Short telomere length is associated with accelerated lung disease progression in rheumatoid arthritis-associated interstitial lung disease

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 transplant or functional respiratory decline (absolute decrease in forced vital capacity (FVC) ≥5%predicted, transfer capacity (TLCO) ≥10%predicted). Results Among 101 patients with RA-ILD, 46% were male, mean age at enrolment was 66±10 years and 43 (43%) had short LTL. Patients with short LTL had lower FVC (82% versus 93%predicted) and TLCO (49% versus 63%predicted) at enrolment, and greater 12-months decline in FVC and DLCO in mixed effects models (−7.7%pred. 95%CI[-11.6,-3.8] p<0.001, −4.5%pred. [−7.2, −1.8] p=0.001, respectively), although transplant-free survival was similar over a median follow-up of 3.6 years (IQR[1.8,7.0]). Lung disease progression was observed within 12 months of enrolment in 33 patients (33%), more frequently in patients with short LTL (47% versus 22%, p univariate=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 2.80 [0.99,8.29] p=0.056, respectively). Conclusions Short LTL is associated with baseline severity and 12-month progression in RA-ILD.