Biomarkers predictive of Lung Function Decline in physiologically Normal Smokers

预测生理正常吸烟者肺功能下降的生物标志物

基本信息

批准号：
9144848
负责人：
FRANK SCIURBA
金额：
$ 23.1万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-15 至 2018-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9144848
关键词：
Biological Markers Blood Proteins Cause of Death Characteristics Childhood Chronic Obstructive Airway Disease Clinical Cohort Studies Data Data Reporting Development Disease Enzyme-Linked Immunosorbent Assay Epithelial Epithelium Event Goals Health Health Care Costs Homeostasis IL6 gene Immune Tolerance Impairment Individual Inflammation Mediators Inflammatory Interleukin-6 Interstitial Collagenase Intervention Lead Life Lung Lung diseases Measurement Measures Modeling Obstruction Participant Pathologic Patients Peptide Hydrolases Peripheral Phenotype Physiological Plasma Proteins Predisposition Prevention strategy Process Protease Inhibitor Pulmonary Function Test/Forced Expiratory Volume 1 Research Respiratory physiology Risk Sampling Severity of illness Smoker Specialized Center Spirometry Sushi Domain TIMP1 gene TIMP2 gene TNF gene Techniques Testing Tobacco Tobacco smoke Training United States Validation Variant base biomarker panel case control cohort disability experience follow-up high risk in utero model development novel marker peripheral blood population based pre-clinical predictive marker prospective protein biomarkers screening smoking cessation treatment strategy

项目摘要

DESCRIPTION (provided by applicant): Tobacco associated diseases of the lung, including chronic obstructive pulmonary disease (COPD), are a leading cause of death and a major contributor to health care costs in the United States. COPD cases are traditionally defined using spirometric thresholds of airflow obstruction. While tobacco smoke may initiate these processes, the susceptibility to decline in lung function or other tobacco associated phenotypes is highly variable. Furthermore, accelerated decline in lung function may continue due to mechanisms such as altered immune tolerance which continue after smoking cessation. The variation in the rate of lung function decline in patients with COPD is poorly described. Because disease definitions are based on single lung function measurements compared to population based standards, lung function decline may be significant even in patients with "normal" lung function studies. By contrast, individuals classified as having abnormal lung function using traditional disease definitions may have physiologic abnormalities reflective of events during childhood or even in utero which are no longer active or progressive. The project's overall goal is to develop a model integrating clinical, demographic, radiologic and physiological parameters and biomarker levels for the prediction of long-term lung function decline in spirometrically normal subjects. The goal will be accomplished by leveraging a large longitudinal cohort (N=1024) of smokers with normal baseline lung function and median long-term follow up of 9 years (range 4 -12). We will define the subjects as cases and controls based on the presence or absence of rapid long-term lung function decline. We will analyze a set of biomarkers selected based on preliminary data in a cohort with 2-year follow-up. We will test our hypotheses that peripheral blood biomarkers (CCP, CRP, IL6, TNFα, PTX3, sFAS, MMP1, TIMP1, TIMP2, TNFRI and TNFRII) are associated with rate of lung function decline and that demographic and clinical characteristics, peripheral protein biomarkers, and other available radiologic and physiologic parameters, in combination, will constitute a powerful set of predictors for rapid lung function decline. Positive results from this study will allow us to define biomarker signatures and other features in spirometrically normal smokers that predict lung function decline. The validated identification strategy will be used for development and testing of interventions in those individuals at risk for rapid decline.

描述（由申请人提供）：在美国，烟草相关肺部疾病，包括慢性阻塞性肺病 (COPD)，是导致死亡的主要原因，也是造成医疗费用的主要原因，传统上是使用肺活量阈值来定义 COPD 病例。虽然烟草烟雾可能引发这些过程，但肺功能下降或其他烟草相关表型的易感性变化很大。此外，由于免疫耐受等机制的持续，肺功能的加速下降可能会持续。戒烟后，慢性阻塞性肺病患者肺功能下降率的变化很少被描述，因为疾病定义是基于单一肺功能测量与基于人群的标准相比，所以即使在“正常”患者中，肺功能下降也可能很显着。相比之下，使用传统疾病定义被分类为肺功能异常的个体可能存在反映儿童时期甚至子宫内事件的生理异常，这些异常不再活跃或进展。、人口统计、放射学和生理学预测肺功能正常受试者长期肺功能下降的参数和生物标志物水平将通过利用具有正常基线肺功能的吸烟者的大型纵向队列（N = 1024）和中位长期随访来实现。 9 年（范围 4 -12）。我们将根据是否存在快速长期肺功能下降将受试者定义为病例和对照。我们将分析根据 2 人队列中的初步数据选择的一组生物标志物。 -年我们将检验我们的假设，即外周血生物标志物（CCP、CRP、IL6、TNFα、PTX3、sFAS、MMP1、TIMP1、TIMP2、TNFRI 和 TNFRII）与肺功能下降率以及人口和临床特征相关。、外周蛋白生物标志物以及其他可用的放射学和生理学参数相结合，将构成肺功能快速下降的一组强大的预测因子，该研究的积极结果将使我们能够定义生物标志物。肺功能正常的吸烟者的特征和其他特征可预测肺功能下降，经过验证的识别策略将用于针对有快速下降风险的个体开发和测试干预措施。