Telomere length dynamics over 10-years and related outcomes in patients with COPD

Abstract

Background: Chronic obstructive pulmonary disease (COPD) has been proposed as a disease of accelerated aging. Several crosssectional studies have related a shorter telomere length (TL), a marker of biological aging, with COPD outcomes. Whether accelerated telomere shortening over time relates to worse outcomes in COPD patients, is not known. Methods: Relative telomere length (T/S) was determined by qPCR in DNA samples from peripheral blood in 263 patients at baseline and up to 10 years post enrolment. Yearly clinical and lung function data of 134 patients with at least twotime measures of T/S over this time were included in the analysis. Results: At baseline, T/S inversely correlated with age (r=−0.236; p<0.001), but there was no relationship between T/S and clinical and lung function variables (p>0.05). Over 10 years of observation, there was a median shortening of TL of 183 bp/year for COPD patients. After adjusting for age, gender, active smoking and mean T/S, patients that shortened their telomeres the most over time, had worse gas exchange, more lung hyperinfation and extrapulmo‑ nary afection during the followup, (PaO2 p<0.0001; KCO p=0.042; IC/TLC p<0.0001; 6MWD p=0.004 and BODE index p=0.009). Patients in the lowest tertile of T/S through the followup period had an increased risk of death [HR=5.48, (1.23–24.42) p=0.026]. Conclusions: This prospective study shows an association between accelerated telomere shortening and progres‑ sive worsening of pulmonary gas exchange, lung hyperinfation and extrapulmonary afection in COPD patients. Moreover, persistently shorter telomeres over this observation time increase the risk for allcause mortality.