S138 Telomere length analysis and next generation sequencing results in patients with fibrotic interstitial lung disease

Carolan, A., Jasmin, J., Ng, W. L., Kannengiesser, C., Borie, R., Morgan, R., Norris, K., Baird, D. ORCID: https://orcid.org/0000-0001-8408-5467, Ozaki, M. and Hurley, K. 2026. S138 Telomere length analysis and next generation sequencing results in patients with fibrotic interstitial lung disease. Thorax 81 (S1) , pp. A100-A101. 10.1136/thorax-2026-btsabstracts.144

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Abstract

Background Telomere biology disorders are a heterogeneous group of diseases, with pulmonary fibrosis being the most common in adults. Short telomere length (TL) is associated with a poorer prognosis in interstitial lung disease (ILD), can indicate the presence of a telomere-related gene (TRG) variant, and may influence clinical care decisions such as immunosuppression. Antifibrotic therapies slow disease progression in progressive pulmonary fibrosis and idiopathic pulmonary fibrosis (IPF); however, lung transplant remains the only cure. New ISHLT guidelines recommend TL measurement for all ILD patients referred for transplant. Aims To determine the prevalence of short TL in ILD and assess its association with TRG variants. Methods Patients were recruited to Precise-PF, a prospective observational cohort study. Individuals with both TL measurement and next-generation sequencing (NGS) panel results were included. Recruitment occurred at a national referral clinic for familial pulmonary fibrosis (FPF). TL was measured using high-throughput single telomere length analysis (HT-STELA). Short TL was defined as TL <10th age-adjusted percentile. Clinical data includes age, sex, comorbidities and PFTs. Results 203 participants were included: 91 FPF, 59 IPF and 53 systemic autoimmune rheumatic disease-associated ILD (SARD-ILD). Short TL was identified in 46 (22.6%) participants: 24(26.4%) FPF, 12(20.3%) IPF, and 10(18.9%) SARD-ILD. In the FPF cohort, 11(12.1%) had a likely pathogenic or pathogenic TRG variant, and 4(4.4%) had a variant of unknown significance (VUS). 8(13.6%) IPF and 2(3.4%) SARD-ILD participants had a VUS. There was a significant association between the presence of a TRG variant and short TL (p=0.045). However, 36(74%) of those with short TL had no identifiable TRG variant; in the familial cohort, and 10(55%) had a TL ≥10th percentile. Conclusion We show that short telomeres were present in greater than 1 in 5 patients with FPF, IPF and SARD-ILD; however, most cases could not be explained by TRG variants. A recent ISHLT statement on TL testing in patients pre-lung transplant will likely increase measurement, but our data suggest that much remains unknown about the causes and implications of short telomeres. Further study and implementation strategies for subsequent genetic testing and risk assessment need to be developed.

Item Type:	Short Communication
Date Type:	Publication
Status:	Published
Schools:	Schools > Medicine
Publisher:	BMJ Publishing Group
ISSN:	0040-6376
Last Modified:	11 Nov 2026 09:45
URI:	https://orca.cardiff.ac.uk/id/eprint/190840

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