Relationship between Emphysema Progression at CT and Mortality in Ever-Smokers: Results from the COPDGene and ECLIPSE Cohorts

Samuel Y. Ash, Raúl San José Estépar, Sean B. Fain, Ruth Tal-Singer, Robert A. Stockley, Lars H. Nordenmark, Stephen Rennard, Mei Lan K. Han, Debora Merrill, Stephen M. Humphries, Alejandro A. Diaz, Stefanie E. Mason, Farbod N. Rahaghi, Carrie L. Pistenmaa, Frank C. Sciurba, Gonzalo Vegas-Sánchez-Ferrero, David A. Lynch, George R. Washko

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Background: The relationship between emphysema progression and long-term outcomes is unclear. Purpose: To determine the relationship between emphysema progression at CT and mortality among participants with emphysema. Materials and Methods: In a secondary analysis of two prospective observational studies, COPDGene (, NCT00608764) and Evaluation of Chronic Obstructive Pulmonary Disease Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE;, NCT00292552), emphysema was measured at CT at two points by using the volume-adjusted lung density at the 15th percentile of the lung density histogram (hereafter, lung density perc15) method. The association between emphysema progression rate and all-cause mortality was analyzed by using Cox regression adjusted for ethnicity, sex, baseline age, pack-years, and lung density, baseline and change in smoking status, forced expiratory volume in 1 second, and 6-minute walk distance. In COPDGene, respiratory mortality was analyzed by using the Fine and Gray method. Results: A total of 5143 participants (2613 men [51%]; mean age, 60 years 6 9 [standard deviation]) in COPDGene and 1549 participants (973 men [63%]; mean age, 62 years 6 8) in ECLIPSE were evaluated, of which 2097 (40.8%) and 1179 (76.1%) had emphysema, respectively. Baseline imaging was performed between January 2008 and December 2010 for COPDGene and January 2006 and August 2007 for ECLIPSE. Follow-up imaging was performed after 5.5 years 6 0.6 in COPDGene and 3.0 years 6 0.2 in ECLIPSE, and mortality was assessed over the ensuing 5 years in both. For every 1 g/L per year faster rate of decline in lung density perc15, all-cause mortality increased by 8% in COPDGene (hazard ratio [HR], 1.08; 95% CI: 1.01, 1.16; P = .03) and 6% in ECLIPSE (HR, 1.06; 95% CI: 1.00, 1.13; P = .045). In COPDGene, respiratory mortality increased by 22% (HR, 1.22; 95% CI: 1.13, 1.31; P , .001) for the same increase in the rate of change in lung density perc15. Conclusion: In ever-smokers with emphysema, emphysema progression at CT was associated with increased all-cause and respiratory mortality.

Original languageEnglish (US)
Pages (from-to)222-231
Number of pages10
Issue number1
StatePublished - Apr 2021

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging


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