The meta-analyses showed that respiratory rehabilitation after acute exacerbation of COPD reduced the risk for hospital admissions and mortality and led to large improvements of HRQL and exercise capacity.
Strengths of this systematic review include the extensive literature search, rigorous adherence to a predefined protocol and contacts to authors of the included trials who all provided additional information about their data. A limitation is the small number of patients included in the trials and methodological shortcomings that limit conclusions.
The effect of respiratory rehabilitation after acute exacerbation appears to be large. For HRQL and exercise capacity, the effects were well above the threshold for the minimal important difference for the CRQ (0.5 point difference [27
]), St. Georges Respiratory Questionnaire (4 points [28
]), SF-36 (5 points[29
]) and Six-minute walking distance (around 53 meters [30
]). In addition, the number of unplanned hospital admissions and mortality was reduced substantially. When one assumes that respiratory rehabilitation improves activity level in patients with COPD, it seems plausible that rehabilitation reduces readmission rate as inactivity has been shown to be a predictor of readmissions[9
Compared to respiratory rehabilitation in stable COPD patients [13
], its effects tend to be even larger after acute exacerbation. Several factors may contribute to this. First, as mentioned above, exacerbations lead to significant reductions in muscle function[14
] and quality of life [1
]. This initial deterioration may render patients more likely to improve from respiratory rehabilitation. Second, since patients were hospitalized, there may be a deficiency in self-management, or education. This may be partially targeted with the rehabilitation intervention, and patient education, as an additional part of multidisciplinary rehabilitation programs, may be of particular benefit to modify behavior. Indeed, a recent study showed impressive results of a patient management program including home exercises for COPD patients after acute exacerbation [31
]. The mean number of hospital admissions per patient was reduced from 1.6 to 0.9 in the year following a hospital admission due to acute exacerbation. It is well known from earlier studies that the recovery period is long even in patients who have no further exacerbations and that another exacerbation within 6 months limits recovery markedly [32
]. Our meta-analyses showed that respiratory rehabilitation during the recovery period is superior compared with usual care to improve prognosis and HRQL.
A word of caution is needed when interpreting the current analysis. A clear limitation of the trials is their relatively small sample size. All trials, in particular the trials reported by Behnke [20
] and Kirsten[22
] showed large effects of respiratory rehabilitation on HRQL and exercise capacity. Small trials tend to overestimate the effect of an intervention compared to large trials [33
]. This phenomenon can partly be attributed to a publication bias, that is, the fact that small trials are more likely to be published if they show statistically significant treatment effects [37
]. On the other hand, methodological shortcomings of small trials such as inadequate generation of the randomisation code, insufficient concealment of random allocation and lack of blinding contribute to discrepancies between the results of single large trials and pooled estimates based on small trials[35
]. In our systematic review, the trials had methodological limitations and it cannot be excluded that the estimates provided by the meta-analyses represent overestimations of the effect of respiratory rehabilitation after acute exacerbation.
Larger trials seem justified to challenge the data presented in this article. Such trials should assess the effect of respiratory rehabilitation on unplanned out- and inpatient care but also include data on patient-important outcomes such as HRQL. Conducting trials on respiratory rehabilitation after acute exacerbation is, however, challenging. First, recruitment of patients is difficult because not all of them may want to be randomly allocated to respiratory rehabilitation or usual care in a situation of poor health status. Second, one needs to take into consideration that exercise capacity is particularly low after acute exacerbations[14
] so that the exercise program should be designed carefully. Strength exercise and tolerable whole body exercise modalities such as interval exercise may be particularly suitable for these patients [38
]. Third, the definition of usual care raises a number of difficulties. Patients willing to participate in the trial are likely to have a preference for respiratory rehabilitation. If they are randomized to the control group, they might ask for respiratory rehabilitation at any time during the follow-up. Given the clear benefits of this intervention in stable patients, confirmed in meta-analyses [13
], patients should not be refrained from rehabilitative strategies. It would perhaps be ethically justifiable to conduct a large rehabilitation trial in places where respiratory rehabilitation is currently not readily available to the general patient. This appears to be the case in many countries including Switzerland [40
], the UK [41
] and Canada [42
]. These countries are just few examples of countries where the lack of access to rehabilitation has been pointed out as an important caveat in health care. In these places patients could be randomized to additional respiratory rehabilitation or standard treatment by general practitioners and respirologists because respiratory rehabilitation can be offered to a small proportion of COPD patients only. Alternatively relatively short term studies (3–6 months follow-up) could be conducted with re-admission as a primary end point. It has been shown that re-admission occurs often soon after discharge [43
]. Obviously, such studies could never address mortality as a primary end point, due to a lack of events. Whatever design investigators choose, a careful discussion of ethical and methodological issues is necessary before conducting large trials.
The present data show that respiratory rehabilitation has the potential to reduce the large COPD-related costs due to hospital admissions. It may not only reduce the number of acute exacerbations but also their severity. Patients may learn to notice imminent exacerbations and seek medical attention earlier leading to a shift from inpatient to the less costly outpatient treatment of acute exacerbations. The significant reduction in hospital readmissions is suggestive of a beneficial cost-benefit balance. However, larger trials should provide the final evidence base for formal cost analyses to test the hypothesis that respiratory rehabilitation after acute exacerbation is cost effective.
The data presented in this review are the first to show a survival benefit of respiratory rehabilitation in patients at risk. Although the results should be interpreted with caution, as mentioned above, this study provides the most solid evidence currently available that mortality is reduced. In summary, current evidence suggests that respiratory rehabilitation reduces unplanned hospital admissions and mortality and improves HRQL and exercise capacity when initiated immediately after acute exacerbations.