Serum Biomarkers of COPD: a population-based prospective study

慢性阻塞性肺病的血清生物标志物：一项基于人群的前瞻性研究

• 批准号: 7573285
• 负责人: Stefano Guerra
• 金额: $ 37.75万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-02-01 至 2014-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7573285
• 关键词: Accounting; Affect; Antibodies; Asthma; Autoantigens; Autoimmune Responses; Biological Markers; Breathing; CD14 gene; Cause of Death; Chlamydophila pneumoniae; Chronic; Chronic Obstructive Airway Disease; Collection; Data; Development; Disease; Disease Progression; Drug Metabolic Detoxication; Early identification; Elastin; Epidemiologic Studies; Epidemiology; Glutathione S-Transferase; IL8 gene; Immune response; Incidence; Infection; Inflammation; Inflammatory; Interleukin-1; Interleukin-6; Interstitial Collagenase; Link; Lung; Measures; Molecular; Morbidity - disease rate; Mycoplasma pneumoniae; Natural Immunity; Nature; Nuclear; Obstructive Lung Diseases; Oxidative Stress; Participant; Pathway interactions; Patients; Peroxidases; Prevention; Prevention strategy; Prospective Studies; Protein C Inhibitor; Proteolysis; Research; Resolution; Respiratory physiology; Risk; Sampling; Serum; Smoker; Subgroup; TNF gene; Testing; Time; Tissue Inhibitor of Metalloproteinase-1; airway inflammation; cigarette smoking; cohort; disease phenotype; disorder risk; follow-up; inflammatory marker; insight; interest; longitudinal design; microbial; microorganism; mortality; novel; population based; prevent; prospective; public health relevance; repository; respiratory

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. PUBLIC HEALTH RELEVANCE: Chronic Obstructive Pulmonary Disease (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 onset and progression of this disease may have critical implications for prevention. This project aims to overcome some of the existing limitations of biomarker studies of COPD by measuring a large panel of biomarkers in serum samples that were collected over 35 years of follow-up in a large epidemiological cohort. These biomarkers will be then tested to determine if they can predict risk of developing COPD and dying of it.

描述（由申请人提供）：慢性阻塞性肺疾病（COPD）是一种慢性气道炎症性疾病，具有重要的全身表现，占其发病率和死亡率的很大一部分。 COPD 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。识别可预测该疾病发生和进展的全身生物标志物可能会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，大多数慢性阻塞性肺病生物标志物的研究都受到一次仅使用少数标志物以及数据的横截面性质的限制，这排除了这些生物标志物是否与慢性阻塞性肺病有因果关系或者它们仅仅是疾病的结果的任何结论性解决方案。为了克服这些限制，在本申请中，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），并提供详细的呼吸道表型信息和在 35 年随访期间从数千名参与者收集的广泛血清样本。在这个队列中，我们建议测试一大批 133 种候选生物标志物，这些生物标志物分别涉及炎症、先天免疫、蛋白水解、解毒和氧化应激、对微生物的适应性免疫反应以及自身免疫反应。这些生物标志物将针对 COPD 表型的发生率和进展（目标 1）以及 COPD 相关和全因死亡风险（目标 2）进行测试。此外，还将在患有和不患有哮喘的受试者之间比较与气流受限相关的生物标志物组（目标 3）。该项目将开展迄今为止最全面的慢性阻塞性肺病前瞻性生物标志物研究。公共卫生相关性：慢性阻塞性肺疾病 (COPD) 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。识别可预测该疾病发病和进展的全身生物标志物可能对预防具有重要意义。该项目旨在通过测量血清样本中的大量生物标志物来克服 COPD 生物标志物研究的一些现有局限性，这些血清样本是在大型流行病学队列中跟踪超过 35 年收集的。然后将对这些生物标志物进行测试，以确定它们是否可以预测患慢性阻塞性肺病和死于慢性阻塞性肺病的风险。