Chronic obstructive pulmonary disease (COPD), the third leading cause of death in the United States, is a heterogeneous syndrome. Comprehensive insight into COPD heterogeneity will require longitudinal data to elucidate the genetic, clinical, and radiographic determinants of disease progression. This proposal will extend the COPDGene Study by performing five-year longitudinal follow-up visits on all available COPDGene subjects, with follow-up chest CT scans on all subjects except control smokers with normal baseline CT scans. The primary goals of COPDGene are: a) To identify new genetic loci that influence the development of COPD and COPD-related phenotypes;and b) To reclassify COPD into subtypes that can ultimately be used to develop effective subtype-specific therapies. The primary hypothesis for this renewal application is that subtypes of COPD which differ in pathophysiological mechanism and disease progression can be identified by integrating imaging, clinical, and genetic characteristics.
The specific aims are: 1) To characterize the determinants of COPD progression over five years using clinical phenotyping and both quantitative and visual analysis of chest CT scans;2) To assess the rare and common genetic determinants of COPD and COPD- related phenotypes by genotyping with the Exome Chip in 10,171 subjects, followed by whole genome sequencing of 2,000 subjects with specific imaging characteristics and validation of the rare variant associations in the remaining 8,171 COPDGene subjects;and 3) To develop a new classification system based on pathophysiologic subtypes of COPD by integrating genetic, clinical, physiologic, and CT-based phenotypes. This novel COPD classification system will be validated in multiple collaborating COPD cohorts.

Public Health Relevance

We propose a five year longitudinal follow-up of subjects in COPDGene, an extensively phenotyped cohort of more than 10,000 non-Hispanic White and African American smokers at risk for or with COPD. Exome Chip genotyping and whole genome followed by candidate DNA sequencing will be performed to identify rare and common genetic determinants of COPD. The comprehensive clinical, imaging, and genetic data will be used to develop a new classification system for COPD.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL089897-08
Application #
8700462
Study Section
Special Emphasis Panel (ZHL1-CSR-X (M2))
Program Officer
Postow, Lisa
Project Start
2007-07-01
Project End
2017-07-31
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
8
Fiscal Year
2014
Total Cost
$7,411,479
Indirect Cost
$1,005,685
Name
National Jewish Health
Department
Type
DUNS #
076443019
City
Denver
State
CO
Country
United States
Zip Code
80206
Budoff, Matthew J; Lutz, Sharon M; Kinney, Gregory L et al. (2018) Coronary Artery Calcium on Noncontrast Thoracic Computerized Tomography Scans and All-Cause Mortality. Circulation 138:2437-2438
Brunette, Amanda M; Holm, Kristen E; Wamboldt, Frederick S et al. (2018) Subjective cognitive complaints and neuropsychological performance in former smokers with and without chronic obstructive pulmonary disease. J Clin Exp Neuropsychol 40:411-422
Adami, Alessandra; Hobbs, Brian D; McDonald, Merry-Lynn N et al. (2018) Genetic variants predicting aerobic capacity response to training are also associated with skeletal muscle oxidative capacity in moderate-to-severe COPD. Physiol Genomics 50:688-690
Chen, Li-Shiun; Zawertailo, Laurie; Piasecki, Thomas M et al. (2018) Leveraging Genomic Data in Smoking Cessation Trials in the Era of Precision Medicine: Why and How. Nicotine Tob Res 20:414-424
Carr, Laurie L; Jacobson, Sean; Lynch, David A et al. (2018) Features of COPD as Predictors of Lung Cancer. Chest 153:1326-1335
Ekström, Magnus; Bornefalk-Hermansson, Anna; Wysham, Nicholas et al. (2018) Spirometric Volumes and Breathlessness Across Levels of Airflow Limitation: The COPDGene Study. Am J Respir Crit Care Med :
Vergara, Candelaria; Parker, Margaret M; Franco, Liliana et al. (2018) Genotype imputation performance of three reference panels using African ancestry individuals. Hum Genet 137:281-292
Boueiz, Adel; Chang, Yale; Cho, Michael H et al. (2018) Lobar Emphysema Distribution Is Associated With 5-Year Radiological Disease Progression. Chest 153:65-76
Copeland, Carla R; Nath, Hrudaya; Terry, Nina L J et al. (2018) Paratracheal Paraseptal Emphysema and Expiratory Central Airway Collapse in Smokers. Ann Am Thorac Soc 15:479-484
Diaz, Alejandro A; Strand, Matthew; Coxson, Harvey O et al. (2018) Disease Severity Dependence of the Longitudinal Association Between CT Lung Density and Lung Function in Smokers. Chest 153:638-645

Showing the most recent 10 out of 234 publications