Heterogeneity of quadriceps muscle phenotype in chronic obstructive pulmonary disease (Copd); implications for stratified medicine?

Authors

  • Samantha A. Natanek PhD,

    1. NIHR Respiratory Biomedical Research Unit of the Royal Brompton, and Harefield NHS Foundation Trust and Imperial College London, London, United Kingdom
    2. Department of Respiratory Medicine, NUTRIM School for Nutrition, Toxicology & Metabolism, Maastricht University Medical Centre, AZ Maastricht, Netherlands
    3. Molecular Medicine Section, National Heart & Lung Institute, Imperial College London, South Kensington Campus, London, United Kingdom
    Search for more papers by this author
  • Harry R. Gosker PhD,

    1. Molecular Medicine Section, National Heart & Lung Institute, Imperial College London, South Kensington Campus, London, United Kingdom
    Search for more papers by this author
  • Ilse G.M. Slot BSc,

    1. Molecular Medicine Section, National Heart & Lung Institute, Imperial College London, South Kensington Campus, London, United Kingdom
    Search for more papers by this author
  • Gemma S. Marsh BSc Physiotherapy,

    1. NIHR Respiratory Biomedical Research Unit of the Royal Brompton, and Harefield NHS Foundation Trust and Imperial College London, London, United Kingdom
    Search for more papers by this author
  • Nicholas S. Hopkinson PhD,

    1. NIHR Respiratory Biomedical Research Unit of the Royal Brompton, and Harefield NHS Foundation Trust and Imperial College London, London, United Kingdom
    Search for more papers by this author
  • William D.-C. Man PhD,

    1. NIHR Respiratory Biomedical Research Unit of the Royal Brompton, and Harefield NHS Foundation Trust and Imperial College London, London, United Kingdom
    Search for more papers by this author
  • Ruth Tal-Singer PhD,

    1. Department of Respiratory Medicine, Denmark Hill Campus, GKT School of Medicine, London, United Kingdom
    Search for more papers by this author
  • John Moxham PhD,

    1. GlaxoSmithKline, King of Prussia, Pennsylvania, USA
    Search for more papers by this author
  • Paul R. Kemp PhD,

    1. Department of Respiratory Medicine, NUTRIM School for Nutrition, Toxicology & Metabolism, Maastricht University Medical Centre, AZ Maastricht, Netherlands
    Search for more papers by this author
  • Annemie M.W.J. Schols PhD,

    1. Molecular Medicine Section, National Heart & Lung Institute, Imperial College London, South Kensington Campus, London, United Kingdom
    Search for more papers by this author
  • Michael I. Polkey PhD

    Corresponding author
    1. NIHR Respiratory Biomedical Research Unit of the Royal Brompton, and Harefield NHS Foundation Trust and Imperial College London, London, United Kingdom
    Search for more papers by this author

ABSTRACT

Introduction

Quadriceps muscle dysfunction is common in COPD. Determining, and, if possible, predicting quadriceps phenotype in COPD is important for patient stratification for therapeutic trials.

Methods

In biopsies from 114 COPD patients and 30 controls, we measured fiber size and proportion and assessed the relationship with quadriceps function (strength and endurance), clinical phenotype (lung function, physical activity, fat-free mass) and exercise performance. In a subset (n = 40) we measured muscle mid-thigh cross-sectional area by computed tomography.

Results

Normal ranges for fiber proportions and fiber cross-sectional area were defined from controls; we found isolated fiber shift in 31% of patients, isolated fiber (predominantly type II) atrophy in 20%, both shift and atrophy in 25%, and normal fiber parameters in 24%. Clinical parameters related poorly to muscle biopsy appearances.

Conclusions

Quadriceps morphology is heterogeneous in COPD and cannot be predicted without biopsy, underlining the need for biomarkers. Muscle Nerve 48: 488–497, 2013

Ancillary