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.