Development, Progression, and Mortality of Suspected Interstitial Lung Disease in COPDGene

Rationale: Some with interstitial lung abnormalities (ILA) are suspected to have interstitial lung disease (ILD), a subgroup with adverse outcomes. Rates of development and progression of suspected ILD and their effect on mortality are unknown. Objectives: To determine rates of development, progression, and mortality in those with suspected ILD and assess effects of individual ILD and progression criteria. Methods: Participants from COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease) with ILA characterization and FVC at enrollment and 5-year follow-up were included. ILD was defined as ILA and fibrosis and/or FVC < 80% predicted. Prevalent ILD was assessed at enrollment and incident ILD and progression were assessed at 5-year follow-up. Computed tomography (CT) progression was assessed visually and FVC decline as relative change. Multivariable Cox regression tested associations between mortality and prevalent ILD, incident ILD, and progression groups. Measurements and Main Results: Of 9,588 participants at enrollment, 268 (2.8%; 51% of ILA) had prevalent ILD. Those with prevalent ILD had 51% mortality after median 10.6 years, which was higher than those with ILA without prevalent ILD (henceforth ILA) (33%; hazard ratio [HR], 2.0; P < 0.001). The subgroup of prevalent ILD with only fibrosis criteria (FVC ≥ 80%) had worse mortality (58%) than ILA (HR, 2.2; P < 0.001). A total of 98 participants with prevalent ILD completed 5-year follow-up: 33% had stable CT and relative FVC decline <10%, 6% had FVC decline ≥10% only, 39% had CT progression only, and 22% had both CT progression and FVC decline ≥10%. Mortality rates were 31%, 50%, 45%, and 45%, respectively; those with only CT progression had worse mortality than those with ILA (HR, 2.6; P = 0.005). At 5-year follow-up, incident ILD occurred in 148/4,842 participants without prevalent ILD (5.5/1,000 person-years) and had worse mortality than ILA (HR, 2.4; P < 0.001). Conclusion: Rates of mortality and progression are high among those with suspected ILD in COPDGene; fibrosis and radiologic progression are important predictors of mortality.