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

Abstract 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