SPIROMICS - Air Pollution Study

描述（由申请人提供）：COPD是美国和全球的主要死因，患者发病率高。更好地了解这种普遍性疾病的进展和负担的促成因素至关重要。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COPD的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，暴露于空气污染加速肺功能丧失的程度，以及对患者报告的结果（如COPD患者的生活质量和呼吸困难）的贡献程度在很大程度上仍然未知。SPIROMICS是一项由NHLBI资助的COPD表型和疾病标志物的独特前瞻性队列研究，计划在美国7个研究中心招募3，200名受试者。一组参与者还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发病率和进展的影响提供了一个非凡的机会。对于特定目标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，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，以精确预测参与者对细颗粒物的环境暴露（PM2.5）、吸光或“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。对于具体目标1b，我们的目标是通过在参与者住宅的子集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。将使用个人监测来评估测量误差。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300名受试者在一年内记录每日症状的每日症状变化和加重风险相关。对于特定目标3，我们将检查诱导痰中的气道巨噬细胞炭黑含量作为空气污染（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相关性。我们的研究建立在具有互补专业知识领域的调查人员网络基础上。这项研究的结果可以为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.