Background
Individuals with chronic obstructive pulmonary disease (COPD) may suffer from lower-limb muscle weakness and poor exercise capacity, in particular those with severe to very severe dyspnea [
1‐
3]. This is most probably due to reductions in weight-bearing daily physical activities [
4]. Therefore, an exercise-based pulmonary rehabilitation program may be beneficial [
5]. Severely dyspneic individuals with COPD (i.e., modified MRC dyspnea grade 3 or 4), however, are less likely to complete a pulmonary rehabilitation program [
6]. This may be due to exercise-induced dyspnea, particularly during whole-body endurance training [
7]. Therefore, strength training [
8] or transcutaneous neuromuscular electrical stimulation (NMES) [
9,
10] may be preferential alternative rehabilitative modalities for severely dyspneic individuals with COPD [
11,
12]. These interventions are safe and effective in severely dyspneic individuals with COPD and quadriceps muscle weakness at baseline [
13]. Indeed, lower-limb muscle function, functional exercise performance, problematic activities of daily life, mood status, and health status improved significantly following eight weeks of strength training, high-frequency (HF, 75 Hertz) NMES, or low-frequency (LF, 15 Hertz) NMES [
13].
A major advantage of strength training and NMES is the relatively low metabolic load (e.g., the intervention-related peak oxygen uptake (VO
2) and ventilation (V
E)), accompanied with relatively low dyspnea symptom scores [
14,
15]. The metabolic load during multiple successive sessions of strength training has been reported once in 11 individuals with COPD [
7]. The leg press strengthening exercise increased significantly during a 12-week pulmonary rehabilitation program (+43% of baseline training load), accompanied by a significant increase in metabolic load over time (+23% of baseline intervention-related peak VO
2; +18% of baseline intervention-related peak V
E) [
7]. The metabolic load during a session of high-frequency (HF) or low-frequency (LF) NMES has only been measured cross-sectionally [
14,
15]. Whether and to what extent the metabolic load will remain stable over time while the NMES pulse amplitude is expected to increase [
16] remains currently unknown in individuals with COPD. Moreover, the actual course of NMES pulse amplitude has never been described in individuals with COPD. This, however, will provide a better insight in the feasibility and efficacy of these types of local muscle training.
The aim of the present study was to analyze the metabolic load of the different local muscle training modalities at baseline, half-way, and at the end of the eight-week program in a subgroup of individuals with COPD who participated in the DICES (Dyspneic Individuals with COPD: Electrical stimulation or Strength training) trial. A priori, we hypothesized that individuals with COPD are able to increase the strength training load or NMES pulse amplitude (irrespective of stimulation frequency), while the metabolic load will remain stable compared to baseline.
Discussion
This is the first study to investigate the metabolic load of various local muscle training modalities in severely dyspneic COPD patients with quadriceps muscle weakness during the course of an inpatient pulmonary rehabilitation program. It showed that the metabolic load measured during successive sessions of strength training, HF-NMES, or LF-NMES remained generally stable, while the NMES pulse amplitude or the strength training load increased significantly during the eight-week intervention period.
The median oxygen uptake during the baseline session of HF-NMES, LF-NMES or strength training ranged between 30 and 99% of the peak aerobic capacity measured during the cardiopulmonary exercise test, and was comparable with previous studies [
7,
14,
15]. The median oxygen uptake was 99% of the peak aerobic capacity in one subject who was characterized with very severe COPD (FEV
1: 17% pred) and a very decreased exercise capacity (peak load: 20% pred; VO
2 peak: 688 ml/min (26% pred)). At all measurement points, intervention-related peak VO
2 and V
E were significantly lower during NMES (LF and HF) compared with strength training. This is in line with previous studies measuring the metabolic load in patients with COPD during NMES or strength training [
14,
15]. However, these results are in contrast with the findings of a study in healthy male recreational athletes comparing one session of voluntary contractions with one session of HF-NMES (75 Hz) [
25]. Theurel and colleagues found that the average oxygen consumption and ventilation were significantly higher during HF-NMES compared with voluntary exercise [
25]. Besides the study design and subjects, an important difference with the present study is the training load [
25]. Theurel and colleagues used an average training load in strength training of 46% of the maximal voluntary contraction instead of 60-70% of the one-repetition maximum which is used in our study and what is recommended by the American College of Sports Medicine [
8].
The present study shows no changes over time in the metabolic load which is not in line with the study of Probst and colleagues [
7]. Probst and colleagues showed a significant increase in oxygen uptake and ventilation during a 12 wk program of leg press exercises [
7]. This could be attributable to a greater increase in the training load. However, the change in training load of leg press exercises was comparable to the present study.
The median increase in pulse amplitude during the study was 24 mA in HF-NMES and 37 mA in LF-NMES. The course in pulse amplitude is comparable with previous studies in severely disabled patients with COPD which respond to NMES [
16,
26]. The low metabolic load accompanied with acceptable low dyspnea and fatigue scores probably explains the applicability of these interventions in severely disabled and dyspneic patients, even during acute COPD exacerbations [
26‐
28]. This is also probably the reason that NMES can easily be applied in bed-bound individuals with chronic hypercapnic respiratory failure due to COPD who are receiving mechanical ventilation [
29] or critically ill patients in the intensive care unit [
30].
Because of the constant metabolic load in combination with stable symptom scores over time, it seems reasonable to hypothesize that the improvements in muscle function are at least partially due to intramuscular changes. Previously, it has been shown that type I and IIa fibers increased following LF-NMES [
31,
32] or HF-NMES [
33,
34]. Strength training generally results in increased levels of glycolytic enzymes [
35] and an increase in percentage and size of type II fibers [
36‐
39].
Obviously, this study has some limitations. First, the inclusion criteria of the
DICES trial limits the external validity of the present findings. Only COPD patients with an mMRC score of 3 and 4 in combination with muscle weakness were included. Secondly, the small sample size and selected patient characteristics for participation in the measurements with the Oxycon mobile may be an important reason for detecting no significant improvements in peak muscle strength in the strength training group and quadriceps muscle endurance in the LF-NMES group and the strength training group. Only patients without long-term oxygen therapy (LTOT) were eligible to participate due to the methodology used [
7], although LTOT patients are also likely to have benefit from these interventions. However, the equipment (Oxycon mobile, a portable metabolic system) is not able to measure oxygen uptake (VO
2) while breathing inspiratory O
2 fractions [
7]. In the DICES trial 51% of the patients used LTOT [
40]. It is unclear if the metabolic load might be different in LTOT patients. Moreover, the small sample size and the exclusion of LTOT patients may limit the external validity and broad applicability of these findings.
Conclusion
To conclude, the metabolic load and symptom scores for dyspnea, fatigue and muscle pain remain acceptable low over time with increasing training loads during HF-NMES, LF-NMES or strength training. For this reason, these interventions are recommended in severely dyspneic patients with COPD for improving their muscle function and exercise performance.
Acknowledgements
The present authors are grateful to the patients who volunteered in the DICES trial. The authors also thank Martijn Cuijpers and Martyna Renckens for their valuable help. This research was supported by grants from the Lung Foundation, Leusden, the Netherlands, Grant 3.4.09.024 and the Weijerhorst Foundation, Maastricht, the Netherlands.
Competing interests
The authors declare that they have no competing interests.
Authors’ contributions
Study concept and design: MJHS, EFMW and MAS; acquisition of data: MJHS, JMLD, AWV; analysis and interpretation of data: MJHS, FMEF and MAS; drafting the article: MJHS, FMEF and MAS; revising it critically for important intellectual content: all authors; final approval of the version to be published: all authors. MJHS had full access to all study data and takes responsibility for the integrity of the data and the accuracy of the data analysis.