SPIROMICS - Air Pollution Study

描述（由申请人提供）：COPD是美国和世界范围内的主要死亡原因，患者发病率高。更好地了解导致这一普遍疾病进展和负担的因素至关重要。尽管基于人群的流行病学证据表明，暴露于环境空气污染物会导致慢性阻塞性肺病住院率和死亡率增加，但人们对暴露于空气污染物对疾病进展的影响知之甚少。例如，暴露于空气污染在多大程度上加速肺功能丧失，并在多大程度上影响COPD患者报告的生活质量和呼吸困难等结果，这在很大程度上仍是未知的。SPIROMICS是一项独特的由nhlbi资助的COPD表型和疾病标志物的前瞻性队列研究，计划在美国7个地点招募3200名受试者。另一组参与者也将记录一年内的每日症状。我们建议增加最先进的空气污染暴露评估，以确定所有SPIROMICS参与者的个人水平的室外和室内空气污染暴露，为了解空气污染物对COPD发病和进展的影响提供了难得的机会。对于Specific Aim 1a，我们的目标是确定长期室外空气污染暴露对COPD发病率的影响，包括肺功能下降、患者报告的结局和加重，通过采用复杂的时空空气污染预测模型，辅以特定队列的室外监测数据，精确预测参与者的环境暴露于细颗粒物（PM2.5）、光吸收或“黑”碳（BC）、二氧化氮（NO2）、氮氧化物（NOx）、臭氧（O3）、二氧化硫（SO2）)以及与作为SPIROMICS研究的一部分收集的现有健康结果的联系。对于Specific Aim 1b，我们的目标是通过在一部分参与者的住所进行室内空气监测，确定室内空气污染物（PM2.5、NO2、NOx、SO2、O3、BC和二手烟）对COPD发病率的影响。这些数据将与在整个队列中收集的经过验证的问卷数据相结合，为所有参与者建立室内暴露模型。个人监测将用于评估测量误差。对于特定目标2，我们将确定室外空气污染的短期变化是否与300名记录一年期间每日症状的受试者的日常变化和恶化风险相关。在特异性目的3中，我们将检测诱导痰中气道巨噬细胞黑碳含量作为空气污染（PM2.5和BC）的生物标志物，并确定其与疾病严重程度和预后的临床和亚临床指标的关系。我们的研究建立在已建立的具有互补专业领域的研究人员网络上。本研究结果可以为COPD患者的公共政策和临床管理提供指导信息。

DESCRIPTION (provided by applicant): COPD is a leading cause of death in the US and worldwide and patients suffer high morbidity. A better understanding of contributing factors to the progression and burden of this pervasive disease is critical. Despite population-based epidemiological evidence suggesting exposure to ambient air pollutants causes increased hospitalizations and mortality from COPD, there is very little known about the impact of exposure to air pollutants on the progression of disease. For example, the extent to which exposure to air pollution accelerates lung function loss and contributes to patient-reported outcomes, such as quality of life and dyspnea in COPD remains largely unknown. SPIROMICS is a unique NHLBI-funded prospective cohort study of COPD phenotypes and markers of disease which plans to enroll 3,200 subjects at seven sites across the US. A subgroup of participants will also record daily symptoms over one year. We propose to add state-of-the art air pollution exposure assessment to determine individual-level outdoor and indoor air pollution exposure for all SPIROMICS participants, providing an extraordinary opportunity to understand effects of air pollutants on COPD morbidity and progression. For Specific Aim 1a, we aim to determine the impact of long-term outdoor air pollution exposure on COPD morbidity, including lung function decline, patient reported outcomes, and exacerbations by employing sophisticated spatio-temporal air pollution prediction models, supplemented with cohort-specific outdoor monitoring data, to precisely predict participants' ambient exposure to fine particulate matter (PM2.5), light absorbing or "black" carbon (BC), nitrogen dioxide (NO2), nitrogen oxides (NOx), ozone (O3), sulfur dioxide (SO2)) and link with existing health outcomes collected as part of the SPIROMICS study. For Specific Aim 1b, we aim to determine the effect of indoor air pollutants (PM2.5, NO2, NOx, SO2, O3, BC and secondhand smoke) on COPD morbidity by conducting indoor air monitoring in a subset of participants' residences. These data will be combined with validated questionnaire data collected on the entire cohort to model indoor exposure for all participants. Personal monitoring will be used to assess measurement error. For Specific Aim 2, we will determine whether short-term changes in outdoor air pollution are associated with day-to-day changes in symptoms and exacerbation risk in 300 subjects recording daily symptoms over a one- year period. For Specific Aim 3 we will examine airway macrophage black carbon content from induced sputum as a biomarker of air pollution (PM2.5 and BC) and determine its association with clinical and subclinical measures of disease severity and prognosis. Our study builds on an established network of investigators with complementary areas of expertise. Findings from this study can provide information to guide public policy and clinical management for individuals with COPD.