Functional and muscular effects of neuromuscular electrical stimulation in patients with severe COPD: a randomized clinical trial

Chest. 2012 Mar;141(3):716-725. doi: 10.1378/chest.11-0839. Epub 2011 Nov 23.


Background: The mechanisms through which neuromuscular electrical stimulation (NMES) training may improve limb muscle function and exercise tolerance in COPD are poorly understood. We investigated the functional and muscular effects of NMES in advanced COPD.

Methods: Twenty of 22 patients with COPD were randomly assigned to NMES (n = 12) or sham (n = 8) training in a double-blind controlled study. NMES was performed on quadriceps and calf muscles, at home, 5 days per week for 6 weeks. Quadriceps and calf muscle cross-sectional area (CSA), quadriceps force and endurance, and the shuttle-walking distance with cardiorespiratory measurements were assessed before and after training. Quadriceps biopsy specimens were obtained to explore the insulin-like growth factor-1/AKT signaling pathway (70-kDa ribosomal S6 kinase [p70S6K] , atrogin-1).

Results: NMES training improved muscle CSA (P < .05), force, and endurance (P < .03) when compared with sham training. Phosphorylated p70S6K levels (anabolism) were increased after NMES as compared with sham (P = .03), whereas atrogin-1 levels (catabolism) were reduced (P = .01). Changes in quadriceps strength and ventilation during walking contributed independently to variations in walking distance after training (r = 0.77, P < .001). Gains in walking distance were related to the ability to tolerate increasing current intensities during training (r = 0.95, P < .001).

Conclusions: In patients with severe COPD, NMES improved muscle CSA. This was associated with a more favorable muscle anabolic to catabolic balance. Improvement in walking distance after NMES training was associated with gains in muscle strength, reduced ventilation during walking, and the ability to tolerate higher stimulation intensity.

Trial registry:; No.: NCT00874965; URL:

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biopsy
  • Double-Blind Method
  • Electric Stimulation Therapy*
  • Exercise Tolerance / physiology
  • Female
  • Humans
  • Insulin-Like Growth Factor I / metabolism
  • Male
  • Muscle Proteins / metabolism
  • Muscle Strength / physiology*
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / pathology
  • Muscle, Skeletal / physiopathology*
  • Neuromuscular Junction / physiology*
  • Physical Endurance / physiology
  • Proto-Oncogene Proteins c-akt / metabolism
  • Pulmonary Disease, Chronic Obstructive / metabolism
  • Pulmonary Disease, Chronic Obstructive / physiopathology*
  • Pulmonary Disease, Chronic Obstructive / therapy*
  • Ribosomal Protein S6 Kinases, 70-kDa / metabolism
  • SKP Cullin F-Box Protein Ligases / metabolism
  • Severity of Illness Index*
  • Signal Transduction / physiology
  • Walking / physiology


  • Muscle Proteins
  • Insulin-Like Growth Factor I
  • FBXO32 protein, human
  • SKP Cullin F-Box Protein Ligases
  • Proto-Oncogene Proteins c-akt
  • Ribosomal Protein S6 Kinases, 70-kDa

Associated data