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

<b>Rationale:</b> 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. <b>Objectives:</b> To determine rates of development, progression, and mortality in those with suspected ILD and assess effects of individual ILD and progression criteria. <b>Methods:</b> 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. <b>Measurements and Main Results:</b> 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; <i>P</i> < 0.001). The subgroup of prevalent ILD with only fibrosis criteria (FVC ≥ 80%) had worse mortality (58%) than ILA (HR, 2.2; <i>P</i> < 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; <i>P</i> = 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; <i>P</i> < 0.001). <b>Conclusion:</b> Rates of mortality and progression are high among those with suspected ILD in COPDGene; fibrosis and radiologic progression are important predictors of mortality.