Pulmonary Rehabilitation Using Regular Physical Exercise for the Management of Patients with Asthma

Background: Regular physical activity increases physical fi tness and lowers ventilation during mild and moderate exercise thereby reducing the likelihood of provoking exercise-induced asthma. Regular exercise may also reduce the perception of breathlessness through a number of mechanisms including strengthening respiratory muscles. Subjectively, many asthmatics report that they are symptomatically better when fi t, but results from trials have varied and have been diffi cult to compare because of different designs and training protocols.


Introduction
The diagnosis of asthma in majority of cases is based on patient symptoms of intermittent wheeze, chest tightness and response to bronchodilator medication. However, it is not as simple to defi ne asthma, mainly due to our poor understanding of its causes. Asthma is defi ned by three characteristics: Prevalence and severity of asthma is increasing and no one doubts that the cause of this increase is due to multitude of factors. However, there is a growing body of evidence that implicates lifestyle changes, specifi cally decreased physical activity as the single most important contributor to the increase in asthma prevalence and severity, seen globally.
There has been a steady decrease in the levels of physical activity of adults and children over the years and this decrease corresponds in time course to the increased prevalence of asthma [4][5][6]. Furthermore, most studies have shown that asthmatic subjects have a lower aerobic fi tness level than their non-asthmatic peers and that this limited fi tness level in asthmatic subjects seems not to be related to their degree of airway obstruction but rather to their decreased levels of habitual activity [7]. Exercise has long been recognized as a possible method of improving subjective and objective asthma indices even though there is the potential for exercise-induced asthma (EIA) while undertaking physical activity. However, it has been well documented that the incidence of EIA after proper medical (and pharmacological) prophylaxis is extremely low [8] and the benefi ts and safety of exercise in asthmatic subjects have been well demonstrated [7][8][9].
People with asthma have a unique response to exercise. In some, exercise can provoke an increase in airways resistance leading to EIA but regular exercise is also considered to be useful in the management of asthma, especially in children and adolescents [10]. However, the fear of inducing an episode of breathlessness inhibits many people from taking part in exercise. A low level of regular exercise leads to a low level of physical fi tness, so it is not surprising that a number of studies [7][8][9][10][11] have found that patients with asthma have lower cardiorespiratory fi tness than their peers although not every study has reported this fi nding [12].
Exercise programs have been designed for people with asthma with the aim of improving physical fi tness, neuromuscular coordination and self-confi dence. Anecdotally, many patients report that they are symptomatically better when fi t, but the physiological basis of this perceived benefi t has not been consistently shown in studies published to date. A possible mechanism is that an increase in regular exercise of suffi cient intensity to increase aerobic fi tness will raise the ventilatory threshold thereby lowering the minute ventilation during mild and moderate exercise. Consequently, breathlessness and the likelihood of provoking EIA will both be reduced. Exercise training may also reduce the perception of breathlessness through other mechanisms including strengthening of the respiratory muscles.

Objectives
This systematic review was undertaken to gain a better understanding of the effects of regular exercise on the health of patients with asthma. The objective was to assess evidence from high quality randomized controlled clinical trials (RCTs) of the effects of regular exercise in the management of asthma.

Types of studies and participants
Only studies that involved subjects with asthma who were randomized to regular exercise (intervention group) or no exercise (control group) were selected. Subjects had to be aged 7 years and older and their asthma had to be diagnosed by a physician or by the use of objective criteria -for example bronchodilator reversibility. Subjects with any degree of asthma severity were included. To qualify for inclusion regular exercise had to include whole body aerobic exercise for at least 20 minutes, two or more times a week, for a minimum of four weeks.

Literature search and study identifi cation
The following terms were used to search for studies: asthma* AND (work capacity OR physical activity OR training OR rehabilitation OR physical fi tness). The Cochrane Trials were reviewed to identify trials not captured by electronic and manual searches. Abstracts were reviewed without language restriction. When more data were required for the systematic review, authors of the study were contacted requesting additional information or clarifi cation. Two reviewers (EMM and FSFR) assessed the trials for inclusion by only looking at the methods section of each paper without reading the results of the study or conclusions [14]. Each reviewer independently applied written inclusion/exclusion criteria to the methods section of each study. Disagreement about inclusion of a study was resolved whenever possible by consensus and an independent person was consulted if disagreement persisted. All trials that appeared potentially relevant were assessed, and if appropriate were included in the review.

Data extraction, analysis and study quality assessment
The methodological quality of the included trials was assessed with particular emphasis on treatment allocation concealment, which was ranked using the following Cochrane studies were excluded (mostly due to not being an RCT) and the remaining 24 were included in this systematic review .
Corresponding authors of included studies were contacted to clarify areas of uncertainty. Most of the trials did not describe the method of randomisation and did not make any references to allocation concealment (blinding). All trials mentioned that subject allocation was carried out randomly.
Using the Cochrane approach for allocation concealment, the trials reporting method of allocation (using coded random numbers and drawing lots) were graded 'A' and all other trials included in this review were allocated a grade 'B' indicating that there was uncertainty as to the method of treatment allocation used by the authors in their trials. All outcomes were graded according to the quality of evidence obtained. This was based on the number and size of trial(s) contributing data towards any particular outcome. Table 1

Discussion
The clearest fi nding of this meta-analysis was that aerobic power (VO 2max ) signifi cantly increased with regular exercise.
This shows that the response of subjects with asthma to regular exercise is similar to that of healthy people [39] and therefore presumably the benefi ts of an increase in cardiorespiratory  fi tness are also accessible to them. In addition, VE max also showed an increase with regular exercise, although the overall result was not statistically signifi cant it is consistent with the observation that VO 2max increased. Further studies would likely confi rm the increase in VE max seen with regular exercise.
This review also showed convincingly that resting lung function does not change with regular exercise. This is not surprising since there is no obvious reason why regular exercise should improve PEFR, FEV 1 or FVC. It seems that any benefi ts of regular exercise in patients with asthma are unrelated to effects on lung function. On the other hand, evidence from this review suggests that regular exercise does not have any detrimental effect on lung function. This is reassuring for the continued promotion of exercise prescription by health professionals [40].
One study [32] reported both 6MWD and quality of life, both of which improved signifi cantly with regular exercise.
However, as only one study to date has reported these outcomes further studies are required to confi rm these fi ndings, prior to any conclusions being drawn on the benefi ts of regular exercise on these outcome measures.
Typically physical training has no effect or slightly reduces the maximum heart rate whereas maximum stroke volume, and thus maximum cardiac output improves [41,42]. In the studies that were included in this review [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35]  Although the solid diamond is situated on the right hand side of the line of no effect (favoring exercise/training indicating that regular exercise increases VEmax), it does cross the line of no effect implying that the overall effect in not statistically signifi cant.  or some other non-cardiac factor may have terminated the baseline tests before a true HR max was achieved. The higher heart rate following regular exercise may refl ect the ability of subjects to exercise for longer. An alternative explanation, which is improbable, is that the medication taken to prevent EIA caused the increased HR max . Inhaled beta agonists can raise heart rate above resting levels but prophylactic medication was not changed during the study period and there is no evidence that physical training alters the cardiac response to beta-agonists. The signifi cance of the effect of these agents on heart rate lies in their alteration of the workload-heart rate relationship and the possible consequences of this for exercise prescription based on heart rate. Unfortunately, there were no data available on a number of outcome measures of interest for this review, the list included exercise endurance (as distinct from VO 2max ), diary symptoms (other than frequency of wheeze), quality of life and bronchodilator use. This review has revealed an important gap in our knowledge about the effects of regular exercise in the management of asthma. There is, however, evidence from one study [43] which was excluded from this review, suggesting that regular exercise may improve these outcomes. The study by Cambach et al., [43], included subjects with asthma, but was not included in our review because they also received education about their disease and breathing retraining. This means that any benefi t could not be ascribed solely to regular physical exercise. Nonetheless, the intervention resulted in signifi cant improvements in exercise endurance time and the total score for the Chronic Respiratory Disease Questionnaire increased by 17 points compared to the control group. In subjects with COPD, pulmonary rehabilitation does not lead to an improvement in these parameters unless the subjects undertake regular exercise training [44] and the same may be true of asthma. A study from Brazil [45], allocated children to physical exercise or a control group. The study was not included in the review because the allocation of the subjects was not truly random, but it did fi nd that regular physical exercise led to signifi cant reductions in the use of both inhaled and oral steroids.
Although there are a number of pitfalls in conducting a systematic review (e.g. incomplete electronic databases, bias in selection of relevant studies and quality of included studies), we believe these were adequately dealt with the methodology employed. Hand searching of journals was used including reference check of all studies obtained, two reviewers independently reviewed all studies obtained for inclusion and the review was restricted to randomized controlled trials only, thus eliminating a substantial source of lower quality study data. Another potential weakness of this review is the small number of subjects included. However, the studies which measured VO 2max were not heterogeneous and all studies showed a similar effect which was statistically signifi cant (p < 0.00001).

Conclusion
This review has shown that aerobic power and ventilation improves following regular exercise in patients with asthma.
The evidence included in this review suggests that a minimum of 20 minutes of exercise, two or more times a week will lead to improvement in cardiorespiratory fi tness in patients with asthma providing the same level of benefi t afforded to people who do not have asthma. This appears to be a normal training effect and is not due to an improvement in resting lung function.
Examples of regular exercise that provided this benefi t included whole body aerobic exercise (for example, running or jogging, gymnastics, basketball, cycling and swimming).
What is also clear from the evidence included in this review is that regular exercise should not be limited due to perceived (and unsubstantiated) limitations of asthma. Fear of inducing an episode of breathlessness inhibits many asthmatic patients from taking part in exercise. However, we found no evidence of any detrimental effect on lung function, deterioration or worsening symptoms in asthmatic patients included in this review. There is no reason to withhold regular physical exercise in patients with asthma. Therefore, it is recommended that all patients with asthma should participate in regular exercise without the fear of asthma inhibiting their participation. This will not only improve asthma management but also provide associated general health benefi ts.
There still remains a need for further trials for assessment of the role of exercise in the management of asthma. It is particularly important to determine whether the improved exercise performance that follows regular exercise is translated into fewer symptoms and an improvement in quality of life.
Further studies are required to confi rm the improvements seen in this systematic review especially symptoms and quality of life.