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: 8431380
• 负责人: Stefano Guerra
• 金额: $ 35.7万
• 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 2015-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8431380
• 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.

描述(申请人提供)：慢性阻塞性肺疾病(COPD)是一种慢性呼吸道炎症性疾病，具有重要的全身表现，是其发病率和死亡率的重要组成部分。慢性阻塞性肺病目前是美国的第四大死因，预计到2020年将成为全球第三大死因。识别可以预测该病发生和发展的系统生物标志物可能会对该病的分子机制提供重要的见解，并对预防具有重要意义。然而，到目前为止，大多数对COPD生物标记物的研究都受到一次只使用几个标记物以及数据横断面性质的限制，这排除了这些生物标记物是与COPD有因果联系还是仅仅是疾病的结果的任何决定性的解决方案。为了克服这些限制，在这项申请中，我们建议使用一个大型的基于人群的前瞻性队列，该队列始于1972年(图森呼吸道阻塞性疾病流行病学研究-TESAOD)，提供了详细的呼吸道表型信息和从数千名参与者的35年随访期间收集的大量血清样本。在这个队列中，我们建议测试133个候选生物标记物的大小组，这些生物标记物涉及炎症、先天免疫、蛋白分解、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。这些生物标记物将针对COPD表型的发病和进展(目标1)以及与COPD相关的和全因死亡风险(目标2)进行测试。此外，与气流受限相关的生物标志物面板将在患有哮喘和不患有哮喘的受试者之间进行比较(目标3)。该项目将导致迄今为止最全面的COPD前瞻性生物标记物研究。

项目成果

Measurement error correction in the least absolute shrinkage and selection operator model when validation data are available.

• DOI: 10.1177/0962280217734241
• 发表时间: 2019-03
• 期刊: Statistical methods in medical research
• 影响因子: 2.3
• 作者: Vasquez MM;Hu C;Roe DJ;Halonen M;Guerra S
• 通讯作者: Guerra S

Serum concentrations of club cell secretory protein (Clara) and cancer mortality in adults: a population-based, prospective cohort study.

• DOI: 10.1016/s2213-2600(13)70220-0
• 发表时间: 2013-12
• 期刊: LANCET RESPIRATORY MEDICINE
• 影响因子: 76.2
• 作者: Guerra, Stefano;Vasquez, Monica M.;Spangenberg, Amber;Halonen, Marilyn;Martinez, Fernando D.
• 通讯作者: Martinez, Fernando D.

Reply to Bush: Low Lung Function in Young Adult Life Is Associated with Early Mortality.

回复布什：年轻时肺功能低下与早期死亡有关。

• DOI: 10.1164/rccm.201708-1647le
• 发表时间: 2018
• 期刊: American journal of respiratory and critical care medicine
• 影响因子: 24.7
• 作者: Vasquez,MonicaM;Zhou,Muhan;Hu,Chengcheng;Martinez,FernandoD;Guerra,Stefano
• 通讯作者: Guerra,Stefano

Exposure to parental smoking in childhood is associated with persistence of respiratory symptoms into young adult life.

童年时期接触父母吸烟与成年后呼吸道症状持续存在相关。

• DOI: 10.1016/j.jaci.2014.07.030
• 发表时间: 2014
• 期刊: The Journal of allergy and clinical immunology
• 作者: Pugmire,Juliana;Vasquez,MonicaM;Zhou,Muhan;Sherrill,DuaneL;Halonen,Marilyn;Martinez,FernandoD;Guerra,Stefano
• 通讯作者: Guerra,Stefano

Least absolute shrinkage and selection operator type methods for the identification of serum biomarkers of overweight and obesity: simulation and application.

至少绝对收缩和选择算子类型的方法，用于鉴定超重和肥胖的血清生物标志物：仿真和应用。

• DOI: 10.1186/s12874-016-0254-8
• 发表时间: 2016-11-14
• 期刊: BMC medical research methodology
• 影响因子: 4
• 作者: Vasquez MM;Hu C;Roe DJ;Chen Z;Halonen M;Guerra S
• 通讯作者: Guerra S