Use of Telomere Length as a Biomarker in Idiopathic Pulmonary Fibrosis

• Published in: Lung Vol. 203; no. 1; p. 78
• Main Authors: Dahlqvist, Caroline, Planté-Bordeneuve, Thomas, Muca, Trejsi, de Leener, Anne, Ghaye, Benoît, Coche, Emmanuel, Decottignies, Anabelle, van Dievoet, Marie-Astrid, Froidure, Antoine
• Format: Journal Article
• Language: English
• Published: New York Springer US 09.07.2025; Springer Nature B.V
• Subjects: Aged; Aged, 80 and over; Aging; Belgium; Biomarkers; Disease Progression; Female; Fibrosis; Humans; Idiopathic Pulmonary Fibrosis - diagnosis; Idiopathic Pulmonary Fibrosis - genetics; Idiopathic Pulmonary Fibrosis - physiopathology; Lung - physiopathology; Lung diseases; Lungs; Male; Medicine; Medicine & Public Health; Middle Aged; Mutation; Patients; Pneumology/Respiratory System; Pulmonary fibrosis; Pulmonary functions; Respiratory function; Respiratory Function Tests; Telomerase - genetics; Telomere - genetics; Telomere Shortening; Telomeres; Vital Capacity; Belgium; Telomeres; Biomarker; Pulmonary fibrosis
• ISSN: 0341-2040; 1432-1750; 1432-1750
• DOI: 10.1007/s00408-025-00830-6

Background Telomere shortening, a hallmark of cellular aging, is associated with poor outcomes in idiopathic pulmonary fibrosis (IPF). This study aimed to explore the relationships between telomere length (TL), pulmonary function tests, and telomere-related gene (TRG) mutations in a real-world IPF population. Methods We included IPF patients from two Belgian academic hospitals, collecting demographic and clinical data. TL was measured using Flow-FISH and expressed as a percentile. Short TL was defined as below the 10th percentile (P10), and very short TL as below the 1st percentile (P1). Results We analysed 143 patients (106 men, 74%), with a median age of 70 years. Thirty patients (21%) met the European Respiratory Society (ERS) criteria for familial pulmonary fibrosis (FPF). Short TL was found in 74 patients (50%), predominantly in men (p < 0.05). Patients with short TL experienced a greater decline in lung function over 24 months compared to those with normal TL (− 4% vs + 3% FVC, p < 0.05; − 7% vs − 3% DLCO, p < 0.05). Patients with very short TL were younger at diagnosis and tended to have a more pronounced FVC decline (− 5% vs − 1%, p = 0.06). TRG variants were identified in 16 individuals, occurring more frequently in those with short (14/27, 52%) or very short TL (10/20, 50%). Conclusion Short TL is common in both sporadic and familial IPF and serves as a predictive biomarker for accelerated lung function decline. Additionally, the presence of short TL is indicative of an underlying TRG mutation.