Pulmonary emphysema and coronary artery calcifications at baseline LDCT and long-term mortality in smokers and former smokers of the ITALUNG screening trial

Cardiovascular disease (CVD), lung cancer (LC), and respiratory diseases are main causes of death in smokers and former smokers undergoing low-dose computed tomography (LDCT) for LC screening. We assessed whether quantification of pulmonary emphysematous changes at baseline LDCT has a predictive value concerning long-term mortality. In this longitudinal study, we assessed pulmonary emphysematous changes with densitometry (volume corrected relative area below - 950 Hounsfield units) and coronary artery calcifications (CAC) with a 0-3 visual scale in baseline LDCT of 524 participants in the ITALUNG trial and analyzed their association with mortality after 13.6 years of follow-up using conventional statistics and a machine learning approach. Pulmonary emphysematous changes were present in 32.3% of subjects and were mild (6% ≤ RA950 ≤ 9%) in 14.9% and moderate-severe (RA950 > 9%) in 17.4%. CAC were present in 67% of subjects (mild in 34.7%, moderate-severe in 32.2%). In the follow-up, 81 (15.4%) subjects died (20 of LC, 28 of other cancers, 15 of CVD, 4 of respiratory disease, and 14 of other conditions). After adjusting for age, sex, smoking history, and CAC, moderate-severe emphysema was significantly associated with overall (OR 2.22; 95CI 1.34-3.70) and CVD (OR 3.66; 95CI 1.21-11.04) mortality. Machine learning showed that RA950 was the best single feature predictive of overall and CVD mortality. Moderate-severe pulmonary emphysematous changes are an independent predictor of long-term overall and CVD mortality in subjects participating in LC screening and should be incorporated in the post-test calculation of the individual mortality risk profile. Densitometry allows quantification of pulmonary emphysematous changes in low-dose CT examinations for lung cancer screening. Emphysematous lung density changes are an independent predictor of long-term overall and cardio-vascular disease mortality in smokers and former smokers undergoing screening. Emphysematous changes quantification should be included in the post-test calculation of the individual mortality risk profile.