Familial Pulmonary Fibrosis Linked to Faster Lung Function Decline, UIP Pattern

Patient-reported family history may provide valuable insights into the genetic probability of aggressive disease phenotypes in patients with familial pulmonary fibrosis (FPF), according to a recent study published in the Annals of the American Thoracic Society.¹

FPF is defined as a fibrosing interstitial lung disease (ILD) that occurs when 1 or more family members have idiopathic pulmonary fibrosis (IPF) or another fibrotic ILD. It is associated with early-onset and more aggressive disease phenotypes. It’s estimated that about 1 in 5 people with pulmonary fibrosis or a fibrotic ILD have FPF.² Yet, access to genetic testing remains limited, in addition to rare monogenic causes. By characterizing the clinical and radiological features of patients with FPF, the study found that those with IPF, fibrotic hypersensitivity pneumonitis (fHP), and/or unclassifiable ILD (uILD) were more likely to be younger and female, less likely to be smokers, and experienced a faster annual decline in forced vital capacity (FVC), compared with patients with other fibrotic ILD subtypes.¹

The primary cohort consisted of clinical data from the Canadian Registry for Pulmonary Fibrosis (CARE-PF). Patients in the primary cohort with IPF included patients with systemic autoimmune rheumatic disease–associated ILD (SARD-ILD), fHP, and uILD.

A subset of patients with baseline high-resolution CT (HRCT) scores was included in a substudy labeled the radiologic cohort. Patients were included in the radiologic cohort if they had radiologic fibrosis characterized by reticulation, traction bronchiectasis, and/or honeycombing on initial HRCT, performed within 12 months of the ILD clinic visit.

There were 6775 patients overall pulled from the CARE-PF. Of them, 5375 were included in the primary analysis and 1519 in the radiologic cohort.

Clinical Characteristics Differed Between Familial and Sporadic ILD

In the primary cohort, 719 of 5375 (13%) had FPF. By diagnostic subgroup, there were 305 of 1662 (18%) patients with IPF, 163 of 1124 (15%) with uILD, 58 of 491 (12%) with fHP, and 193 of 2098 (9%) with SARD-ILD who were classified as having FPF. Although patients with FPF and those with sporadic ILD had similar pulmonary function data, those with FPF had a higher baseline diffusion capacity of the lungs for carbon monoxide (DL_CO) percentage.

When combined, patients in each diagnostic subgroup, when combined, the FPF subgroup was significantly younger, more often female, less likely to have smoked, and had a higher baseline DL_CO percentage.

The mean annual rate of FVC decline was modest but still significantly greater in patients with FPF when compared with sporadic ILD across the overall cohort (mean difference, –0.40; 95% CI, –0.74 to –0.05; P = .024). There was no observed difference in the rate of FVC decline between FPF and sporadic cases of IPF.

Radiologist-Assigned UIP Pattern Was More Common in Familial Disease

In the radiologic cohort, 197 (13%) of patients had FPF. There were no observed differences in the frequency of guideline-defined radiologic patterns between FPF and sporadic cases for either usual interstitial pneumonia (UIP) or fHP. But patients with FPF had a significantly greater likelihood of radiologist-assigned UIP (42.6% vs 33.4%; P = .004) when compared with sporadic ILD.

The mean annual rate of FVC decline was greater in radiologist-assigned UIP compared to non-UIP patterns in patients with FPF (–1.78, 95% CI, –2.95 to –0.61; P = .003) and sporadic ILD (–1.00; 95% CI, –1.45 to –0.56; P < .0001).

The study was limited, as family history could not be independently verified. Additionally, the absence of pathology, genetic, and telomere length data limits the generalizability of the findings. Medication-related outcomes were not evaluated, as retrospective data were limited.

“These findings support routine family history ascertainment as a simple prognostic tool and highlight the need for improved screening, genetic integration, and tailored management strategies in familial disease,” the study authors concluded.

References

1. Orser AG, Marinescu DC, Hague CJ, et al. Clinical and radiologic characteristics of familial pulmonary fibrosis. Ann Am Thorac Soc. Published online June 1, 2026. doi:10.1093/annalsats/aaoag145

2. Familial pulmonary fibrosis (FPF): genetics, testing, and care. National Jewish Health. Accessed June 23, 2026. https://www.nationaljewish.org/interstitial-lung-disease-ild-center/what-is-ild/what-is-fpf