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

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不良健康影响相关，特别是癌症和心肺疾病的发病率和死亡率[1-3]。全身性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增强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，因为在将其结果外推到人类时，这些方法存在固有的不确定性。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，空气污染浓度最初急剧下降，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，以调查人类暴露于PM变化的急性生物学反应，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查奥运会期间PM暴露的变化是否与选定的DNA/脂质/蛋白质损伤和抗氧化防御标志物的变化有关，或者与呼吸和全身炎症反应的变化有关。为了实现所提出的目标，我们在中国北京的空气质量改善计划之前招募了201名成年男性和女性，并在奥运会期间跟踪这些人。180名参与者完成了一系列的三次采访：在奥运会之前，期间和之后。每次访谈包括面对面访谈、体格检查和生物标本采集（血液、尿液和痰液）。在整个研究期间，测量了研究区域的环境PM浓度。提出了多分析物多重测定来分析所选择的炎症标志物。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，我们将观察到全身炎症和氧化损伤标志物的水平随着空气质量的改善而降低，抗炎细胞因子和抗氧化酶的水平增加。我们的假设将进一步评估，通过检查炎症和氧化损伤的变化，在北京的空气质量恢复到奥运会前的水平，在第二个随访期。 公共卫生相关性：我们的建议与NIH/国家环境卫生科学研究所的使命高度相关。空气污染是一种普遍存在的全球性暴露，被假设为诱导氧化应激和免疫反应，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，我们拟议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.