 负责人: JUNFENG ZHANG
• 金额: $ 36.62万
• 依托单位: UNIV OF MED/DENT NJ-SCH OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-01-15 至 2010-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7387939
• 关键词: Acute; Affect; Air; Air Pollutants; Air Pollution; Alleles; Asians; Automobiles; Autonomic Dysfunction; Biological Markers; Blood; Blood Platelets; Blood coagulation; Candidate Disease Gene; Chemicals; China; Chinese People; Chronic; Cities; Condition; Daily; Data; Disease Pathway; Ensure; Epidemiologic Studies; Event; Exhibits; Exposure to; Female; Functional disorder; GSTM1 gene; Genes; Genetic Polymorphism; Genotype; Government; Health; Heart Rate; Hospitals; Hour; Immune response; Individual; Inflammation; Inherited; Investigation; Laboratories; Life; Lung; Lung diseases; Measures; Medical; Molecular; Morbidity - disease rate; Mortality Decline; Outcome; Oxidative Stress; Particulate Matter; Pathway interactions; Pneumonia; Predisposition; Public Health; Range; Relaxation; Series; Source; Testing; Time; Week; Woman; Work; air pollution control; base; day; design; glutathione S-transferase M1; improved; male; men; mortality; non-smoking; pollutant; respiratory; response; ultrafine particle; vascular endothelial dysfunction

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.

描述(申请人提供)：2008年北京奥运会和残奥会期间(2008年7月25日至9月17日)将采取前所未有的行动，以确保世界上污染最严重的地区之一的环境空气质量将得到显著改善。细颗粒物(PM2.5)的目标降幅比奥运会前100 5克/立方米的水平下降了约70%。这项拟议的研究将利用这一独特的机会来检验以下假设：(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、凝血功能障碍、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重大变化。此外，随着奥运会结束后空气污染控制的放松，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组分将分别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将因他们在分子通路上的遗传多态而有所不同，这些分子通路直接与所测量的生物标记物或PM诱导的氧化应激机制有关。拟议的小组研究将在50名男性和50名女性、健康、不吸烟的住院医生中进行，他们在同一家医院工作和居住，在那里将测量空气污染物和生物标志物。具体地说，我们将：(1)在三个研究时期(奥运前、奥运期间和奥运后)连续或每天测量PM组分和协同污染物；(2)在每个受试者中测量一套反映肺部和全身炎症、内皮功能障碍、凝血功能障碍、自主神经功能障碍和氧化应激的生物标志物，每期两次(总共6次)；(3)分析每个受试者的候选基因多态；(4)进行统计分析，以检验上述假设。流行病学证据有力地表明，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不明确；机械性研究非常有限，主要局限于可能不能反映现实生活条件的实验室暴露。通过扩展PM组成测量的套装，同时测量多个生物标记物和途径相关基因，并检查生物标记物响应的广泛时间范围(从几小时到几天到几周)，这项现实世界的研究是对几个突出的PM效应假想机制的全面调查。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。