Emphysema progression, as measured on chest computed tomography (CT), is associated with increased all-cause and respiratory mortality in ever-smokers with emphysema, according to study results published in Radiology.

Researchers conducted a secondary analysis of the COPDGene (ClinicalTrials.gov Identifier: NCT00608764) and the Evaluation of Chronic Obstructive Pulmonary Disease Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE; ClinicalTrials.gov Identifier: NCT00292552) studies. They used the volume-adjusted lung density at the 15th percentile of the lung density histogram (lung density perc15) method to measure emphysema on CT at 2 points in ever-smokers.

The population included 5143 participants (mean age, 60 years) in COPDGene and 1549 participants (mean age, 62 years) in ECLIPSE. Of these patients, 2097 participants in COPDGene and 1179 in ECLIPSE had emphysema. The investigators performed follow-up imaging after 5.5±0.6 years in COPDGene and 3.0±0.2 years in ECLIPSE. Additionally, mortality was examined over the ensuing 5 years in both studies.

Continue Reading

To assess the association between all-cause mortality and the emphysema progression rate, researchers of the secondary analysis used Cox regression analyses adjusted for ethnicity, sex, baseline age, pack-years, and lung density perc15;, baseline and change in smoking status, baseline forced expiratory volume in 1 second, and baseline 6-minute walk distance.

All-cause mortality increased by 8% for every 1 g/L per year faster rate of decline in lung density perc15 in COPDGene (hazard ratio [HR], 1.08; 95% CI, 1.01-1.16; P =.03) and by 6% for every 1 g/L per year faster rate of decline in lung density perc15 in ECLIPSE (HR, 1.06; 95% CI, 1.00-1.13; P =.045).

Respiratory mortality increased by 22% in COPDGene (HR, 1.22; 95% CI, 1.13-1.31; P <.001). Ever-smokers with emphysema who had a loss of density more than the repeatability coefficient in the COPDGene cohort also had a 65% higher mortality (HR, 1.65; 95% CI, 1.10-2.47; P =.02) compared with those who did not, according to the dichotomized analyses.

A potential limitation of this study was the use of objective quantitative measures for defining emphysema and measuring its progression, which the researchers say is difficult to accomplish with currently available objective means.

In spite of these limitations, the researchers concluded that their findings suggest “that objectively measured emphysema at CT is a clinically meaningful imaging biomarker that can be used for measuring disease progression.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Ash SY, San José Estépar R, Fain SB, et al; for the COPDGene Investigators and the COPD Biomarker Qualification Consortium. Relationship between emphysema progression at CT and mortality in ever-smokers: results from the COPDGene and ECLIPSE cohorts. Radiology. Published online February 16, 2021. doi:10.1148/radiol.2021203531