Progressive Early Interstitial Lung Abnormalities in Persons at Risk for Familial Pulmonary Fibrosis: A Prospective Cohort Study

Abstract

Rationale: Relatives of patients with familial pulmonary fibrosis (FPF) are at increased risk to develop FPF. Interstitial lung abnormalities (ILAs) are a radiologic biomarker of subclinical disease, but the implications of very mild abnormalities remain unclear. Objectives: To quantify the progression risk among FPF relatives with abnormalities below the threshold for ILAs as described by the Fleischner Society and to describe the characteristics of participants with new or progressive ILAs during observation. Methods: Asymptomatic FPF relatives undergo serial screening high-resolution chest computed tomography. For this analysis, early ILAs (no minimum threshold of lung involvement) were subclassified as mild (all interstitial abnormalities involve <5% of a lung zone) or moderate (any abnormality involves >5%). Identification of new or progressive ILAs on high-resolution chest computed tomography and the development of pulmonologist-diagnosed clinical FPF were defined as progression. Covariate-adjusted logistic regression identified progression-associated characteristics. Measurements and Main Results: From 2008 to 2023, 273 participants in follow-up procedures were 53.2 ± 9.4 years of age at enrollment, 95 (35%) were men, and 73 of 268 (27%) were ever-smokers. During a mean follow-up period of 6.2 ± 3.0 years, progression occurred among 31 of 211 (15%) of those with absence of ILAs at enrollment, 32 of 49 (65%) of those with mild ILAs, and 10 of 13 (77%) of those with moderate ILAs. Subjects with mild ILAs had 9.15 (95% confidence interval, 4.40-19.00; P < 0.0001) times and those with moderate ILAs had 17.14 (95% confidence interval, 4.42-66.49; P < 0.0001) times the odds of progression as subjects without ILAs. Conclusions: In persons at risk for FPF, minor interstitial abnormalities, including reticulation that is unilateral or involves <5% of a lung zone, frequently represent subclinical disease.

Keywords: interstitial lung disease; pulmonary fibrosis; secondary disease prevention.