Value of supplemental interventions to enhance the effectiveness of physical exercise during respiratory rehabilitation in COPD patients. A systematic review

Abstract

Background: There is a controversy about the additional benefit of various supplemental interventions used in clinical practice to further enhance the effectiveness of respiratory rehabilitation in patients with Chronic obstructive pulmonary disease (COPD). The aim of this research was to assess randomised controlled trials (RCTs) testing the additional benefit of supplemental interventions during respiratory rehabilitation in COPD patients.

Methods: Systematic review with literature searches in six electronic databases, extensive hand-searching and contacting of authors. Two reviewers selected independently eligible RCTs, rated the methodological quality and extracted the data, which were analyzed considering the minimal important difference of patient-important outcomes where possible.

Findings: We identified 20 RCTs whereof 18 provided sufficient data for analysis. The methodological quality was low and sample sizes were too small for most trials to produce meaningful results (median total sample size = 28). Data from five trials showed that supplemental oxygen during exercise did not have clinically meaningful effects on health-related quality of life while improvements of exercise capacity may be even larger for patients exercising on room air. RCTs of adding assisted ventilation, nutritional supplements or a number of anabolically acting drugs do not provide sufficient evidence for or against the use any of these supplemental interventions.

Interpretation: There is insufficient evidence for most supplemental interventions during respiratory rehabilitation to estimate their additional value, partly due to methodological shortcomings of included RCTs. Current data do not suggest benefit from supplemental oxygen during exercise, although the methodological quality of included trials limits conclusions. To appropriately assess any of the various supplemental interventions used in clinical practice, pragmatic trials on respiratory rehabilitation of COPD patients need to consider methodological aspects as well as appropriate sample sizes.

Figure 1

Study flow from identification to final inclusion of studies.

Figure 2

Effect of supplemental oxygen on health-related quality of life. The forest plot shows the results from three trials comparing physical exercise with and without oxygen, separately for each domains of the Chronic Respiratory Questionnaire (CRQ). The x-axis represents the difference in change scores between study groups with negative values favoring exercise on room air and positive values favoring exercise with supplemental oxygen. A difference of 0 means that both study groups changed to the same amount. Boxes with 95% confidence intervals represent point estimates for the difference between the CRQ change scores (from baseline to follow-up) of the study groups. Dotted lines represent the minimal important difference of the CRQ (change of 0.5). On the right of the forest plot, point estimates for differences between groups and 95% confidence intervals are shown.

Figure 3

Effect of supplemental oxygen on exercise capacity. The forest plot shows the results from five trials comparing respiratory rehabilitation with and without oxygen. Walking tests, incremental and constant work rate exercise tests were used to assess the additional effect of supplemental oxygen during exercise. The x-axis represents the difference in change scores between study groups with negative values favoring exercise on room air and positive values favoring exercise with supplemental oxygen. A difference of 0 means that both study groups changed to the same amount. Boxes with 95% confidence intervals represent point estimates for the difference between the walking distance and maximum exercise capacity change scores (from baseline to follow-up) of the study groups. Dotted lines represent the minimal important difference of the six-minute walking distance (53 meters). On the right of the forest plot, point estimates for differences between groups and 95% confidence intervals are shown.

Figure 4

Sample size and interpretation of randomized controlled trials in respiratory rehabilitation. Forest plot with simulated results from two trials with varying sample size, in which the CRQ was used. Boxes with 95% confidence intervals represent point estimates for the difference between CRQ change scores (from baseline to follow-up) of the study groups. Dotted lines represent the minimal important difference of the CRQ (change of 0.5). Trial 1 shows the results from a typical explanatory trial comparing respiratory rehabilitation and no respiratory rehabilitation (usual care) with differences in CRQ change scores around 0.75[5]. Because of the large effect, trial results are interpretable also with imprecise results. Trial 2 shows the results from a pragmatic trial assessing the additional effect of a supplemental intervention (for example oxygen during exercise). The difference between groups is 0.3 and sample size must be large (80 per group) to produce results that are precise enough to allow interpretation.