Participants

The 16 studies contributed data on 267 participants with COPD, of whom 150 (56%) received NMES. The mean age of the participants ranged from 56 to 76 years and 179 (67%) were men. The mean FEV₁ of the participants ranged from 15% to 50% of the predicted value in healthy adults. Common inclusion criteria related to a diagnosis of severe or very severe COPD and severe functional limitation due to dyspnoea. Common exclusion criteria were the presence of an implanted cardiac pacemaker or comorbidities that may have interfered with participation in the study. For further description of the participants included in the studies in these meta‐analyses, refer to the Characteristics of included studies table.

Intervention

The intervention was undertaken:

• at home by five studies (Akinlabi 2013; Maddocks 2016; Neder 2002; Tardif 2015; Vivodtzev 2012);

• with supervision as well as in the home by one study (Latimer 2013);

• at a pulmonary rehabilitation or outpatient centre by three studies (Bourjeily‐Habr 2002; Dang 2011; Tasdemir 2015);

• on a hospital ward then at home following discharge by one study (Giavedoni 2012);

• at an inpatient rehabilitation facility by two studies (Kucio 2016; Vivodtzev 2006);

• in a high dependency unit by one study (Zanotti 2003); and

• in the ICU by two studies (Abdellaoui 2011; Akar 2017).

One study did not state the location for the intervention (Vieira 2014), but it was likely that this study provided the intervention in the home.

The lower limb muscles stimulated were:

• bilateral quadriceps by eight studies (Akar 2017; Dang 2011; Maddocks 2016; Neder 2002; Tardif 2015; Tasdemir 2015; Vieira 2014; Vivodtzev 2006);

• bilateral quadriceps and the hamstrings by two studies (Abdellaoui 2011; Akinlabi 2013);

• bilateral quadriceps, hamstrings and calf muscles by one study (Bourjeily‐Habr 2002);

• bilateral quadriceps and calf muscles by two studies (Kucio 2016; Vivodtzev 2012); or

• bilateral quadriceps and gluteals by one study (Zanotti 2003).

Both studies that randomly assigned one leg to receive NMES and used the other leg to receive control stimulated only unilateral quadriceps (Giavedoni 2012; Latimer 2013).

Regarding intensity, when described (either in the paper or through communication with the authors), most studies reported that stimulation was set to the maximum current that was perceived to be tolerable (Abdellaoui 2011; Akar 2017; Dang 2011; Giavedoni 2012; Latimer 2013; Neder 2002; Tardif 2015; Tasdemir 2015; Vieira 2014; Vivodtzev 2006; Vivodtzev 2012). One study described setting an intensity that elicited a muscle contraction, and increasing by 5 mA per week (Bourjeily‐Habr 2002), and another study described setting the intensity to produce a muscular contraction equivalent to 15% to 25% of force generated during a maximum voluntary contraction (Maddocks 2016). Waveforms were most commonly symmetric or biphasic (or both) (Abdellaoui 2011; Akar 2017; Akinlabi 2013; Dang 2011; Giavedoni 2012; Kucio 2016; Latimer 2013; Neder 2002; Tasdemir 2015; Vieira 2014; Vivodtzev 2006; Vivodtzev 2012; Zanotti 2003). Regarding frequency, nine studies stimulated using 50 Hz (Akar 2017; Bourjeily‐Habr 2002; Giavedoni 2012; Latimer 2013; Maddocks 2016; Neder 2002; Tasdemir 2015; Vivodtzev 2012). Other studies reported using frequencies that ranged between 8 Hz and 45 Hz (Dang 2011), 10 Hz and 50 Hz (Akinlabi 2013), 5 Hz and 35 Hz (Vivodtzev 2006), 8 Hz and 35 Hz (Zanotti 2003), or 35 Hz (Abdellaoui 2011; Kucio 2016; Tardif 2015). Regarding duration, most studies stimulated once or twice a day for 30 to 60 minutes on four to seven days per week for four to eight weeks (Abdellaoui 2011; Latimer 2013; Maddocks 2016; Neder 2002; Tardif 2015; Vieira 2014; Vivodtzev 2006; Vivodtzev 2012; Zanotti 2003).

Exercise programmes

For the four studies that were conducted in an ICU, high dependency area or inpatient rehabilitation facility, and compared the effect of NMES plus conventional exercise training versus conventional exercise training alone, exercise training comprised active movement, active‐assisted movement or passive range of motion if the participant was unable to perform active movement through full range (Abdellaoui 2011; Akar 2017; Vivodtzev 2006; Zanotti 2003). One study described a programme that also facilitated participants to walk on a treadmill and use light arm weights once able (Vivodtzev 2006). The one study that was conducted in participants who were hospitalised (but clinically stable), and compared the effect of NMES plus conventional exercise training versus conventional exercise training alone, offered breathing exercises together with treadmill walking and resistance exercises (Kucio 2016). For the four studies that were conducted at home or in a rehabilitation or outpatient centre, and compared the effect of NMES plus conventional exercise training versus conventional exercise training alone, exercise training was described as low intensity symptom‐limited exercise (Akinlabi 2013), or usual exercise training/pulmonary rehabilitation (Dang 2011; Tardif 2015; Tasdemir 2015).

Outcome measures

Regarding the assessment of peripheral muscle force, two studies assessed quadriceps force used an isokinetic chair‐mounted dynamometer (Bourjeily‐Habr 2002; Neder 2002), and six studies assessed quadriceps force using a strain gauge or digital load cell that was fixed to a chair or rig (Dang 2011; Giavedoni 2012; Latimer 2013; Maddocks 2016; Vivodtzev 2006; Vivodtzev 2012). For the one study that measured quadriceps force during both a maximal voluntary isometric contraction and as twitch force in response to supramaximal femoral nerve stimulation (Maddocks 2016), the former, but not the latter measure was used in a meta‐analysis. One study assessed quadriceps force using a device that appeared to be hanging scale (Abdellaoui 2011), and one measured the one‐repetition maximum (Tasdemir 2015). Two studies described performing manual muscle testing of the 'peripheral muscles' or 'lower extremity muscles,' and although it was not clear which muscles were included in this assessment, it seemed likely that this assessment would have included quadriceps as both studies stimulated this muscle (Akar 2017; Zanotti 2003).

Three studies reported the assessment of quadriceps endurance. One study described a fatigue index in which high values were indicative of worse endurance (Neder 2002). Two studies described muscle endurance as time to fatigue during a given task, in which high values were indicative of better endurance (Dang 2011; Vivodtzev 2012). However, one study provided incomplete data on this outcome (Dang 2011), and therefore neither a meta‐analysis nor narrative discussion of these data was possible. One study reported collecting measures of quadriceps endurance, but these measures were of functional performance, such as squat tests in which the participant was required to perform as many squats as possible in 30 seconds (Tasdemir 2015). Therefore, neither a meta‐analysis nor narrative discussion of these data were undertaken.

Five studies reported the assessment of thigh muscle size (Latimer 2013; Maddocks 2016; Vieira 2014; Vivodtzev 2006; Vivodtzev 2012). Maddocks 2016 obtained measures of rectus femoris cross‐sectional area by ultrasound and Vivodtzev 2012 obtained measures of mid‐thigh cross‐sectional area by computed tomography. Latimer 2013 obtained measures of thigh muscle mass by dual‐energy X‐ray absorptiometry (DEXA) and Vieira 2014 and Vivodtzev 2006 obtained measures of thigh circumference via anthropometry.

We collected mortality data as part of our assessment of serious adverse events. Twelve studies contributed mortality data (Abdellaoui 2011; Akinlabi 2013; Bourjeily‐Habr 2002; Dang 2011; Kucio 2016; Maddocks 2016; Neder 2002; Tardif 2015; Tasdemir 2015; Vieira 2014; Vivodtzev 2012; Zanotti 2003 ). For minor adverse events related specifically to the stimulation itself, all but five studies reported data (Akar 2017; Giavedoni 2012; Kucio 2016; Vieira 2014; Vivodtzev 2006).

The most common measure of assessment of exercise capacity was the 6MWD (Abdellaoui 2011; Akinlabi 2013; Dang 2011; Kucio 2016; Maddocks 2016; Tardif 2015; Vieira 2014; Vivodtzev 2006). Other field‐based walking tests were less common, such as the incremental shuttle walk test (ISWT) (Bourjeily‐Habr 2002; Tasdemir 2015), and ESWT (Tasdemir 2015; Vivodtzev 2012). Measures of exercise capacity also comprised peak rate oxygen consumption (VO_2peak) expressed as litres per minute (Neder 2002; Vivodtzev 2012), millilitres per minute (Bourjeily‐Habr 2002; Vieira 2014), or millilitres per kilogram per minute (Dang 2011). However, one study that reported on VO_2peak could not be included in the meta‐analyses (due to differences in the units of measurement) and narrative discussion was not possible as the data that were provided were incomplete (Dang 2011). Four studies expressed exercise capacity as peak power (Bourjeily‐Habr 2002; Dang 2011; Neder 2002; Tardif 2015), and two studies expressed time to symptom limitation cycling at a constant submaximal intensity (Neder 2002; Vieira 2014). However, two studies that reported peak power and compared NMES plus conventional exercise training with conventional exercise training alone provided incomplete data (Dang 2011; Tardif 2015). Therefore, neither a meta‐analysis nor a narrative discussion of these data was possible (Dang 2011; Tardif 2015).

Two studies reported functional performance giving the time required for the participants in both groups to achieve specific mobility milestones, such as sitting out of bed (Akar 2017; Zanotti 2003).

Six studies assessed symptoms and reported dyspnoea at the end of an exercise test or at iso‐time during an exercise test using the Borg 0 to 10 scale (Maddocks 2016; Neder 2002Tasdemir 2015; Vieira 2014; Vivodtzev 2006; Vivodtzev 2012). Five studies reported leg fatigue or leg effort at the end of an exercise test using the Borg 0 to 10 scale (Maddocks 2016; Neder 2002; Tasdemir 2015; Vieira 2014; Vivodtzev 2012), and one study reported general fatigue during daily life using the Fatigue Severity Scale (Tasdemir 2015). However, Maddocks 2016 reported dyspnoea and leg fatigue on completion of the 6MWT performed at baseline only (i.e. no postintervention period data reported) and therefore neither a meta‐analysis nor narrative discussion of these data was possible. Three studies reported dyspnoea during daily life using the dyspnoea domain of the Chronic Respiratory Disease Questionnaire (CRDQ) (Dang 2011; Maddocks 2016; Neder 2002), and one study used the Maugeri Foundation Respiratory Failure questionnaire (MRF‐28) (Vivodtzev 2006). However, one study that reported dyspnoea during daily life using the CRDQ presented these data at baseline only (i.e. no postintervention period data reported) and therefore neither a meta‐analysis nor narrative discussion of these data was possible (Maddocks 2016). Although two studies that compared NMES plus conventional exercise training with conventional exercise training alone reported dyspnoea during daily life (Dang 2011; Vivodtzev 2006), Vivodtzev 2006 did not report data in a way that could be included in a meta‐analysis and therefore a meta‐analysis for this outcome was not possible. Grades from the modified Medical Research Council Scale were not included in the assessment of dyspnoea, as this scale assesses functional limitation resulting from dyspnoea rather than the severity of dyspnoea itself.

Regarding the assessment of HRQoL, five studies used the St George's Respiratory Questionnaire (SGRQ) in which high values represented worse HRQoL (Akinlabi 2013; Maddocks 2016; Tardif 2015; Tasdemir 2015; Vieira 2014), three used the CRDQ in which high values represented better HRQoL (Dang 2011; Maddocks 2016; Neder 2002), and one used the MRF‐28 in which high values represented worse HRQoL (Vivodtzev 2006). However, one study did not provide data on total CRDQ scores and therefore neither a meta‐analysis nor narrative discussion of these data was possible (Neder 2002). As one study reported HRQoL using both the SGRQ and CRDQ, we used only data collected using the SGRQ in the meta‐analysis (Maddocks 2016).

Peripheral muscle force

Six studies compared NMES with usual care and reported on measures of quadriceps muscle force (Bourjeily‐Habr 2002; Giavedoni 2012; Latimer 2013; Maddocks 2016; Neder 2002; Vivodtzev 2012). Meta‐analysis of these studies demonstrated a significant effect, however, the CIs were wide (SMD 0.34, 95% CI 0.02 to 0.65; participants = 159; low‐quality evidence; Analysis 1.1; Figure 4). One study included in this meta‐analysis also assessed quadriceps twitch force elicited in response to stimulation of the femoral nerve and demonstrated no significant between‐group difference (Maddocks 2016). As the meta‐analysis included the two studies that randomly assigned one leg to receive NMES and the other leg to receive control (Giavedoni 2012; Latimer 2013), we conducted a sensitivity analysis that excluded these studies. For this sensitivity analysis, the SMD from the remaining four studies was 0.39 (95% CI ‐0.00 to 0.78) (Bourjeily‐Habr 2002; Maddocks 2016; Neder 2002; Vivodtzev 2012). Regarding subgroup analyses based on whether or not the participants were clinically stable at the time of recruitment, of the six studies that compared NMES with usual care, only one recruited participants during a period of exacerbation (Giavedoni 2012). Therefore, rather than performing subgroup analyses based on the clinical stability of participants at the time of recruitment, we undertook a sensitivity analysis that excluded the study that recruited people during a period of exacerbation. The SMD for this subgroup analysis that included only participants with COPD who recruited during a period of clinical stability was 0.34 (95% CI 0.00 to 0.68) (Bourjeily‐Habr 2002; Latimer 2013; Maddocks 2016; Neder 2002; Vivodtzev 2012).

Figure 4

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Forest plot of comparison: 1 Neuromuscular electrostimulation (NMES) versus usual care, outcome: 1.1 Peripheral muscle force.

One study reported a significant increase in hamstring force following NMES that was greater than any seen in the control group (Bourjeily‐Habr 2002). One additional study, published as an abstract with a small number of participants, that could not be included in the meta‐analysis, compared the effect of two NMES training protocols on quadriceps force (Dolmage 2016). This study suggested that the gains in muscle force may be greater following an NMES training programme designed to increase strength (i.e. high‐frequency, low‐duty cycle) when compared with an NMES training protocol designed to increase endurance (i.e. low ‐frequency, high‐duty cycle) (Dolmage 2016). There were insufficient studies to undertake planned subgroup analyses based on stimulation frequency, disease severity, method used to assess muscle force or number of training sessions.

Six studies compared NMES plus conventional exercise training with conventional exercise training alone and reported measures of quadriceps muscle force (Abdellaoui 2011; Dang 2011; Tasdemir 2015; Vivodtzev 2006), or used manual muscle testing to report on peripheral muscle strength (which was likely to include measures of quadriceps muscle force) (Akar 2017; Zanotti 2003). However, data from two studies reported data as median and interquartile range or minimum and maximum values, and therefore were not included in the meta‐analyses (Abdellaoui 2011; Akar 2017). Meta‐analysis of the remaining four studies produced an uncertain effect with an SMD of 0.47 (95% CI ‐0.10 to 1.04; participants = 84; very low‐quality evidence; Analysis 2.1; Figure 5). Regarding the subgroup analyses based on whether or not the method used to measure muscle force was deemed to be robust, two studies used robust methods (Dang 2011; Vivodtzev 2006), and the SMD for these studies was 0.44 (95% CI ‐0.25 to 1.14; participants = 33) and two studies used less robust methods (Tasdemir 2015; Zanotti 2003), and the SMD for these studies was 0.53 (95% CI ‐0.74 to 1.80; participants = 51; Analysis 2.2; Figure 6). The SMD for these subgroups was not different (Chi² = 0.01; P = 0.91). Only the analysis for muscle force assessed using less robust methods had high statistical heterogeneity (I² = 79%). Regarding subgroup analyses based on the minimum number of training sessions, of the four studies, only one completed fewer than 10 sessions in four weeks (Tasdemir 2015). Therefore, rather than performing a subgroup analysis based on the minimum number of training sessions, we undertook a sensitivity analysis that excluded the study where participants completed fewer than 10 sessions over four weeks. For this sensitivity analysis, the SMD from the remaining three studies was 0.73 (95% CI 0.19 to 1.28; participants = 57; Analysis 2.3) (Dang 2011; Vivodtzev 2006; Zanotti 2003). One study also undertook manual muscle testing of the upper limbs; however, it was unclear whether the improvement in this measure was different between the groups (Akar 2017). There were insufficient studies to undertake planned subgroup analyses based on clinical stability at the time of recruitment, stimulation frequency or disease severity.

Figure 5

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Forest plot of comparison: 2 Neuromuscular electrostimulation (NMES) plus exercise versus exercise only, outcome: 2.1 Peripheral muscle force.

Figure 6

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Forest plot of comparison: 2 Neuromuscular electrostimulation (NMES) plus exercise versus exercise only, outcome: 2.2 Peripheral muscle force with subgroups based on methods used to assess muscle force.

Peripheral muscle endurance/fatigability

Two studies compared NMES with usual care, and reported on measures of endurance of the quadriceps (Neder 2002; Vivodtzev 2012). Meta‐analysis of these studies demonstrated a significant effect in favour of NMES (SMD 1.36, 95% CI 0.59 to 2.12; participants = 35; low‐quality evidence; Analysis 1.2). One additional study, published as an abstract with a small numbers of participants, that could not be included in the meta‐analysis, compared the effect of two NMES training protocols on quadriceps endurance (Dolmage 2016). This study suggested that the gains in endurance may have been greater following an NMES training programme designed to increase endurance (i.e. low‐frequency, high‐duty cycle) when compared with an NMES training protocol designed the increase strength (i.e. high‐frequency, low‐duty cycle) (Dolmage 2016). There were insufficient studies to undertake planned subgroup analyses based on clinical stability at the time of recruitment, stimulation frequency, disease severity or the number of training sessions.

No studies compared NMES plus conventional exercise training with conventional exercise training alone, and reported on measures of quadriceps endurance.

Thigh muscle size

Four studies compared NMES with usual care, and reported on measures of thigh muscle size (Latimer 2013; Maddocks 2016; Vieira 2014; Vivodtzev 2012). Meta‐analysis of these studies produced an uncertain effect (SMD 0.25, 95% CI ‐0.11 to 0.61; participants = 124; low‐quality evidence; Analysis 1.3). As this analysis included the one study that randomly assigned one leg to receive NMES and the other leg to receive control (Latimer 2013), we conducted a sensitivity analysis that excluded this study. For this sensitivity analysis, the SMD from the remaining three studies was 0.32 (95% CI ‐0.09 to 0.74; participants = 92) (Maddocks 2016; Vieira 2014; Vivodtzev 2012). There were insufficient studies to undertake planned subgroup analyses based on clinical stability of the participants at the time of recruitment, stimulation frequency, disease severity or the number of training sessions.

The one study that compared NMES plus conventional exercise training with conventional exercise training alone, and reported on measures of thigh circumference demonstrated no between‐group difference in this outcome (Vivodtzev 2006).

Serious adverse events

Although six studies compared NMES with usual care, and reported data on mortality (Bourjeily‐Habr 2002; Latimer 2013; Maddocks 2016; Neder 2002; Vieira 2014; Vivodtzev 2012), we excluded data from the study that randomly assigned one leg to receive NMES and the other leg to receive control (Latimer 2013). Meta‐analysis of the remaining five studies demonstrated no risk difference between groups (RD ‐0.02, 95% CI ‐0.08 to 0.05; participants = 131; Analysis 1.4). These studies were undertaken in participants who were clinically stable at the time of recruitment.

Seven studies compared NMES plus conventional exercise training with conventional exercise training alone, and provided information on mortality (Abdellaoui 2011; Akinlabi 2013; Dang 2011; Kucio 2016; Tardif 2015; Tasdemir 2015; Zanotti 2003). Meta‐analysis of these studies demonstrated no risk difference between groups (RD 0.00, 95% CI ‐0.05 to 0.05; participants = 183; Analysis 2.4).

Exercise capacity

Two studies compared NMES with usual care, and reported on measures of 6MWD (Maddocks 2016; Vieira 2014). Meta‐analysis of these studies demonstrated a significant effect (MD 39.26 m, 95% CI 16.31 to 62.22; low‐quality evidence; participants = 72; Analysis 1.5). Both studies were undertaken in participants who were clinically stable at the time of recruitment. There were insufficient studies to undertake planned subgroup analyses for the effect on 6MWD based on clinical stability of the participants at the time of recruitment, stimulation frequency, disease severity or the number of training sessions. The one study that reported on measures of incremental shuttle walk distance (ISWD) demonstrated a significant between‐group increase in favour of NMES (Bourjeily‐Habr 2002). Four studies reported on measures of VO_2peak (Bourjeily‐Habr 2002; Neder 2002; Vieira 2014; Vivodtzev 2012), and meta‐analysis of these studies demonstrated a significant effect in favour of NMES (MD 0.10 L/min, 95% CI 0.00 to 0.19; participants = 73; Analysis 1.6). These studies were undertaken in participants who were clinically stable at the time of recruitment. There were insufficient studies to undertake planned subgroup analyses for the effect on VO_2peak based on clinical stability of the participants at the time of recruitment, stimulation frequency, disease severity or the number of training sessions. Two studies reported on measures of peak power (Bourjeily‐Habr 2002; Neder 2002), and meta‐analysis of these studies produced an uncertain effect (MD 5.77 W, 95% CI ‐6.00 to 17.53; participants = 33; Analysis 1.7). Both studies were undertaken in participants who were clinically stable at the time of recruitment. There were insufficient studies to undertake planned subgroup analyses for the effect on peak power based on clinical stability of the participants at the time of recruitment, stimulation frequency, disease severity or the number of training sessions. Three studies reported on endurance time during a constant power test on a bike (Neder 2002; Vieira 2014), or on the ESWT (Vivodtzev 2012), and meta‐analysis of these studies demonstrated a significant effect (MD 3.62 minutes, 95% CI 2.33 to 4.91; participants = 55; Analysis 1.8). These studies were undertaken in participants who were clinically stable at the time of recruitment. There were insufficient studies to undertake planned subgroup analyses for the effect on endurance time based on clinical stability of the participants at the time of recruitment, stimulation frequency, disease severity or the number of training sessions.

Six studies compared NMES plus conventional exercise training with conventional exercise training alone, and reported on measures of 6MWD (Abdellaoui 2011; Akinlabi 2013; Dang 2011; Kucio 2016; Tardif 2015; Vivodtzev 2006). Meta‐analysis of these studies demonstrated a significant effect (MD 25.87 m, 95% CI 1.06 to 50.69; participants = 138; very low‐quality evidence; Analysis 2.5). Regarding subgroup analyses based on whether or not the participants were clinically stable at the time of recruitment, of the six studies that compared NMES plus conventional exercise training with conventional exercise training alone, only one recruited participants during a period of exacerbation (Abdellaoui 2011). Therefore, rather than perform a subgroup analysis based on clinical stability, we undertook a sensitivity analysis that excluded the study that recruited participants during a period of exacerbation. The MD for this meta‐analysis that included only people with COPD who were clinically stable at the time of recruitment was 17.80 m (95% CI ‐6.81 to 42.41; participants = 123) (Akinlabi 2013; Dang 2011; Kucio 2016; Tardif 2015; Vivodtzev 2006). Regarding subgroup analyses based on the minimum number of training sessions, of the six studies, only one completed fewer than 10 sessions in four weeks (Akinlabi 2013). Therefore, rather than performing a subgroup analysis based on the minimum number of training sessions, we undertook a sensitivity analysis that excluded the study in which participants completed fewer than 10 sessions over four weeks. For this sensitivity analysis, the MD from the remaining five studies was 25.86 m (95% CI ‐3.17 to 54.89; participants = 128; Analysis 2.6) (Abdellaoui 2011; Dang 2011; Kucio 2016; Tardif 2015; Vivodtzev 2006). There were insufficient studies to undertake planned subgroup analyses for the effect on 6MWD based on stimulation frequency or disease severity. The one study that reported on measures of exercise capacity expressed as ISWD and performance on the ESWT demonstrated a significant between‐group difference in favour of NMES plus conventional exercise training on ISWD, but not performance on the ESWT (expressed in seconds) (Tasdemir 2015).

Functional performance

None of the studies comparing NMES with usual care reported on measures of functional performance.

Two studies compared NMES plus conventional exercise training with conventional exercise training alone (Akar 2017; Zanotti 2003), and reported on the same measure of functional performance; number of days between randomisation and when the participant first transferred out of bed. Meta‐analysis of these studies demonstrated a significant effect on when the participant first transferred out of bed in favour of NMES plus conventional exercise training (MD ‐4.98 days, 95% CI ‐8.55 to ‐1.41; participants = 44; very low‐quality evidence; Analysis 2.7). Although both studies included in this meta‐analysis reported the same direction of effect, this analysis had high statistical heterogeneity (I² = 60%). One of these studies was undertaken in participants who were clinically stable at the time of recruitment (Zanotti 2003), and the other was undertaken in participants who were experiencing an exacerbation at the time of recruitment (Akar 2017).

Symptoms of dyspnoea and fatigue

Three studies compared NMES with usual care, and reported on measures of dyspnoea reported on completion of a symptom‐limited exercise test (Neder 2002; Vieira 2014; Vivodtzev 2012). Meta‐analysis of these studies produced an uncertain effect (MD ‐1.03 units, 95% CI ‐2.13 to 0.06; participants = 55; very low‐quality evidence; Analysis 1.9). This analysis had high statistical heterogeneity (I² = 59%). All studies were undertaken in participants who were clinically stable at the time of recruitment. The one study that reported on dyspnoea at iso‐time during the ESWT demonstrated no between‐group difference (Vivodtzev 2012). The one study that reported on measures of dyspnoea during daily life using the CRDQ demonstrated a significant between‐group difference in favour of NMES (Neder 2002). Three studies compared NMES with usual care, and reported on measures of leg fatigue reported on completion of an exercise test (Neder 2002; Vieira 2014; Vivodtzev 2006). Meta‐analysis of these studies demonstrated a significant effect (MD ‐1.12 units, 95% CI ‐1.81 to ‐0.43; participants = 55; Analysis 1.10). These studies were undertaken in participants who were clinically stable at the time of recruitment.

Two studies compared NMES plus conventional exercise training with conventional exercise training alone (Tasdemir 2015; Vivodtzev 2006), and reported on measures of dyspnoea reported on completion of an exercise test. Meta‐analysis of these studies produced an uncertain effect (MD ‐0.44 units, 95% CI ‐2.27 to 1.38; participants = 44; very low‐quality evidence; Analysis 2.8). This analysis had high statistical heterogeneity (I² = 69%). Both studies were undertaken in participants who were clinically stable at the time of recruitment. Two studies compared NMES plus conventional exercise training with conventional exercise training alone on measures of dyspnoea during daily life (Dang 2011; Vivodtzev 2006). However, for one study, it was unclear whether the improvement in this measure was different between the groups (Dang 2011), and the between‐group difference reported in the other study was of borderline significance (P = 0.05) (Vivodtzev 2006). The one study that compared NMES plus conventional exercise training with conventional exercise training alone and reported on measures of leg fatigue on completion of an exercise test and general fatigue during daily life using the Fatigue Severity Scale demonstrated no between‐group differences in either of these outcomes (Tasdemir 2015).

Health‐related quality of life

Two studies compared NMES with usual care, and reported on measures of HRQoL measured using the SGRQ (Maddocks 2016; Vieira 2014). Meta‐analysis of these studies produced an uncertain effect (MD ‐4.12 %points, 95% CI ‐12.60 to 4.35; participants = 72; very low‐quality evidence; Analysis 1.11). This analysis had high statistical heterogeneity (I² = 74%). One of these studies also demonstrated no between‐group difference in HRQoL assessed using the CRDQ (Maddocks 2016). These studies were undertaken in participants who were clinically stable at the time of recruitment.

Of the five studies that compared NMES plus conventional exercise training with conventional exercise training alone and reported on measures of HRQoL, three used the SGRQ (Akinlabi 2013; Tardif 2015; Tasdemir 2015), one used the CRDQ (Dang 2011), and one used the MRF‐28 (Vivodtzev 2006). Data from one study was reported as median and minimum and maximum and therefore were not included in the meta‐analysis (Tasdemir 2015). Meta‐analysis of the remaining four studies produced an uncertain effect (SMD ‐0.56, 95% CI ‐1.27 to 0.15; participants = 95; very low‐quality evidence; Analysis 2.9). This analysis had high statistical heterogeneity (I² = 55%). These studies were undertaken in participants who were clinically stable at the time of recruitment.

Minor adverse events

Five studies compared NMES with usual care, and reported data on minor adverse events related to the intervention (Bourjeily‐Habr 2002; Latimer 2013; Maddocks 2016; Neder 2002; Vivodtzev 2012). Meta‐analysis of these studies demonstrated no risk difference between groups; however, there was inconsistency between individual studies (RD 0.00, 95% CI ‐0.07 to 0.07; participants = 139; low‐quality evidence; Analysis 1.12).

Six studies compared NMES plus conventional exercise training with conventional exercise training alone and reported data on minor adverse events related to the intervention (Abdellaoui 2011; Akinlabi 2013; Dang 2011; Tardif 2015; Tasdemir 2015; Zanotti 2003). Meta‐analysis of these studies demonstrated no risk difference between groups (RD 0.00, 95% CI ‐0.05 to 0.05; participants = 144; low‐quality evidence; Analysis 2.10). Of the six studies that compared NMES plus conventional exercise training with conventional exercise training alone, only one recruited participants during a period of exacerbation (Abdellaoui 2011).