Observational Study

. 2019 May 22;20(1):100.

doi: 10.1186/s12931-019-1073-3.

It's more than low BMI: prevalence of cachexia and associated mortality in COPD

Merry-Lynn N McDonald^{1

2

3

4}, Emiel F M Wouters⁵, Erica Rutten⁵, Richard Casaburi⁶, Stephen I Rennard^{7

8}, David A Lomas⁹, Marcas Bamman¹⁰, Bartolome Celli¹¹, Alvar Agusti^{12

13}, Ruth Tal-Singer¹⁴, Craig P Hersh^{11

15}, Mark Dransfield¹⁶, Edwin K Silverman^{11

15}

Affiliations

¹ Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, USA. mmcdonald@uab.edu.
² Department of Genetics, University of Alabama at Birmingham, Birmingham, AL, USA. mmcdonald@uab.edu.
³ Lung Health Center, University of Alabama at Birmingham, 701 19th Street S, LHRB 440, Birmingham, AL, 35233, USA. mmcdonald@uab.edu.
⁴ Center for Exercise Medicine, University of Alabama at Birmingham, 701 19th Street S, LHRB 440, Birmingham, AL, 35233, USA. mmcdonald@uab.edu.
⁵ Centre of expertise for chronic organ failure, Horn, the Netherlands and Department of Respiratory Medicine, Maastricht University Medical Center, Maastricht, the Netherlands.
⁶ Rehabilitation Clinical Trials Center, Los Angeles Biomedical Research Institute at Harbor Harbor-UCLA Medical Center, Torrance, CA, USA.
⁷ Department of Medicine, Nebraska Medical Center, Omaha, NE, USA.
⁸ Biopharma R&D, AstraZeneca, Cambridge, UK.
⁹ UCL Respiratory, University College London, London, UK.
¹⁰ Center for Exercise Medicine and Departments of Cell, Developmental & Integrative Biology; Medicine; and Neurology, University of Alabama at Birmingham, Birmingham, AL, USA.
¹¹ Division of Pulmonary and Critical Care, Brigham and Women's Hospital, Boston, MA, USA.
¹² Fundació Investigació Sanitària Illes Balears (FISIB), Ciber Enfermedades Respiratorias (CIBERES), Barcelona, Catalunya, Spain.
¹³ Thorax Institute, Hospital Clinic, IDIBAPS, Univ. Barcelona, Barcelona, Spain.
¹⁴ GSK R&D, Collegeville, PA, USA.
¹⁵ Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.
¹⁶ Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.

PMID: 31118043
PMCID: PMC6532157
DOI: 10.1186/s12931-019-1073-3

Observational Study

It's more than low BMI: prevalence of cachexia and associated mortality in COPD

Merry-Lynn N McDonald et al. Respir Res. 2019.

. 2019 May 22;20(1):100.

doi: 10.1186/s12931-019-1073-3.

Authors

Affiliations

¹ Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, USA. mmcdonald@uab.edu.
² Department of Genetics, University of Alabama at Birmingham, Birmingham, AL, USA. mmcdonald@uab.edu.
³ Lung Health Center, University of Alabama at Birmingham, 701 19th Street S, LHRB 440, Birmingham, AL, 35233, USA. mmcdonald@uab.edu.
⁴ Center for Exercise Medicine, University of Alabama at Birmingham, 701 19th Street S, LHRB 440, Birmingham, AL, 35233, USA. mmcdonald@uab.edu.
⁵ Centre of expertise for chronic organ failure, Horn, the Netherlands and Department of Respiratory Medicine, Maastricht University Medical Center, Maastricht, the Netherlands.
⁶ Rehabilitation Clinical Trials Center, Los Angeles Biomedical Research Institute at Harbor Harbor-UCLA Medical Center, Torrance, CA, USA.
⁷ Department of Medicine, Nebraska Medical Center, Omaha, NE, USA.
⁸ Biopharma R&D, AstraZeneca, Cambridge, UK.
⁹ UCL Respiratory, University College London, London, UK.
¹⁰ Center for Exercise Medicine and Departments of Cell, Developmental & Integrative Biology; Medicine; and Neurology, University of Alabama at Birmingham, Birmingham, AL, USA.
¹¹ Division of Pulmonary and Critical Care, Brigham and Women's Hospital, Boston, MA, USA.
¹² Fundació Investigació Sanitària Illes Balears (FISIB), Ciber Enfermedades Respiratorias (CIBERES), Barcelona, Catalunya, Spain.
¹³ Thorax Institute, Hospital Clinic, IDIBAPS, Univ. Barcelona, Barcelona, Spain.
¹⁴ GSK R&D, Collegeville, PA, USA.
¹⁵ Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.
¹⁶ Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.

PMID: 31118043
PMCID: PMC6532157
DOI: 10.1186/s12931-019-1073-3

Abstract

Background: Cachexia is associated with increased mortality risk among chronic obstructive pulmonary disease (COPD) patients. However, low body mass index (BMI) as opposed to cachexia is often used, particularly when calculating the BODE (BMI, Obstruction, Dyspnea and Exercise) index. For this reason, we examined mortality using a consensus definition and a weight-loss definition of cachexia among COPD cases and compared two new COPD severity indices with BODE.

Methods: In the current report, the consensus definition for cachexia incorporated weight-loss > 5% in 12-months or low BMI in addition to 3/5 of decreased muscle strength, fatigue, anorexia, low FFMI and inflammation. The weight-loss definition incorporated weight-loss > 5% or weight-loss > 2% (if low BMI) in 12-months. The low BMI component in BODE was replaced with the consensus definition to create the CODE (Consensus cachexia, Obstruction, Dyspnea and Exercise) index and the weight-loss definition to create the WODE (Weight loss, Obstruction, Dyspnea and Exercise) index. Mortality was assessed using Kaplan-Meier survival and Cox Regression. Performance of models was compared using C-statistics.

Results: Among 1483 COPD cases, the prevalences of cachexia by the consensus and weight-loss definitions were 4.7 and 10.4%, respectively. Cachectic patients had a greater than three-fold increased mortality by either the consensus or the weight-loss definition of cachexia independent of BMI and lung function. The CODE index predicted mortality slightly more accurately than the BODE and WODE indices.

Conclusions: Cachexia is associated with increased mortality among COPD patients. Monitoring cachexia using weight-loss criteria is relatively simple and predictive of mortality among COPD cases who may be missed if only low BMI is used.

Keywords: BMI; BODE; COPD; Cachexia; Weight loss.

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Conflict of interest statement

M-LNM reports grants from National Institutes of Health, other from Parker B. Francis Foundation, during the conduct of the study and personal fees from Pfizer, outside the submitted work.

EFMW has received personal fees from Nycomed, Boehringer, AstraZeneca, GSK, Novartis and Chiesi. EFMW has received grants from AstraZeneca and GSK.

ER has no competing interests.

RC has received personal fees from GSK, Boehringer Ingelheim, Astra Zeneca, Genentech and Regeneron.

SIR reports other from AstraZeneca, outside the submitted work. S.I.R. is employed by AstraZeneca.

DAL reports grants, personal fees and non-financial support from GSK during the conduct of the study and personal fees from Griffols, outside the submitted work.

MB has no competing interests.

BC reports personal fees and other from Astra Zeneca, personal fees from GlaxoSmithKline, personal fees from Boehringer Ingelheim, personal fees from Novartis, personal fees from Sanofi Aventis and personal fess form Menarini other from outside the submitted work.

AA reports personal fees from GSK, during the conduct of the study.

RT-S is an employee and shareholder of GSK, the ECLIPSE study sponsor.

CPH reports personal fees from Mylan, personal fees from AstraZeneca, personal fees from Concert Pharmaceuticals, personal fees from 23andMe, grants from Novartis, grants from Boehringer-Ingelheim, grants from NHLBI, outside the submitted work.

MD reports grants from Department of Defense, personal fees and other from Boehringer Ingelheim, personal fees and other from GSK, other from Novartis, personal fees and other from AstraZeneca, other from Yungjin, personal fees and other from PneumRx/BTG, other from Pulmonx, personal fees from Genentech, personal fees and other from Boston Scientific, personal fees from Quark Pharmaceuticals, grants from NIH, outside the submitted work.

EKS reports grants, personal fees and other from GSK, during the conduct of the study; personal fees from Novartis, outside the submitted work.

Figures

**Fig. 1**
Prevalence of cachexia (consensus and weight-loss definitions) stratified by GOLD and BMI category among COPD cases at Year 1 Visit in ECLIPSE stratified by GOLD (a, b) and BMI category (c, d). Numbers above bars represent prevalence in each group. Percentage of COPD cases with cachexia by the consensus definition significantly (p < 0.001) increased with increasing GOLD stage, COPD cases with low BMI were more likely (p < 0.001) to have cachexia by both the consensus and weight-loss definitions. Note: Cochran Armitage test was used to assess trends

**Fig. 2**
Overlap in classification of consensus and weight-loss classifications among COPD cases in ECLIPSE

**Fig. 3**
Kaplan Meier Survival Stratified by Cachexia as compared to the remaining cohort. a. Cachexia defined using consensus definition, b. Cachexia defined by weight-loss and c. Cachexia defined as either consensus definition or weight-loss

**Fig. 4**
Kaplan Meier Survival Comparison between. a. BODE b. WODE and c. CODE quartiles

See this image and copyright information in PMC

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References

1. Evans WJ, Morley JE, Argiles J, Bales C, Baracos V, Guttridge D, Jatoi A, Kalantar-Zadeh K, Lochs H, Mantovani G, Marks D, Mitch WE, Muscaritoli M, Najand A, Ponikowski P, Rossi Fanelli F, Schambelan M, Schols A, Schuster M, Thomas D, Wolfe R, Anker SD. Cachexia: a new definition. Clin Nutr. 2008;27:793–799. doi: 10.1016/j.clnu.2008.06.013. - DOI - PubMed
1. Schols AM, Broekhuizen R, Weling-Scheepers CA, Wouters EF. Body composition and mortality in chronic obstructive pulmonary disease. Am. J. Clin. Nutr. 2005;82:53–59. doi: 10.1093/ajcn/82.1.53. - DOI - PubMed
1. von Haehling S, Anker SD. Cachexia as major underestimated unmet medical need: facts and numbers. Int. J. Cardiol. 2012;161:121–123. doi: 10.1016/j.ijcard.2012.09.213. - DOI - PubMed
1. Haehling S Von, Anker MS, Anker SD. Prevalence and clinical impact of cachexia in chronic illness in Europe , USA , and Japan : facts and numbers update 2016. 2016; : 507–509. - PMC - PubMed
1. Celli BR, Cote CG, Marin JM, Casanova C, Montes de Oca M, Mendez RA, Pinto Plata V, Cabral HJ. The body-mass index, airflow obstruction, dyspnea, and exercise capacity index in chronic obstructive pulmonary disease. N Engl J Med. 2004;350:1005–1012. doi: 10.1056/NEJMoa021322. - DOI - PubMed

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It's more than low BMI: prevalence of cachexia and associated mortality in COPD

Affiliations

It's more than low BMI: prevalence of cachexia and associated mortality in COPD

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