Minhee Jin1, Eun Chong Lee1, Seung Won Ra2, Nick Fishbane3, Sheena Tam1, Gerard J Criner4, Prescott G Woodruff5, Stephen C Lazarus5, Richard Albert6, John E Connett7, MeiLan K Han8, Fernando J Martinez9, Shawn D Aaron10, Robert M Reed11, S F Paul Man1, Janice M Leung1, Don D Sin12. 1. Centre for Heart Lung Innovation, St. Paul's Hospital, and Department of Medicine (Respiratory Division), University of British Columbia, Vancouver, BC, Canada. 2. Centre for Heart Lung Innovation, St. Paul's Hospital, and Department of Medicine (Respiratory Division), University of British Columbia, Vancouver, BC, Canada; Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea. 3. GenomeDx Biosciences Inc, Vancouver, BC, Canada. 4. Department of Thoracic Medicine and Surgery, Temple University, Philadelphia, PA. 5. Department of Medicine, University of California San Francisco, San Francisco, CA. 6. Pulmonary Sciences and Critical Care Medicine, University of Colorado, Denver, CO. 7. School of Public Health, University of Minnesota, Minneapolis, MN. 8. Department of Internal Medicine, University of Michigan, Ann Arbor, MI. 9. Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medical College, Cornell University, New York, NY. 10. Department of Medicine, University of Ottawa, Ottawa, ON, Canada. 11. Division of Pulmonary and Critical Care Medicine, University of Maryland School of Medicine, Baltimore, MD. 12. Centre for Heart Lung Innovation, St. Paul's Hospital, and Department of Medicine (Respiratory Division), University of British Columbia, Vancouver, BC, Canada. Electronic address: Don.Sin@hli.ubc.ca.
Abstract
BACKGROUND: COPD is an age-related disease. The role of cellular senescence in COPD has not been fully elucidated. This study examined the relationship between telomere length of peripheral blood leukocytes and clinical outcomes, including health status, rate of exacerbations, and risk of mortality in individuals with COPD. METHODS: Using quantitative polymerase chain reaction, we measured the absolute telomere length (aTL) of DNA extracted from blood samples of 576 participants with moderate-to-severe COPD treated with eitherazithromycin or placebo for 12 months in the Macrolide Azithromycin for Prevention of Exacerbations of COPD (MACRO) study. All participants were followed for approximately 13 months, during which time health status and exacerbations were carefully ascertained, and an additional 29 months for mortality. The rates of exacerbation and mortality were determined by dividing the aTL into two groups using the median value as the cutoff. RESULTS: Participants with shorter telomere length had worse health status defined by higher St. George's Respiratory Questionnaire scores (β = -0.09, P = .034). In the placebo arm of the study, the rate of exacerbation (rate ratio, 1.50; 95% CI, 1.16-1.95; P = .002) and the risk of mortality (hazard ratio, 9.45; 95% CI, 2.85-31.36; P = .015) were significantly higher in the shorter telomere group than in the longer telomere group; these differences were not observed in the azithromycin arm (interaction P = .008 for exacerbation and interaction P = .017 for mortality) CONCLUSIONS: These data suggest that replicative senescence may help to predict poor outcomes in COPD. Shorter leukocyte telomere lengths may represent a clinically translatable biomarker for identifying individuals at increased risk of poor clinical outcomes in COPD.
RCT Entities:
BACKGROUND: COPD is an age-related disease. The role of cellular senescence in COPD has not been fully elucidated. This study examined the relationship between telomere length of peripheral blood leukocytes and clinical outcomes, including health status, rate of exacerbations, and risk of mortality in individuals with COPD. METHODS: Using quantitative polymerase chain reaction, we measured the absolute telomere length (aTL) of DNA extracted from blood samples of 576 participants with moderate-to-severe COPD treated with either azithromycin or placebo for 12 months in the MacrolideAzithromycin for Prevention of Exacerbations of COPD (MACRO) study. All participants were followed for approximately 13 months, during which time health status and exacerbations were carefully ascertained, and an additional 29 months for mortality. The rates of exacerbation and mortality were determined by dividing the aTL into two groups using the median value as the cutoff. RESULTS:Participants with shorter telomere length had worse health status defined by higher St. George's Respiratory Questionnaire scores (β = -0.09, P = .034). In the placebo arm of the study, the rate of exacerbation (rate ratio, 1.50; 95% CI, 1.16-1.95; P = .002) and the risk of mortality (hazard ratio, 9.45; 95% CI, 2.85-31.36; P = .015) were significantly higher in the shorter telomere group than in the longer telomere group; these differences were not observed in the azithromycin arm (interaction P = .008 for exacerbation and interaction P = .017 for mortality) CONCLUSIONS: These data suggest that replicative senescence may help to predict poor outcomes in COPD. Shorter leukocyte telomere lengths may represent a clinically translatable biomarker for identifying individuals at increased risk of poor clinical outcomes in COPD.
Authors: Jarrett D Morrow; Robert P Chase; Margaret M Parker; Kimberly Glass; Minseok Seo; Miguel Divo; Caroline A Owen; Peter Castaldi; Dawn L DeMeo; Edwin K Silverman; Craig P Hersh Journal: Respir Res Date: 2019-04-02
Authors: Li Zuo; Evan R Prather; Mykola Stetskiv; Davis E Garrison; James R Meade; Timotheus I Peace; Tingyang Zhou Journal: Int J Mol Sci Date: 2019-09-10 Impact factor: 5.923
Authors: E Córdoba-Lanús; S Cazorla-Rivero; M A García-Bello; D Mayato; F Gonzalvo; J Ayra-Plasencia; B Celli; C Casanova Journal: Respir Res Date: 2021-02-15
Authors: Emily S Wan; Rebekah L Goldstein; Vincent S Fan; Huong Q Nguyen; Jaime E Hart; Eric Garshick; Esther H Orr; Immaculata DeVivo; Marilyn L Moy Journal: PLoS One Date: 2019-10-17 Impact factor: 3.240