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

说明(申请人提供)：颗粒物(PM)，特别是细/超细颗粒物，与越来越多的短期和长期不利健康影响有关，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起着关键作用，并可能是PM加重这些疾病的共同机制。然而，体外和体内研究只能提供间接证据，因为在将结果外推到人类时，方法本身存在不确定性。2008年奥运会期间，北京的一项空气质量改善计划创造了一个独特的自然实验：空气污染浓度最初大幅下降，随后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，以调查人类对PM暴露变化的急性生物反应，并更好地了解PM在这些疾病中的关键作用途径。这项拟议研究的具体目的是研究在奥运会期间PM暴露的变化是否与选定的DNA/脂肪/蛋白质损伤和抗氧化防御标记物的变化有关，或者与呼吸和全身炎症反应的变化有关。为了实现提出的目标，我们招募了201名成年男性和女性，在北京的空气质量改善倡议之前，中国，并在奥运会期间跟踪调查了这些人。180名参与者完成了一系列的三次采访：奥运会前、奥运会期间和奥运会后。每次面谈包括面谈、体检和生物标本采集(血液、尿液和痰)。在整个研究期间对研究区域的环境PM浓度进行了测量。建议采用多分析多重分析方法来分析选定的炎症标志物。自动酶动力学分析、高效液相色谱、酶联免疫吸附试验和EIA将用于评估氧化DNA/脂肪/蛋白质损伤和抗氧化防御。我们预测，随着空气质量的改善，我们将观察到全身炎症和氧化损伤的标志物水平在第一个随访期内下降，而抗炎细胞因子和抗氧化酶水平上升。我们的假设将通过检测炎症和氧化损伤的变化来进一步评估，因为北京的空气质量在第二个跟踪期恢复到奥运前的水平。 公共卫生相关性：我们的建议与美国国立卫生研究院/国家环境健康科学研究所的使命高度相关。空气污染是一种无处不在的世界性暴露，假设会引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。我们的研究将对空气污染可能增加癌症和心肺疾病风险的这些潜在机制提供洞察；此外，我们拟议的研究的流行病学性质确保所产生的数据将直接适用于人类。

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.