Telomere length in COPD: Relationships with physical activity, exercise capacity, and acute exacerbations

Autoři: Emily S. Wan aff001;  Rebekah L. Goldstein aff001;  Vincent S. Fan aff004;  Huong Q. Nguyen aff006;  Jaime E. Hart aff002;  Eric Garshick aff001;  Esther H. Orr aff007;  Immaculata DeVivo aff002;  Marilyn L. Moy aff001
Působiště autorů: VA Boston Healthcare System, Boston, MA, United States of America aff001;  Channing Division of Network Medicine, Brigham and Women’s Hospital, Boston, MA, United States of America aff002;  Harvard Medical School, Boston, MA, United States of America aff003;  VA Puget Sound, Seattle, WA, United States of America aff004;  University of Washington, Seattle, WA, United States of America aff005;  Department of Research & Evaluation, Kaiser Permanente Southern California, Pasadena, CA, United States of America aff006;  Harvard T.H. Chan School of Public Health, Boston, MA, United States of America aff007;  Brigham & Women’s Hospital, Boston, MA, United States of America aff008
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article



Shorter leukocyte telomere length (LTL) is associated with reduced health-related quality of life and increased risk for acute exacerbations (AEs) and mortality in chronic obstructive pulmonary disease (COPD). Increased physical activity and exercise capacity are associated with reduced risk for AEs and death. However, the relationships between LTL and physical activity, exercise capacity, and AEs in COPD are unknown.


Data from 3 COPD cohorts were examined: Cohort 1 (n = 112, physical activity intervention trial), Cohorts 2 and 3 (n = 182 and 294, respectively, separate observational studies). Subjects completed a 6-minute walk test (6MWT) and provided blood for LTL assessment using real-time PCR. Physical activity was measured as average daily step count using an accelerometer or pedometer. Number of self-reported AEs was available for 1) the year prior to enrollment (Cohorts 1 and 3) and 2) prospectively after enrollment (all cohorts). Multivariate models examined associations between LTL and average daily step count, 6MWT distance, and AEs.


A significant association between longer LTL and increased 6MWT distance was observed in the three combined cohorts (β = 3x10-5, p = 0.045). No association between LTL and average daily step count was observed. Shorter LTL was associated with an increased number of AEs in the year prior to enrollment (Cohorts 1 and 3 combined, β = -1.93, p = 0.04) and with prospective AEs (Cohort 3, β = -1.3388, p = 0.0003).


Among COPD patients, increased LTL is associated with higher exercise capacity, but not physical activity. Shorter LTL was associated with AEs in a subgroup of cohorts.

Klíčová slova:

Exercise – Chronic obstructive pulmonary disease – Observational studies – Physical activity – Telomere length – Telomeres – Walking – White blood cells


1. Codd V, Mangino M, van der Harst P, Braund PS, Kaiser M, Beveridge AJ, et al. Common variants near TERC are associated with mean telomere length. Nat Genet. 2010;42(3):197–9. Epub 2010/02/09. doi: 10.1038/ng.532 20139977; PubMed Central PMCID: PMC3773906.

2. Levy D, Neuhausen SL, Hunt SC, Kimura M, Hwang SJ, Chen W, et al. Genome-wide association identifies OBFC1 as a locus involved in human leukocyte telomere biology. Proc Natl Acad Sci U S A. 2010;107(20):9293–8. Epub 2010/04/28. doi: 10.1073/pnas.0911494107 20421499; PubMed Central PMCID: PMC2889047.

3. Martens DS, Cox B, Janssen BG, Clemente DBP, Gasparrini A, Vanpoucke C, et al. Prenatal Air Pollution and Newborns' Predisposition to Accelerated Biological Aging. JAMA Pediatr. 2017;171(12):1160–7. Epub 2017/10/20. doi: 10.1001/jamapediatrics.2017.3024 29049509.

4. Whiteman VE, Goswami A, Salihu HM. Telomere length and fetal programming: A review of recent scientific advances. Am J Reprod Immunol. 2017;77(5). Epub 2017/05/14. doi: 10.1111/aji.12661 28500672.

5. Aubert G, Lansdorp PM. Telomeres and aging. Physiol Rev. 2008;88(2):557–79. Epub 2008/04/09. doi: 10.1152/physrev.00026.2007 18391173.

6. Andujar P, Courbon D, Bizard E, Marcos E, Adnot S, Boyer L, et al. Smoking, telomere length and lung function decline: a longitudinal population-based study. Thorax. 2018;73(3):283–5. Epub 2017/07/21. doi: 10.1136/thoraxjnl-2017-210294 28724638.

7. Lee J, Sandford AJ, Connett JE, Yan J, Mui T, Li Y, et al. The relationship between telomere length and mortality in chronic obstructive pulmonary disease (COPD). PLoS One. 2012;7(4):e35567. Epub 2012/05/05. doi: 10.1371/journal.pone.0035567 22558169; PubMed Central PMCID: PMC3338848.

8. Astuti Y, Wardhana A, Watkins J, Wulaningsih W, Network PR. Cigarette smoking and telomere length: A systematic review of 84 studies and meta-analysis. Environ Res. 2017;158:480–9. Epub 2017/07/14. doi: 10.1016/j.envres.2017.06.038 28704792; PubMed Central PMCID: PMC5562268.

9. Kachuri L, Saarela O, Bojesen SE, Davey Smith G, Liu G, Landi MT, et al. Mendelian Randomization and mediation analysis of leukocyte telomere length and risk of lung and head and neck cancers. Int J Epidemiol. 2018. Epub 2018/07/31. doi: 10.1093/ije/dyy140 30059977.

10. Savale L, Chaouat A, Bastuji-Garin S, Marcos E, Boyer L, Maitre B, et al. Shortened telomeres in circulating leukocytes of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2009;179(7):566–71. Epub 2009/01/31. doi: 10.1164/rccm.200809-1398OC 19179485; PubMed Central PMCID: PMC4850213.

11. Cordoba-Lanus E, Cazorla-Rivero S, Espinoza-Jimenez A, de-Torres JP, Pajares MJ, Aguirre-Jaime A, et al. Telomere shortening and accelerated aging in COPD: findings from the BODE cohort. Respir Res. 2017;18(1):59. Epub 2017/04/15. doi: 10.1186/s12931-017-0547-4 28407775; PubMed Central PMCID: PMC5390353.

12. Jin M, Lee EC, Ra SW, Fishbane N, Tam S, Criner GJ, et al. Relationship of Absolute Telomere Length With Quality of Life, Exacerbations, and Mortality in COPD. Chest. 2018;154(2):266–73. Epub 2018/07/19. doi: 10.1016/j.chest.2018.05.022 30017346.

13. Kocks JW, Asijee GM, Tsiligianni IG, Kerstjens HA, van der Molen T. Functional status measurement in COPD: a review of available methods and their feasibility in primary care. Prim Care Respir J. 2011;20(3):269–75. Epub 2011/04/28. doi: 10.4104/pcrj.2011.00031 21523316.

14. LaRocca TJ, Seals DR, Pierce GL. Leukocyte telomere length is preserved with aging in endurance exercise-trained adults and related to maximal aerobic capacity. Mech Ageing Dev. 2010;131(2):165–7. Epub 2010/01/13. doi: 10.1016/j.mad.2009.12.009 20064545; PubMed Central PMCID: PMC2845985.

15. Sillanpaa E, Tormakangas T, Rantanen T, Kaprio J, Sipila S. Does telomere length predict decline in physical functioning in older twin sisters during an 11-year follow-up? Age (Dordr). 2016;38(2):34. Epub 2016/03/05. doi: 10.1007/s11357-016-9898-x 26940017; PubMed Central PMCID: PMC5005900.

16. Celli BR, Cote CG, Marin JM, Casanova C, Montes de Oca M, Mendez RA, et al. The body-mass index, airflow obstruction, dyspnea, and exercise capacity index in chronic obstructive pulmonary disease. N Engl J Med. 2004;350(10):1005–12. Epub 2004/03/05. doi: 10.1056/NEJMoa021322 14999112.

17. Waschki B, Kirsten A, Holz O, Muller KC, Meyer T, Watz H, et al. Physical activity is the strongest predictor of all-cause mortality in patients with COPD: a prospective cohort study. Chest. 2011;140(2):331–42. Epub 2011/01/29. doi: 10.1378/chest.10-2521 21273294.

18. Moy ML, Teylan M, Weston NA, Gagnon DR, Danilack VA, Garshick E. Daily step count is associated with plasma C-reactive protein and IL-6 in a US cohort with COPD. Chest. 2014;145(3):542–50. Epub 2013/10/05. doi: 10.1378/chest.13-1052 24091482.

19. Moy ML, Gould MK, Liu IA, Lee JS, Nguyen HQ. Physical activity assessed in routine care predicts mortality after a COPD hospitalisation. ERJ Open Res. 2016;2(1). Epub 2016/10/13. doi: 10.1183/23120541.00062–2015 27730174; PubMed Central PMCID: PMC5005157.

20. Moy ML, Teylan M, Weston NA, Gagnon DR, Garshick E. Daily step count predicts acute exacerbations in a US cohort with COPD. PLoS One. 2013;8(4):e60400. Epub 2013/04/18. doi: 10.1371/journal.pone.0060400 23593211; PubMed Central PMCID: PMC3617234.

21. Nguyen HQ, Chu L, Amy Liu IL, Lee JS, Suh D, Korotzer B, et al. Associations between physical activity and 30-day readmission risk in chronic obstructive pulmonary disease. Ann Am Thorac Soc. 2014;11(5):695–705. Epub 2014/04/10. doi: 10.1513/AnnalsATS.201401-017OC 24713094.

22. Wan ES, Kantorowski A, Homsy D, Teylan M, Kadri R, Richardson CR, et al. Promoting physical activity in COPD: Insights from a randomized trial of a web-based intervention and pedometer use. Respir Med. 2017;130:102–10. Epub 2017/12/06. doi: 10.1016/j.rmed.2017.07.057 29206627; PubMed Central PMCID: PMC5718161.

23. Chen Z, Fan VS, Belza B, Pike K, Nguyen HQ. Association between Social Support and Self-Care Behaviors in Adults with Chronic Obstructive Pulmonary Disease. Ann Am Thorac Soc. 2017;14(9):1419–27. Epub 2017/07/19. doi: 10.1513/AnnalsATS.201701-026OC 28719225; PubMed Central PMCID: PMC5711401.

24. Nguyen HQ, Fan VS, Herting J, Lee J, Fu M, Chen Z, et al. Patients with COPD with higher levels of anxiety are more physically active. Chest. 2013;144(1):145–51. Epub 2013/02/02. doi: 10.1378/chest.12-1873 23370503; PubMed Central PMCID: PMC3747724.

25. Nguyen HQ, Herting JR, Pike KC, Gharib SA, Matute-Bello G, Borson S, et al. Symptom profiles and inflammatory markers in moderate to severe COPD. BMC Pulm Med. 2016;16(1):173. Epub 2016/12/05. doi: 10.1186/s12890-016-0330-1 27914470; PubMed Central PMCID: PMC5135800.

26. Laboratories ATSCoPSfCPF. ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med. 2002;166(1):111–7. Epub 2002/07/02. doi: 10.1164/ajrccm.166.1.at1102 12091180.

27. Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, et al. Standardisation of spirometry. Eur Respir J. 2005;26(2):319–38. Epub 2005/08/02. doi: 10.1183/09031936.05.00034805 16055882.

28. Cawthon RM. Telomere measurement by quantitative PCR. Nucleic Acids Res. 2002;30(10):e47. Epub 2002/05/10. doi: 10.1093/nar/30.10.e47 12000852; PubMed Central PMCID: PMC115301.

29. Crous-Bou M, Fung TT, Prescott J, Julin B, Du M, Sun Q, et al. Mediterranean diet and telomere length in Nurses' Health Study: population based cohort study. BMJ. 2014;349:g6674. Epub 2014/12/04. doi: 10.1136/bmj.g6674 25467028; PubMed Central PMCID: PMC4252824.

30. Mui TS, Man JM, McElhaney JE, Sandford AJ, Coxson HO, Birmingham CL, et al. Telomere length and chronic obstructive pulmonary disease: evidence of accelerated aging. J Am Geriatr Soc. 2009;57(12):2372–4. Epub 2010/02/04. doi: 10.1111/j.1532-5415.2009.02589.x 20122000

31. Chilosi M, Carloni A, Rossi A, Poletti V. Premature lung aging and cellular senescence in the pathogenesis of idiopathic pulmonary fibrosis and COPD/emphysema. Transl Res. 2013;162(3):156–73. Epub 2013/07/09. doi: 10.1016/j.trsl.2013.06.004 23831269.

32. Ito K, Barnes PJ. COPD as a disease of accelerated lung aging. Chest. 2009;135(1):173–80. Epub 2009/01/13. doi: 10.1378/chest.08-1419 19136405.

33. Alder JK, Guo N, Kembou F, Parry EM, Anderson CJ, Gorgy AI, et al. Telomere length is a determinant of emphysema susceptibility. Am J Respir Crit Care Med. 2011;184(8):904–12. Epub 2011/07/16. doi: 10.1164/rccm.201103-0520OC 21757622; PubMed Central PMCID: PMC3208661.

34. Houben JM, Mercken EM, Ketelslegers HB, Bast A, Wouters EF, Hageman GJ, et al. Telomere shortening in chronic obstructive pulmonary disease. Respir Med. 2009;103(2):230–6. Epub 2008/10/24. doi: 10.1016/j.rmed.2008.09.003 18945604.

35. Rode L, Bojesen SE, Weischer M, Vestbo J, Nordestgaard BG. Short telomere length, lung function and chronic obstructive pulmonary disease in 46,396 individuals. Thorax. 2013;68(5):429–35. Epub 2012/12/27. doi: 10.1136/thoraxjnl-2012-202544 23268483.

36. Garcia-Aymerich J, Lange P, Benet M, Schnohr P, Anto JM. Regular physical activity reduces hospital admission and mortality in chronic obstructive pulmonary disease: a population based cohort study. Thorax. 2006;61(9):772–8. Epub 2006/06/02. doi: 10.1136/thx.2006.060145 16738033; PubMed Central PMCID: PMC2117100.

37. Loprinzi PD. Cardiorespiratory Capacity and Leukocyte Telomere Length Among Adults in the United States. Am J Epidemiol. 2015;182(3):198–201. Epub 2015/07/15. doi: 10.1093/aje/kwv056 26153476.

38. Ogawa EF, Leveille SG, Wright JA, Shi L, Camhi SM, You T. Physical Activity Domains/Recommendations and Leukocyte Telomere Length in U.S. Adults. Med Sci Sports Exerc. 2017;49(7):1375–82. Epub 2017/03/07. doi: 10.1249/MSS.0000000000001253 28263285.

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