Telomere Length and Genetic Variant Associations with Interstitial Lung Disease Progression and Survival

Leukocyte telomere length (LTL), MUC5B rs35705950, and TOLLIP rs5743890 have been associated with idiopathic pulmonary fibrosis (IPF). In this observational cohort study, we assessed the associations between these genomic markers and outcomes of survival and rate of disease progression in patients with interstitial pneumonia with autoimmune features (IPAF, n=250) and connective tissue disease-associated interstitial lung disease (CTD-ILD, n=248). IPF (n=499) was used as a comparator. LTL of IPAF and CTD-ILD patients (mean age-adjusted log-transformed T/S of −0.05, [sd 0.29] and −0.04 [0.25], respectively) are longer than IPF (−0.17 [0.32]). For IPAF, LTL versus −0.86%/year, p versus −0.01 [0.23], p=0.00055) and higher MUC5B minor allele frequency (34.6 [95% CI 24.4–46.3] versus 14.1 [9.8–20.0], p=0.00025). Neither LTL nor MUC5B are associated with transplant-free CTD-ILD survival. LTL and MUC5B minor allele frequency have different associations with lung function progression and survival for IPAF and CTD-ILD.