Clinical and Radiologic Characteristics of Familial Pulmonary Fibrosis.

RATIONALE: Familial pulmonary fibrosis (FPF), defined as fibrosing interstitial lung disease (ILD) affecting two or more family members, is associated with earlier-onset and a more aggressive disease phenotype. Imaging findings may vary between relatives, complicating diagnosis. While genetic testing exists, it is limited by accessibility and the rarity of monogenic causes. Patient-reported family history may serve as a valuable adjunct prognostic marker.

OBJECTIVES: This study aimed to characterize the clinical and radiological features of patients with FPF using a multicenter ILD registry. We compared lung function and transplant-free survival between patients with FPF and sporadic ILD, overall and by radiologic pattern.

METHODS: The multicenter Canadian Registry for Pulmonary Fibrosis includes patients with fibrotic ILD. Demographics, forced vital capacity (FVC%), diffusion capacity for carbon monoxide (DLCO%), and death or lung transplant data were collected. Family history was determined via physician or patient documentation. A subset underwent re-evaluation where baseline radiologic features and patterns were described. Statistical comparisons used chi-square tests, Cox proportional hazards, omnibus test and mixed models to assess outcomes.

RESULTS: Of 5375 patients, 719 (13%) had FPF. Demographics were similar between FPF and sporadic ILD. When grouping idiopathic pulmonary fibrosis, fibrotic hypersensitivity pneumonitis and unclassifiable ILD together, those with FPF were younger (P < .001), more likely female (P < .001), less likely to have smoked (P = .007), and had higher baseline DLCO% (P < .001). Antifibrotics were more often prescribed to FPF patients with fibrotic hypersensitivity pneumonitis, unclassifiable ILD, and systemic autoimmune rheumatic disease-ILD versus their sporadic counterparts. The mean annual rate of FVC% decline was greater in patients with FPF compared to those with sporadic ILD (P = .024). FPF more frequently received referral for transplant (P < .001), but transplant-free survival did not differ between FPF and sporadic disease. In the radiologic cohort (n = 1519) those with FPF had a higher likelihood of radiologic usual interstitial pneumonia than those with sporadic ILD (P = .004).

CONCLUSIONS: FPF accounts for a meaningful proportion of ILD cases and exhibits distinct clinical features in certain disease subtypes. Although survival outcomes were similar in this study, earlier onset and accelerated progression highlight the need for refined diagnostic and prognostic approaches to familial disease.