SPIROMICS - Air Pollution Study

描述(由申请人提供)：慢性阻塞性肺病是美国和世界范围内的主要死亡原因，患者的发病率很高。更好地了解导致这种普遍疾病进展和负担的因素是至关重要的。尽管基于人群的流行病学证据表明，暴露在环境空气污染物中会导致COPD住院人数和死亡率增加，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，暴露在空气污染中会在多大程度上加速肺功能丧失，并对患者报告的结果做出贡献，如COPD的生活质量和呼吸困难，目前在很大程度上仍不清楚。SPIROMICS是一项由NHLBI资助的针对COPD表型和疾病标志物的独特前瞻性队列研究，计划在全美七个地点招募3200名受试者。参与者的一个小组也将在一年内记录每天的症状。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发病率和进展的影响提供了一个非同寻常的机会。针对具体目标1a，我们旨在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、患者报告的结果和病情恶化，方法是采用复杂的时空空气污染预测模型，辅以队列特定的室外监测数据，以准确预测参与者周围环境中细颗粒物(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)的暴露情况，并与作为SPIROMICS研究一部分收集的现有健康结果相联系。对于特定的目标1b，我们的目标是通过在参与者的住宅中进行室内空气监测来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，以模拟所有参与者的室内暴露。将使用个人监控来评估测量误差。对于具体目标2，我们将确定室外空气污染的短期变化是否与一年内记录每日症状的300名受试者的症状和恶化风险的日常变化有关。为达到特定目的3，我们将检测诱导痰中的呼吸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措施的相关性。我们的研究建立在现有的调查人员网络的基础上，这些调查人员拥有互补的专业领域。这项研究的结果可以为指导COPD患者的公共政策和临床管理提供信息。

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.