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Number of Figures and Tables Figures: Tables: 6 1
Key Words 1. Neuromuscular electrical stimulation (NMES) 2. Chronic Obstructive Pulmonary Disease (COPD) 3. Triaxial accelerometer 4. Activity levels 5. Exercise capacity
Abstract Background Activity levels and exercise capacity are decreased in Chronic Obstructive Pulmonary disease (COPD) patients and Pulmonary Rehabilitation (PR) programs can be difficult, particularly for individuals with severe COPD, who experience incapacitating dyspnoea. Neuromuscular electrical stimulation (NMES) is a passive form of muscle stimulation which does not stress the ventilatory system. This study examined the effects of an 8 week NMES program on the activity levels and exercise capacity of individuals with moderate to severe COPD. Methods This single group cohort control study was performed with 8 participants of mean (SD) age 61.5 (6.16) years with moderate to severe COPD (FEV1/FVC range 0.35-0.79 and FEV1 range 35%-70% predicted). Participants were instructed to carry out NMES training 5 days a week for 8 weeks and were assessed before and after the intervention for activity levels, using a triaxial accelerometer and exercise capacity, as measured by the 6 minute walk test (6MWT). Activity levels were expressed as vector magnitude units per min (VMU/min) and percentage of time spent above 500 VMU. Results Activity levels failed to show statistically significant changes post intervention, but individual changes for VMU/min (p = 0.575) and time spent above 500 VMU (p = 0.327) indicated a trend towards improvement. A statistically and clinically significant improvement for 6MWT distances were observed (p = 0.012). No significant correlation between activity levels and exercise capacity was found. Conclusions NMES may be useful adjunct to PR for patients with moderate to severe COPD in order to improve exercise capacity and activity levels.
Abbreviation List ATS COPD HR Hz NMES PR RCT SaO SD SPSS VMU 6MWT American Thoracic Society Chronic Obstructive Pulmonary Disease Heart Rate Hertz Neuromuscular Electrical Stimulation Pulmonary Rehabilitation Randomised Controlled Trial Oxygen Saturation Standard Deviation Statistical Package for Social Sciences Vector Magnitude Unit Six Minute Walk Test
Introduction Chronic obstructive pulmonary disease (COPD) is a progressive disease characterised by airflow limitation which is not fully reversible.1 The global prevalence of COPD in adults over 40 years of age has been quantified as being 9-10%.2 The airflow limitation associated with COPD is caused by destruction of lung parenchyma and the increased airway resistance occurs due to inflammation and fibrosis, bronchospasm and mucus production.3 Apart from these pulmonary impairments, patients with COPD have various systemic manifestations including peripheral muscle dysfunction, right-sided heart failure, malnutrition and depression.3 Therefore, multiple mechanisms contribute to a limitation of physical activity and exercise participation in this pathology.
Exercise is defined as the planned, structured, and repetitive movement carried out to improve or maintain one or more aspects of physical fitness.4 Physical activity is the total amount of voluntary movement used to carry out daily functions.4 Programs aimed at increasing the ability to perform physical activity in individuals with COPD have traditionally included pulmonary rehabilitation (PR) exercise classes. A recent systematic review5 included 31 randomised controlled trials (RCTs) studying the effects of PR programs on COPD patients. This review found statistically significant improvements in functional exercise capacity as measured by timed walk tests with clinically and statistically significant improvements in several important domains of quality of life.
Previous research has indicated that an individual’s exercise capacity is not always limited owing to dyspnoea and that exercise tolerance is better correlated with leg muscle strength, mass and cross sectional area.6 Recently, neuromuscular electrical stimulation (NMES) has been investigated as a potential adjunct to COPD management with the aim of increasing lower limb muscle strength and function, thereby improving exercise capacity. Two recent systematic reviews1,3 have reported on five randomised controlled trials (RCT) with the aim of determining the effect of NMES on muscle function and exercise performance in patients with severe or very severe COPD. A meta analysis revealed that muscle function (isokinetic muscle torque measurements) increased significantly in three of the studies.3,7,8,9 A significant effect on walking distance compared to the control was also found following a metaanalysis of a different set of three studies3,7, 9, 10, with this distance being similar to the minimal clinically important distance of the 6-minute walk test.
In order to measure the benefits of either PR or NMES on functional activity, the ability to perform activities of daily living can be objectively assessed by measuring activity levels using a device such as an accelerometer.11 Precise, objective measurement of daily activity is especially pertinent when assessing a COPD population as small improvements can result in significant functional outcomes; therefore this study was conducted using a tri-axial motion sensor device which is more sensitive to low levels of activity.12 The reliability, validity and stability of triaxial accelerometers for walking and daily activity measurement in COPD patients has previously been established.12 The 6MWT has been described as the test of choice for measuring exercise capacity in a COPD population owing to its high external validity.13 A number of studies14-18 have previously demonstrated reliability of the
6MWT as an outcome measure for assessing aerobic fitness capacity among a COPD population. The aim of this investigation was to examine the activity levels and exercise capacity of a moderate to severe COPD population before and after an 8 week NMES training program.
Materials and Methods Participants Ethics approval was obtained by the ethics committee of the local hospital affiliated with the study. Participants were recruited from the hospital database, following a medical respiratory consultant review, according to inclusion criteria which dictated that the participants selected had a diagnosis of COPD based on clinical features, genotyping and a pulmonary function test, and were aged between 18-75 years. The screening process excluded patients with the following: a metabolic or hormonal disorder; metal implants or a cardiac pacemaker; inflammatory rheumatological disease; lower extremity trauma during the past 6 months; various pharmacological agents; any other condition or history that the investigator considered might increase the risk to the individual or interfere with the evaluation of data. Potential participants were provided with a patient information leaflet and an introductory familiarisation session with NMES, following which, informed consent was obtained by willing participants.
Study Design This study was a single group cohort control design. Participants underwent 3 testing sessions, of which one was a control period of two weeks (M1), one midway through
(M2) and following (M3) an eight week NMES intervention period. The NMES program was delivered using a specially designed hand held muscle stimulator (NT2010, BioMedical Research Ltd, Galway, Ireland). Impulses were delivered through four adhesive electrodes (polymer hydrogel) placed over the proximal and distal quadriceps and hamstring muscles on each leg (area per leg = 75 cm2). The electrodes were applied to the body via a neoprene garment that was wrapped around the leg and secured to the thigh with velcro straps. The first phase of the program (30 minutes) consisted of a 5 minute warm up at a non-tetanic frequency of 3 Hertz (Hz) and 25 minutes training at 4 Hz. This was followed immediately by the second phase (30 minutes) which involved increasing the impulses to a tetanic frequency of 19 Hz, and adding in concomitant voluntary leg extension and flexion movements for the final 5 minutes. Participants were instructed to train five days per week for a period of eight weeks and were encouraged to progressively increase the stimulation amplitude to a strong but tolerable intensity.
The authors confirm that the study objectives and procedures are honestly disclosed and that procedures were followed to an extent that convinces all authors that the results are valid and can be applied to a population similar to that enrolled in this study.
Measurements Daily physical activity output was recorded in vector magnitude units (VMU) using an RT3 accelerometer (Stayhealthy, Monrovia, California, USA). All participants were given an RT3 unit which they wore for at least five days within a two week window, between M1 and M2 and after M3, in order to measure activity outside the 7
intervention period. The pager-size RT3 was worn by attaching it to participants’ waist belts with a clip and removed during sleeping or showering. The RT3 tri-axial device measures physical activity in three dimensions: anteroposterior, vertical, and mediolateral.19 Each device was set to mode three, which samples data for all three axes every second for one minute, then stores the values in a buffer. The average for each axis is calculated and logged once a minute. The recorded data was then downloaded to a personal computer using a specific RT3 software package (Stayhealthy, Monrovia, California, USA) which generated a Microsoft Excel file of each participant’s activity data. The mean VMU per minute was calculated by dividing the total VMU by the number of minutes the device was worn. We did not remove time spent travelling in a motor vehicle as Steele et al (2003) have found no significant difference in mean VMU calculations between measurement periods.20 These variables were chosen for analysis based on previous studies20,21 which report VMU per minute as a more reliable measure of activity than energy expenditure. We also calculated activity above 500 VMU as these studies20,21 indicated that activity above this level can be classed as high level activity. We included data for which participants wore the RT3 at least 10 waking hours.19
Exercise capacity was measured using the 6MWT and a standardised testing protocol was used along a 30 metre (m) indoor course, as devised by the American Thoracic Society (ATS).22 Participants were instructed to walk maximally and were allowed to take rests as required. Measurements included walking distance, rest periods, dyspnoea (using the standardised BORG scale) and both oxygen saturation (SaO2) and heart rate (HR) using a portable pulse oximeter (BCI 3303 Oximeter, Smyth’s
Medical PM, Inc., WI, USA). Only standardised phrases of encouragement were used during the test. 22
Statistical Analysis All variables were analysed using the Wilcoxon signed rank test for repeated measures comparisons as the data set was considered to be non-parametric owing to its small size. The significance level was chosen as α = 0.05 for all tests. The Spearman test was carried out to examine any correlation between the VMW/min and the 6MWT data. All statistical analyses were carried out using the PASW Statistics software (Version 18, IBM, NY, USA).
The authors have reviewed the efficacy data, understand the statistical methods employed and confirm that the methods are clearly described and are a fair way to report the results.
Results 10 participants completed this study however 2 participant’s results were excluded due to insufficient time worn of the RT3. Results from 8 participants (4 male, 4 female) were analysed with mean age (±SD) 61.5 years (±6.16); mean height (±SD) 1.65m (±0.1); mean weight (±SD) 65.18kg (±16.05), mean Body Mass Index (±SD) 23.76 kg/m2 (±3.91), FEV1/FVC range 0.35-0.79 and FEV1 range 35%-70% predicted. Results for all variables analysed are outlined in Table 1.
No statistically significant difference between pre and post intervention for any of the activity variables was found [Table 1]. However, individual changes for VMU/min and time spent above 500 VMU show improvements for the majority of the participants [Figures 1 & 2 respectively]. Exercise Capacity A statistically and clinically significant improvement for 6MWT distances was observed post intervention (p=0.012) [Figure 3].
Relationship between Activity Levels and Exercise Capacity No statistically significant correlations were found between 6MWT distances and VMU/min before the intervention (r = 0.131; p = 0.757) [Figure 4], after the intervention (r = 0.621 p = 0.10) [Figure 5] or between the changes in 6MWT distances and VMU/min (r = -0.161; p = 0.70) [Figure 6].
Discussion The principal findings of this study were a non-significant trend towards improvement of activity levels as indicated by the majority of individuals and both a statistically and clinically significant change in exercise capacity measured by the 6MWT. No significant correlation between activity levels and exercise capacity was found.
To the authors knowledge this study is the first study to examine the effect of an NMES program on activity levels using an RT3 in a moderate to severe COPD population. Mador et al23 investigated activity levels (VMU/min and time spent above 250 and 500 VMU) using a triaxial accelerometer after PR found no significant changes, despite significant changes in exercise capacity and suggests the need for
behavioural change in order for activity levels to improve. Interestingly, Pitta et al24 did find improvements in activity levels when measurements were taken at 3 and 6 months after PR, possibly indicating that the behavioural change required for improving activity levels occurs over longer time periods.
In terms of the role of NMES in improving exercise capacity, a recent study10 performed with 17 patients with severe COPD found a statistically and clinically significant within group difference in 6MWT distances for the group receiving both NMES and usual rehabilitation (UR), but no significant changes between groups (NMES + UR compared to UR). Our study suggests that improvements in exercise capacity can be achieved with NMES alone for a moderate to severe COPD population. This is supported by Bourjeily-Habr et al9 who examined the effects of NMES on exercise capacity with a similar population (n=18), as measured by a shuttle walk test. Dal Corso et al8 found that tetanic (50Hz) NMES was ineffective in enhancing walking capacity as measured by the 6MWT in a group of moderately impaired COPD patients, but interestingly an increase in type II muscle fibres was found. These results indicate the need for further studies to investigate the relationships between different NMES settings and the various aspects of COPD impairments, activity limitations and participation restrictions.
The lack of significant correlation between the exercise capacity and activity level results has also been found by a recent study25 investigating the relationship between activity levels and exercise capacity after a PR program. Walker et al25 offer a possible explanation in that activity levels do not simply reflect exercise capacity, but other factors such as lifestyle. Further research is required to investigate the possible
behavioural issues which determine how much of the available exercise capacity an individual uses after rehabilitation.
Clinical Implications The impaired exercise performance associated with COPD is related to a decrease in health status and mortality, therefore the aim of PR programs is to improve exercise performance.25 An advantage of NMES is the absence of ventilatory stress during exercise, therefore the potential use as adjunct to PR programs for severely disabled patients with incapacitating dyspnoea.7 Nici et al26 state that improvement in exercise capacity does not necessarily translate into increases in activities of daily living. Walker et al25 suggest the usefulness of assessing activity limitation using as accelerometer which investigates levels of activity individuals actually achieve as opposed to what they are capable of doing. This study suggests that an NMES program, used as an adjunct to PR, can improve exercise capacity and possibility positively affect activity levels in the long term in individuals with moderate to severe COPD.
Limitations of the Study There is a possibility that lack of significance of results was due to type B error as there was inadequate statistical power due to the small number of participants. Another limitation of this study was the absence of a diary completed by participants identifying the time period the RT3 was worn. This would have been useful in order to select the most accurate and representative measure of that groups activity i.e. whether VMU/day or VMU/min is more appropriate.20 We analysed data from files
with at least 10 hours saved12 and this meant the data analysed was occasionally from non-consecutive days, but not necessarily days with more activity. However this meant that two participant’s data could not be included in the analysis and therefore a diary may also aid compliance of wearing the device, thereby increasing the amount of data generated.
In summary, an 8 week NMES program significantly improves exercise capacity of patients with moderate to severe COPD. A trend towards improvement was observed for activity levels despite not being statistically significant. Larger studies are required to make more definite conclusions regarding the role of NMES in treating patients with COPD. Assessment of potential effects on activity levels may require longer follow up periods.
References Figures and legends
Figure 1: Individual VMU/min Changes
0.00 1 2 3 4 5 6 7 8
Figure 1: Individual values of VMU/min measured before (pre) and after (post) the 8 week NMES program.
Figure 2: Individual % time (min) above 500 VMU
% time > 500 VMU
0 1 2 3 4 5 6 7 8
Figure 2: Individual values of percentage (%) time spent (minutes) above 500 VMU measured before (pre) and after (post) the 8 week NMES program.
Figure 3: Individual 6MWT Changes
6MWT distance (m)
0.00 1 2 3 4 5 6 7 8
Figure 3: Individual values of 6MWT distances (metres) measured before (pre) and after (post) the 8 week NMES program.
Figure 4: Relationship of 6MWT to Mean VMU/min week 0 600 500 Mean VMU/min 400 300 200 100 0 0 100 200 300 400 500 600 700 6MWT distance (m)
Figure 4: Relation between VMU/min and 6MWT measurements before the 8 week NMES program. The Spearman correlation coefficient was r = 0.131 (p = 0.757).
Figure 5: Relationship of 6MWT to Mean VMU/min Week 8
600 Mean VMU/min 500 400 300 200 100 0 0 100 200 300 400 500 600 700 6MWT distance (m)
Figure 5: Relation between VMU/min and 6MWT measurements after the 8 week NMES program. The Spearman correlation coefficient was r = 0.621 (p = 0.10).
Figure 6: Relation between changes in 6MWT distance and VMU/min after Week 8
Changes in 6MWT (m)
200 150 100 50 0 0.00
Changes in Mean VMU/min
Figure 6: Relation between changes in VMU/min and changes in 6MWT measurements after the 8 week NMES program. The Spearman correlation coefficient was r = -0.161 (p = 0.70).
Tables Table 1 Effects of NMES training on Activity Levels and Exercise Capacity Differenc e 28.79 40158.25 21.36 122.38 0.03 67.23 0.02 1.43 4.32 3.48 89.16
Variable Mean time worn (min) Mean VMU / day Mean VMU / min Mean TC / day Mean TC / min Mean AC / day Mean AC / min % AC/TC Mean % activity >500 VMU Mean % time (min) >500 VMU 6 MWT
Pre 842.17 186504.10 229.03 1376.52 1.65 515.14 0.62 37.42 45.34 12.06 425.49
Post 870.96 226662.35 250.38 1498.90 1.68 582.38 0.64 38.85 49.66 15.54 514.65
% Change 3.42 21.53 9.32 8.89 1.89 13.05 3.05 3.82 9.52 28.89 20.96
P Value 0.674 0.401 0.575 0.575 0.575 0.484 0.575 0.575 0.674 0.327 0.012
NMES = neuromuscular electrical stimulation; Pre = pre-intervention; Post = postintervention; Min = minutes; VMU= vector magnitude unit; TC = total calories; AC = activity calories; 6MWT = 6 minute walk test.
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