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

Abstract

Objectives 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. Methods 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. Results 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. Conclusions 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. Key Points • 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.

Cardiac troponin I as predictor for cardiac and other mortality in the German randomized lung cancer screening trial (LUSI)

“…Current research focuses on the complementary use of CT-images for identifying individuals at elevated risk of cardiovascular mortality, on the basis of radiologic ascertainments of emphysema, COPD or coronary artery calcification scores 28 , 29 . A limitation of our study is that for the present analyses we did not dispose of CT-based assessment of emphysema and coronary artery calcification; thus, we could not examine the added value of cTnI measurements for this purpose, compared to radiologic data.…”

Lung Cancer Screening with Low-Dose CT: What We Have Learned in Two Decades of ITALUNG and What Is Yet to Be Addressed

“…In the wave of the special interest of our group in the assessment of COPD with CT or LDCT, clinically and in phantoms [ 74 , 75 , 76 ], in ITALUNG, we specifically investigated pulmonary emphysema. In particular, by applying lung densitometry, which is a more objective tool as compared to visual assessment [ 77 , 78 ], in subjects undergoing screening LDCT we assessed emphysema frequency and distribution (prevalence) [ 46 , 52 ], progression over time [ 47 , 48 ], and relevance in terms of long-term mortality [ 52 ].…”

“…Pulmonary emphysema was observed in about one-third of the ITALUNG participants [ 46 , 52 ] and was moderate or severe in 17% [ 52 ]. It infrequently and mildly progressed over time [ 48 ].…”

“…It infrequently and mildly progressed over time [ 48 ]. However, when moderate or severe at baseline LDCT, it was significantly associated with long-term overall and CVD mortality after adjustment for age, sex, smoking history, and CAC [ 52 ].…”

“…However, unexpectedly, the people with a greater smoking burden are not those with the larger benefit of LC screening. This is due, on the one hand, to the higher incidence in these subjects of more aggressive and less curable LC histotypes as small-cell carcinoma and squamous-cell carcinoma [ 73 , 100 , 101 ] and, on the other hand, to the effect of comorbidities as competing causes of death, especially CVD, which substantially decrease the years of life that can be potentially gained in subjects with screening-detected LC [ 50 , 52 , 73 , 102 , 103 ].…”