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

基本信息

批准号：
7555954
负责人：
JUNFENG ZHANG
金额：
$ 39.22万
依托单位：
UNIV OF MED/DENT NJ-SCH OF PUBLIC HEALTH
依托单位国家：
美国
项目类别：
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/7555954
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 Data Disease Pathway Ensure Epidemiologic Studies Epidemiology Event Exhibits Exposure to Female Functional disorder GSTM1 gene Genes Genetic Polymorphism Genotype Government Health 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 Relaxation Series Source Testing Time Woman Work air pollution control base design heart rate variability improved male men mortality non-smoking pollutant respiratory response ultrafine particle vascular endothelial dysfunction

项目摘要

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（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，以确保世界上最污染最严重的地区之一的环境空气质量将得到显着改善。靶向颗粒物的靶向降低（PM2.5）的距离> 100 5g/m3的前水平约为70％。拟议的研究将利用这一独特的机会来检验以下假设：（1）肺和全身性炎症，血管内皮功能障碍，血液凝结，自主功能障碍以及在当地居民中测得的氧化应激的响应将对这种实质性空气污染减少的响应发生显着变化。此外，在奥运会结束后，这些生物标志物将在空气污染控制下放松后返回奥运会前水平。（2）PM2.5，Ultrafine颗粒和某些PM成分将在整个研究期间与特定的生物标志物相关。（3）受试者对污染物暴露变化的反应将根据其遗传的多态性而有所不同，该多态性直接与测量的生物标志物或PM诱导的氧化应激的机制直接相关。拟议的小组研究将在50名男性和50位女性，健康，无吸烟的医疗居民中进行，他们在同一医院设施中工作并居住在同一医院设施中，在那里可以测量空气污染物和生物标志物。具体而言，我们将：（1）在整个三个研究期间连续或每天测量PM成分和共污染物（奥运会前，奥运会期间和奥运会）；（2）测量一个反映肺和全身性炎症，内皮功能障碍，血液凝结，自主功能障碍和氧化应激的生物标志物的套件，每个受试者每期两次（总共6倍）；（3）分析每个受试者的候选基因多态性；（4）执行统计分析以检验上述假设。流行病学证据强烈表明，急性和慢性心脏呼吸疾病和事件与暴露于空气污染，尤其是PM2.5有关。但是，这些结果的具体机制仍然不明确。机械研究非常有限，并且在很大程度上仅限于可能反映现实情况的实验室暴露。通过扩大PM组成量度的套件，同时测量多个生物标志物和与途径相关的基因，并检查广泛的时间范围（从小时到几天到几周）以进行生物标志物响应，这项现实世界中的研究是对几种突出的PM效应的几种突出假设机制的全面研究。它还将提供宝贵的数据，以改善减少空气污染的公共卫生影响的评估。