Boston Early-Onset COPD Study: This study has enrolled subjects with severe COPD (forced expiratory volume in one second (FEV1) < 40% predicted) at an early age (< 53 years) without alpha-1 antitrypsin deficiency (a known Mendelian risk factor for COPD). Extended pedigrees are enrolled, primarily in New England, although some more geographically distant subjects have been included. This study has been used for epidemiological studies, familial aggregation analysis, linkage analysis, and candidate gene association analysis. Approximately 100 of the severe, early-onset COPD probands will undergo whole genome sequencing in this project. Sequencing data from the subjects with IRB approval for data sharing will be submitted to dbGaP. The Boston Early-Onset COPD Study web site is: http://bostoncopd.org/
COPDGene: COPDGene (also known as the Genetic Epidemiology of COPD Study) is an NIH-funded, multicenter study. A study population of more than 10,000 smokers (1/3 African American and 2/3 non-Hispanic White) has been characterized with a study protocol including pulmonary function tests, chest CT scans, six minute walk testing, and multiple questionnaires. Five years after this initial visit, all available study participants are being brought back for a follow-up visit with a similar study protocol. This study has been used for epidemiologic and genetic studies. Previous genetic analysis in this study has been based on genome-wide SNP genotyping data.Approximately 1900 subjects will undergo whole genome sequencing in this NHLBI WGS project, including severe COPD subjects and resistant smoking controls. The COPDGene Study web site is: http://www.copdgene.org/
ECLIPSE: The “Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints” (ECLIPSE) study was a longitudinal, multicenter, observational investigation of 2164 COPD subjects and a smaller number of smoking controls (337) and nonsmoking controls (245) followed regularly for three years, with three chest CT scans (at baseline, one year, and three years) (Vestbo, European Respiratory Journal 2008; 31: 869). The COPD cases and smoking controls have been included in TOPMed. Inclusion criteria included age 40-75, at least 10 pack-years of smoking, and spirometry in GOLD grades 2-4 (COPD cases) or normal spirometry with post-bronchodilator FEV1>85% predicted and FEV1/FVC>0.7 (controls). Study visits were performed at enrollment, three months, and every six months thereafter with spirometry, questionnaires, and other clinical evaluations. The ECLIPSE CT scans have been analyzed with the VIDA software for emphysema and airway phenotypes. ECLIPSE has provided key insights into the clinical epidemiology of COPD, including COPD exacerbations (Hurst, NEJM 2010; 363: 1128) and lung function decline in COPD (Vestbo, NEJM 2011; 365: 1184). ECLIPSE has been used in a number of genetic studies of COPD susceptibility and protein biomarkers (Faner, Thorax 2014; 69: 666).