Short telomere length is associated with accelerated lung disease progression in rheumatoid arthritis-associated interstitial lung disease
- PMID: 40967766
- DOI: 10.1183/13993003.00587-2025
Short telomere length is associated with accelerated lung disease progression in rheumatoid arthritis-associated interstitial lung disease
Abstract
Background: Shorter leukocyte telomere length (LTL) has been reported in patients with rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) and linked to increased disease severity and mortality in idiopathic pulmonary fibrosis, which shares similarities with RA-ILD. We aimed to evaluate the impact of short LTL on baseline respiratory disease severity, disease progression and survival in patients with RA-ILD.
Methods: Patients diagnosed with RA-ILD following multidisciplinary assessment were enrolled in a prospective French observational study. LTL was measured at enrolment using qPCR. Short LTL was defined as age-adjusted LTL <10th percentile. Lung disease progression was defined as death, lung transplantation or functional respiratory decline (absolute decrease in forced vital capacity (FVC) ≥5% predicted or diffusing capacity of the lung for carbon monoxide (D LCO) ≥10% predicted).
Results: Among 101 patients with RA-ILD, 46% were male, mean±sd age at enrolment was 66±10 years and 43 (43%) had short LTL. Patients with short LTL had lower FVC % predicted (82% versus 93%) and D LCO % predicted (49% versus 63%) at enrolment, and greater 12-month decline in FVC % predicted and D LCO % predicted in mixed effects models (-7.7% (95% CI -11.6- -3.8%); p<0.001 and -4.5 (95% CI -7.2- -1.8%); p=0.001, respectively), although transplant-free survival was similar over a median (interquartile range) follow-up of 3.6 (1.8-7.0) years. Lung disease progression was observed within 12 months of enrolment in 33 (33%) patients, more frequently in patients with short LTL (47% versus 22%; univariate p=0.011) and lower FVC at enrolment. Multivariate logistic regression identified lower FVC and short LTL as predictors of 12-month progression (OR 0.97 (95% CI 0.94-1.00); p=0.031 and OR 2.80 (95% CI 0.99-8.29); p=0.056, respectively).
Conclusion: Short LTL is associated with baseline severity and 12-month progression in RA-ILD.
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Conflict of interest statement
Conflict of interest: R. Borie reports consultancy fees from Boehringer Ingelheim, Ferrer and Sanofi, and payment or honoraria for lectures, presentations, manuscript writing or educational events and support for attending meetings from Boehringer Ingelheim. M-P. Debray reports consultancy fees, payment or honoraria for lectures, presentations, manuscript writing or educational events and support for attending meetings from Boehringer Ingelheim. C. Richez reports grants from Nordic Pharma, Lilly and Biogen, consultancy fees from AbbVie, AstraZeneca, Biogen, Bristol Myers Squibb, GSK, Lilly, Novartis and Pfizer, support for attending meetings from AstraZeneca, Lilly and Novartis, and leadership roles with EULAR, ERN ReCONNET, FAI2R and SFR. H. Nunes reports consultancy fees from Boehringer Ingelheim, Roche, Bristol Myers Squibb and Pliant Therapeutics, payment or honoraria for lectures, presentations, manuscript writing or educational events and support for attending meetings from Boehringer Ingelheim, and participation on a data safety monitoring board or advisory board with Boehringer Ingelheim and Galapagos. J. Avouac reports grants from Nordic Pharma, Pfizer, Galapagos/Alfasigma and Novartis, payment or honoraria for lectures, presentations, manuscript writing or educational events from Galapagos, Lilly, Pfizer, AbbVie, Bristol Myers Squibb, Sanofi, Nordic Pharma, Medac, Novartis, Biogen, Fresenius Kabi, Janssen and Celltrion, and participation on a data safety monitoring board or advisory board with AbbVie, Pfizer and Galapagos. L. Kawano-Dourado reports grants from European Respiratory Society, Bristol Myers Squibb and Boehringer Ingelheim, participation on a data safety monitoring board or advisory board with Sarava, and receipt of equipment, materials, drugs, medical writing, gifts or other services from Fisher & Paykel. P.J. Wolters reports grants from Boehringer Ingelheim, Roche, Sanofi and Pliant Therapeutics, and payment or honoraria for lectures, presentations, manuscript writing or educational events from Boehringer Ingelheim. B. Granger reports consultancy fees from BSC. P. Dieudé reports grants from Bristol Myers Squibb and Pfizer, consultancy fees from Boehringer Ingelheim, Bristol Myers Squibb, Janssen and AbbVie, payment or honoraria for lectures, presentations, manuscript writing or educational events from Boehringer Ingelheim and Pfizer, and participation on a data safety monitoring board or advisory board with Boehringer Ingelheim, Bristol Myers Squibb and Pfizer. The remaining authors have no potential conflicts of interest to disclose.
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