Introduction

Idiopathic pulmonary fibrosis (IPF) relates to senescence and telomere attrition, but the clinical utility of telomere length (TL) remains elusive.

Material and methods

In this prospective trial (PNEU-ILD-04) on IPF patients, we performed TL measurement by FlowFISH following informed consent. We looked at the relationship between TL and clinical features including age, sex, familial fibrosis, exposure to smoking and/or pollutants. We also used multiple logistic regression and stepwise approach to predict lung function decline. 

Results

We recruited 88 patients (median age 71, 70% male sex, 77% ex/current smokers). Seventy-nine patients (90%) had definite IPF and 9 had a working diagnosis of IPF. 81 (92%) received antifibrotics. 42 patients (48%) had short telomeres (TL<10th percentile). Male sex, non-UIP pattern, environmental exposure and familial fibrosis were significantly associated with short TL. Seventeen patients (20%) with familial pulmonary fibrosis and 5 (6%) with clinical features of telomere disease without familial clustering underwent DNA sequencing to identify telomere-related gene (TRG) mutation; having very short TL (<P2.5) was significantly associated with the presence of a TRG mutation (P=0.03). Finally, our logistic regressions showed that age was the best predictor of lung function decline.

Conclusions

The results of this pilot study confirm the association between short TL and IPF, especially in non-UIP patterns and patients exposed to toxics. Furthermore, the strong association between very short TL and TRG suggest that TL may serve as a screening tool prior to genome sequencing. Finally, TL was not predictive of lung function decline. Our data should be replicated in derivation cohorts.