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: 8217147
• 负责人: Stefano Guerra
• 金额: $ 37.5万
• 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/8217147
• 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; Health; 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; Pulmonary Function Test/Forced Expiratory Volume 1; 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; 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。系统性生物标志物的识别，可以预测发病和进展的这种疾病可能会提供重要的见解，其分子机制，并有重要的意义，预防。然而，到目前为止，大多数COPD生物标志物的研究都受到限制，一次只使用几个标志物，并且数据的横截面性质，这排除了这些生物标志物是否与COPD有因果关系或它们只是疾病的结果的任何结论性解决方案。为了克服这些局限性，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），并提供详细的呼吸表型信息和在35年随访期间从数千名参与者中收集的大量血清样本。在该队列中，我们提出测试涉及炎症、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应答和自身免疫应答的133个候选生物标志物的大组。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，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（目的3）。该项目将导致迄今为止最全面的COPD前瞻性生物标志物研究。公共卫生关系：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。确定可以预测这种疾病的发作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一个大型流行病学队列中35年随访收集的血清样本中的大量生物标志物，克服COPD生物标志物研究的一些现有局限性。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COPD和死于COPD的风险。