Interstitial lung abnormality presence associates with mortality in a lung cancer screening cohort independent of multi-organ comorbidities

Interstitial lung abnormalities (ILAs) are frequent findings in lung cancer screening (LCS) and may represent an early form of pulmonary fibrosis (PF). Importantly, ILA presence is associated with increased mortality. Excessive multi-organ comorbidity has been associated with PF and shown to correlate with reduced survival. We examined whether ILA presence associated with mortality, independent of the presence of multiple comorbidities in the SUMMIT Study, the largest LCS study in Europe. <bold>Methods:</bold> Of 11,635 individuals, 417 participants identified with ILA on CT were compared to an age, sex and smoking pack-year history matched control group. Primary analyses examined associations between ILA presence and cumulative comorbidity numbers (coded as 0,1,2,3 or more comorbidities) and mortality, using multivariable Cox regression proportional hazards models. <bold>Results:</bold> ILA subjects had more prevalent comorbidities than controls: stable angina (p=0.03), cerebrovascular disease (p=0.007), renal disease (p<0.05). Prevalent comorbidities increased in incidence (versus controls) from approximately 10 years prior to ILA identification. Mortality was increased in participants with ILAs (p<0.0001) independent of comorbidity number. ILA deaths were mostly coded as cardiac, respiratory and cerebrovascular diseases, cancer and COVID-19. <bold>Conclusion:</bold> We demonstrate an increased prevalent comorbidity burden in ILA subjects occurring ten years before ILA identification. The increased comorbidity burden though not associating with time to death was reflected in cause of death, suggesting the importance of referral for multisystem medical work-up in ILA subjects.