Relationship of Absolute Telomere Length With Quality of Life, Exacerbations, and Mortality in COPD

Minhee Jin; Eun Chong Lee; Seung Won Ra; Nick Fishbane; Sheena Tam; Gerard J. Criner; Prescott G. Woodruff; Stephen C. Lazarus; Richard Albert; John E. Connett; Mei Lan K. Han; Fernando J. Martinez; Shawn D. Aaron; Robert M. Reed; S. F.Paul Man; Janice M. Leung; Don D. Sin

doi:10.1016/j.chest.2018.05.022

Relationship of Absolute Telomere Length With Quality of Life, Exacerbations, and Mortality in COPD

Minhee Jin, Eun Chong Lee, Seung Won Ra, Nick Fishbane, Sheena Tam, Gerard J. Criner, Prescott G. Woodruff, Stephen C. Lazarus, Richard Albert, John E. Connett, Mei Lan K. Han, Fernando J. Martinez, Shawn D. Aaron, Robert M. Reed, S. F.Paul Man, Janice M. Leung, Don D. Sin

Biostatistics

Research output: Contribution to journal › Article › peer-review

17 Scopus citations

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 either azithromycin 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.

Original language	English (US)
Pages (from-to)	266-273
Number of pages	8
Journal	CHEST
Volume	154
Issue number	2
DOIs	https://doi.org/10.1016/j.chest.2018.05.022
State	Published - Aug 2018

Bibliographical note

Funding Information:
Author contributions: M. J., E. C. L., and S. W. R. had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. D. D. S. conceived the project, funding, and study design. S. T. managed the experimental portion of the study. M. J., E. C. L., S. W. R., and N. F. performed the statistical analysis and interpretations. M. J. and E. C. L. wrote the first draft of the manuscript. G. J. C., P. G. W., S. C. L., R. A., J. E. C., M. K. H., F. J. M., S. D. A., R. M. R., S. F. P. M., J. M. L., and D. D. S. contributed to critical revision of the manuscript for important statistical, intellectual, clinical content and approved the final version. Financial/nonfinancial disclosures: The authors have reported to CHEST the following: N. F. is a paid employee of GenomeDx Biosciences Inc. P. G. W. has served as a consultant to Astra-Zeneca, Theravance, Regeneron, Sanofi, and Genentech. M. K. H. has consulted for GSK, Boehringer Ingelheim, Astra-Zeneca, Novartis, and Sunovion and has received in kind support from Novartis and Sunovion. D. D. S. has received research funding support from Merck, AstraZeneca, and Boehringer Ingelheim and has served on advisory boards of Sanofi-Aventis, Regeneron and AstraZeneca. None declared (M. J., E. C. L., S. W. R., S. T., G. J. C., S. C. L., R. A., J. E. C., F. J. M., S. D. A., R. M. R., S. F. P. M., J. M. L.). Role of sponsors: The sponsor had no role in the design of the study, the collection and analysis of the data, or the preparation of the manuscript. Additional information: The e-Figures and e-Tables can be found in the Supplemental Materials section of the online article.

Funding Information:
Financial/nonfinancial disclosures: The authors have reported to CHEST the following: N. F. is a paid employee of GenomeDx Biosciences Inc. P. G. W. has served as a consultant to Astra-Zeneca, Theravance, Regeneron, Sanofi, and Genentech. M. K. H. has consulted for GSK, Boehringer Ingelheim, Astra-Zeneca, Novartis, and Sunovion and has received in kind support from Novartis and Sunovion. D. D. S. has received research funding support from Merck, AstraZeneca, and Boehringer Ingelheim and has served on advisory boards of Sanofi-Aventis, Regeneron and AstraZeneca. None declared (M. J., E. C. L., S. W. R., S. T., G. J. C., S. C. L., R. A., J. E. C., F. J. M., S. D. A., R. M. R., S. F. P. M., J. M. L.).

Publisher Copyright:
© 2018 American College of Chest Physicians

Keywords

COPD
exacerbation
mortality
quality of life
telomere

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10.1016/j.chest.2018.05.022

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Jin, M., Lee, E. C., Ra, S. W., Fishbane, N., Tam, S., Criner, G. J., Woodruff, P. G., Lazarus, S. C., Albert, R., Connett, J. E., Han, M. L. K., Martinez, F. J., Aaron, S. D., Reed, R. M., Man, S. F. P., Leung, J. M., & Sin, D. D. (2018). Relationship of Absolute Telomere Length With Quality of Life, Exacerbations, and Mortality in COPD. CHEST, 154(2), 266-273. https://doi.org/10.1016/j.chest.2018.05.022

Jin, M, Lee, EC, Ra, SW, Fishbane, N, Tam, S, Criner, GJ, Woodruff, PG, Lazarus, SC, Albert, R, Connett, JE, Han, MLK, Martinez, FJ, Aaron, SD, Reed, RM, Man, SFP, Leung, JM & Sin, DD 2018, 'Relationship of Absolute Telomere Length With Quality of Life, Exacerbations, and Mortality in COPD', CHEST, vol. 154, no. 2, pp. 266-273. https://doi.org/10.1016/j.chest.2018.05.022

@article{39299635f6be472fac95b36a4f57c6e7,

title = "Relationship of Absolute Telomere Length With Quality of Life, Exacerbations, and Mortality in COPD",

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 either azithromycin 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.",

keywords = "COPD, exacerbation, mortality, quality of life, telomere",

author = "Minhee Jin and Lee, {Eun Chong} and Ra, {Seung Won} and Nick Fishbane and Sheena Tam and Criner, {Gerard J.} and Woodruff, {Prescott G.} and Lazarus, {Stephen C.} and Richard Albert and Connett, {John E.} and Han, {Mei Lan K.} and Martinez, {Fernando J.} and Aaron, {Shawn D.} and Reed, {Robert M.} and Man, {S. F.Paul} and Leung, {Janice M.} and Sin, {Don D.}",

note = "Funding Information: Author contributions: M. J., E. C. L., and S. W. R. had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. D. D. S. conceived the project, funding, and study design. S. T. managed the experimental portion of the study. M. J., E. C. L., S. W. R., and N. F. performed the statistical analysis and interpretations. M. J. and E. C. L. wrote the first draft of the manuscript. G. J. C., P. G. W., S. C. L., R. A., J. E. C., M. K. H., F. J. M., S. D. A., R. M. R., S. F. P. M., J. M. L., and D. D. S. contributed to critical revision of the manuscript for important statistical, intellectual, clinical content and approved the final version. Financial/nonfinancial disclosures: The authors have reported to CHEST the following: N. F. is a paid employee of GenomeDx Biosciences Inc. P. G. W. has served as a consultant to Astra-Zeneca, Theravance, Regeneron, Sanofi, and Genentech. M. K. H. has consulted for GSK, Boehringer Ingelheim, Astra-Zeneca, Novartis, and Sunovion and has received in kind support from Novartis and Sunovion. D. D. S. has received research funding support from Merck, AstraZeneca, and Boehringer Ingelheim and has served on advisory boards of Sanofi-Aventis, Regeneron and AstraZeneca. None declared (M. J., E. C. L., S. W. R., S. T., G. J. C., S. C. L., R. A., J. E. C., F. J. M., S. D. A., R. M. R., S. F. P. M., J. M. L.). Role of sponsors: The sponsor had no role in the design of the study, the collection and analysis of the data, or the preparation of the manuscript. Additional information: The e-Figures and e-Tables can be found in the Supplemental Materials section of the online article. Funding Information: Financial/nonfinancial disclosures: The authors have reported to CHEST the following: N. F. is a paid employee of GenomeDx Biosciences Inc. P. G. W. has served as a consultant to Astra-Zeneca, Theravance, Regeneron, Sanofi, and Genentech. M. K. H. has consulted for GSK, Boehringer Ingelheim, Astra-Zeneca, Novartis, and Sunovion and has received in kind support from Novartis and Sunovion. D. D. S. has received research funding support from Merck, AstraZeneca, and Boehringer Ingelheim and has served on advisory boards of Sanofi-Aventis, Regeneron and AstraZeneca. None declared (M. J., E. C. L., S. W. R., S. T., G. J. C., S. C. L., R. A., J. E. C., F. J. M., S. D. A., R. M. R., S. F. P. M., J. M. L.). Publisher Copyright: {\textcopyright} 2018 American College of Chest Physicians",

year = "2018",

month = aug,

doi = "10.1016/j.chest.2018.05.022",

language = "English (US)",

volume = "154",

pages = "266--273",

journal = "CHEST",

issn = "0012-3692",

publisher = "American College of Chest Physicians",

number = "2",

}

TY - JOUR

T1 - Relationship of Absolute Telomere Length With Quality of Life, Exacerbations, and Mortality in COPD

AU - Jin, Minhee

AU - Lee, Eun Chong

AU - Ra, Seung Won

AU - Fishbane, Nick

AU - Tam, Sheena

AU - Criner, Gerard J.

AU - Woodruff, Prescott G.

AU - Lazarus, Stephen C.

AU - Albert, Richard

AU - Connett, John E.

AU - Han, Mei Lan K.

AU - Martinez, Fernando J.

AU - Aaron, Shawn D.

AU - Reed, Robert M.

AU - Man, S. F.Paul

AU - Leung, Janice M.

AU - Sin, Don D.

N1 - Funding Information: Author contributions: M. J., E. C. L., and S. W. R. had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. D. D. S. conceived the project, funding, and study design. S. T. managed the experimental portion of the study. M. J., E. C. L., S. W. R., and N. F. performed the statistical analysis and interpretations. M. J. and E. C. L. wrote the first draft of the manuscript. G. J. C., P. G. W., S. C. L., R. A., J. E. C., M. K. H., F. J. M., S. D. A., R. M. R., S. F. P. M., J. M. L., and D. D. S. contributed to critical revision of the manuscript for important statistical, intellectual, clinical content and approved the final version. Financial/nonfinancial disclosures: The authors have reported to CHEST the following: N. F. is a paid employee of GenomeDx Biosciences Inc. P. G. W. has served as a consultant to Astra-Zeneca, Theravance, Regeneron, Sanofi, and Genentech. M. K. H. has consulted for GSK, Boehringer Ingelheim, Astra-Zeneca, Novartis, and Sunovion and has received in kind support from Novartis and Sunovion. D. D. S. has received research funding support from Merck, AstraZeneca, and Boehringer Ingelheim and has served on advisory boards of Sanofi-Aventis, Regeneron and AstraZeneca. None declared (M. J., E. C. L., S. W. R., S. T., G. J. C., S. C. L., R. A., J. E. C., F. J. M., S. D. A., R. M. R., S. F. P. M., J. M. L.). Role of sponsors: The sponsor had no role in the design of the study, the collection and analysis of the data, or the preparation of the manuscript. Additional information: The e-Figures and e-Tables can be found in the Supplemental Materials section of the online article. Funding Information: Financial/nonfinancial disclosures: The authors have reported to CHEST the following: N. F. is a paid employee of GenomeDx Biosciences Inc. P. G. W. has served as a consultant to Astra-Zeneca, Theravance, Regeneron, Sanofi, and Genentech. M. K. H. has consulted for GSK, Boehringer Ingelheim, Astra-Zeneca, Novartis, and Sunovion and has received in kind support from Novartis and Sunovion. D. D. S. has received research funding support from Merck, AstraZeneca, and Boehringer Ingelheim and has served on advisory boards of Sanofi-Aventis, Regeneron and AstraZeneca. None declared (M. J., E. C. L., S. W. R., S. T., G. J. C., S. C. L., R. A., J. E. C., F. J. M., S. D. A., R. M. R., S. F. P. M., J. M. L.). Publisher Copyright: © 2018 American College of Chest Physicians

PY - 2018/8

Y1 - 2018/8

N2 - 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 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.

AB - 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 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.

KW - COPD

KW - exacerbation

KW - mortality

KW - quality of life

KW - telomere

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UR - http://www.scopus.com/inward/citedby.url?scp=85049335749&partnerID=8YFLogxK

U2 - 10.1016/j.chest.2018.05.022

DO - 10.1016/j.chest.2018.05.022

M3 - Article

C2 - 30017346

AN - SCOPUS:85049335749

SN - 0012-3692

VL - 154

SP - 266

EP - 273

JO - CHEST

JF - CHEST

IS - 2

ER -

Relationship of Absolute Telomere Length With Quality of Life, Exacerbations, and Mortality in COPD

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