Development and Progression of Radiologic Abnormalities in Individuals at Risk for Familial Interstitial Lung Disease.

Abstract

<b>Rationale:</b> The preclinical natural history of progressive lung fibrosis is poorly understood.<b>Objectives:</b> Our goals were to identify risk factors for interstitial lung abnormalities (ILA) on high-resolution computed tomography (HRCT) scans and to determine progression toward clinical interstitial lung disease (ILD) among subjects in a longitudinal cohort of self-reported unaffected first-degree relatives of patients with familial interstitial pneumonia.<b>Methods:</b> Enrollment evaluation included a health history and exposure questionnaire and HRCT scans, which were categorized by visual assessment as no ILA, early/mild ILA, or extensive ILA. The study endpoint was met when ILA were extensive or when ILD was diagnosed clinically. Among subjects with adequate study time to complete 5-year follow-up HRCT, the proportion with ILD events (endpoint met or radiographic ILA progression) was calculated.<b>Measurements and Main Results:</b> Among 336 subjects, the mean age was 53.1 (SD, 9.9) years. Those with ILA (early/mild [<i>n</i> = 74] or extensive [<i>n</i> = 3]) were older, were more likely to be ever smokers, had shorter peripheral blood mononuclear cell telomeres, and were more likely to carry the <i>MUC5B</i> risk allele. Self-reported occupational or environmental exposures, including aluminum smelting, lead, birds, and mold, were independently associated with ILA. Among 129 subjects with sufficient study time, 25 (19.4%) had an ILD event by 5 years after enrollment; of these, 12 met the study endpoint and another 13 had radiologic progression of ILA. ILD events were more common among those with early/mild ILA at enrollment (63.3% vs. 6.1%; <i>P</i> < 0.0001).<b>Conclusions:</b> Rare and common environmental exposures are independent risk factors for radiologic abnormalities. In 5 years, progression of ILA occurred in most individuals with early ILA detected at enrollment.