Abstract Family history is a determinant of disease behaviour in fibrotic interstitial lung disease (f-ILD). Familial pulmonary fibrosis (FPF) occurs when a patient with a f-ILD has at least one relative diagnosed with f-ILD. FPF appears to have an earlier onset and a more progressive clinical course than sporadic idiopathic pulmonary fibrosis (IPF). Rare monogenic causes, such as telomere-related gene (TRG) variants, contribute to approximately 25% of familial cases. Prospective studies of FPF are few. The PRECISE-PF prospective observational cohort study of FPF aims to evaluate disease behaviour of FPF compared to non-familial usual interstitial pneumonia (UIP). Patients were recruited from a FPF National Referral Centre and followed prospectively for one year, with follow-up ongoing. Data collected include comorbidities, environmental exposures, PFTs, 6MWT, CT imaging, next-generation sequencing (NGS), and quality-of-life scores. 168 participants enrolled in the study: 90 to the FPF and 78 to the non-familial UIP (NFUIP) cohort. The FPF-cohort was 52.2% female and younger than the NFUIP-cohort (68 versus 75 years, p = 0.0001). The majority of the FPF-cohort, 53%, had a definite or probable UIP radiological pattern. Median percentage predicted FVC and DLCO were similar in both groups. NFUIP-cohort had a shorter six-minute walk distance (375m) than the FPF-cohort (405m; p = 0.0319). GAP-ILD score was higher in the NFUIP-cohort (p = 0.0001). The FPF-cohort reported higher scores than the NFUIP-cohort (71 vs 62, p = 0.0025) on the EuroQol-5D-3L visual analogue scale. The NFUIP-cohort scored lower in the physical domain of the Leicester Cough Questionnaire (5.31 vs 5.74, p = 0.024). NGS results were available for 143 individuals: 87 FPF and 76 NFUIP. No pathogenic variants were found in the NFUIP-cohort; 13.2% (n = 10) had a variant of unknown significance (VUS) identified. NGS identified gene variants, mostly TRGs, in 21.8% (n = 19) of the FPF-cohort. 9.2% of the FPF-cohort had likely pathogenic/pathogenic variants identified. Following discussion at a Genetic ILD MDM, 84.6% of cases discussed had a change in ACMG classification. Interim analysis of 6-month data shows that 3 patients with IPF and 4 with FPF had died or had a transplant, and there was a greater decline in FVC in the FPF cohort, although not statistically significant. Participants in the FPF-cohort were younger and were more likely to be female than those in the NFUIP-cohort. Discussion at the genetic ILD MDM led to changes in the ACMG classification of the majority of the VUS. Longitudinal data from this observational cohort will further our understanding of disease behaviour. This abstract is funded by: RCSI StAR MD Programme
Carolan et al. (Fri,) studied this question.