Epigenetic marker of telomeric age is associated with exacerbations and hospitalizations in chronic obstructive pulmonary disease

Ana I. Hernández Cordero, Chen Xi Yang, Xuan Li, Stephen Milne, Virginia Chen, Zsuzsanna Hollander, Raymond Ng, Gerard J. Criner, Prescott G. Woodruff, Stephen C. Lazarus, John E. Connett, Mei Lan K. Han, Fernando J. Martinez, Robert M. Reed, S. F.Paul Man, Janice M. Leung, Don D. Sin

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Background: Chronic obstructive pulmonary disease (COPD) is an age-related condition that has been associated with early telomere attrition; the clinical implications of telomere shortening in COPD are not well known. In this study we aimed to determine the relationship of the epigenetic regulation of telomeric length in peripheral blood with the risk of exacerbations and hospitalization in patients with COPD. Methods: Blood DNA methylation profiles were obtained from 292 patients with COPD enrolled in the placebo arm of the Macrolide Azithromycin to Prevent Rapid Worsening of Symptoms Associated with Chronic Obstructive Pulmonary Disease (MACRO) Study and who were followed for 1-year. We calculated telomere length based on DNA methylation markers (DNAmTL) and related this biomarker to the risk of exacerbation and hospitalization and health status (St. George Respiratory Questionnaire [SGRQ]) score over time using a Cox proportional hazards model. We also used linear models to investigate the associations of DNAmTL with the rates of exacerbation and hospitalization (adjusted for chronological age, lung function, race, sex, smoking, body mass index and cell composition). Results: Participants with short DNAmTL demonstrated increased risk of exacerbation (P = 0.02) and hospitalization (P = 0.03) compared to those with longer DNAmTL. DNAmTL age acceleration was associated with higher rates of exacerbation (P = 1.35 × 10–04) and hospitalization (P = 5.21 × 10–03) and poor health status (lower SGRQ scores) independent of chronological age (P = 0.03). Conclusion: Telomeric age based on blood DNA methylation is associated with COPD exacerbation and hospitalization and thus a promising biomarker for poor outcomes in COPD.

Original languageEnglish (US)
Article number316
JournalRespiratory research
Issue number1
StatePublished - Dec 2021

Bibliographical note

Funding Information:
A.I.H.C and S.M. are supported by MITACS and Providence Airway Centre. J.M.L. is supported by the Michael Smith for Health Research Foundation Health Professional Investigator Award and the CIHR/AstraZeneca Early Career Investigator Award. D.D.S. is a Tier 1 Canada Research Chair in COPD and holds the De Lazzari Family Chair at the Centre for Heart Lung Innovation.

Funding Information:
The project was funded by a grant from Genome Canada, CIHR and St. Paul’s Foundation.

Publisher Copyright:
© 2021, The Author(s).


  • COPD
  • DNA methylation
  • Epigenetics
  • Telomeres


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