Prognostic Interaction between Emphysema and Interstitial Lung Abnormalities for Mortality in a Korean National Lung Cancer Screening Cohort

Purpose To investigate the prognostic interaction between emphysema and interstitial lung abnormalities (ILAs) in relation to mortality among individuals undergoing lung cancer screening (LCS). Materials and Methods This retrospective cohort study included individuals screened in the Korean National Lung Cancer Screening Program between August 2019 and December 2020. Emphysema and ILAs were identified from CT study reports found in the program records. The primary study outcomes were mortality after a lung cancer diagnosis and mortality without a lung cancer diagnosis, analyzed using Fine-Gray subdistribution hazard models. Results Among 124 121 LCS participants (mean age, 61.6 years ± 5.3; 121 876 male), 13.8% (17 082) and 2.6% (3275) had emphysema and ILAs, respectively, with ILAs present in 7.0% (1200 of 17 082) of those with emphysema. The association between emphysema and mortality after a lung cancer diagnosis differed based on ILA status (<i>P</i> for interaction = .003). Emphysema was associated with increased mortality only in the absence of ILAs (adjusted subdistribution hazard ratio [sHR], 2.32; 95% CI: 1.97, 2.73; <i>P</i> < .001). In contrast, ILAs were associated with elevated mortality regardless of emphysema status, although the association was attenuated in the presence of emphysema (adjusted sHR without emphysema, 5.29 [95% CI: 4.12, 6.78]; with emphysema, 3.04 [95% CI: 2.32, 3.96]; both <i>P</i> < .001). The combined presence of ILAs and emphysema conferred the highest mortality risk (adjusted sHR: 7.04; 95% CI: 5.42, 9.15), albeit not significantly higher than ILAs alone (<i>P</i> = .09), suggesting that ILAs drive the increased risk when the conditions coexist. Similar patterns were observed for mortality without a preceding lung cancer diagnosis. Conclusion ILAs diminished the prognostic significance of emphysema and were the primary driver of mortality risk when both conditions were present. <b>Keywords:</b> Lung Cancer Screening, Low-Dose CT, Interstitial Lung Abnormalities, Interstitial Lung Diseases, Emphysema <i>Supplemental material is available for this article.</i> © RSNA, 2026.