Emphysema During Lung Cancer Screening Predicts All-Cause Mortality up to 25 Years Later

Baseline emphysema at low-dose chest CT (LDCT was predictive of all-cause, chronic obstructive pulmonary disease (COPD), and cardiovascular disease (CVD) mortality in a prospective lung cancer screening cohort of asymptomatic adults for up to 25 years.1

“Until now, we didn’t know if baseline visual emphysema scoring on LDCT in the lung cancer screening setting had any prognostic value,” investigator Claudia I. Henschke, PhD, MD, radiologist and professor of radiology, Department of Diagnostic, Molecular, and Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York, said in a statement.2 “Our study stands out for its long follow-up and comprehensive analysis of the causes of death in a large lung cancer screening cohort.”

Henschke and colleagues conducted a prospective cohort study with 9047 asymptomatic adults aged 40–85 years (4614 female; median age, 65 years [IQR, 61–69]) with a median 43 pack-years of smoking (IQR, 28–64); 29.1% (n = 2637) had emphysema (mild in 1908 [21.1%], moderate in 512 [5.7%], and severe in 217 [2.4%]).1

The participants underwent baseline LDCT screening for lung cancer between June 2000 and December 2008. Participants were followed up until death, loss to follow-up, or December 31, 2024, for a median follow-up of 23.3 years. Four experienced chest radiologists assessed emphysema at baseline LDCT and assigned scores of 0 (none) to 3 (severe). Participants self-reported baseline smoking history and comorbidities. Investigators obtained causes of death from the U.S. National Death Index, physicians, and family and evaluated associations between emphysema and mortality using adjusted Cox proportional hazards and adjusted Fine-Gray competing risks models.

At baseline, 70.9% of participants had no evidence of emphysema, 21.1% had mild, 5.7% had moderate, and 2.4% had severe emphysema, respectively. Notably, 79.2% of participants identified with emphysema on their baseline LDCT had not been previously diagnosed, although 5% of those participants had moderate or severe emphysema.1

“Lung cancer screening shouldn’t just be looking for nodules,” Henschke said.2 “That’s a small part of what we see on the CT scan. As radiologists, we’re responsible for the entire image.”

By year-end 2024, 3,738 participants (41.3%) had died, commonly due to cardiovascular disease (12.7%) and COPD (3.3%). The median age was 81 at the time of all-cause mortality and COPD, 82 from, cardiovascular disease, and 81 from other causes.

Henschke and colleagues found that emphysema was predictive of all-cause mortality (hazard ratio [HR], 1.29; 95% CI: 1.21, 1.38; P < .001), COPD mortality (HR, 3.29; 95% CI: 2.59, 4.18; P < .001), and CVD mortality (HR, 1.14; 95% CI: 1.01, 1.29; P = .04) independent of other factors. Furthermore, emphysema severity had a dose-response relationship with all-cause and COPD mortality, but not CVD mortality. In the adjusted competing risk analysis, emphysema remained associated with COPD mortality (HR, 3.06; 95% CI: 2.40, 3.90; P < .001), but not CVD mortality (HR, 1.04; 95% CI: 0.91, 1.18; P = .59).1

“Clinically, these findings suggest emphysema is not merely an incidental CT finding, but a distinct disease entity associated with worst outcomes and increased mortality, not only from lung cancer but also from respiratory and cardiovascular diseases,” Henschke said.2 “The findings show an increased risk of all causes of death by the presence of emphysema and its severity, ranging from a 1.15-fold increase for mild disease and a 2.28-fold increase for severe emphysema. For deaths due to COPD, the increased risk ranged from a 2.07-fold for mild disease to 12.06-fold increase for severe emphysema.”

In a statement from Radiological Society of North America, Henschke discussed the importance of implementing a comprehensive lung cancer screening program that also assesses COPD and cardiovascular disease risk to improve targeted interventions.

“The amount of information you get and the ability to act on it in a meaningful way is something preventive health only dreamed of being just a few years ago,” Henschke said. “Pulmonologists, cardiologists and radiologists need to work together, because one influences the other,” she said. “We have to work towards solutions holistically.”

Henschke also stressed that about a third of lung cancer deaths per year occur in nonsmokers and hence annual lung cancer screening recommendations should be expanded to reflect this.

References

1. Gutiérrez JG, Yip R, Zulueta JJ, et al. Emphysema at Baseline Low-Dose CT Lung Cancer Screening Predicts Death from Chronic Obstructive Pulmonary Disease and Cardiovascular Disease Up to 25 Years Later. Radiology. Published online September 9, 2025. doi: 10.1148/radiol.250949

2. Emphysema at CT Lung Screening Increases Death Risk in Asymptomatic Adults. News release. Radiological Society of North America. September 9, 2025. https://www.rsna.org/news/2025/september/emphysema-predicts-mortality-risk