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Original research
Respiratory exacerbations are associated with muscle loss in current and former smokers
  1. Stefanie Elizabeth Mason1,
  2. Rafael Moreta-Martinez2,
  3. Wassim W Labaki3,
  4. Matthew Strand4,
  5. David Baraghoshi4,
  6. Elizabeth A Regan5,
  7. Jessica Bon6,
  8. Ruben San Jose Estepar2,
  9. Richard Casaburi7,
  10. Merry-Lynn N McDonald8,
  11. Harry Rossiter7,
  12. Barry J Make9,
  13. Mark T Dransfield8,
  14. MeiLan K Han3,
  15. Kendra A Young10,
  16. Greg Kinney10,
  17. John E Hokanson10,
  18. Raul San Jose Estepar2,
  19. George R Washko1
  20. COPDGene Investigators
    1. 1Division of Pulmonary and Critical Care, Brigham and Women's Hospital, Boston, Massachusetts, USA
    2. 2Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts, USA
    3. 3Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, Michigan, USA
    4. 4Division of Biostatistics and Bioinformatics, National Jewish Health, Denver, Colorado, USA
    5. 5Division of Rheumatology, National Jewish Health, Denver, Colorado, USA
    6. 6Division of Pulmonary, Allergy and Critical Care, UPMC, Pittsburgh, Pennsylvania, USA
    7. 7Division of Respiratory and Critical Care Physiology and Medicine, Los Angeles Biomedical Research Institute, Torrance, California, USA
    8. 8Division of Pulmonary, Allergy, and Critical Care, University of Alabama at Birmingham, Birmingham, Alabama, USA
    9. 9Division of Pulmonary, Critical Care, and Sleep Medicine, National Jewish Health, Denver, Colorado, USA
    10. 10Department of Epidemiology, Colorado School of Public Health, Aurora, Colorado, USA
    1. Correspondence to Dr Stefanie Elizabeth Mason, Division of Pulmonary and Critical Care, Brigham and Women's Hospital, Boston, MA 02115, USA; smason8{at}bwh.harvard.edu

    Abstract

    Objectives Muscle wasting is a recognised extra-pulmonary complication in chronic obstructive pulmonary disease and has been associated with increased risk of death. Acute respiratory exacerbations are associated with reduction of muscle function, but there is a paucity of data on their long-term effect. This study explores the relationship between acute respiratory exacerbations and long-term muscle loss using serial measurements of CT derived pectoralis muscle area (PMA).

    Design and setting Participants were included from two prospective, longitudinal, observational, multicentre cohorts of ever-smokers with at least 10 pack-year history.

    Participants The primary analysis included 1332 (of 2501) participants from Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) and 4384 (of 10 198) participants from Genetic Epidemiology of COPD (COPDGene) who had complete data from their baseline and follow-up visits.

    Interventions PMA was measured on chest CT scans at two timepoints. Self-reported exacerbation data were collected from participants in both studies through the use of periodic longitudinal surveys.

    Main outcome measures Age-related and excess muscle loss over time.

    Results Age, sex, race and body mass index were associated with baseline PMA. Participants experienced age-related decline at the upper end of reported normal ranges. In ECLIPSE, the exacerbation rate over time was associated with an excess muscle area loss of 1.3% (95% CI 0.6 to 1.9, p<0.001) over 3 years and in COPDGene with an excess muscle area loss of 2.1% (95% CI 1.2 to 2.8, p<0.001) over 5 years. Excess muscle area decline was absent in 273 individuals who participated in pulmonary rehabilitation.

    Conclusions Exacerbations are associated with accelerated skeletal muscle loss. Each annual exacerbation was associated with the equivalent of 6 months of age-expected decline in muscle mass. Ameliorating exacerbation-associated muscle loss represents an important therapeutic target.

    • COPD exacerbations
    • imaging/CT MRI etc
    • pulmonary rehabilitation

    Statistics from Altmetric.com

    Footnotes

    • Twitter @stef_mason

    • Collaborators James D. Crapo (Administrative Center), Edwin K. Silverman (Administrative Center), Barry J. Make (Administrative Center), Elizabeth A. Regan (Administrative Center), Terri Beaty (Genetic Analysis Center), Ferdouse Begum (Genetic Analysis Center), Peter J. Castaldi (Genetic Analysis Center), Michael Cho (Genetic Analysis Center), Dawn L. DeMeo (Genetic Analysis Center), Adel R. Boueiz (Genetic Analysis Center), Marilyn G. Foreman (Genetic Analysis Center), Eitan Halper-Stromberg (Genetic Analysis Center), Lystra P. Hayden (Genetic Analysis Center), Craig P. Hersh (Genetic Analysis Center), Jacqueline Hetmanski (Genetic Analysis Center), Brian D. Hobbs (Genetic Analysis Center), John E. Hokanson (Genetic Analysis Center), Nan Laird (Genetic Analysis Center), Christoph Lange (Genetic Analysis Center), Sharon M. Lutz (Genetic Analysis Center), Merry-Lynn McDonald (Genetic Analysis Center), Margaret M. Parker (Genetic Analysis Center), Dmitry Prokopenko (Genetic Analysis Center), Dandi Qiao (Genetic Analysis Center), Elizabeth A. Regan (Genetic Analysis Center), Phuwanat Sakornsakolpat (Genetic Analysis Center), Edwin K. Silverman (Genetic Analysis Center), Emily S. Wan (Genetic Analysis Center), Sungho Won (Genetic Analysis Center), Juan Pablo Centeno (Imaging Center), Jean-Paul Charbonnier (Imaging Center), Harvey O. Coxson (Imaging Center), Craig J. Galban (Imaging Center), MeiLan K. Han (Imaging Center), Eric A. Hoffman (Imaging Center), Stephen Humphries (Imaging Center), Francine L. Jacobson (Imaging Center), Philip F. Judy (Imaging Center), Ella A. Kazerooni (Imaging Center), Alex Kluiber (Imaging Center), David A. Lynch (Imaging Center), Pietro Nardelli (Imaging Center), John D. Newell, Jr. (Imaging Center), Aleena Notary (Imaging Center), Andrea Oh (Imaging Center), Elizabeth A. Regan (Imaging Center), James C. Ross (Imaging Center), Raul San Jose Estepar (Imaging Center), Joyce Schroeder (Imaging Center), Jered Sieren (Imaging Center), Berend C. Stoel (Imaging Center), Juerg Tschirren (Imaging Center), Edwin Van Beek (Imaging Center), Bram van Ginneken (Imaging Center), Eva van Rikxoort (Imaging Center), Gonzalo Vegas Sanchez-Ferrero (Imaging Center), Lucas Veitel (Imaging Center), George R. Washko (Imaging Center), Carla G. Wilson (Imaging Center), Robert Jensen (PFT QA Center), Douglas Everett (Data Coordinating Center and Biostatistics, National Jewish Health), Jim Crooks (Data Coordinating Center and Biostatistics, National Jewish Health), Katherine Pratte (Data Coordinating Center and Biostatistics, National Jewish Health), Matt Strand (Data Coordinating Center and Biostatistics, National Jewish Health), Carla G. Wilson (Data Coordinating Center and Biostatistics, National Jewish Health), John E. Hokanson (Epidemiology Core, University of Colorado Anschutz Medical Campus), Gregory Kinney (Epidemiology Core, University of Colorado Anschutz Medical Campus), Sharon M. Lutz (Epidemiology Core, University of Colorado Anschutz Medical Campus), Kendra A. Young (Epidemiology Core, University of Colorado Anschutz Medical Campus), Surya P. Bhatt (Mortality Adjudication Core), Jessica Bon, Alejandro A. Diaz (Mortality Adjudication Core), MeiLan K. Han (Mortality Adjudication Core), Barry Make (Mortality Adjudication Core), Susan Murray (Mortality Adjudication Core), Elizabeth Regan (Mortality Adjudication Core), Xavier Soler (Mortality Adjudication Core), Carla G. Wilson (Mortality Adjudication Core), Russell P. Bowler (Biomarker Core), Katerina Kechris (Biomarker Core), Farnoush Banaei-Kashani (Biomarker Core), Jeffrey L. Curtis, Perry G. Pernicano, Nicola Hanania (Baylor College of Medicine), Mustafa Atik (Baylor College of Medicine), Aladin Boriek (Baylor College of Medicine), Kalpatha Guntupalli (Baylor College of Medicine), Elizabeth Guy (Baylor College of Medicine), Amit Parulekar (Baylor College of Medicine), Dawn L. DeMeo (Brigham and Women’s Hospital), Alejandro A. Diaz (Brigham and Women’s Hospital), Lystra P. Hayden (Brigham and Women’s Hospital), Brian D. Hobbs (Brigham and Women’s Hospital), Craig Hersh (Brigham and Women’s Hospital), Francine L. Jacobson (Brigham and Women’s Hospital), George Washko (Brigham and Women’s Hospital), R. Graham Barr (Columbia University), John Austin (Columbia University), Belinda D’Souza (Columbia University), Byron Thomashow (Columbia University), Neil MacIntyre (Duke University Medical Center), H. Page McAdams (Duke University Medical Center), Lacey Washington (Duke University Medical Center), Eric Flenaugh (Grady Memorial Hospital), Silanth Terpenning (Grady Memorial Hospital), Charlene McEvoy (HealthPartners Research Institute), Joseph Tashjian (HealthPartners Research Institute), Robert Wise (Johns Hopkins University), Robert Brown (Johns Hopkins University), Nadia N. Hansel (Johns Hopkins University), Karen Horton (Johns Hopkins University), Allison Lambert (Johns Hopkins University), Nirupama Putcha (Johns Hopkins University), Richard Casaburi (Lundquist Institute for Biomedical Innovationat Harbor UCLA Medical Center), Alessandra Adami (Lundquist Institute for Biomedical Innovationat Harbor UCLA Medical Center), Matthew Budoff (Lundquist Institute for Biomedical Innovationat Harbor UCLA Medical Center), Hans Fischer (Lundquist Institute for Biomedical Innovationat Harbor UCLA Medical Center), Janos Porszasz (Lundquist Institute for Biomedical Innovationat Harbor UCLA Medical Center), Harry Rossiter (Lundquist Institute for Biomedical Innovationat Harbor UCLA Medical Center), Michael E. DeBakey (VAMC), Amir Sharafkhaneh (VAMC), Charlie Lan (VAMC), Russell Bowler (National Jewish Health), David A. Lynch (National Jewish Health), Richard Rosiello (Reliant Medical Group), David Pace (Reliant Medical Group), Gerard Criner (Temple University), David Ciccolella (Temple University), Francis Cordova (Temple University), Chandra Dass (Temple University), Gilbert D’Alonzo (Temple University), Parag Desai (Temple University), Michael Jacobs (Temple University), Steven Kelsen (Temple University), Victor Kim (Temple University), A. James Mamary (Temple University), Nathaniel Marchetti (Temple University), Aditi Satti (Temple University), Kartik Shenoy (Temple University), Robert M. Steiner (Temple University), Alex Swift (Temple University), Irene Swift (Temple University), Maria Elena Vega-Sanchez (Temple University), Mark Dransfield (University of Alabama), William Bailey (University of Alabama), Surya P. Bhatt (University of Alabama), Anand Iyer (University of Alabama), Hrudaya Nath (University of Alabama), J. Michael Wells (University of Alabama), Douglas Conrad (University of California), Xavier Soler (University of California), Andrew Yen (University of California), Alejandro P. Comellas (University of Iowa), Karin F. Hoth (University of Iowa), John Newell (University of Iowa), Brad Thompson (University of Iowa), MeiLan K. Han (University of Michigan), Ella Kazerooni (University of Michigan), Wassim Labaki (University of Michigan), Craig Galban (University of Michigan), Dharshan Vummidi (University of Michigan), Joanne Billings (University of Minnesota), Abbie Begnaud (University of Minnesota), Tadashi Allen (University of Minnesota), Frank Sciurba (University of Pittsburgh), Jessica Bon (University of Pittsburgh), Divay Chandra (University of Pittsburgh), Joel Weissfeld (University of Pittsburgh), Antonio Anzueto (University of Texas Health), Sandra Adams (University of Texas Health), Diego Maselli-Caceres (University of Texas Health), Mario E. Ruiz (University of Texas Health), Harjinder Singh (University of Texas Health)

    • Contributors SEM wrote the manuscript. SEM, GRW, DB and MS were responsible for study design and statistical analysis. RM-M, RubenSJE and RaulSJE contributed to the computational imaging methodology. RM-M, WWL, MS, DB, EAR, JB, RC, M-LNM, HR, BJM, MTD, MKH, KAY, GK, JEH, RaulSJE and GRW revised the manuscript for critical intellectual content.

    • Funding This work was supported by NIH HL089856 and HL089897 and T32 HL007633 (SEM). The COPDGene (Genetic Epidemiology of COPD) project is also supported by the COPD Foundation through contributions made to an industry advisory board comprised AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Pfizer, Siemens and Sunovion.

    • Disclaimer The funders had no role in the study design, data collection, data analysis, data interpretation, writing of the report or the decision to publish.

    • Competing interests MTD reports grant funding from the National Institutes of Health relevant to the submitted work. Outside the submitted work, he reports grants from the American Lung Association, Department of Veterans Affairs, and the Department of Defense. He reports consulting fees from Boehringer Ingelheim, GlaxoSmithKline, AstraZeneca, PneumRx, Quark Pharmaceuticals and Mereo. He is involved in contracted clinical trials with Boehringer Ingelheim, GlaxoSmithKline, Novartis, AstraZeneca, Yungjin, PneumRx, Pulmonx, Boston Scientific, Gala and Nuvaira. RC reports grant funding from the National Institutes of Health relevant to the submitted work. Outside the submitted work, he reports consulting fees or advisory board membership from Boehringer Ingelheim, GlaxoSmithKline, Astra Zeneca, Abbott, Genentech and Regeneron. He is involved in contracted clinical trials with Boehringer Ingelheim, GlaxoSmithKline, AstraZeneca, Genentech and Regeneron. HR reports grant funding from the National Institutes of Health and the Tobacco Related Disease Research Program relevant to the submitted work. Outside the submitted work, he is involved in contracted clinical trials with Boehringer Ingelheim, GlaxoSmithKline, Novartis, AstraZeneca, Astellas, Genentech and Regeneron. WWL reports funding from the National Institutes of Health, non-financial support from Pulmonx, and personal fees from Konica Minolta, outside of the submitted work. MKH reports grant funding from the National Institutes of Health relevant to the submitted work. Outside the submitted work she reports grant funding from Verona, Mylan and Merck. She reports personal fees from GlaxoSmithKline, AstraZeneca and Boehringer Ingelheim. She reports other support from Novartis and Suovion. KAY and MS report grant funding from the National Institutes of Health relevant to the submitted work. RaulSJE reports funding from the National Institutes of Health relevant to the submitted work. Outside the submitted work, he reports grants from Boehringer Ingelheim and personal fees from Leuko labs and Chiesi. He is also a founder and co-owner of Quantitative Imaging Solutions which is a company that provides image based consulting and develops software to enable data sharing. BJM reports grants from AstraZeneca, GlaxoSmithKline, Sunovion, Pearl Research and the National Heart Lung Blood Institute. He reports trial related activity from AzatraZeneca, Spiration, GlaxoSmithKline, Sunovision, Third Pole and Takeda. He reports CME related support from Mt Sinai, WebMD, National Jewish Health, American College of Chest Physicians, Projects in Knowledge, Hybrid Communications, Medscape, Ultimate Medical Academy, Eastern Pulmonary Society, Catamount Medical, Eastern Va Medical Center, Academy Continued Health Learning and Wolters Kluwer Health, from outside the submitted work. He is involved with the medical advisory board for Verona, Boehringer Ingelheim, Theravance, Circassia, Phillips, Science 24/7, AstraZeneca and GlaxoSmithKline. All activities are outside of the submitted work. GRW reports grants from the National Institutes of Health, Boehringer Ingelheim, BTG Interventional Medicine, and Janssen Pharmaceuticals. He reports consulting work for Boehringer Ingelheim, PulmonX, Janssen Pharmaceuticals, GlaxoSmithKline, Novartis, Vertex and CSL Behring. He reports advisory board involvement with Boehringer Ingelheim, Vertex and CSL Behring. He is also a founder and co-owner of Quantitative Imaging Solutions which is a company that provides image based consulting and develops software to enable data sharing. All activities are outside the submitted work.

    • Patient consent for publication Not required.

    • Ethics approval Each study was approved by the relevant Institutional Review Board(s). For a complete list of the sites and corresponding IRB approval numbers, please see online supplemental tables E4 and E5. Written informed consent was obtained from all participants.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data availability statement Data may be obtained from a third party and are not publicly available. Investigators can contact the data coordinating centers for each study with data requests. ECLIPSE: https://eclipse-copd.com/COPDGene: http://www.copdgene.org/

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