Clinical and Radiologic Characteristics of Familial Pulmonary Fibrosis

Area of Science:

• Pulmonology
• Genetics
• Radiology

Background:

• Familial pulmonary fibrosis (FPF) is defined as fibrosing interstitial lung disease (ILD) in two or more family members.
• FPF is associated with earlier onset and more aggressive disease, complicating diagnosis due to variable imaging findings among relatives.
• Genetic testing for FPF is limited by accessibility and the rarity of monogenic causes, making patient-reported family history a valuable prognostic marker.

Purpose of the Study:

• To characterize the clinical and radiological features of FPF patients using a multicenter ILD registry.
• To compare lung function and transplant-free survival between FPF and sporadic ILD patients, overall and by radiologic pattern.

Main Methods:

• Utilized the multicenter Canadian Registry for Pulmonary Fibrosis, collecting demographics, lung function (FVC%, DLCO%), and transplant/death data.
• Determined family history through physician or patient documentation and re-evaluated radiologic features in a subset of patients.
• Employed statistical comparisons including chi-square tests, Cox proportional hazards, and mixed models to assess outcomes.

Main Results:

• FPF was identified in 719 (13%) of 5375 ILD patients, showing similar demographics to sporadic ILD.
• FPF patients were younger, more likely female, less likely to have smoked, and had higher baseline DLCO% compared to sporadic ILD when grouping specific ILD subtypes.
• FPF patients experienced a greater annual decline in FVC% and were more frequently referred for transplant, though transplant-free survival did not differ significantly.

Conclusions:

• FPF represents a significant proportion of ILD cases with distinct clinical features in certain subtypes.
• Despite similar survival outcomes in this study, the earlier onset and accelerated progression of FPF underscore the need for improved diagnostic and prognostic strategies.
• Refined approaches are essential for managing familial pulmonary fibrosis, considering its unique characteristics and potential for faster disease progression.