Use of telomere length in the management of idiopathic pulmonary fibrosis

<bold>Background:</bold> Idiopathic pulmonary fibrosis (IPF) relates to cellular senescence. Telomere shortening, a marker of cellular ageing, is associated with poor outcome in IPF. In the present study, we aimed to analyse the links between telomere length (TL) measured by Flow-FISH, pulmonary function tests and the presence of a telomere-related gene mutation in a real life IPF population. <bold>Methods:</bold> We included IPF patients from two Belgian academic hospitals and collected all relevant demographical and clinical data. We measured TL by Flow-FISH and expressed it as percentile. We chose the 10th percentile as a threshold for having short telomeres. We looked for an association between TL and lung function decline, familial fibrosis and the presence of a genetic variant. <bold>Results:</bold> We included 143 patients (106 men, 74%), median age 70. 93% received antifibrotics. Thirty (21%) fulfilled the ERS definition for familial fibrosis. 74 patients (52%) had short telomeres, including 42 (29%) with very short (<P2.5) telomeres. Short TL was associated with male sex (P<0.05). Having short TL was related with a greater risk of having a >5% FVC decline at 24 months after diagnosis (OR 2.2, P<0.05). 24-months FVC and DLCO decline were higher in patients with short TL (−4% vs +1% for FVC, P<0.05; -9% vs -4% for DLCO, P<0.05). The association between short TL and FVC decline was age-related and was mostly significant under the age of 75. Patients with familial fibrosis did not have a shorter TL but having short TL was associated with the presence of a genetic variant (P<0.05). <bold>Conclusion:</bold> Our study confirms the association of short TL and IPF, both sporadic and familial. TL is a predictive biomarker for outcome and the identification of a mutation.