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Clinical interventions in COPD
P144 Muscle fibre atrophy and aerobic to anaerobic fibre type shift in the quadriceps in COPD
  1. S A Natanek1,
  2. H R Gosker1,
  3. I Slot2,
  4. G S Marsh1,
  5. R C J Langen2,
  6. N S Hopkinson1,
  7. W D-C Man1,
  8. J Moxham3,
  9. P R Kemp4,
  10. A M W J Schols2,
  11. M I Polkey1
  1. 1NIHR Respiratory Biomedical Research Unit of the Royal Brompton and Harefield NHS Foundation Trust and National Heart & Lung Institute, Imperial College London, London, UK
  2. 2NUTRIM School for Nutrition, Toxicology & Metabolism, Maastricht University , Maastricht, the Netherlands
  3. 3Guy's, King's and Thomas' School of Medicine, London, UK
  4. 4Molecular Medicine Section, National Heart & Lung Institute, Imperial College London, London, UK

Abstract

Introduction Quadriceps dysfunction is associated with reduced exercise tolerance and survival in COPD. Quadriceps dysfunction has been attributed to quadriceps fibre atrophy (FA) and oxidative to glycolytic (type I to II) fibre shift (FS) but the prevalence of FA and FS and their individual relationships with exercise capacity are not clear.

Methods We measured lung function, physical activity, fat-free mass index (FFMI), quadriceps strength and endurance and exercise performance (6-min walk and incremental cycle ergometry) in 114 COPD patients and 30 healthy age-matched controls and measured mid-thigh muscle cross-sectional area (MTCSA) by CT in 30 patients and 10 controls. Each subject had a quadriceps biopsy and type I, IIa and IIx fibre proportions and CSA were determined by immunohistochemistry. FA and FS were defined using reference intervals for quadriceps fibre characteristics derived from the controls.

Results 24% of patients had quadriceps fibre characteristics within normal limits, 31% had isolated FS, 20% had isolated FA (predominantly type II FA) and 25% had both FS and FA. Muscle FA could not be discerned by FFMI, MTCSA or quadriceps strength values. Patients with isolated FS had a poorer exercise performance than patients with normal fibres (6MW % predicted 66 (46,82) vs 77 (63,95), p=0.025 and peak VO2 % predicted 41 (28,48) vs 50 (38,58), p=0.008), patients with isolated FA (6MW % predicted 66(46,82) vs 91(70,103), p=0.001 and peak VO2 % predicted 41(28,48) v 49(39,62), p=0.006) and patients with both FS and FA (6MW % predicted 66 (46,82) vs 79 (63, 89), p=0.01). Patients with isolated FA or both FS and FA did not have a reduced exercise performance vs patients with normal muscle (6MW % predicted p=0.14 and 0.53 and peak VO2 % predicted p=0.98 and FA vs normal and FS plus FA vs normal respectively). Stepwise multiple regression confirmed that type I fibre proportion was a positive predictor and type IIa fibre CSA was a negative predictor of 6MW and cycle performance in patients, independent of lung function impairment.

Conclusion Quadriceps FA and FS do not necessarily co-occur in COPD. FS is associated with impaired exercise tolerance whereas FA is associated with preserved exercise capacity in COPD.

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