Chest
Volume 141, Issue 3, March 2012, Pages 716-725
Journal home page for Chest

Original Research
COPD
Functional and Muscular Effects of Neuromuscular Electrical Stimulation in Patients With Severe COPD: A Randomized Clinical Trial

https://doi.org/10.1378/chest.11-0839Get rights and content

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.

Section snippets

Patient Population

Patients included in this study had severe COPD and a 6-min walking distance of < 400 m. The inclusion and exclusion criteria are detailed further in e-Appendix 1.

Study Design

This was a randomized, double-blind, controlled, and parallel group study. Patients were randomly assigned to NMES or sham training. Patients were evaluated at baseline and at the end of training. Each evaluation included anthropometric measurements, pulmonary function testing, plasma levels of proinflammatory cytokines (IL-6, tumor

Patient Characteristics

The study flow diagram is provided in Figure 1. Of the 53 eligible patients, 22 were randomly assigned to one of the study interventions. One patient assigned to the sham intervention withdrew after the first training session because of discomfort during NMES, and one patient assigned to the active NMES training declined further participation after one session because of anxiety/depression. The remaining results pertain to the 20 patients (NMES, n = 12; sham, n = 8) who completed the study.

Discussion

This exploratory clinical trial was intended to evaluate the physiologic effects of NMES in patients with severe COPD. We found that NMES, delivered entirely at home, promoted muscle growth of the lower limbs and that the improvements in functional capacity were related to the gain in muscle CSA. Furthermore, significant correlations were found between the ability to increase current intensity during training and improvements in muscle CSA and strength and walking capacity. The assessment of

Conclusions

NMES delivered to the thigh and calf muscles in a home-based setting was a useful strategy to increase lower-limb muscle CSA and strength, with a tendency to enhance walking performance in patients with severe to very severe COPD. At the quadriceps level, this training modality helped restore the anabolic/catabolic balance in favor of the former. We found that some patients with COPD were intolerant to the progression of the current intensity and, as such, were not ideal candidates for NMES

Acknowledgments

Author contributions: Dr Maltais was the principal investigator and takes responsibility for the integrity of the work as a whole, from inception to published article.

Dr Vivodtzev: contributed to the study design, the recruitment of patients, the acquisition and analysis of the data, the interpretation of the results, and the redaction of the manuscript.

Dr Debigaré: contributed to the acquisition, analysis, and interpretation of the muscle biopsy samples and/or to the redaction of the

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    Funding/Support: This work was supported by Canadian Institutes of Health Research (CIHR) [Grant MOP-115136]. F. Maltais holds a GSK/CIHR Research Chair on COPD at Université Laval.

    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).

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