Biological Response to Air Quality Change in Beijing pre-, mid- and post-Olympics

北京奥运会前、中、后空气质量变化的生物响应

基本信息

批准号：
8223211
负责人：
Lina Mu
金额：
$ 42.13万
依托单位：
STATE UNIVERSITY OF NEW YORK AT BUFFALO
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-02-04 至 2013-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8223211
关键词：
4 hydroxynonenal Acute Adult Air Air Pollutants Air Pollution Animals Anti-Inflammatory Agents Anti-inflammatory Antioxidants Area Back Biological Biological Assay Biological Markers Blood Chemicals China Chinese People Cohort Studies Collection Complex Critical Pathways DNA DNA Markers Data Disease Enrollment Ensure Enzyme Kinetics Enzyme-Linked Immunosorbent Assay Enzymes Epidemiologic Studies Epidemiology Exposure to Female Government Health Heart High Pressure Liquid Chromatography Human Human Characteristics IgE Immune response In Vitro Individual Inflammation Inflammatory Inflammatory Response Interferons Interleukin-1 Interleukin-10 Interleukin-13 Interleukin-2 Interleukin-4 Interleukin-5 Interleukin-6 Interleukin-8 Intervention Interview Link Lipid Peroxidation Lipids Lung Malignant Neoplasms Malondialdehyde Measures Mission Morbidity - disease rate Motor Vehicles National Institute of Environmental Health Sciences Natural experiment Nature Oxidative Stress Participant Particulate Matter Pathogenesis Persons Physical Examination Physiological Play Property Proteins Pulmonary Heart Disease Research Risk Sampling Series Serum Specimen Sputum TNF gene Testing Time Tissues Ultrafine Uncertainty United States National Institutes of Health Urine airway inflammation biological adaptation to stress cancer risk chemokine cytokine design dosage exposed human population follow-up improved in vivo inflammatory marker innovation insight male mortality operation oxidation oxidative DNA damage oxidative damage prospective public health relevance respiratory response trafficking

项目摘要

DESCRIPTION (provided by applicant): Particulate Matter (PM), particularly fine/ultrafine PM, has been associated with an increasing number of adverse short- and long-term health effects, particularly morbidity and mortality from cancer and cardiopulmonary diseases [1-3]. It has become evident that systemic inflammation and oxidative stress play key roles in the pathogenesis of these diseases and may serve as the common mechanisms by which PM potentiates these diseases. However, in vitro and in vivo studies can only provide indirect evidence due to the inherent uncertainty in the approaches when extrapolating their results to humans. An air quality improvement initiative in Beijing during the 2008 Olympics created a unique natural experiment with an initial dramatic decline in air pollution concentrations followed by a return to pre- Olympic concentrations. We took advantage of this unique opportunity, and designed a prospective cohort study in Beijing to investigate the acute biological response to changes in human exposure to PM and to better understand the critical pathways through which PM operates in these diseases. The specific aims of the proposed study are to examine whether changes in PM exposure over the course of the Olympics are related to changes in selected markers of DNA/lipid/protein damage and antioxidant defense, or to changes in respiratory and systemic inflammatory response. To achieve the proposed aims, we enrolled 201 adult males and females prior to the air quality improvement initiative in Beijing, China and followed these individuals over the course of the Olympics. One hundred eighty participants completed a series of three interviews: before, during and after the Olympics. Each interview consisted of an in-person interview, physical examination, and biospecimen collection (blood, urine and sputum). Ambient PM concentration in the study area was measured throughout the study period. Multianalyte multiplexed assays are proposed to analyze the selected inflammatory markers. Automated enzyme kinetic analysis, HPLC, ELISA and EIA will be used to assess oxidative DNA/lipid/protein damage and antioxidant defense. We predict that we will observe a decrease in the levels of markers for systemic inflammation and oxidative damage in response to improvements in air quality, and an increase in the levels of anti- inflammatory cytokines and antioxidant enzymes in the first follow-up period. Our hypotheses will be further evaluated by examining changes in inflammation and oxidative damage as air quality in Beijing returns to pre-Olympic levels in the second follow-up period. PUBLIC HEALTH RELEVANCE: Our proposal is highly relevant to the mission of the NIH/National Institute of Environmental Health Sciences. Air pollution is a ubiquitous, worldwide exposure hypothesized to induce oxidative stress and immune responses that have been linked to cancer and cardiopulmonary disease. Our study will provide insight on these potential mechanisms through which air pollution may increase the risk of cancer and cardiopulmonary diseases; moreover, the epidemiologic nature of our proposed research ensures that the data generated will be directly applicable to humans.

描述（由申请人提供）：颗粒物 (PM)，特别是细/超细 PM，与越来越多的短期和长期健康不良影响有关，特别是癌症和心肺疾病的发病率和死亡率[1-3 ]。很明显，全身炎症和氧化应激在这些疾病的发病机制中发挥着关键作用，并且可能是 PM 增强这些疾病的共同机制。然而，由于将结果外推到人类时方法固有的不确定性，体外和体内研究只能提供间接证据。 2008 年奥运会期间，北京的一项空气质量改善举措创造了一次独特的自然实验，空气污染浓度最初急剧下降，随后又恢复到奥运会前的浓度。我们利用这一独特的机会，在北京设计了一项前瞻性队列研究，以调查人类接触 PM 的变化所产生的急性生物反应，并更好地了解 PM 在这些疾病中发挥作用的关键途径。拟议研究的具体目的是检验奥运会期间 PM 暴露的变化是否与 DNA/脂质/蛋白质损伤和抗氧化防御的选定标志物的变化有关，或者与呼吸系统和全身炎症反应的变化有关。为了实现拟议的目标，我们在中国北京实施空气质量改善计划之前招募了 201 名成年男性和女性，并在奥运会期间对这些人进行了跟踪。一百八十名参与者完成了一系列三项采访：奥运会之前、期间和之后。每次访谈均包括面对面访谈、体检和生物样本采集（血液、尿液和痰）。在整个研究期间测量了研究区域的环境 PM 浓度。建议采用多分析物多重检测来分析选定的炎症标志物。自动酶动力学分析、HPLC、ELISA 和 EIA 将用于评估氧化 DNA/脂质/蛋白质损伤和抗氧化防御。我们预测，在第一个随访期间，我们将观察到随着空气质量的改善，全身炎症和氧化损伤标志物的水平下降，抗炎细胞因子和抗氧化酶的水平增加。随着北京空气质量在第二个后续阶段恢复到奥运会前的水平，我们的假设将通过检查炎症和氧化损伤的变化来进一步评估。公共卫生相关性：我们的提案与 NIH/国家环境健康科学研究所的使命高度相关。空气污染是一种在世界范围内普遍存在的污染，人们推测它会诱发氧化应激和免疫反应，而这些反应与癌症和心肺疾病有关。我们的研究将深入了解空气污染可能增加癌症和心肺疾病风险的潜在机制；此外，我们提出的研究的流行病学性质确保了生成的数据将直接适用于人类。