Specific situations at assessment

Frequency of supervised pulmonary rehabilitation sessions

• Pulmonary rehabilitation programmes should be a minimum of twice-weekly supervised sessions. (Grade D)

• In line with published pulmonary rehabilitation studies and the outcomes they demonstrate, a third session of prescribed exercise is recommended. This can be performed unsupervised. (√)

• Encouragement of regular physical activity five times a week for 30 min each time is encouraged in line with standard healthy living advice. (√)

Duration of pulmonary rehabilitation programmes

• Pulmonary rehabilitation programmes of 6–12 weeks are recommended. (Grade A)

• Pulmonary rehabilitation programmes including the attendance at a minimum of 12 supervised sessions are recommended, although individual patients can gain some benefit from fewer sessions. (Grade A)

• If training for less than 6 weeks is considered, this should be individualised and objective/subjective measures of benefit in place before patients graduate. For some individuals, reassessment at 4 weeks and graduation to independent gym training is a feasible possibility. (√)

Rolling or cohort programmes

• Cohort or rolling programmes of pulmonary rehabilitation are both acceptable forms of delivery depending on local considerations. (Grade D)

Nature of training

• To ensure strength and endurance benefits in patients with COPD, a combination of progressive muscle resistance and aerobic training should be delivered during a pulmonary rehabilitation programme. (Grade B)

• Relevant expertise is required to deliver resistance training. (√)

• Patients should be capable of continuing effective resistance training once supervised sessions have ended. The supervising rehabilitation therapist should ensure that patients are able and willing to continue with unsupervised resistance training. (√)

• Prescribing of progressive strength exercise should be individualised for each patient, taking into consideration the initial health screening and any increase in risk from comorbidities. (√)

Interval and continuous aerobic training

• Interval and continuous training can be applied safely and effectively within the context of pulmonary rehabilitation to patients with COPD. (Grade A)

• The choice of interval or continuous training will be down to the patient and/or therapist preference. (√)

• In clinical practice, interval training may require a higher therapist to patient ratio to ensure adequate work rate and rest intervals are achieved compared with continuous training. (√)

Goal setting in pulmonary rehabilitation

• Generic exercise training as opposed to individually targeted exercise training is recommended for pulmonary rehabilitation. (Grade D)

• While generic exercise training is recommended as opposed to an individually targeted exercise programme, the prescription of exercise is individualised to provide correct intensity. (√)

• Besides the exercise elements of pulmonary rehabilitation, healthcare professionals commonly use goal setting to address specific hurdles. Given the personalised nature of this intervention to a patient's needs, evidence is difficult to quantify. (√)

• The term ‘goal setting’ may require discussion with the patient. (√)

Supervision in pulmonary rehabilitation

• A supervised pulmonary rehabilitation programme is recommended for patients with COPD. (Grade A)

• If considering a structured home-based rehabilitation programme for patients with COPD, the following important factors need careful consideration: mechanisms to offer remote support and/or supervision, provision of home exercise equipment and patient selection. (Grade B)

• There would be some benefit to increasing the options for pulmonary rehabilitation available to individuals with COPD, and increase the scope of the service. Geography may limit or stimulate options. (√)

Outcomes in post-exacerbation pulmonary rehabilitation

• Patients hospitalised for acute exacerbation of COPD should be offered pulmonary rehabilitation at hospital discharge to commence within 1 month of discharge. (Grade A)

• Providing post-exacerbation pulmonary rehabilitation alongside elective pulmonary rehabilitation courses can cause practical issues. Evaluation of innovative ways of delivering a combination of both modes of pulmonary rehabilitation in tandem would be useful. (√)

Completion of post-exacerbation pulmonary rehabilitation

• Clinical services providing post-exacerbation pulmonary rehabilitation commencing within 1 month of hospital discharge should carefully record uptake, adherence and completion rates. (Grade D)

• Patients who initially decline pulmonary rehabilitation commencing within 1 month of hospital discharge should be offered elective pulmonary rehabilitation. (Grade D)

Inspiratory muscle training and pulmonary rehabilitation

• Inspiratory muscle training (IMT) is not recommended as a routine adjunct to pulmonary rehabilitation. (Grade B)

Hormones and nutritional supplements and pulmonary rehabilitation

• No specific hormonal or nutritional supplement can currently be recommended as a routine adjunct to pulmonary rehabilitation. (Grade B)

• The optimal approaches for addressing malnutrition, sarcopenia or obesity in COPD are uncertain and this is a wider issue than this guideline covers. However, attendance at a pulmonary rehabilitation course presents an ideal opportunity to screen and educate patients on nutrition. (√)

• Patients with a body mass index (BMI) in the underweight or obese range should be considered for specific dietetic support. (√)

Non-invasive ventilation during pulmonary rehabilitation

• Long-term domiciliary non-invasive ventilation (NIV) should not be provided for the sole purpose of improving outcomes during pulmonary rehabilitation. (Grade D)

• Patients who already receive long-term domiciliary NIV for chronic respiratory failure should be offered the opportunity to exercise with NIV during pulmonary rehabilitation if acceptable and tolerable to the patient. (Grade D)

Supplemental oxygen in patients undergoing rehabilitation

• Supplemental oxygen should not be routinely used for all patients undergoing pulmonary rehabilitation. (Grade B)

• Supplemental oxygen during pulmonary rehabilitation should be offered to those who fulfil the assessment criteria for long-term or ambulatory oxygen unless there are compelling clinical reasons to use alternative criteria. (Grade D)

• Individuals who are prescribed oxygen but decline to use it during exercise should have this clearly documented in their notes. (√)

• Pulmonary rehabilitation provides an opportunity to assess the adequacy of the prescribed flow rate for patients already in receipt of long-term oxygen therapy (LTOT) or ambulatory oxygen. (√)

Supplemental heliox in patients undergoing rehabilitation

• Heliox should not be used as an adjunct to pulmonary rehabilitation unless there are comorbidities which require its administration. (Grade D)

Neuromuscular electrical stimulation and pulmonary rehabilitation

• If expertise in neuromuscular electrical stimulation (NMES) is available, selected patients (low BMI with evidence of quadriceps weakness) who are unable or unwilling to participate in pulmonary rehabilitation could be considered for NMES. (Grade D)

Non-cystic fibrosis bronchiectasis

• Patients with non-cystic fibrosis (CF) bronchiectasis who have breathlessness affecting their activities of daily living (ADL) should have access to and be considered for pulmonary rehabilitation. (Grade D)

• Unlike in patients with CF, in patients with COPD and non-CF bronchiectasis with multidrug-resistant organisms, for example Pseudomonas aeruginosa, there is no current evidence of cross infection. (√)

Interstitial lung diseases

• The benefits of exercise and the recommendation of incorporating exercise activities into a healthy lifestyle should be discussed with all patients with interstitial lung disease (ILD). Such discussion needs to be tailored to realistic achievability for that person's condition. (√)

• If healthcare professionals consider referring certain patients with stable ILD who are limited by breathlessness in ADL to pulmonary rehabilitation, they should discuss with the patient the likely benefits. (√)

• Patients with idiopathic pulmonary fibrosis (IPF) have a potential for significant desaturation during exercise related activities. (√)

Asthma

• The routine referral of patients with asthma to pulmonary rehabilitation is not recommended. (Grade D)

• The benefits of exercise and the recommendation of incorporating exercise activities into a healthy lifestyle should be discussed with all patients with asthma. (√)

• If healthcare professionals consider referring certain patients with stable asthma who are limited by breathlessness in ADL to pulmonary rehabilitation when on optimal therapy, they should discuss with the patient the likely benefits. (√)

• The British Thoracic Society (BTS)/Scottish Intercollegiate Guidelines Network (SIGN) asthma guideline draws attention to exercise-induced asthma and precautions to prevent this should be followed if appropriate. (√)

Other chronic respiratory diseases—in general

• Minimal clinically important different (MCID) changes and tools used to assess exercise capacity and quality of life for pulmonary rehabilitation in COPD are not necessarily transferable to other chronic respiratory diseases. While future research should address this, failure of rehabilitation should not be implied if failure to reach the COPD MCID for outcomes. (√)

• The educational element of pulmonary rehabilitation should be adapted for other chronic respiratory diseases if appropriate. (√)

• Practically, inclusion of patients with other chronic respiratory diseases into pulmonary rehabilitation will be alongside subjects with COPD. (√)

• General exercise should be encouraged for all patients with chronic respiratory disease. (√)

Repeat pulmonary rehabilitation programmes

• Repeat pulmonary rehabilitation should be considered in patients who have completed a course of pulmonary rehabilitation more than 1 year previously. The likely benefits should be discussed and willing patients referred. (Grade B)

• Earlier repeat pulmonary rehabilitation should be considered in individuals with accelerated physiological decline or if additional benefits on a shorter timescale would be clinically valuable. (Grade D)

• It is unlikely that if the patient completed the pulmonary rehabilitation course originally and failed to gain a benefit, they would benefit a second time round, unless circumstances such as an exacerbation interrupted the initial programme. (√)

Maintenance

• All patients completing pulmonary rehabilitation should be encouraged to continue to exercise beyond the programme. (Grade A)

• Patients graduating from a pulmonary rehabilitation programme should be provided with opportunities for physical exercise beyond their rehabilitation programme. (√)

Exercise capacity

Change in exercise capacity following pulmonary rehabilitation has been subject to a Cochrane Review (updated 2009).11 In this review a meta-analysis of the 13 trials in relation to maximal exercise capacity measured by a cycle ergometer test (268 patients received pulmonary rehabilitation, 243 received usual care) showed the weighted mean difference was 8.43 W. Other studies used other measures of maximal exercise capacity. In an adequately powered randomised controlled trial (RCT), Griffiths et al12 showed a between-group difference in incremental shuttle walk test (ISWT) scores of 75.9 m favouring the pulmonary rehabilitation group upon completion of the programme. Singh et al13 reported the minimally clinical important improvement for ISWT of 47.5 m. The Cochrane review also described a treatment effect of 48 m favouring pulmonary rehabilitation in a meta-analysis of 16 trials (346 patients received pulmonary rehabilitation, 323 received usual care) that used the 6 min walk test (6MWT) to measure functional exercise capacity.14 The minimally clinically important difference for the 6MWT in subjects with COPD is 54 m.15 Different values have been published using alternative approaches.

Dyspnoea and health status

In the same Cochrane review the effect of pulmonary rehabilitation on dyspnoea and health status were also reviewed.11 This meta-analysis included Chronic Respiratory Questionnaire (CRQ) data showing an unequivocal reduction in dyspnoea following pulmonary rehabilitation. The other CRQ domains of fatigue, emotional function and patients’ sense of control (mastery) were also shown to improve. In fact, the lower limits of all domains of the CRQ were found to exceed the MCID of 0.5 points, indicating that a significant clinical improvement in health status follow pulmonary rehabilitation.16 The St Georges Respiratory Questionnaire (SGRQ) scores were also subject to a meta-analysis in the Cochrane review. This demonstrated that the weighted mean difference of the six trials reported exceeded the MCID of 4 for the total and domain scores.16 Subsequently, other tools for health status such as the COPD assessment test (CAT) have been found to be responsive to pulmonary rehabilitation.17–19

Physical activity

There has been increasing interest in physical activity, as inactivity has been linked with reduced survival, poorer quality of life and increased healthcare utilisation.20–22 A recent systematic review and meta-analysis of physical activity was unable to find any published RCT examining the effect of pulmonary rehabilitation compared with usual care.23 They reviewed two randomised trials and five single-group interventional studies.24 ,25 They concluded that current data suggest supervised exercise training may lead to a small but statistically significant effect on activity but the lack of a control limited interpretation. One of the randomised trials reported significant improvements in physical activity compared with a ‘pre-control group’ but patients in this group went on to receive a pulmonary rehabilitation intervention.25 One of the single group studies reported no change at 3 months but improvement with 6 months of rehabilitation.26 In summary, a consistent finding is a small increase in physical activity following pulmonary rehabilitation, though its clinical significance is unknown.

Activities of daily living

Increased independence in ADL remains an important aim of pulmonary rehabilitation. However, the impact of pulmonary rehabilitation upon ADL has not yet been reported in a RCT. Measurement of physical activity with activity monitors provides a snapshot of the quantity of activity but does not provide information with regard to individual task completion. Self-reported measures of ADL have been shown to be reliable and sensitive to change following pulmonary rehabilitation programmes in the UK. These include the Canadian Occupational Performance Measure (COPM), London Chest ADL (LCADL) Scale, Manchester Respiratory ADL Scale and the Pulmonary Functional Status and Dyspnoea Questionnaire.27–30 Prospective uncontrolled studies suggest that pulmonary rehabilitation does impact on ADL.25 ,31 ,32 Sewell et al25 compared an individualised exercise programme with a generic exercise programme and demonstrated statistically significant within-group improvements in COPM performance and satisfaction scores for both treatment groups. A further uncontrolled study has shown improvements in LCADL Scale scores.31 A small study of 22 patients compared three measures of self-reported ADL and concluded that the LCADL and modified version of the pulmonary functional status and dyspnoea questionnaire (PFSDQ-M) were more responsive than the MRC scale.32 However, the impact of pulmonary rehabilitation upon ADL has not been reported in a RCT comparing pulmonary rehabilitation with usual care.

Muscle strength

Muscle strength, in particular the quadriceps, is an important systemic marker in COPD and weakness is associated with increased mortality and healthcare utilisation.33 ,34 Interventions that can demonstrate improvements in strength are therefore desirable. It was decided to narrow the influence on pulmonary rehabilitation to quadriceps strength for this guideline, as this has been highlighted as an important muscle group in COPD.33

No RCTs of pulmonary rehabilitation that measured quadriceps strength were identified. As such, the GDG reviewed eight RCTs of exercise training versus control.35–42 There were six studies composed solely of resistance training35 ,36 ,38 ,40–42; one study including a combination of aerobic and resistance training39; and one study including mobility training.37 All studies incorporating resistance training demonstrated an increase in muscle strength. The seven positive studies demonstrated an increase of at least 16% (16.2%–37%) in quadriceps strength.

Psychological status

A meta-analysis of six RCTs concluded that pulmonary rehabilitation was more effective than standard care for the reduction of anxiety and depression.43 Of the six trials in the review, one was methodologically weak and two were underpowered as outlined in the evidence table. However, the strongest data were from a large RCT comparing pulmonary rehabilitation (n=99) with usual care (n=101) completed by Griffiths et al,12 who demonstrated a significant improvement in anxiety and depression as measured by the Hospital Anxiety and Depression Scale (HADS).

Nutritional status

Studies have shown variable results for weight change with pulmonary rehabilitation programmes. People presenting to pulmonary rehabilitation have differing body habitus and hence differing objectives of the multidisciplinary rehabilitation. This complicates looking for an overall change in weight in a group with pulmonary rehabilitation. Lan et al44 showed an 0.8 kg weight increase following pulmonary rehabilitation in an underweight population. In normal weight patients, a similar gain of 0.6 kg following exercise training has been described.45 However, in a trial examining the effect of nutritional supplementation, Steiner et al46 showed weight loss of 0.6 kg in their placebo group following pulmonary rehabilitation. The magnitude of weight change in all these studies is of doubtful clinical significance. The effect of pulmonary rehabilitation on weight in the obese population is unknown. Recent retrospective data of a large pulmonary rehabilitation cohort has shown that baseline nutritional status (measured by BMI) has no effect on the efficacy of pulmonary rehabilitation in terms of exercise capacity or health status.47

Self-efficacy

Self-efficacy describes the level of belief someone has in their ability to complete a chosen task or goal.48 Self-efficacy for walking has been shown to be associated with adherence in pulmonary rehabilitation and is therefore an important outcome measure in pulmonary rehabilitation. To date there have not been any RCTs that measure the impact of pulmonary rehabilitation on self-efficacy compared with usual care. However, an early RCT compared pulmonary rehabilitation with education alone and demonstrated that self-efficacy improved in the intervention group.49 Other prospective observational studies have also demonstrated that self-efficacy scores improve following pulmonary rehabilitation.31 ,50 More recently, the PRAISE self-efficacy tool has been developed to measure levels of self-efficacy in relation to behaviours specific to pulmonary rehabilitation and has been shown to be reliable and sensitive to change following pulmonary rehabilitation in a prospective cohort study.51

Survival

One RCT has explored the effect of pulmonary rehabilitation on survival in 119 people with COPD when stable.49 The study was almost certainly underpowered to detect a mortality difference between the groups. In addition, the intervention and ‘usual care’ groups received education and the intervention group received monthly ‘reinforcement’ sessions for a year after completion of rehabilitation. Both groups had at least 6-monthly assessments by the research team for the following 6 years. Overall 6-year survival was 61% and there was no statistically significant difference between the intervention and control groups.

Measuring pulmonary rehabilitation outcomes

Although the benefits of pulmonary rehabilitation are shown in a variety of ways in this chapter, there are several key outcomes that should be the core part of any assessment of the individual and of the efficacy of the programme.

Referral process

There are certain aspects of the referral process to pulmonary rehabilitation that are recommended. Patients who are likely to benefit from pulmonary rehabilitation have their exercise capacity limited by breathlessness or muscle fatigue and may have difficulty understanding the rationale behind referral for exercise training. From qualitative studies, success and outcome of rehabilitation are positively influenced by the initial clinician interaction and detail provided about pulmonary rehabilitation.52 ,53 Studies report that lack of understanding of the benefits of pulmonary rehabilitation may influence uptake.54 ,55 In addition, addressing patients’ concerns may improve uptake and completion.54 A discussion should take place with the patient about their aims from pulmonary rehabilitation. This can be documented and may aid motivation.56 Patient information and referral are covered in appendices C and E.

The period from referral to assessment

Cognitive behavioural therapy (CBT) is an evidence-based psychological treatment focusing on thoughts, beliefs and attitudes, how these impact on behaviour and dealing with problems and whether there are alternative ways. It was therefore considered whether CBT might improve the adherence to pulmonary rehabilitation if delivered immediately before the programme. In an uncontrolled study, the introduction of a group opt-in 1.5 h session which incorporated CBT techniques post referral was evaluated.57 Compared with historical practice, fewer patients proceeded to the initial assessment but a similar proportion commenced pulmonary rehabilitation. There appeared to be less dropout for ‘non-illness’ reasons, such as transport difficulties or dislike of group activities.

Assessment

Initial assessment for pulmonary rehabilitation should include a detailed description of the programme—for example, the requirement for exercise within a group setting. It should also confirm that there is no contraindication to rehabilitation. The initial assessment presents an opportunity to assess comorbidities and risk factors, for example, hypertension (see section ‘Cardiovascular disease comorbidity’) and consider referral for management to optimise benefit from the programme. Information on service specification of pulmonary rehabilitation is addressed in appendix F.

Smoking status

There has been some debate as to whether current smoking should be an exclusion criterion for pulmonary rehabilitation.

A retrospective non-analytic study of 239 predominantly male patients with COPD showed that current smokers were less likely to attend at least two-thirds of training sessions while another uncontrolled study of 91 patients with COPD identified lower completion rates in current smokers.58 ,59 However, in these studies a considerable proportion of current smokers attended and completed rehabilitation. There was no evidence that smokers failed to benefit to a similar degree as non-smokers. Pulmonary rehabilitation can provide an excellent opportunity to facilitate smoking cessation.60

Chronic respiratory failure

The issue of safety of pulmonary rehabilitation was considered in patients with chronic respiratory failure. Patients with chronic respiratory failure (defined as PaO₂<8kPa, PaCO₂>6kPa or both) appear to gain similar benefit from pulmonary rehabilitation compared with patients without respiratory failure.61 A prospective observational study of 1130 patients with severe COPD who underwent inpatient pulmonary rehabilitation showed that patients with and without chronic respiratory failure showed a similar response.61 The GDG discussed this in light of the available studies and concluded that patients should not be excluded from pulmonary rehabilitation on this basis. Later sections of this guideline discuss the use of oxygen and non-invasive ventilation as an adjunct to pulmonary rehabilitation; see section on Adjuncts to pulmonary rehabilitation.

Cardiovascular disease comorbidity

From a safety perspective it is logical that patients with unstable cardiovascular disease (eg, unstable angina, unstable arrhythmias) should not enter a rehabilitation programme until stabilised. Accordingly, all such patients are excluded from studies of pulmonary rehabilitation. However, patients should not be excluded from pulmonary rehabilitation on the basis of having stable cardiovascular disease and the initial assessment offers a potential opportunity to assess this aspect of their general health.

A retrospective observational study of 2962 patients with moderate to severe COPD completing pulmonary rehabilitation evaluated the impact of comorbidities, including cardiovascular comorbidity, on outcomes. Patients with a higher number of comorbidities, assessed using the Charlson index, were less likely to gain clinically significant improvement in walking distance and health-related quality of life but the level of comorbidity had no effect on improvement in breathlessness. Relating to cardiovascular comorbidities, their presence led to patients being less likely to show a significant improvement in quality of life, equally likely to gain significant improvement in breathlessness and more likely to demonstrate an improvement in walking distance.62 Further, the GDG considered that the standard MCID used for pulmonary rehabilitation may not be applicable in those with comorbidities—that is, patients may clinically improve by a noticeable amount at values less than the MCID traditionally used for a general rehabilitation population.

A prospective study from the same authors of 316 patients with moderate to severe COPD completing outpatient pulmonary rehabilitation showed no evidence that patients with cardiovascular comorbidity gained less benefit from pulmonary rehabilitation.63 Furthermore there is emerging evidence that pulmonary rehabilitation may favourably benefit cardiovascular risk factors (eg, blood pressure).64 ,65

A further consideration is abdominal aortic aneurysm (AAA) and exercise. Indeed, AAAs are reported as more prevalent in patients with COPD than in the general population and are related to tobacco smoking and impaired lung function.66–69 There was no literature exploring AAA's in patients with chronic respiratory disease and pulmonary rehabilitation. The guideline from the Society for Vascular Surgery (USA) documents that AAA rupture is not precipitated by moderate physical activity.70 A small pilot reported relative safety of exercise in people who have AAAs but only studied people with ‘small’ AAA's (defined as 30–50 mm in diameter).71 The GDG additionally sought vascular opinions, including that of the Vascular Society, UK, and concluded that in people with an AAA <5.5 cm with controlled blood pressure, a standard multidisciplinary pulmonary rehabilitation incorporating moderate intensity aerobic training should be considered safe.

An AAA>5.5 cm should usually lead to consideration for surgical intervention, although severity of COPD or other comorbidities may preclude surgery. The opinion of the Vascular Society UK was sought: there is no evidence that mild to moderate exercise is associated with an increased risk of rupture. This would include aerobic exercise, for example, walking or riding a bicycle at a steady pace without the need to become too uncomfortable. However, this would exclude exercise which is associated with a risk of transient blood pressure rise, such as lifting weights, press ups or sit ups. The GDG concluded that in subjects with COPD where surgery has been deemed inappropriate by a cardiac or vascular surgeon, pulmonary rehabilitation incorporating mild–moderate aerobic exercise can be considered.

Anxiety and depression

It has been considered whether anxiety and depression should be addressed prior to pulmonary rehabilitation in case they affect adherence or willingness to adopt change. Harris et al54 reported that patients who scored more highly for anxiety and depression were more likely to report breathlessness and fear exercise, irrespective of the MRC breathlessness score. However, we know that pulmonary rehabilitation conveys significant improvement in such parameters for those with mild to moderate depression who undergo rehabilitation.

A prospective non-analytic study of 81 patients with predominantly severe COPD showed no evidence that patients with higher levels of anxiety or depression (assessed using the HADS) obtain reduced benefit from pulmonary rehabilitation.72 Indeed another observational study of 95 patients with COPD suggested that patients with a higher baseline level of anxiety gained greater benefit from exercise training.73 A retrospective analysis of 518 patients entering pulmonary rehabilitation demonstrated a significant improvement in anxiety and depression according to the HADS score in those who had ‘presence’ or ‘probable’ anxiety or depression at baseline.74 Baseline HADS score did not relate to completion or non-completion.

A systematic review of factors associated with completion of pulmonary rehabilitation indicated that patients with depression have a lower completion rate.75 However, many do complete the programme and gain significant benefit.

MRC dyspnoea grade

The traditional view of pulmonary rehabilitation has been to refer patients with an MRC breathless score of 3 or worse. The majority of outcome studies have included patients with COPD who had MRC scores of 3–5 and who attended outpatient programmes. There is overwhelming evidence of benefit from these studies incorporating hundreds of patients, albeit few of these studies stratified according to MRC grade.11 ,12 However, in general, there has been a shift towards addressing COPD earlier in the natural history of the disease and debate has ensued as to whether pulmonary rehabilitation may be of benefit to those with MRC dyspnoea grade 2.

Two retrospective observational studies have shown that patients who have a MRC dyspnoea score of 2 obtain similar improvement in exercise capacity to patients with MRC scores of 3–5.76 ,77 Both studies examined approximately 450 patients who completed outpatient pulmonary rehabilitation and in each study more than 100 patients with MRC dyspnoea scores of 2 were included.

There is one single-centre, unblinded RCT of 61 patients with COPD who had moderate Global Initiative for Chronic Obstructive Lung Disease (GOLD) II airflow obstruction. Some of these patients had a MRC dyspnoea score of 2 but were not stratified by their MRC breathlessness. They were randomised to either pulmonary rehabilitation or usual care and the group completing pulmonary rehabilitation showed improvement in walking distance and quality of life.78 In even milder airflow obstruction (symptomatic GOLD I), ventilatory responses with incremental cycling exercise show reduced exercise capacity compared with matched controls.64 A flexible approach may be required to facilitate these patients completing exercise training.

There are conflicting results of pulmonary rehabilitation for those with MRC grade 5 breathlessness, depending on whether or not they are housebound. A well conducted, randomised, placebo-controlled trial of 60 patients with MRC breathless grade 5 who were housebound due to their breathlessness gained little benefit from supervised exercise training in their home.79 In contrast, another large retrospective observational study which included 146 patients graded as MRC breathless grade 5, but who were able to attend and complete outpatient pulmonary rehabilitation, gained similar benefit to patients who had MRC scores of 3–4.76 The location and nature of the programmes used in these studies and the level of functional limitation of recruited patients with MRC grade 5 may confound the outcomes.

Bronchodilator therapy

The exercise component of pulmonary rehabilitation is beneficial, but the magnitude of benefit may be limited by modifiable factors. Bronchodilator drugs that reduce dyspnoea and dynamic hyperinflation may permit a greater amount of exercise and thus a greater gain from the rehabilitation programme. Two RCTs have assessed the effect of tiotropium bromide (Spiriva, Boehringher) as an adjunct to pulmonary rehabilitation.80 ,81 The generalisability of the findings of these trials is limited as they did not permit the use of long-acting β agonists or short-acting anti-cholinergics in any subject (thus any additional benefit in the treatment arm could be at least partially explained by treatment reduction in the placebo arm) and a large proportion of subjects took inhaled corticosteroids. In this context, both trials found the addition of tiotropium bromide to further improve dyspnoea, but only one found benefits in walk distance and quality of life. It should be noted that the larger showed pulmonary rehabilitation to be only modestly effective (6MWT improvement of around 10%) and there were no common tests of exercise capacity across the two trials. These studies did not set out to investigate whether there was a synergistic effect of commencing a COPD medication before pulmonary rehabilitation or whether the effects of the two interventions were simply additive. No trial has investigated any other standard COPD medication introduced specifically to attempt to increase the benefit gained from pulmonary rehabilitation.

Other considerations regarding referral to pulmonary rehabilitation

The decision to refer may be influenced by other factors—for example, when it may be unsafe, inappropriate or impossible for patients to engage in pulmonary rehabilitation. Studies of pulmonary rehabilitation routinely include a number of standard clinical exclusion criteria resulting in such patients not being included in clinical trials. The main criteria include the presence of unstable cardiac disease, locomotor or neurological difficulties precluding exercise (eg, severe arthritis or peripheral vascular disease), patients in a terminal phase of their illness or the presence of significant cognitive or psychiatric impairment.12 ,82 ,83

Frequency of supervised pulmonary rehabilitation sessions

The frequency of supervised sessions during a course of pulmonary rehabilitation has not been clearly established. Traditionally in the UK, pulmonary rehabilitation takes place as an outpatient (either in a hospital or community setting) comprising a minimum of two supervised sessions per week. There is a large body of literature supporting the benefits of pulmonary rehabilitation and these have encompassed two supervised sessions and either a third supervised or formalised unsupervised pulmonary rehabilitation session.11 ,12 In parallel with this, the general advice from the Department of Health recommends five sessions of 30 min of physical activity per week.84

A pilot feasibility study evaluating the effectiveness of a once weekly versus a twice weekly supervised programme and a randomised, parallel-group single-blind study experienced significant dropout rates, resulting in neither study being statistically powered.85 ,86 The GDG noted that the improvement in walking distance with pulmonary rehabilitation in the once and twice weekly groups was minimal, raising concern about the programme in the parallel-group study.86

The optimum frequency of pulmonary rehabilitation is not known. There is insufficient evidence to demonstrate that once-weekly pulmonary rehabilitation is as effective as twice weekly in terms of improvement in exercise performance and health status. Most pulmonary rehabilitation studies showing benefit in the key outcome measures are based on at least two supervised pulmonary rehabilitation sessions a week.11 ,12

Duration of pulmonary rehabilitation programmes

The optimal pulmonary rehabilitation programme duration is unclear, with huge variation in the length of programme seen across Europe and the rest of the world. In the UK, for practical and economic reasons, programmes lasting longer than 6–8 weeks are not standard; however, there is some ongoing debate as to the efficacy of programmes lasting less than 6 weeks. Consequently we have examined the effect on exercise performance and health status of pulmonary rehabilitation lasting less than 6 weeks to programmes lasting 6–12 weeks. However, we have also commented on studies examining prolonged rehabilitation (greater than 12 weeks).

Rolling or cohort programmes

There is much debate regarding the comparative effectiveness of either a rolling or cohort-based rehabilitation programme. There is no high-quality evidence comparing the two formats. The GDG felt it was important to list the aspects of both types, which might be informative for those considering setting up a service; see appendix G.

Education

The educational components of pulmonary rehabilitation are fundamentally integral to the format and success of the programme. Education comes into every aspect of pulmonary rehabilitation and in discrete educational sessions. Educational talks are discussed in more detail in appendix H.

The intention of the educational element is to support the lifestyle and behavioural change and assist self-management to promote decision making and self-efficacy. The educational and cultural backgrounds of the subjects and any physical (eg, impaired sight or hearing) and cognitive barriers need to be considered.

Nature of training

Lower limb weakness is common in patients with COPD and a poor prognostic indicator.33 The standard training delivered for pulmonary rehabilitation is based around aerobic training, usually lower limb endurance training (commonly walking or cycling). The precise intensity for the endurance component has not yet been confirmed for individuals with chronic respiratory disease, although a target intensity of 60% of peak work rate is regarded as a minimum. The aim is to accumulate 30–60 min per session. For some individuals a single bout of 30 min is not achievable and shorter bouts should therefore be advised in order to accumulate 30 min. Progression should be observed in the longest achieved bout, aiming for 30 min of continuous activity.

We explored the evidence for additional resistance (strength) training, involving focused training of specific muscle groups with repetitive manoeuvres against heavy loads. Resistance training involves the major muscle groups, in particular the quadriceps muscles, and two to four sets should be completed, with each set comprising 10–15 repetitions. The weights chosen should be individualised and progressed once all sets can be completed with the selected weight. A minimum of 48 h between each session is advised.

The volume of evidence addressing this was low, with some methodological limitations in a number of trials. A systematic review encompassed several comparisons—combination approach, resistance training alone and resistance training compared with another intervention.93 Individual trials addressing the potential role of combined resistance compared with endurance training were reviewed. Of seven trials, four carried a high risk of bias.94–97 There were three good-quality, albeit relatively small, randomised trials.98–100 These trials did not demonstrate any significant additional benefits with the combined approach compared with endurance training alone regarding exercise tolerance as measured with field walking tests. There was an improvement in peripheral muscle strength; however this does not appear to translate into a demonstrable significant improvement in health-related quality of life. Functional outcome measures such as stair climbing were only assessed in the trials with a high risk of bias.95 ,96

One narrative review considering the longer term effects of resistance training has reported on three trials with inconsistent results.101 Our patient representative acknowledged that patients often report it is harder to maintain progressive resistance exercise at an adequate intensity once supervision is no longer provided. It is of note that trials reviewed focused mainly on progressive resistance exercise delivered at an outpatient programme using weight-lifting exercise machinery. Lastly, the GDG considered that resistance training has other benefits, such as proven to reduce falls in older people in general. An in-depth review of these other benefits is outside the scope of the pulmonary rehabilitation guideline.102

Interval and continuous aerobic training

Interval training delivers short periods of high-intensity aerobic training interspersed with rest or low-intensity periods. The rationale is that it allows periods of work to be conducted at a higher intensity compared with aerobic training.

A Cochrane review directly considered this subject.103 Zainuldin et al included RCTs comparing higher training intensity with lower training intensity or comparing continuous training with interval training in people with COPD. Studies that compared exercise training with no exercise training were excluded. Only RCTs were included and the review considered the following outcome measures:

• Maximal incremental cardiopulmonary exercise test: peak exercise intensity, peak oxygen consumption, peak minute ventilation and lactate threshold at isotime or isowork.

• Endurance cardiopulmonary exercise test (cycle or treadmill): exercise time.

• Functional exercise capacity: 6-min walk distance, incremental shuttle walk distance or endurance shuttle walk time (ESWT).

• Symptom scores, health-related quality of life and muscle strength.

Eleven studies were included in the meta-analysis (five being translations from foreign language). Of these, eight studies were specifically related to this subject, with three judged to be of low risk of randomisation bias. Studies had examined a diversity of training protocols, moderate to low sample sizes and potential selective reporting of outcomes. Furthermore, studies investigating interval versus continuous training in patients with COPD tended to compare training of equal work duration.

The results of the review conclude that interval training was not superior to continuous training for improving physiological outcomes, walking time or symptoms in people with moderate to severe COPD.

It must be noted that the training studies reported in the literature have all been completed on a cycle ergometer using a complex training programme and this may present challenges within the programme and pursuing this type of training regime at home and after graduation from rehabilitation.

Goal setting in pulmonary rehabilitation

There has been discussion whether individualising the pulmonary rehabilitation programme to personal goals may improve outcomes of the programme. Individualised activity programmes have been investigated by a described RCT but trials of goal setting focusing on other aspects of pulmonary rehabilitation have not been reported.25 Sewell et al25 randomised 180 patients to either an individually targeted exercise programme or the control arm: a conventional general exercise programme. The ‘individually targeted exercise’ group chose ADL derived from completed COPM questionnaires—a questionnaire designed to detect changes in domestic function over time; whilst the general exercise programme group was made up of 10 standard exercises focusing on upper and lower limbs, and the trunk. The RCT demonstrated no significant difference between the goal-based therapies and standard treatment, although both groups improved similarly. The authors comment their intervention groups may have been too similar to the control with regard to exercises performed.25

Two other studies were considered in relation to this work but did not address the specific question of goal setting.104 ,105 One aimed to gradually reduce dependency on centre-based group exercising in favour of increasing free living activity levels104; while a small RCT explored different combinations of pulmonary rehabilitation—exercise training alone, exercise training plus activity training or exercise training plus lectures in 43 people.105

Supervision in pulmonary rehabilitation

The majority of the evidence for the role of pulmonary rehabilitation is based on supervised programmes. There is a limited evidence base describing unsupervised pulmonary rehabilitation. Most reported evidence is centred on home-based rehabilitation compared with a hospital-based supervised programme. However, caution is advised, given some of the home rehabilitation schemes included varying degrees of supervision or support.

Studies were reviewed if they randomised rehabilitation participants to a home rehabilitation programme or a supervised programme. Studies comparing home-based rehabilitation with a control group were excluded. All studies reported exercise performance and quality of life as important outcomes. Only one ‘home’ study was conducted in the UK.106 The largest study (n=252) comparing home rehabilitation with conventional rehabilitation was conducted in Canada, where the structure of the hospital-based rehabilitation is similar to that offered in the UK.107 It was powered for non-inferiority. In this study the home exercise training was preceded with 4 weeks of educational sessions at hospital outpatients and then an exercise bike was provided in the home. Exercise was not supervised but was initiated by an exercise specialist in the patient's own home and weekly phone calls were made. Changes in cycle endurance time were similar between and within group, while changes in the 6MWT were minimal (gain of 8–11 m) in both groups, but not different between the groups. A similar approach was adopted by Guell et al,108 with group education before allocating exercise training to either home or hospital; again there were no important differences between the groups after 9 weeks in this small RCT but this was unlikely to be powered for equivalence. Two studies adopted a broadly similar approach to that delivered in the UK; one over 8 weeks and one over 12 weeks.109 ,110 Puente-Maestu et al109 showed differences in the physiological response to the two environments but performance was similar. Both groups had structured exercise regimes to follow. While not supervised exercise, there was a weekly hospital visit to record and encourage compliance with the home programme. A further 12-week home-based rehabilitation incorporated supervised exercise in the hospital and the home pulmonary rehabilitation setting.111 The UK-based study compared brief advice with hospital-based pulmonary rehabilitation with a greater improvement observed in the hospital-based group in terms of exercise performance, although benefit in health-related quality of life was similar (though both small improvements) between groups.106

The approaches across studies are not consistent and methodological quality is variable. Furthermore, overall the population recruited seems similar at baseline to those routinely recruited to a studied pulmonary rehabilitation programme. All studies recruited patients with moderate to severe COPD with a moderate degree of disability. However, the exercise capacity at baseline seems to be higher than that reported in UK studies, reflecting the selection bias of this trial; that is, recruiting patients who are more able to accommodate a home-based training programme. The largest study provided personal exercise bicycle equipment for the participants to use at home. The education component of rehabilitation was delivered prior to engaging in the unsupervised exercise; this ranged from a 1:1 contact to a 4-week group programme of education.106 ,112

These trials may allow the scope of pulmonary rehabilitation to be increased in the UK. However, the educational needs of the individual need attention; mechanisms to offer remote supervision, provision of home exercise equipment and patient selection are important factors that need careful consideration.

Telehealth is an innovative consideration of delivering health services to patients with COPD. In the context of pulmonary rehabilitation, technology has the potential to be used as an adjunct to rehabilitation or even provide a ‘rehabilitative’ service to individuals in isolated areas or with transport difficulties. To date there have been few reports integrating technology into the rehabilitation service.

There are reports of using simple pedometers as adjuncts to rehabilitation or telephone counselling as an alternative approach to improve exercise performance, but there are limited data on using technology in the form of e-health, mobile ‘smart’ phones or telemedicine.113 ,114 One notable exception showed benefits of mobile phone technology incorporating downloaded music with a tempo to match walking speed and global positioning system to monitor. However, the benefits seen were compared with a no-intervention group.115

Outcomes in post-exacerbation pulmonary rehabilitation

A recent Cochrane review aimed to assess the effects of ‘early’ pulmonary rehabilitation within 3 weeks after COPD exacerbations (the majority requiring hospitalisation or hospital at home services) on future hospital admissions (primary outcome) and other patient-important outcomes (mortality, health-related quality of life and exercise capacity).116 Nine trials involving 432 patients were identified which compared ‘early’ pulmonary rehabilitation with conventional community care. Pulmonary rehabilitation significantly reduced hospital admissions with a number needed to treat of 4. However, as healthcare utilisation was only assessed over the short to medium duration of the study, it is unclear whether the reduction in hospital admissions was a result of the programme or increased contact with the study team. Pulmonary rehabilitation also reduced mortality, although the effect of the intervention may have been overestimated due to the small number of events. Nevertheless, no study reported any excess adverse events with the intervention.

There were also statistically and clinically significant improvements in health-related quality of life. Significant improvements (in excess of the recognised minimally important differences) were also seen in exercise capacity (6MWT and ISWT). The longer term benefits in exercise capacity and quality of life are not known.

A further RCT by Ko et al117, published after the Cochrane review, was also considered. This trial recruited 60 subjects and compared early post-exacerbation pulmonary rehabilitation within 2–3 weeks of hospital discharge with usual care. Although health-related quality of life was improved at 3 months and 6 months, no differences were seen by 12 months. Furthermore, although there was a trend towards fewer admissions in the first 3 months in the early pulmonary rehabilitation group, this waned with time. However, the study cohort was probably not medically optimised.

To date, only one study has compared ‘early’ post-exacerbation pulmonary rehabilitation with ‘late’ post-exacerbation pulmonary rehabilitation (delivered 6 months after exacerbation) with an 18-month follow-up.118 No significant differences were seen in health-related quality of life or exacerbation rates between the groups. However, due to recruitment issues this study was underpowered.

Completion of post-exacerbation pulmonary rehabilitation

It is well recognised that a proportion of patients fail to adhere to or complete elective pulmonary rehabilitation. Given that patients are physically and psychologically vulnerable in the early post-hospital discharge period, and that infective exacerbations often cluster, the GDG considered whether completion rates of ‘early’ post-exacerbation pulmonary rehabilitation (commenced within 1 month of hospital discharge) might be lower than with providing elective pulmonary rehabilitation to the same patients post hospital admission for an exacerbation but when the patient becomes more stable.119

There were no studies that directly addressed this issue. From 12 potential abstracts; nine compared early post-exacerbation pulmonary rehabilitation with usual care; one was a review paper and the ‘early’ intervention in one study was more than 4 weeks after exacerbation. Only one study was reviewed in full.118 This compared ‘early’ (within 2 weeks of exacerbation) with ‘late’ pulmonary rehabilitation delivered 6 months after exacerbation. However, a proportion of exacerbations in this study did not necessitate hospitalisation. The study was also significantly underpowered due to recruitment problems and there were high numbers of dropouts and deviations from planned intervention. Furthermore, the intervention delivered was a mixture of inpatient and outpatient pulmonary rehabilitation which was inconsistent in both groups.

We further examined the individual RCTs considered in the Cochrane review that compared early post-exacerbation pulmonary rehabilitation shortly after hospital discharge with usual care.116 ‘Completion rate’ data were often completion of the research study rather than completion for pulmonary rehabilitation. Only four studies reported any data on the attendance at pulmonary rehabilitation. Man et al120 reported 67% of the intervention group attending more than 50% of pulmonary rehabilitation sessions, while in the cohort of Seymour et al121, 77% attended more than 50% of pulmonary rehabilitation sessions. Ko et al117 reported that 73% of the intervention group attended at least 70% of sessions while only 40% attended more than 75% of sessions in the study of Eaton et al,122 despite the investigators providing free door-to-door transport.

The GDG considered these data to be in line with published figures of elective pulmonary rehabilitation. There was insufficient evidence to suggest that attendance was lower with pulmonary rehabilitation started within 1 month of hospital discharge compared with elective pulmonary rehabilitation.

However, it should be noted that these patients are highly selected (consenting to participate in a RCT). Studies have suggested poor recruitment for the early post-exacerbation trials, and by extension, poor uptake (acceptance of the referral and commencing the course) for early post-exacerbation pulmonary rehabilitation. Seymour et al121 only managed to recruit 60 patients from three hospitals over a 3-year period. In other studies, less than 50% of patients eligible for the study consented.117 ,122 This raises questions as to whether the benefits of pulmonary rehabilitation shortly after hospital discharge can be generalised to unselected patients.

IMT and pulmonary rehabilitation

The exercise capacity of patients with COPD is usually limited by dyspnoea.124 An intervention that reduced dyspnoea could therefore potentially permit greater exercise and increase the benefits seen with pulmonary rehabilitation programmes. IMT attempts to improve respiratory muscle strength and endurance through two types of training. Inspiratory resistive training uses devices that permit inhalation against resistance at a certain threshold. With normocapnic hyperpnoea the individual is required to achieve supranormal target ventilation while PaCO₂ is kept constant. IMT may improve dyspnoea by favourably altering the ratio between the current inspiratory pressure generated and the maximal inspiratory pressure (PI/PImax)125–127 and by reducing compromising dynamic hyperinflation128 ,129 through a reduction in inspiratory time.130

Normocapnoeic hyperpnoea involves exercising the inspiratory muscles using periods of rapid breathing and deep inhalation of a controlled gas mix to ensure circulating normocapnoea. It is therefore more akin to endurance training, but appears to have relevant potential beneficial effects.131 Its use as an adjunct to pulmonary rehabilitation has been examined in one small quasi-randomised study where it resulted in greater respiratory muscle endurance and PImax, but had no effect on exercise outcome or quality of life.132

Threshold load training is delivered using small handheld devices that allow flow only when inspiratory pressure reaches a preset but adjustable level. It can therefore deliver strength and endurance type training. It appears safe and well tolerated in individuals with a variety of diagnoses, including COPD.133 A pilot study in 36 patients with COPD found that use of IMT in addition to an exercise programme led to greater improvement in walk test distance than those who undertook exercise alone,134 although a subsequent RCT in 25 patients with COPD found no such benefit.135 Similarly, another pilot study in 42 patients found IMT led to greater improvement in cardiopulmonary exercise test parameters after an exercise programme.136 These study findings appear at considerable risk of bias given their limitations in key areas (see evidence tables). These findings were not subsequently replicated in two RCTs assessing IMT as an adjunct to exercise programmes, with low risk of bias.135 ,137

Given the lack of consistency and the considerable limitations of the studies considered, IMT is not recommended as a routine adjunct to pulmonary rehabilitation. After assessment a respiratory physiotherapist may feel this is an appropriate adjunct for individual patients. However, post hoc subgroup analysis of the available studies did not identify a specific type of patient most likely to respond to IMT, so it cannot presently be recommended more broadly.

Hormones and nutritional supplements and pulmonary rehabilitation

Although the exercise component of pulmonary rehabilitation is beneficial, the degree of benefit may be limited by modifiable factors in many patients with COPD. Therefore, there has been research interest in maximising the effects of pulmonary rehabilitation by attempting to address nutritional constraints and the general catabolic state in COPD.

COPD is a catabolic state and individuals are at risk of becoming underweight, which is a poor prognostic feature.138 Subclinical nutritional deficiencies may also exist that could constrain the benefits of pulmonary rehabilitation.139 Supplementation of calories may therefore allow anabolism during pulmonary rehabilitation programmes and specific supplements may promote improvements in muscle efficiency and strength. The use of a standard supplement drink containing protein, fat and carbohydrate has been evaluated in a well described RCT and an inpatient trial with historical controls.46 ,140 Both studies report additional weight gain of around 1 kg in those receiving supplements but no robust differences in strength or endurance measures.

Several small trials have evaluated specific nutritional supplements, but limitations in study design and lack of replication limit the inference that can be made regarding the efficacy of supplementation with L-carnitine,141 amino acids142 ,143 or polyunsaturated fatty acids.144 Creatine supplementation has been studied more widely, though not using the same dose: one trial found significant improvements in limb strength and endurance,145 but this finding was not replicated in a subsequent study or a larger well conducted RCT.146 ,147 All three studies concurred on the lack of benefit in walk test performance. Despite a lack of evidence supporting any specific nutritional intervention in pulmonary rehabilitation to date, it should be acknowledged that a referral to pulmonary rehabilitation provides an ideal opportunity for anthropometrical and nutritional assessment to take place, thus providing an opportunity to identify individuals at greatest risk of malnutrition, enabling a referral to specialised dietetic primary or secondary care services.

Anabolic steroids have been used to augment the effects of training in healthy individuals and for cachexia in chronic diseases.148 Their use has been considered as to whether it may therefore augment the gains seen with pulmonary rehabilitation, potentially to a greater extent than in the healthy population due to the general catabolic state in COPD. The effects of testosterone and nandrolone have been explored in randomised placebo controlled clinical trials (in men only).35 ,149 Both of these studies found that anabolic steroids increased fat-free mass. There was no clinically significant improvement in measures of exercise capacity, though maximal leg strength improved with testosterone.

The aforementioned studies have focused on single interventions, but it may be argued that applying concurrent complementary interventions is a more logical approach. Nutritional supplementation, anabolic steroids and pulmonary rehabilitation appear to confer some benefit over controls when used together.150 However, this multifaceted approach has not been tested against a course of standard pulmonary rehabilitation and as such it is difficult to draw firm conclusions for usual practice.

NIV during pulmonary rehabilitation

Given the integration of NIV to the care of some patients with ventilatory failure in COPD, there has been discussion as to whether the use of the NIV during the exercise of pulmonary rehabilitation might improve walking distance and dyspnoea. The GDG were aware of studies that addressed the effects of concurrent domiciliary NIV with pulmonary rehabilitation,151–153 and others, including a systematic review,154 that examined the acute effects of NIV on exercise capacity rather than as part of a pulmonary rehabilitation/exercise training programme.

There were seven small RCTs which compared assisted ventilation during pulmonary rehabilitation with exercise training alone in patients with COPD. The presence of type II respiratory failure was not necessary for inclusion and the available data suggested that for the most part there was no resting hypercapnia. One study was not reviewed as mild patients were recruited and type II respiratory failure was specifically excluded.155 Of the remaining studies,156–161 all suggested some improvement in exercise performance with NIV either directly or indirectly (eg, lactate levels), but none showed clinically significant improvements in walk distance compared with pulmonary rehabilitation alone. In general, the studies had small numbers, were often unblinded and the randomisation process was unclear. Furthermore, these studies were performed in the laboratory setting with supervised training rather than in the real life outpatient pulmonary rehabilitation setting. Little information was given about patient tolerability/preference and health economic data were lacking.

There was consensus from the GDG that patients with stable type II respiratory failure should not be excluded from pulmonary rehabilitation referral (see section Referral and assessment of patients for pulmonary rehabilitation – Assessment). Furthermore, it is acceptable for patients established on domicillary NIV to exercise with NIV during pulmonary rehabilitation if acceptable and tolerable to the patient.

Supplemental oxygen in patients undergoing rehabilitation

Individuals with COPD are limited by their breathlessness,128 and in contrast to healthy individuals, their exertions are predominantly curtailed by limitation of ventilation and oxygenation rather than reaching their maximum heart rate.162 As supplemental oxygen can increase exercise capacity acutely in those with severe COPD,163 it is possible that such supplementation could increase the amount of training that patients with COPD could undertake. Simply being able to undertake a greater amount of training was postulated to augment the benefits from pulmonary rehabilitation. In addition, alleviation of a degree of pulmonary limitation was proposed to allow greater cardiac and muscular stress and thus have further beneficial effects on stroke volume and oxygen extraction.

In light of the above, trials investigating the use of supplemental oxygen with pulmonary rehabilitation have tended to recruit patients with more severe COPD indicated by a variety of criteria: spirometry,164 desaturation on exercise,165 both166 or by fulfilling criteria for ambulatory oxygen.167 The one trial that was more inclusive still reported a mean forced expiratory volume in 1 s in the total study populations of less than 50% predicted.168 The heterogeneity of baseline performance in these papers highlights the difficulty in using a single parameter to assess the severity of COPD. All of these trials were small and only one was double blinded and placebo controlled.164 This study by Emtner et al reported an improvement in health-related quality of life (Short Form 36) and in respiratory rate at isotime (the only trial to study effort independent isotime measurements) but not in other parameters such as dyspnoea, peak work or Chronic Respiratory Disease Questionnaire. These findings are consistent with the lack of additional benefit in walk test distance and short questionnaires seen in other studies.165 ,166 ,168 A randomised trial considered only individuals who were hypoxaemic on exertion and had improved saturations with supplemental oxygen. This trial reports a very large additional benefit in ESWT,167 though no commensurate additional gains in quality of life or breathlessness. The GDG felt the study carried a significant risk of bias that influenced its findings. Therefore its results require replication before they can be widely applied.

It would seem to be of limited benefit to combine these study results in a formal meta-analysis given the variation in inclusion criteria, interventions, rehabilitation/training programmes and assessment methods.

Overall, there is no clear evidence supporting the routine use of supplementary oxygen for all patients to augment the benefits of pulmonary rehabilitation. Supplemental oxygen may be of benefit in selected individuals, but there is currently little information to inform this choice, especially given the intra-individual variability of oxygen saturations on exercise on a day-to-day basis. No clinical measures have been demonstrated to robustly predict those individuals with COPD who may gain additional benefit (in terms of exercise or quality of life parameters) from supplemental oxygen during pulmonary rehabilitation. Likewise, no parameters have been shown to assess the risk of hypoxia-related harm during rehabilitation or predict who may avoid this with the administration of supplemental oxygen.

The BTS guidance on ambulatory oxygen prescription therefore appears to be a reasonable criterion to apply for patients attending pulmonary rehabilitation in this regard, although previous guidance has always recommended assessing for ambulatory oxygen on completion of pulmonary rehabilitation and hence does not directly address the rehabilitation period itself. At the time of the BTS pulmonary rehabilitation guideline publication, the BTS domiciliary oxygen guideline is being prepared. Pulmonary rehabilitation also provides an opportunity to assess the adequacy of the prescribed flow rate for patients already in receipt of LTOT or ambulatory oxygen.

Profound desaturation on exercise has the potential to lead to end-organ impairment and compromise the benefits of exercise. The trials discussed above largely did not permit saturations to fall below 90% but it is unclear if this threshold is of special significance. No trial reported adverse events during exercise that could have been attributed to hypoxia, and the experience of the guideline group was that this was representative of the apparent safety of pulmonary rehabilitation programmes. Until further evidence is available, the level of exercise-induced hypoxia that is acceptable will depend on clinical judgement in individual cases, and practitioners will have their own thresholds that will prompt further investigation for occult comorbidity or perhaps influence decisions on the nature of the programme instituted. These decisions may be more difficult in patients with lung fibrosis who tend to desaturate more readily on exercise but often with lesser symptomatic awareness. No trials reported adverse events related to oxygen toxicity.

Supplemental heliox in patients undergoing rehabilitation

Heliox is a mixture of helium and oxygen. Most often a mixture of 21% oxygen and 79% helium is used, but up to 40% oxygen has been studied. It has a similar viscosity to air but a significantly lower density. This means it is more likely to be laminar rather than turbulent flow in a given airway, which generates less resistance and can reduce the work of breathing. The administration of heliox has therefore been used for the treatment of large airway obstruction and vocal cord dysfunction, but it is of uncertain benefit in acute obstructive airways disease (potentially because the lower gas density exacerbates small airway collapse).169 ,170 As heliox reduces the work of breathing, it may permit greater exercise capacity in more stable patients with COPD, and as described above potentially increases the benefit from pulmonary rehabilitation.

Two studies have evaluated this intervention. The studies did not find additional benefits in their heliox arm when heliox (60% helium) was compared with supplemental oxygen,171 or heliox (79% helium) was compared with bi-level pressure support NIV156 or pulmonary rehabilitation alone.156 These trials were small and the study groups were heterogeneous in baseline function and response to rehabilitation. Hence, a small but meaningful additional beneficial effect of heliox cannot be discounted, but this is unlikely to be cost effective.

NMES and pulmonary rehabilitation

Despite the unequivocal benefits of whole body exercise training in stable disease, such intervention may be difficult to deliver in patients with severe ventilatory limitation during acute exacerbations or those with severe muscle wasting. Non-volitional techniques, such as NMES, which are independent of these factors, have been proposed as alternative therapeutic modalities.

The GDG were aware of several randomised studies and systematic reviews that addressed the effects of NMES in COPD.172 ,173 However, only two studies examined the adjuvant use of NMES with exercise training.174 ,175 One of these studies recruited inpatients receiving mechanical ventilation which was beyond the scope of these guidelines175; hence only one study was reviewed in detail.

In a RCT, 17 highly selected patients with COPD (low BMI, quadriceps weakness, severe limitation in cycle ergometry, recent exacerbation requiring hospitalisation or intensive care) received either 4 weeks of quadriceps NMES (four 30-min sessions per week) with usual rehabilitation or usual rehabilitation alone.174 The usual rehabilitation included active limb mobilisations with or without aerobic exercise and an educational component. Large improvements were seen in quadriceps maximum voluntary contraction after NMES plus usual rehabilitation compared with usual rehabilitation alone. Furthermore, there was a more significant reduction in breathlessness. Both groups significantly improved 6 min walk distance, but there was no between-group difference. Caution needs to be applied when interpreting the results. The patient group was highly selected and may not be typical of the general outpatient pulmonary rehabilitation population in the UK. The randomisation procedure was not described, there was no sham NMES and the tester was not blinded. Although patients seemed to tolerate NMES, it was not clear whether the NMES was set up by the therapist or the patient themselves. This is potentially important given that staff time is the major contributor to pulmonary rehabilitation costs.

There have been several small, single-centre studies supporting the benefits of NMES in improving quadriceps strength and exercise capacity, particularly in patients with more severe COPD or in the post-exacerbation setting.174 ,176–180

Non-CF bronchiectasis

A small RCT of subjects with non-CF bronchiectasis compared pulmonary rehabilitation, pulmonary rehabilitation with IMT and a control group; n=32 in total.181 Both pulmonary rehabilitation groups showed significant improvements in walking distance using ISWT and endurance exercise compared with the control group. There was a significant improvement in quality of life in the pulmonary rehabilitation plus IMT group but not in the pulmonary rehabilitation group alone compared with the controls, although the study was not powered for this outcome. The GDG additionally considered the evidence in the BTS bronchiectasis guideline (2010) and the bronchiectasis quality standards state that all patients with bronchiectasis should have access to and be considered for referral for pulmonary rehabilitation.6 ,182 ,183

Interstitial lung diseases

ILDs represent a broad diagnosis and the presentation and prognosis vary according to the specific diagnosis, which makes considering the impact of pulmonary rehabilitation complicated if they are considered as a whole. More specifically idiopathic pulmonary fibrosis (IPF) is often associated with progressive clinical and physiological deterioration over 6–12 months and patients with IPF often show marked desaturation during exercise. Importantly, we have focused on ILD as opposed to the breadth of all restrictive lung diseases, such as chest wall disease and other extra-thoracic causes.

A RCT from Japan included 30 patients with IPF randomised to pulmonary rehabilitation or a control arm. The study showed improvements in walking distance on a 6MWT and in quality of life using the SGRQ, but not in dyspnoea rating.184

Forty-four patients with ILD, including 25 with IPF, were studied before and after an 8-week pulmonary rehabilitation programme and 6 months later in an uncontrolled study.185 There was improvement in 6 min walking distance with pulmonary rehabilitation in the IPF (mean 21 m improvement) and other ILD group (mean 43 m), with 40% of the IPF group and 52% of the other ILD group reaching a minimally important difference of 34 m at rehabilitation completion. Similarly, dyspnoea improved in both groups. There was marked variability in response between individuals.185

Holland et al185 suggested that patients with IPF have greater improvements in functional exercise capacity when pulmonary rehabilitation is delivered early in the course of disease. Patients with other ILDs achieve significant gains in exercise capacity regardless of disease severity and are more likely than those with IPF to achieve sustained improvements in dyspnoea.185

The GDG were aware of a further well conducted exercise-based RCT in 57 patients with ILD (60% with IPF). This was not pulmonary rehabilitation and discussion ensued as to whether it should be included, given the paucity of literature otherwise. This study demonstrated modest improvements in functional exercise tolerance, dyspnoea and quality of life compared with telephone support.186 Importantly it was safe and feasible. There were four deaths (two per arm) during the study period, highlighting that patients with ILD can be critically ill. The effects of the exercise training were lost at the 6-month follow-up but this cannot be assumed post pulmonary rehabilitation. The GDG also considered that lack of any sustained benefit at 6 months may be due to underlying disease progression.

The GDG recognised the wide individual variation in the course of the conditions comprising ILD. This may make pulmonary rehabilitation a consideration for some. However, for others, a formalised pulmonary rehabilitation programme would be futile and management should focus on other palliative measures.

Asthma

One RCT studying patients with asthma and COPD (divided into diagnostic groups a posteriori) showed improvements in exercise tolerance and quality of life in those who completed a 12-week programme of pulmonary rehabilitation. However, the study findings are limited by a lack of power calculation in methodology and likely underpowered for the subgroup analysis. Compared with usual care, patients with asthma showed improvements in exercise tolerance, quality of life and a dyspnoea score.187

While not pulmonary rehabilitation, there is a Cochrane review supporting physical training in subjects with asthma, although the majority of the small population studies were conducted in children and did not focus on symptomatic subjects. It is therefore of little relevance here. The conclusions of the review acknowledged the diversity of the intervention type, duration, subjects and outcome measures of the studies.188

Standard asthma management should be managed according to the BTS/SIGN asthma guideline and the reader is drawn to the recommendation that physical training should be seen as part of a general approach to improving a healthy lifestyle following a Cochrane review.8 ,189 The BTS/SIGN asthma guideline raises standard precautions regarding observation for exercise-induced asthma if appropriate.

The GDG accepted that there is often overlap in asthma and COPD diagnoses and that many patients diagnosed with asthma have fixed airflow limitation and present with symptoms of persisting breathlessness and exercise intolerance in a similar manner to COPD. These patients are likely to benefit from pulmonary rehabilitation.

Other chronic respiratory diseases—in general

Repeat pulmonary rehabilitation programmes

The clinical conditions for which pulmonary rehabilitation is routinely offered result in progressive loss of function over time. It is therefore likely that any benefits arising from an initial programme of pulmonary rehabilitation will decay toward baseline function. There is the potential that a further course of pulmonary rehabilitation at a distant time point may provide further benefit.

Several RCTs and observational studies in which pulmonary rehabilitation is compared with standard care or education alone have followed participants for a protracted period. All studies have found that the initial beneficial effects diminish over time. However, those completing pulmonary rehabilitation courses have significantly greater quality of life, exercise capacity and fewer days in hospital than those in the control groups in the year after the intervention.12 ,190 ,191 The benefits appear to persist to some degree at 18 months,39 but there are conflicting data on whether a meaningful difference in exercise capacity persists at 2 years.192 ,193

Repeating pulmonary rehabilitation in those whose condition has deteriorated over time after their initial programme leads to improvements in quality of life and exercise capacity that have been reported to be similar in magnitude to those seen with the first intervention in retrospective reviews and two likely underpowered RCTs.192 ,194–196 A third session is again of short-term benefit.194 In those completing pulmonary rehabilitation in the NETT study, patients who had completed pulmonary rehabilitation previously (n=777) did not gain as much improvement in terms of exercise and quality of life on repeat as those for which it was their first programme (n=441), although they did improve.197

The timing of a repeat course of pulmonary rehabilitation would appear to be influenced by the aim of the intervention. As noted above, the great majority of the initial benefit is lost by 24 months, and two RCTs of routinely repeated pulmonary rehabilitation at a lesser interval have shown no major additional benefit from an intervening extra session in terms of exercise capacity at the end of the study.194 ,195 However, earlier repeat courses do lead to short-term benefits in exercise capacity and quality of life, which may be important in specific circumstances (eg, preoperatively). Additionally, in these studies the frequency of exacerbations appears lower in those who received additional courses,194 with fewer days spent in hospital.195 Although these findings are based on a small number of events, it raises the possibility that there is a subgroup of patients who are prone to frequent exacerbation who may benefit from early repeat pulmonary rehabilitation. A single small study followed patients after an initial course of pulmonary rehabilitation and randomised those who had an exacerbation during follow-up to either a further rehabilitation course or standard care.198 This study found no benefit in its major endpoints, although the occurrence of further exacerbations during follow-up makes it difficult to interpret the results.

Two small studies have sought baseline factors associated with a sustained response to pulmonary rehabilitation: a higher initial PaCO₂ was independently (positively) associated with a maintained initial improvement in quality of life, and a low baseline quality of life with a poor response.199 ,200 Neither of these studies provides sufficient evidence for the creation of a predictive tool.

Maintenance

Studies evaluating post-pulmonary rehabilitation maintenance exercise demonstrated a range of strategies in terms of exercise type, level of supervision, duration and frequency of maintenance programme. No consensus emerged from the literature about the definition of post-pulmonary rehabilitation exercise maintenance, making it difficult in some cases to distinguish between a ‘maintenance’ programme and extension of the initial pulmonary rehabilitation programme.

A small number of RCTs investigated the benefit of maintenance compared with no clear strategy post rehabilitation. Three studies describe the value of a structured maintenance approach after a standard out-patient course of rehabilitation.201–203 One UK-based study examined the value of telephone follow-up.204 One small RCT (n=20) described the value of an unsupervised home programme compared with no advice at all, which would essentially reflect best usual care; it would be unusual to graduate from a rehabilitation programme with no advice at all.205 The studies that described maintenance strategies chose different approaches over differing lengths of time. Brooks et al201 described a monthly supervised exercise session with telephone support in the interim. Measurements were taken at 3-monthly intervals up to 12 months and no benefit was observed in either exercise tolerance or quality of life compared with the control group for this approach. Ries et al202 described a large study (n=172), again offering 12 months of maintenance, comprising weekly telephone contact and monthly exercise sessions. Patients were followed up for 24 months. During the intervention period, there were benefits observed in exercise capacity but not in quality of life. Between 12 and 24 months there was no support provided and the difference between the groups narrowed and was not significant. A more intense maintenance programme was provided by Ringbaek et al203 with weekly sessions for 6 months after a 7-week outpatient programme, fortnightly sessions for a second 6 months and no supervision for a final 6 months. At 18 months there was no difference between the two groups. Again, however, examining the ‘maintenance’ group over the first 12 months, some advantages were observed, largely associated with a decline in performance in the control group, and maintenance of benefit acquired as a consequence of the initial rehabilitation phase with the intervention group. The study by Waterhouse et al,204 a UK-based study, looked at a telephone support system only. After completing a RCT of community versus hospital-based rehabilitation, participants were randomised to either telephone maintenance or usual care. There was no discernible benefit associated with this strategy at any time point up to 18 months post graduation from rehabilitation.

There have been a couple of studies exploring maintenance after alternative forms of delivering the initial rehabilitation. Wijkstra et al206 ,207 explored two maintenance strategies after a 3-month course of home-based rehabilitation; the study also recruited a control group. The intervention group was divided to receive either weekly exercise supervised by a physical therapist or monthly sessions for a further 15 months. The study was underpowered (n=11 and n=12 respectively) but demonstrated an advantage of both maintenance strategies in quality of life and physical performance. The quality of life was significantly improved in the group receiving the monthly support compared with the control group. The 6MWT distance was maintained during the 18-month period in the maintenance groups, while the control group declined. This was not different between groups but there was a significant within-group decline observed in the control group. More recently, there has been an examination of a maintenance programme after an initial inpatient programme.208 The maintenance approach was coordinated with a health community network that included self-help organisations. In total, the maintenance group received 96 sessions supervised by a healthcare professional over a 12-month period (exercise and psychosocial support). This study ‘consecutively allocated’ individuals (assume not randomised) to this package of care (n=14) or standard care (n=26). Although a small study, the data suggested important benefits in exercise capacity and quality of life. Interestingly there was also a reduction in hospital days for respiratory illness. This form of maintenance was probably not dissimilar to many rehabilitation programmes offered in the UK.