Differentiating clinically important interstitial lung abnormalities in lung cancer screening

Abstract

BACKGROUND: Interstitial lung abnormalities (ILAs) are common incidental findings in lung cancer screening (LCS). However, challenges remain in identifying clinically relevant ILAs as highlighted in a joint statement by a European multidisciplinary task force led by the European Respiratory Society (ERS). To address these challenges, we analysed ILAs identified in one of Europe's largest LCS studies. METHODS: Of 11 635 LCS individuals, 417 screen-detected ILAs were evaluated using a new visual classification system focused on traction bronchiolectasis: non-fibrotic ILA (no traction bronchiolectasis), fibrotic ILA (traction bronchiolectasis in ≤2 lobes); undiagnosed interstitial lung disease (traction bronchiolectasis in >2 lobes). Observer agreement was compared with Fleischner Society ILA classification using Cohen's Kappa. An age, sex and smoking history-matched control group allowed the examination of associations between baseline ILA/UILD and comorbidities, forced vital capacity (FVC), hospitalisations (Student's t-tests) and mortality (univariable and multivariable Cox proportional hazards models). FINDINGS: Our visual ILA classification showed superior interobserver agreement (K=0.76) versus the Fleischner ILA classification (K=0.64). ILA/UILD subjects had more prevalent comorbidities, increasing (vs controls) approximately 10 years prior to ILA/UILD diagnosis. Compared with controls, mortality rates were 6-fold higher for UILD participants and 3-fold higher for fibrotic and non-fibrotic ILA subtypes. On multivariable Cox regression analysis, ILA/UILD presence (HR=4.90, 95% CI =2.36 to 10.10, p<0.001) showed stronger independent associations with mortality than baseline FVC (HR=0.98, 95% CI =0.96 to 1.00, p=0.04). CONCLUSION: We demonstrate a new reproducible classification of clinically important ILA/UILDs in LCS populations. We highlight that FVC shows limited associations with mortality in ILA/UILD subjects. Increased multiorgan comorbidity in ILA/UILD subjects highlights a need for comprehensive early multisystem evaluation.