Sphingolipids and inflammatory biomarkers of COPD progression in healthy smokers

健康吸烟者 COPD 进展的鞘脂和炎症生物标志物

• 批准号: 8997390
• 负责人: RUSSELL Paul BOWLER
• 金额: $ 39.51万
• 依托单位: NATIONAL JEWISH HEALTH
• 依托单位国家: 美国
• 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/8997390
• 关键词: Biological Markers; Blood; Blood Proteins; Blood specimen; CCL20 gene; Cause of Death; Ceramides; Chronic; Chronic Obstructive Airway Disease; Clinical; Data; Development; Diagnosis; Diagnostic tests; Disease; Disease Progression; Distal; Early Intervention; Early treatment; Fibrinogen; Gelatinase B; Genetic; Genetic study; Genotype; Goals; High Resolution Computed Tomography; Inflammatory; Intercellular adhesion molecule 1; Interleukin-6; International; Intervention Studies; Knowledge; Lipids; Longitudinal Studies; Lung diseases; Measures; Medical Genetics; Minority; Modeling; Molecular Profiling; Obstruction; Onset of illness; Phenotype; Plasma; Prevention; Proteins; Proteomics; Publishing; Pulmonary Emphysema; Pulmonary Surfactant-Associated Protein D; Research; Respiratory physiology; Risk; Risk Factors; Sampling; Smoker; Smoking; Specimen; Sphingolipids; Sphingomyelins; Sweden; Testing; Time; Tumor Necrosis Factor-alpha; United States; Work; X-Ray Computed Tomography; abstracting; adiponectin; blood lipid; clinical phenotype; cohort; disorder risk; follow-up; genetic association; genome wide association study; genome-wide; imaging biomarker; improved; molecular phenotype; novel; novel diagnostics; prevent; public health relevance; research study; smoking cessation

 DESCRIPTION (provided by applicant): Chronic obstructive pulmonary disease (COPD) is the 3rd leading cause of death in the US1, 2. Although COPD occurs predominantly in smokers, it is unknown why only a minority of smokers (~20-40%) develop chronic airflow limitation or destruction of distal airspaces (emphysema). Furthermore, most subjects will spend many years in a presymptomatic disease state (pre-COPD) before the onset of disease, even after smoking cessation. Identification of the at-risk presymptomatic current or former smoker is the crucial firt step needed to study early interventions that can prevent the development of COPD and emphysema. In pilot work we have identified multiple novel blood lipid (sphingomyelin and ceramide species) and protein biomarkers of COPD and emphysema. We hypothesize that some of these biomarkers will be stable molecular signature that can identify presymptomatic current and former smokers who are at risk for progression to symptomatic lung disease such as COPD and emphysema. Our proposal will measure candidate biomarkers in previously collected blood from three international longitudinal cohorts (COPDGene, SPIROMICS, and Big3) that contain large numbers of pre-symptomatic former or current smokers without COPD or emphysema, who have genome wide genotyping, and are followed 3-5 years with extensive clinical phenotyping including lung function and qHRCT. The first aim will identify which biomarkers are association with progression of airflow limitation and emphysema in those who do not have COPD at baseline. The second aim will investigate whether these signatures are stable over time and identify the genetic associations contributing to the biomarker signature.