Serum Biomarkers of COPD: a population-based prospective study

描述（由申请人提供）：慢性阻塞性肺疾病（COPD）是一种具有重要全身性表现的慢性气道炎症性疾病，占其发病率和死亡率的很大一部分。慢性阻塞性肺病目前是美国第四大死因，预计到2020年将成为全球第三大死因。识别系统生物标志物，可以预测该疾病的开始和进展，可能为其分子机制提供重要见解，并对预防具有重要意义。然而，迄今为止，大多数COPD生物标志物的研究都受到一次仅使用少数标志物和数据的横断面性质的限制，这使得无法确定这些生物标志物是否与COPD有因果关系，或者它们仅仅是疾病的后果。为了克服这些限制，在本应用中，我们建议使用1972年启动的大型前瞻性人群队列（图森气道阻塞性疾病流行病学研究- TESAOD），该队列提供了详细的呼吸表型信息和广泛收集的血清样本，这些样本收集了数千名参与者的35年随访期。在这个队列中，我们建议测试133个候选生物标志物，这些生物标志物不同程度地参与炎症、先天免疫、蛋白质水解、解毒和氧化应激、对微生物的适应性免疫反应和自身免疫反应。这些生物标志物将测试COPD表型的发病率和进展（Aim 1）以及COPD相关和全因死亡风险（Aim 2）。此外，与气流限制相关的生物标志物将在哮喘和非哮喘受试者之间进行比较（目的3）。该项目将产生迄今为止最全面的COPD前瞻性生物标志物研究。

DESCRIPTION (provided by applicant): Chronic Obstructive Pulmonary Disease (COPD) is a chronic airway inflammatory disease with important systemic manifestations that account for a substantial part of its morbidity and mortality. COPD is currently the fourth leading cause of death in the US and the projected third leading cause of death worldwide by 2020. The identification of systemic biomarkers that can predict inception and progression of this disease may provide important insights into its molecular mechanisms and have critical implications for prevention. Yet, to date, most studies of biomarkers of COPD have been limited by the use of only a few markers at a time and by the cross-sectional nature of the data, which has precluded any conclusive resolution of whether these biomarkers are causally linked to COPD or they are simply a consequence of the disease. To overcome these limitations, in this application we propose to use a large prospective population-based cohort that was initiated in 1972 (Tucson Epidemiological Study of Airway Obstructive Disease - TESAOD) and provides detailed respiratory phenotypic information and an extensive collection of serum samples that were collected over the 35-year follow-up period from several thousand participants. In this cohort, we propose to test a large panel of 133 candidate biomarkers variably involved in inflammation, innate immunity, proteolysis, detoxification and oxidative stress, adaptive immune responses to microorganisms, and auto- immune responses. These biomarkers will be tested against incidence and progression of COPD phenotypes (Aim 1) as well as COPD-related and all-cause mortality risk (Aim 2). In addition panels of biomarkers associated with airflow limitation will be compared between subjects with and without asthma (Aim 3). This project will result in the most comprehensive prospective biomarker study of COPD to date.