B41-06 Familial Interstitial Lung Disease (F-ILD): Verification of Diagnosis and Correlation of Phenotype-genotypes in Patients With F-ILD

Rationale Germline genetic and telomere length (TL) testing are appropriate to evaluate for pathogenic variants or telomere shortening in patients with interstitial lung disease (ILD), particularly familial ILD (F-ILD). Pathogenic variants in telomere maintenance genes are associated with worse outcomes among patients with F-ILD. Most studies rely on self-reported family history to define F-ILD, but confirming relatives’ ILD diagnoses may improve phenotype-genotype correlations. We aim to verify diagnoses in probands and biological first-degree relatives (BFDR) and correlate disease type with genetic and TL results to better define phenotype-genotype relationships in F-ILD. Methods Ongoing, prospective, observational and pragmatic study of consecutive adults with presumed F-ILD referred to the UW Center for ILD (IRB: STUDY00022520). A three-generation pedigree was constructed, and clinical data were reviewed during multidisciplinary discussions (MDDs). BFDRs without sufficient data to verify a diagnosis remained classified as “presumed.” Germline genetic and/or TL testing was offered to all probands and completed in those who consented. Definitions Presumed F-ILD: Patients with self-reported family history of ILD in ≥ 2 BFDRs, including the proband. Confirmed F-ILD: Confirmed ILD diagnoses in the proband and at least one BFDR upon review of available clinical data through MDDs (1). Familial Idiopathic Pulmonary Fibrosis (F-IPF) Confirmed: IPF in both the proband and at least one BFDR.The diagnosis of IPF was in accordance with guideline criteria (2). F-Non-IPF ILD: Cases in which ILD other than IPF was confirmed. Results We enrolled 53 participants with presumed F-ILD and confirmed F-ILD in 18/53 (34%) to date. The cohort was predominantly composed of white males. Of 18 confirmed F-ILD cases, 7 (39%) met criteria for F-IPF and 11 (61%) for F-Non IPF ILD. Among those who completed genetic and TL testing, the majority in both F-IPF and F-Non-IPF ILD groups had short telomeres (ST) but had negative genetic results (Table 1).Among F-IPF patients, 3 had ST, 1 had normal telomeres, 1 declined testing, and 2 results are pending. Among non-IPF ILD patients, 3 had ST, 1 had normal telomeres, 1 declined testing, and 6 results are pending. Conclusions F-ILD was confirmed in 34% of presumed F-ILD; 39% have true F-IPF and 61% have F-Non-IPF ILD. Among participants who completed genetic and TL testing, most in both the F-IPF and F-non-IPF groups had ST but negative genetic results. The study is ongoing and further verification of presumed cases and additional cases of F-ILD will be presented at ATS 2026. This abstract is funded by: None