Pulmonary rehabilitation for interstitial lung disease
Abstract
Background
Interstitial lung disease (ILD) is characterised by reduced functional capacity, dyspnoea and exercise‐induced hypoxia. Pulmonary rehabilitation, an intervention that includes exercise training, is beneficial for people with other chronic lung conditions; however its effects in ILD have not been well characterised.
Objectives
• To determine whether pulmonary rehabilitation in patients with ILD has beneficial effects on exercise capacity, symptoms, quality of life and survival compared with no pulmonary rehabilitation in patients with ILD.
• To assess the safety of pulmonary rehabilitation in patients with ILD.
Search methods
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 6), MEDLINE (Ovid), EMBASE (Ovid), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (EBSCO) and the Physiotherapy Evidence Database (PEDro) (all searched from inception to June 2014). We also searched the reference lists of relevant studies, international clinical trial registries and respiratory conference abstracts to look for qualifying studies.
Selection criteria
Randomised and quasi‐randomised controlled trials in which pulmonary rehabilitation was compared with no pulmonary rehabilitation or with other therapy in people with ILD of any origin were included.
Data collection and analysis
Two review authors independently selected trials for inclusion, extracted data and assessed risk of bias. Study authors were contacted to provide missing data and information regarding adverse effects. A priori subgroup analyses were specified for participants with idiopathic pulmonary fibrosis (IPF) and participants with severe lung disease (low diffusing capacity or desaturation during exercise). We planned to subgroup according to training modality applied, but there were insufficient data.
Main results
Nine studies were included, six of which were published as abstracts. Five studies were included in the meta‐analysis (86 participants who undertook pulmonary rehabilitation and 82 control participants). One study used a blinded assessor and intention‐to‐treat analysis. No adverse effects of pulmonary rehabilitation were reported. Pulmonary rehabilitation improved the six‐minute walk distance with weighted mean difference (WMD) of 44.34 metres (95% confidence interval (CI) 26.04 to 62.64 metres) and improved oxygen consumption (VO2) peak with WMD of 1.24 mL/kg/min‐1 (95% CI 0.46 to 2.03 mL/kg/min‐1). Improvements in six‐minute walk distance and VO2 peak were also seen in the subgroup of participants with idiopathic pulmonary fibrosis (IPF) (WMD 35.63 metres, 95% CI 16.02 to 55.23 metres; WMD 1.46 mL/kg/min‐1, 95% CI 0.54 to 2.39 mL/kg/min‐1, respectively). Reduced dyspnoea (standardised mean difference (SMD) ‐0.66, 95% CI ‐1.05 to ‐0.28) following pulmonary rehabilitation was also seen in the IPF subgroup (SMD ‐0.68, 95% CI ‐1.12 to ‐0.25). Quality of life improved following pulmonary rehabilitation for all participants on a variety of measures (SMD 0.59, 95% CI 0.20 to 0.98) and for the subgroup of people with IPF (SMD 0.59, 95% CI 0.14 to 1.03). Two studies reported longer‐term outcomes, with no significant effects of pulmonary rehabilitation on clinical variables or survival at three or six months. Available data were insufficient to allow examination of the impact of disease severity or exercise training modality.
Authors' conclusions
Pulmonary rehabilitation seems to be safe for people with ILD. Improvements in functional exercise capacity, dyspnoea and quality of life are seen immediately following pulmonary rehabilitation, with benefits also evident in IPF. Because of inadequate reporting of methods and small numbers of included participants, the quality of evidence was low to moderate. Little evidence was available regarding longer‐term effects of pulmonary rehabilitation.
PICOs
Plain language summary
Pulmonary rehabilitation for interstitial lung disease (ILD)
Review question: We reviewed available evidence on the effects of pulmonary rehabilitation on exercise capacity, shortness of breath and quality of life in people with interstitial lung disease (ILD).
Background: People with ILD often have reduced exercise capacity and shortness of breath during exercise. Pulmonary rehabilitation can improve well‐being in people with other chronic lung disease, but little is known regarding pulmonary rehabilitation in ILD. We wanted to discover whether pulmonary rehabilitation was safe for people with ILD, and whether it provided advantages over usual care. We also looked at whether people with idiopathic pulmonary fibrosis (IPF), a type of ILD that can progress rapidly, could benefit from pulmonary rehabilitation.
Study characteristics: Nine studies were included; however only five studies provided sufficient information for the analysis (86 participants receiving pulmonary rehabilitation and 82 participants not receiving pulmonary rehabilitation). Three studies included only people with IPF, and the other six studies included people with a variety of ILDs. The average age of participants ranged from 36 to 71 years.
Key results: No reports described unwelcome effects of pulmonary rehabilitation. Immediately following pulmonary rehabilitation, participants could walk farther than those who had not undertaken pulmonary rehabilitation (on average, 44 metres farther in six minutes). Participants also improved their maximum exercise capacity and reported less shortness of breath and improved quality of life. People with IPF also experienced improvements in exercise capacity, dyspnoea and quality of life following pulmonary rehabilitation. Information was insufficient to establish whether ongoing effects were noted once pulmonary rehabilitation had stopped.
Quality of the evidence: Because of inadequate reporting of methods and small numbers of participants, the quality of evidence was low to moderate.
This Cochrane plain language summary is current to June 2014.
Authors' conclusions
Summary of findings
| Pulmonary rehabilitation compared with no pulmonary rehabilitation for interstitial lung disease | ||||||
| Patient or population: people with interstitial lung disease | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | Number of participants | Quality of the evidence | Comments | |
| Assumed risk | Corresponding risk | |||||
| No pulmonary rehabilitation | Pulmonary rehabilitation | |||||
| Change in 6‐minute walk distance Follow‐up: end of rehabilitation (8‐12 weeks) | Mean change in 6‐minute walk distance ranged across control groups from | Mean change in 6‐minute walk distance in the intervention groups was | MD 44.34 (26.04 to 62.64) | 168 | ⊕⊕⊕⊝ | |
| Change in peak oxygen uptake Follow‐up: end of rehabilitation (8‐12 weeks) | Mean change in peak oxygen uptake ranged across control groups from | Mean change in peak oxygen uptake in the intervention groups was | MD 1.24 (0.46 to 2.13) | 80 | ⊕⊕⊝⊝ | |
| Change in maximum ventilation Follow‐up: end of rehabilitation (8 weeks) | Mean change in maximum ventilation in control groups was | Mean change in maximum ventilation in the intervention groups was | MD 4.71 (0.10 to 9.32) | 52 | ⊕⊕⊝⊝ | |
| Change in dyspnoea score Follow‐up: end of rehabilitation (8‐12 weeks) | Mean change in dyspnoea score ranged across control groups from | Mean change in dyspnoea score in the intervention groups was | SMD ‐0.66 (‐1.05 to ‐0.28) | 113 | ⊕⊕⊝⊝ | Scores estimated using SMD ‐0.66 (‐1.05 to ‐0.28) Lower value post intervention is favourable, indicating improvement in dyspnoea |
| Change in quality of life Follow‐up: end of rehabilitation (8‐12 weeks) | Mean change in quality of life in control groups was | Mean change in quality of life in the intervention groups was | SMD 0.59 (0.2 to 0.98) | 106 | ⊕⊕⊝⊝ | Scores estimated using SMD 0.59 (0.2 to 0.98) Higher value post intervention is favourable, indicating improvement in quality of life |
| 6‐Month survival | 74 per 1000 | 67 per 1000 | RR 0.9 | 57 | ⊕⊕⊝⊝ | |
| Adverse events Follow‐up: 6 months | See comment | See comment | Not estimable | 85 | See comment | No adverse events were reported during the study period |
| *The basis for the assumed risk (e.g. median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence. | ||||||
| aMethods of randomisation were not described for most studies, and only 1 study reported blinding of the assessor (risk of bias ‐1). | ||||||
| Pulmonary rehabilitation compared with no pulmonary rehabilitation for idiopathic pulmonary fibrosis | ||||||
| Patient or population: people with idiopathic pulmonary fibrosis | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | Number of participants | Quality of the evidence | Comments | |
| Assumed risk | Corresponding risk | |||||
| No pulmonary rehabilitation | Pulmonary rehabilitation | |||||
| Change in 6‐minute walk distance Follow‐up: end of rehabilitation (8‐12 weeks) | Mean change in 6‐minute walk distance ranged across control groups from | Mean change in 6‐minute walk distance in the intervention groups was | MD 35.63 (16.02 to 55.23) | 111 | ⊕⊕⊕⊝ | |
| Change in peak oxygen uptake Follow‐up: end of rehabilitation (8‐12 weeks) | Mean change in peak oxygen uptake ranged across control groups from | Mean change in peak oxygen uptake in the intervention groups was | MD 1.46 (0.54 to 2.39) | 58 | ⊕⊕⊝⊝ | |
| Change in maximum ventilation Follow‐up: end of rehabilitation (8 weeks) | Mean change in maximum ventilation in the control groups was | Mean change in maximum ventilation in the intervention groups was | MD 6.97 (0.87 to 13.07) | 30 | ⊕⊕⊝⊝ | |
| Change in dyspnoea Follow‐up: end of rehabilitation (8‐12 weeks) | Mean change in dyspnoea ranged across control groups from | Mean change in dyspnoea in the intervention groups was | SMD ‐0.68 (‐1.12 to ‐0.25) | 90 | ⊕⊕⊝⊝ | Scores estimated using SMD ‐0.68 (‐1.12 to ‐0.25) Lower value post intervention is favourable, indicating improvement in dyspnoea |
| Change in quality of life Follow‐up: end of rehabilitation (8‐12 weeks) | Mean change in quality of life in the control groups was | Mean change in quality of life in the intervention groups was | SMD 0.59 (0.14 to 1.03) | 83 | ⊕⊕⊝⊝ | Scores estimated using SMD 0.59 (0.14 to 1.03) Higher value post intervention is favourable, indicating improvement in quality of life |
| 6‐Month survival | 143 per 1000 | 100 per 1000 | OR 0.67 | 34 | ⊕⊕⊝⊝ | |
| Adverse events Follow‐up: 6 months | See comment | See comment | Not estimable | 62 | See comment | No adverse events were reported during the study period |
| *The basis for the assumed risk (e.g. median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence. | ||||||
| aMethods of randomisation were not described for most studies, and only 1 study reported blinding of the assessor (risk of bias ‐1). | ||||||
Background
Description of the condition
Interstitial lung disease (ILD) is a highly disabling group of conditions including idiopathic pulmonary fibrosis (IPF), acute and chronic interstitial pneumonias, connective tissue diseases and sarcoidosis. People with ILD frequently experience breathlessness on exertion, which limits their ability to undertake daily activities. Patients report low levels of physical functioning and vitality and high levels of dyspnoea and fatigue. Those with the greatest exercise limitations have the worst quality of life (Chang 1999). Available treatments for patients with ILD have proved largely ineffective, offering no improvement in survival and demonstrating only limited impact on quality of life.
The mechanisms of reduced exercise capacity in ILD are multi‐factorial. Impaired gas exchange occurs as a result of destruction of the pulmonary capillary bed, resulting in ventilation‐perfusion mismatch and oxygen diffusion limitations (Agusti 1991). Circulatory limitation results from pulmonary capillary destruction and pulmonary vasoconstriction and leads to pulmonary hypertension and cardiac dysfunction in some patients (Hansen 1996). Ventilatory limitations to exercise may also occur, although these are not thought to be a major contributor in most patients (Harris‐Eze 1996). Peripheral muscle dysfunction may play a significant role in limiting exercise capacity (Markovitz 1998) as a result of physical deconditioning. Patients who experience dyspnoea and fatigue with functional activity commonly reduce their activity levels, leading to a vicious cycle of worsening exercise capacity and increasing symptoms. In addition, treatments for ILD such as corticosteroids and immunosuppressive therapy may lead to drug‐induced myopathy.
Description of the intervention
Pulmonary rehabilitation includes patient assessment, regular participation in an exercise training programme, education and behavioural change (Spruit 2013). The role of pulmonary rehabilitation is well established in people with other chronic lung diseases such as chronic obstructive pulmonary disease (COPD), for whom it improves exercise performance and reduces symptoms (Spruit 2013). Several authors have postulated that similar effects of pulmonary rehabilitation may be seen in patients with ILD.
How the intervention might work
The mechanism by which pulmonary rehabilitation might improve outcomes in people with ILD has not been established. In people with other respiratory diseases, pulmonary rehabilitation may improve aerobic capacity and improves peripheral muscle performance (Spruit 2013). Effects on these outcomes in ILD are unclear. Despite this, recently published guidelines for pulmonary rehabilitation have advocated its use in 'individuals with chronic respiratory disorders other than COPD' as 'there is now more robust evidence to support inclusion of some of these patient groups in pulmonary rehabilitation programs' (Spruit 2013). However, it has been suggested that the benefits of pulmonary rehabilitation in ILD are smaller than those generally seen in COPD, and its ongoing effects are not sustained beyond six months (Spruit 2013). Guidelines for clinical management of both ILD (Wells 2008) and IPF (ATS 2011) indicate that more information is needed on the benefits of pulmonary rehabilitation for these patients. The greater prevalence of exercise‐induced hypoxia, pulmonary hypertension and arrhythmia compared with other chronic lung diseases in this patient population raises the possibility that response to exercise rehabilitation may also differ (ATS 2011).
Why it is important to do this review
This review was conducted to summarise results reported in the literature of studies evaluating the safety and efficacy of pulmonary rehabilitation in adult patients with ILD, and to determine the effects of pulmonary rehabilitation on exercise capacity, symptoms, quality of life and survival in this patient group. This is an update of a review originally published in 2008.
Objectives
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To determine whether pulmonary rehabilitation in patients with ILD has beneficial effects on exercise capacity, symptoms, quality of life and survival compared with no pulmonary rehabilitation in patients with ILD.
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To assess the safety of pulmonary rehabilitation in patients with ILD.
Methods
Criteria for considering studies for this review
Types of studies
Only randomised and quasi‐randomised controlled trials in which a prescribed regimen of pulmonary rehabilitation was compared with no pulmonary rehabilitation or with other therapy in study participants with ILD were considered for this review. Single‐blind and open studies were considered for inclusion.
Types of participants
People with ILD of any origin, diagnosed according to investigator definitions, were included. No exclusions were based on age, gender or physiological status.
Types of interventions
We considered any type of prescribed exercise training, supervised or unsupervised, provided with or without education. We recorded, when possible, the precise nature of the training (intensity, frequency, duration and whether supplemental oxygen was applied). Trials in which pulmonary rehabilitation was combined with another intervention (e.g. pharmacological therapy) were eligible for inclusion.
Comparisons to be examined included the following.
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Pulmonary rehabilitation versus no pulmonary rehabilitation.
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Pulmonary rehabilitation versus another intervention.
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Pulmonary rehabilitation combined with another intervention versus no pulmonary rehabilitation.
Types of outcome measures
Primary outcomes
Functional or maximal exercise capacity, measured during formal exercise tests (maximal oxygen uptake (VO2 max), peak oxygen uptake (VO2 peak), maximal ventilation (Ve max), maximum heart rate (HR max)) or field exercise tests (increase in distance walked).
Secondary outcomes
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Dyspnoea: All measures of dyspnoea used were considered.
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Quality of life: This was measured by generic or disease‐specific quality of life instruments. All quality of life instruments used were considered.
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Adverse effects: Adverse cardiovascular events during exercise training were recorded, as were fractures, skeletal muscle injuries and deaths.
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Survival
Search methods for identification of studies
Electronic searches
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 6), MEDLINE (Ovid), EMBASE (Ovid), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (EBSCO) and the Physiotherapy Evidence Database (PEDro). All databases were searched from the period of their inception to June 2014. No language restriction was applied.
The full database search strategies are listed in the appendices (Appendix 1, Appendix 2, Appendix 3, Appendix 4 and Appendix 5).
Searching other resources
The reference lists of relevant studies and related review papers were handsearched for qualifying studies. Clinical trial registries were reviewed to search for relevant planned, ongoing and unpublished trials. Annual conference abstracts for the American Thoracic Society (ATS), the European Respiratory Society (ERS), the Asian Pacific Society of Respirology (APSR) and the Thoracic Society of Australia and New Zealand (TSANZ) were reviewed for relevant studies. In addition, we contacted the authors of randomised controlled trials to ask for information on other published and unpublished studies.
Data collection and analysis
Selection of studies
Two review authors (LD and AH) independently coded for relevance studies identified in the literature searches by examining titles, abstracts and keyword fields as follows.
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Include: Study categorically meets all review criteria.
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Unclear: Study appears to meet some review criteria, but available information is insufficient for review authors to categorically determine relevance.
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Exclude: Study does not categorically meet all review criteria.
Two review authors (LD and AH) used a full‐text copy of studies in categories 1 and 2 to decide on study inclusion. Disagreements were resolved by consensus. A full record of decisions was kept, and simple agreement and kappa statistics were calculated.
Data extraction and management
Data were extracted independently by two review authors (LD and AH) who used a prepared checklist; they were then entered into Review Manager by the primary review author with random checks on accuracy. Disagreements were resolved by consensus. Data included characteristics of included studies (methods, participants, interventions, outcomes) and results of included studies. Authors of included studies were asked to provide details of missing data where applicable.
Assessment of risk of bias in included studies
Two review authors (LD and AH) assessed the internal validity of included studies using a component approach (including sequence generation for randomisation, allocation concealment, blinding of participants and assessors, loss to follow‐up, completeness of outcome assessment and other possible bias prevention). Disagreements were resolved by consensus. We wrote to study authors to seek clarification when information was inadequate for review authors to judge the risk of bias.
Measures of treatment effect
For continuous variables, we recorded mean change from baseline or mean postintervention values and standard deviation (SD) for each group. When measures of improvement had opposite directions of effect on different scales (e.g. quality of life scales), all improvements were recorded as positive values, and all deteriorations were recorded as negative values. Mean differences (MDs) for outcomes measured with the same metrics or standardised mean differences (SMDs) for outcomes measured with different metrics with 95% confidence intervals (95% CIs) were calculated using RevMan 5.2. For binary outcome measures, we recorded the number of participants with each outcome event, by allocated treated group, to allow intention‐to‐treat analysis. Odds ratios (ORs) with 95% CIs were calculated for each study.
Data synthesis
We performed a pooled quantitative analysis when trials were clinically homogeneous. A fixed‐effect model or a random‐effects model was used, depending on assessment of heterogeneity.
Subgroup analysis and investigation of heterogeneity
Subgroup analyses were conducted to explore possible sources of heterogeneity. Three subgroup analyses were specified a priori.
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Type of interstitial lung disease: idiopathic pulmonary fibrosis (IPF) versus other: As a result of the progressive nature of IPF, pulmonary rehabilitation could be less effective in this form of ILD.
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Severity of lung disease: Patients with more advanced disease may be less able to participate in pulmonary rehabilitation. Participants were considered to have severe disease if diffusing capacity for carbon monoxide (TLCO) was less than 45% predicted (Flaherty 2001). In addition, participants who desaturated during exercise testing (SpO2 less than or equal to 88%) were compared with those who did not desaturate.
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Type of exercise: Aerobic exercise training programmes may be more effective in improving symptoms and functional exercise tolerance than resistance training programmes. However, data were insufficient to allow review authors to perform this subgroup analysis.
Sensitivity analysis
The small number of studies precluded performance of sensitivity analyses and the creation of funnel plots to test for publication bias. If in future updates, more studies are included, sensitivity analysis will be performed to analyse the effects of allocation concealment, and intention‐to‐treat analysis will be performed on study results.
Results
Description of studies
Results of the search
See Figure 1 for the study flow diagram.
Study flow diagram for 2009‐2013 literature searches.
In the original version, 4783 records were identified from the initial search of databases. From the studies on this list, 15 full‐text articles were retrieved for closer inspection. No additional studies were identified upon handsearching of reference lists or contact with study authors. Review authors achieved agreement on 13 of the 15 full‐text articles (87%) with kappa = 0.74, indicating substantial agreement. Disagreement was resolved by consensus. Five articles were deemed to meet the inclusion criteria for the original review. An update search conducted in December 2009 identified no relevant studies for inclusion in the review. The 2014 updated search of databases returned 1901 potential studies. Eight full‐text articles from this list were retrieved for closer inspection. Six additional studies were identified upon handsearching of reference lists and review of international clinical trial registries and annual international respiratory conference abstracts. Correspondence with Jackson 2014 indicated that the final results of the study had been submitted and accepted for publication. Data from the accepted manuscript were used in the analysis. Agreement between review authors was achieved on 13 of the 14 full‐text articles (92%) with kappa = 0.81, indicating substantial agreement. Disagreement was resolved by consensus. Four studies from the updated search were deemed to meet the inclusion criteria; one article is awaiting classification and therefore was not included in the analysis. Nine articles in total from the original and updated searches were included in this review. Common reasons for exclusion were that studies were not randomised controlled trials (n = 5), studies included participants without lung disease (n = 3), studies included mixed disease groups (n = 3) and studies did not include pulmonary rehabilitation (n = 2). Full details of excluded studies and of studies awaiting classification can be found in the Characteristics of excluded studies and Characteristics of studies awaiting classification tables.
Included studies
Nine studies met the inclusion criteria for this review; all were parallel randomised controlled trials. Full details can be found in the Characteristics of included studies table. Six studies had been published in abstract form only (Baradzina 2005; Mejia 2000; Menon 2011; Perez Bogerd 2011; Vainshelboim 2013; Wewel 2005). Sample sizes ranged from 21 to 99 participants.
Participants
Most studies included participants with a variety of ILDs (Holland 2008; Mejia 2000; Menon 2011; Perez Bogerd 2011; Wewel 2005), one of which was stratified for IPF (Holland 2008). Three studies included only participants with IPF (Jackson 2014; Nishiyama 2008; Vainshelboim 2013), whilst another study included only participants with sarcoidosis (Baradzina 2005). All participants were adults with mean age ranging from 36 to 71 years. One study did not report mean age (Menon 2011).
Interventions
All studies compared pulmonary rehabilitation versus no pulmonary rehabilitation or a sham training control group. Eight studies examined pulmonary rehabilitation programmes conducted in the outpatient setting (Baradzina 2005; Holland 2008; Jackson 2014; Mejia 2000; Menon 2011; Nishiyama 2008; Perez Bogerd 2011; Vainshelboim 2013), whilst one study evaluated a home‐based pulmonary rehabilitation programme (Wewel 2005). The length of pulmonary rehabilitation programmes varied from five to 12 weeks for outpatient rehabilitation and six months for home‐based rehabilitation.
Three studies examined the effects of aerobic training (Baradzina 2005; Mejia 2000; Wewel 2005), four studies used a combination of aerobic and resistance training (Holland 2008; Jackson 2014; Nishiyama 2008; Vainshelboim 2013) and the remaining studies did not specify the exercise modality used (Menon 2011; Perez Bogerd 2011). No study evaluated resistance training alone; therefore no subgroup analyses for type of exercise were possible. Four studies comprised exercise training alone (Holland 2008; Mejia 2000; Vainshelboim 2013; Wewel 2005), whereas four studies added interventions to exercise training that were not offered to the control group; these included educational lectures (Baradzina 2005; Jackson 2014; Nishiyama 2008; Perez Bogerd 2011), nutritional advice (Baradzina 2005; Perez Bogerd 2011), stress management (Baradzina 2005), physiotherapy (Baradzina 2005) and psychosocial support (Perez Bogerd 2011). Inclusion of additional interventions with exercise training was unclear in one study (Menon 2011).
Outcomes
All studies used a measure of functional exercise tolerance, most commonly the six‐minute walk test (Holland 2008; Jackson 2014; Menon 2011; Nishiyama 2008; Perez Bogerd 2011; Vainshelboim 2013; Wewel 2005). Three studies also performed a cardiopulmonary exercise test (Holland 2008; Vainshelboim 2013; Wewel 2005). Quality of life was assessed in eight studies, using the Chronic Respiratory Disease Questionnaire (Holland 2008; Mejia 2000; Perez Bogerd 2011), the St George's Respiratory Questionnaire (Nishiyama 2008; Perez Bogerd 2011; Vainshelboim 2013; Wewel 2005), the St George's Respiratory Questionnaire (idiopathic pulmonary fibrosis version) (Jackson 2014) or the World Health Organization (WHO) questionnaire (Baradzina 2005). Dyspnoea was assessed in five studies using the modified Medical Research Council Scale (Holland 2008; Vainshelboim 2013), the Baseline Dyspnoea Index (Nishiyama 2008) and an unspecified measure (Baradzina 2005; Wewel 2005).
Risk of bias in included studies
An overview of the risk of bias for the domains listed below is provided in Figure 2.
Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
Allocation
All studies reported random allocation to groups; no study specified the method by which the sequence was generated. Four studies reported that the allocation sequence was concealed (Holland 2008; Jackson 2014; Nishiyama 2008; Vainshelboim 2013), three studies used sealed envelopes (Holland 2008; Nishiyama 2008; Vainshelboim 2013) and in the other study, group allocation was provided by an independent researcher (Jackson 2014). The remaining studies, all of which were available only in abstract form, did not provide sufficient information to permit assessment of whether the allocation sequence was concealed (Baradzina 2005; Mejia 2000; Menon 2011; Perez Bogerd 2011; Vainshelboim 2013; Wewel 2005).
Blinding
One study (Holland 2008) reported use of a blinded assessor for all outcome measures, and three studies indicated that the assessors were unblinded (Jackson 2014; Perez Bogerd 2011; Vainshelboim 2013). Insufficient data were available to show whether assessors were blinded in the other studies (Baradzina 2005; Mejia 2000;Menon 2011; Nishiyama 2008; Wewel 2005). Blinding of participants was not possible for any study because of the physical nature of the intervention. No studies reported whether data analysts were blinded to treatment allocation.
Incomplete outcome data
Three studies reported dropouts and loss to follow‐up (Holland 2008; Jackson 2014; Nishiyama 2008). One of these reported that two participants in the exercise group withdrew before baseline data had been collected (Nishiyama 2008), and another study reported that three participants in the exercise group and one in the control group did not complete the intervention period (Jackson 2014). Data from these participants were not included in the analysis in either study (Jackson 2014; Nishiyama 2008). The other study reported a significant number of dropouts, with data analysis performed according to the intention‐to‐treat principle; the last observation carried forward method was used when data were not available (Holland 2008). The other studies did not report whether dropouts or losses to follow‐up occurred.
Selective reporting
Four studies were listed on a clinical trial registry (Holland 2008; Jackson 2014; Perez Bogerd 2011; Vainshelboim 2013). Results were reported for all outcomes at all time points for two studies (Holland 2008; Jackson 2014), whereas the other two studies did not report all outcome measures mentioned in the clinical registry (Perez Bogerd 2011; Vainshelboim 2013). These studies were provided only in abstract form, and it is likely that not all data are currently available. It was not possible for review authors to determine whether all data were available for the other studies, all of which were provided only in abstract form (Baradzina 2005; Mejia 2000; Menon 2011; Wewel 2005); therefore it is likely that not all data from these studies are currently available.
Effects of interventions
See: Summary of findings for the main comparison Pulmonary rehabilitation compared with no pulmonary rehabilitation for interstitial lung disease; Summary of findings 2 Pulmonary rehabilitation compared with no pulmonary rehabilitation for idiopathic pulmonary fibrosis
Data and analyses tables summarise results of the meta‐analysis for comparison of pulmonary rehabilitation versus no pulmonary rehabilitation. Sufficient data were available from five studies for pooling in a meta‐analysis (Holland 2008; Jackson 2014; Nishiyama 2008; Perez Bogerd 2011; Vainshelboim 2013). summary of findings Table for the main comparison and summary of findings Table 2 summarise the quality of the evidence. For functional exercise capacity, maximal exercise capacity and quality of life, positive values reflect improvement. For measures of dyspnoea, negative values reflect improvement.
Functional exercise capacity
Eight trials including 365 participants reported that pulmonary rehabilitation resulted in significant improvement in functional exercise capacity immediately following the programme, whilst no significant change was seen in six‐minute walk distance following pulmonary rehabilitation in the remaining study (Jackson 2014). Five trials provided sufficient data on the six‐minute walk test for meta‐analysis, with a total of 86 participants in the pulmonary rehabilitation group and 82 participants in the control group (Holland 2008; Jackson 2014; Nishiyama 2008; Perez Bogerd 2011; Vainshelboim 2013). Results of the meta‐analysis are shown in Figure 3. The common effect (mean difference, MD) for change in distance walked was 44.34 metres in favour of the pulmonary rehabilitation group (95% CI 26.04 to 66.64 metres). A significant effect of pulmonary rehabilitation was also seen in the subgroup of participants with IPF (four trials, n = 59 pulmonary rehabilitation, n = 52 control) with a common effect of 35.63 metres (95% CI 16.02 to 55.23 metres). Only one study provided sufficient data to show the effects of pulmonary rehabilitation among participants with severe lung disease (n = 23) or in participants who desaturated (n = 30), and no significant effects of pulmonary rehabilitation were evident in these groups (Holland 2008). One study (Holland 2008) reported results of the six‐minute walk test at six‐month follow‐up (Analysis 1.2), and another study evaluated the six‐minute walk test after a subsequent three‐month observation period (Jackson 2014). No significant effect of pulmonary rehabilitation was evident at either time point. Tests of heterogeneity for all analyses of functional exercise capacity were not significant.
Forest plot of comparison: 1 Pulmonary rehabilitation versus no pulmonary rehabilitation, outcome: 1.1 Change in 6‐minute walk test immediately following pulmonary rehabilitation.
Maximal exercise capacity
Three studies reported that cardiopulmonary exercise testing was performed following pulmonary rehabilitation; however data were available from only two studies with 42 participants in the pulmonary rehabilitation group and 38 participants in the control group (Holland 2008; Vainshelboim 2013). A significant increase in VO2 peak was noted between baseline and follow‐up with an MD of 1.24 mL/kg/min (95% CI 0.46 to 2.03 mL/kg/min‐1) in favour of the pulmonary rehabilitation group (Figure 4). A similar effect was seen in the subgroup of participants with IPF (two trials, n = 32 pulmonary rehabilitation, n = 26 control) with a common effect of 1.46 mL/kg/min‐1 (95% CI 0.54 to 2.39 mL/kg/min‐1). No significant differences in VO2 peak were observed among participants with severe lung disease or in participants who desaturated. Both studies reported that pulmonary rehabilitation resulted in a significant increase in maximum ventilation; however only one study with 57 participants (Holland 2008) provided sufficient data for meta‐analysis (Analysis 1.4). The MD between groups was 4.71 L/min‐1 (95% CI 0.10 to 9.32) in favour of the pulmonary rehabilitation group. The effect was more pronounced in the subgroup of participants with IPF (one study, 30 participants, MD 6.97 L/min‐1, 95% CI 0.87 to 13.07). No significant effects of pulmonary rehabilitation on maximum exercise parameters were seen in the subgroups of severe disease or in desaturators. No significant effect of pulmonary rehabilitation on maximum heart rate was evident (Analysis 1.5).
Forest plot of comparison: 1 Pulmonary rehabilitation versus no pulmonary rehabilitation, outcome: 1.3 VO2 peak immediately following pulmonary rehabilitation, mL/kg/min.
Dyspnoea
Dyspnoea was measured in five studies including 281 participants, with three reporting reduced dyspnoea immediately following pulmonary rehabilitation (Baradzina 2005; Holland 2008; Vainshelboim 2013) and two studies reporting no change (Nishiyama 2008; Wewel 2005). Data from three studies were pooled for meta‐analysis with a total of 58 participants in the pulmonary rehabilitation group and 55 participants in the control group (Figure 5). Two studies utilised the modified Medical Research Council Scale (Holland 2008; Vainshelboim 2013), and the other used the Baseline Dyspnoea Index (Nishiyama 2008). The common effect (standardised mean difference, SMD) for change in dyspnoea was ‐0.66 in favour of the pulmonary rehabilitation group (95% CI ‐1.05 to ‐0.28). A similar reduction in dyspnoea was seen among participants with IPF (48 participants in the pulmonary rehabilitation group and 42 participants in the control group), with an MD of ‐0.68 (95% CI ‐1.12 to ‐0.25, three studies, 90 participants). An effect in favour of pulmonary rehabilitation was seen in participants with severe disease and in those who desaturated; however this finding reached significance only for the desaturators (Figure 5). One study reported dyspnoea at six‐month follow‐up (Analysis 1.7). No significant effect of pulmonary rehabilitation on dyspnoea was evident at this time. Tests of heterogeneity for all analyses of dyspnoea were not significant.
Forest plot of comparison: 1 Pulmonary rehabilitation versus no pulmonary rehabilitation, outcome: 1.6 Dyspnoea score immediately following pulmonary rehabilitation.
Quality of life
Health‐related quality of life was measured in eight studies, with significant differences between groups reported immediately following pulmonary rehabilitation in three studies (Holland 2008; Nishiyama 2008; Vainshelboim 2013). Two studies reported improvement in heath‐related quality of life following pulmonary rehabilitation; however this finding did not reach statistical significance (Jackson 2014; Perez Bogerd 2011); in the remaining studies it was unclear whether differences were noted between groups. Data were available for pooling from three studies with a total of 54 participants in the pulmonary rehabilitation group and 52 participants in the control group (Figure 6). Two studies utilised the Chronic Respiratory Disease Questionnaire (Holland 2008), one used the St George's Respiratory Questionnaire (Nishiyama 2008) and the other used the St George's Respiratory Questionnaire (idiopathic pulmonary fibrosis version) (Jackson 2014). A common effect indicated improvement in quality of life associated with pulmonary rehabilitation (SMD 0.59, 95% CI 0.20 to 0.98). A similar effect in favour of pulmonary rehabilitation was seen in participants with IPF (SMD 0.59, 95% CI 0.14 to 103, three studies, 83 participants). Data regarding effects on quality of life in participants with severe disease and in those who desaturated were available from one study (Holland 2008), in which trends favouring pulmonary rehabilitation did not reach statistical significance. Data regarding longer‐term effects on quality of life were available from two studies (Holland 2008; Jackson 2014) with one study reporting results at six‐month follow‐up (Analysis 1.9), and the other evaluating quality of life after a subsequent three‐month observation period (Jackson 2014). No effects of pulmonary rehabilitation were noted at three months or six months, except in the subgroup of participants with severe disease, who had significantly improved quality of life compared with controls at six‐month follow‐up (SMD 14.93, 95% CI 0.54 to 29.32, one study, 23 participants).
Forest plot of comparison: 1 Pulmonary rehabilitation versus no pulmonary rehabilitation, outcome: 1.8 Change in quality of life immediately following pulmonary rehabilitation.
Adverse events
Information regarding adverse events was available from two studies (Holland 2008; Nishiyama 2008), neither of which reported adverse events during the study period. One study reported the death of one pulmonary rehabilitation participant during the intervention period; however this was believed to be unrelated to the intervention received, and the data were not included in the analysis (Jackson 2014).
Survival
Six‐month survival was reported in one study including 57 participants (Holland 2008) in which two deaths were reported in each group (Analysis 1.6).
Discussion
Summary of main results
This review identified nine studies comparing pulmonary rehabilitation versus no pulmonary rehabilitation or sham control among people with ILD. No adverse effects of this treatment were identified. Pulmonary rehabilitation resulted in a clear improvement in functional exercise capacity, as measured by the six‐minute walk test, and a small increase in maximum exercise capacity. Significant reduction in dyspnoea and improvement in quality of life were seen immediately following pulmonary rehabilitation. Effects were similar in the subgroup of participants with IPF. Insufficient data were available to allow conclusions regarding the effects of pulmonary rehabilitation among those with severe disease and those who desaturated. To date, data are insufficient to allow conclusions regarding the long‐term effects of pulmonary rehabilitation in ILD.
Mean improvement in the six‐minute walk test following pulmonary rehabilitation was 44.34 metres, which is similar to the mean improvement of 48 metres seen in people with COPD who have undergone pulmonary rehabilitation (Lacasse 2006). This suggests that people with ILD receive comparable benefit from pulmonary rehabilitation. This improvement exceeds the minimal important difference for six‐minute walk distance among people with ILD, which ranges from 30 to 33 metres (Holland 2009). This indicates that providing a pulmonary rehabilitation programme that is well aligned with current guidelines for pulmonary rehabilitation (Spruit 2013) results in clinically important changes in functional capacity. Significant improvements were also seen in dyspnoea and in health‐related quality of life following pulmonary rehabilitation, supporting the view that the observed improvement may be meaningful for patients.
Overall completeness and applicability of evidence
Included studies involved participants with a range of ILDs, and studies often included samples of participants with mixed diagnoses (Holland 2008; Mejia 2000; Menon 2011; Perez Bogerd 2011; Wewel 2005). This recruitment strategy probably reflects the relatively uncommon nature and the shared pathophysiological features of many ILDs. Participants with IPF often have more severe physiological derangement and a more rapid disease course compared with those with other ILDs (Lama 2004), and we hypothesised that pulmonary rehabilitation might be less effective in people with IPF. However, this review indicates that participants with IPF did achieve significant improvement in six‐minute walk test results, maximum exercise capacity, dyspnoea and health‐related quality of life. Improvement in the six‐minute walk test was smaller among participants with IPF (35.63 m vs 44.34 m); however this mean improvement still exceeded the minimal important difference for the six‐minute walk distance in people with IPF, which is in the range of 29to 34 m (Holland 2009). Changes in quality of life, dyspnoea and maximum exercise capacity were also comparable in the subgroup of participants with IPF. Although patients with IPF appear to have smaller gains in functional capacity than those with other ILDs, they are equally important and meaningful for patients. Differences in functional outcomes do indicate that response to exercise may vary across the disease spectrum, which is not unexpected given the marked heterogeneity in clinical presentation and course. It should be noted however that of the five studies contributing to the meta‐analysis, three included only participants with IPF (Jackson 2014; Nishiyama 2008; Vainshelboim 2013), whilst another included a majority of participants with IPF (Holland 2008); thus overall results of the meta‐analysis are heavily influenced by the response of participants with IPF.
All studies in this review utilised aerobic exercise training or a combination of aerobic and resisted exercise training. These strategies are well aligned with current guidelines for pulmonary rehabilitation (Spruit 2013), and the results therefore are readily applicable to clinical practice in pulmonary rehabilitation programmes. However, we were unable to draw inferences regarding the most effective exercise training strategy for people with ILD. Given the relatively modest improvements in exercise capacity documented here, this may be an important area for future research. The included studies used a range of programme durations (five weeks to six months) and training frequencies (two to five sessions per week). Longer programmes and more frequent sessions appear to yield greater benefit for people with other chronic lung diseases (Spruit 2013). To date the most effective dose of pulmonary rehabilitation for people with ILD has not been established.
Quality of the evidence
Several potential sources of bias were identified in this review. Of the nine studies identified, six were available only in abstract form (Baradzina 2005; Mejia 2000; Menon 2011: Perez Bogerd 2011; Vainshelboim 2013; Wewel 2005). These publications provided limited data on the outcomes of interest, and it was not possible for review authors to obtain additional data from study authors. Data that could be pooled for meta‐analysis were usually limited to two or three studies. Despite this limitation, consistency was seen in most reported outcomes, with all but one study (Jackson 2014) reporting improved functional exercise capacity following pulmonary rehabilitation. Reasons for lack of improvement in functional exercise capacity in the remaining study (Jackson 2014) are unclear but may have been related to the method by which the six‐minute walk test was conducted or may have involved the small numbers of included participants. Assessment of study quality was also difficult because available data were limited. As pulmonary rehabilitation is a physical intervention, it can be assumed that no participants were blinded; however only one study reported blinding of the assessor (Holland 2008). Only one study reported use of an intention‐to‐treat analysis (Holland 2008). Given the progressive nature of many ILDs, a significant dropout rate is likely and may impact both the size of the reported treatment effect and the feasibility of the intervention.
Review outcomes were rated as of moderate quality (six‐minute walk distance) or low quality (all other outcomes) using the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) system. Risk of bias was increased by poor reporting of methods and lack of assessor blinding. Imprecision was increased by the small numbers of included studies and participants, with one to five studies and 52 to 168 participants contributing to each outcome.
Potential biases in the review process
All data were extracted independently by two review authors, and discrepancies were resolved through discussion. Risk of bias ratings were also completed independently by two review authors.
We conducted a broad search, which included handsearching of conference abstracts and trial registries. We included studies that were published only in abstract form, to ensure that all available trials were included. However, despite attempts to contact the authors of abstracts, in many cases additional data were not available. This may have influenced assessment of trial quality and some estimates of effect.
Agreements and disagreements with other studies or reviews
This is an update of a Cochrane review published in 2008. Data included in the previous review suggested that improvement in functional exercise capacity following pulmonary rehabilitation in ILD was smaller than that seen in people with COPD (Lacasse 2006); however this update has found comparable improvements. This is a significant finding that supports the recent international statement suggesting that people with ILD should be included in pulmonary rehabilitation programmes (Spruit 2013). Although the previous review found that the effect of pulmonary rehabilitation tended to be smaller in people with IPF than in those with other types of ILD, this update has found similar, clinically important effects of rehabilitation in both groups, likely due to the larger number of trials including people with IPF that were included in this update.
Study flow diagram for 2009‐2013 literature searches.
Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
Forest plot of comparison: 1 Pulmonary rehabilitation versus no pulmonary rehabilitation, outcome: 1.1 Change in 6‐minute walk test immediately following pulmonary rehabilitation.
Forest plot of comparison: 1 Pulmonary rehabilitation versus no pulmonary rehabilitation, outcome: 1.3 VO2 peak immediately following pulmonary rehabilitation, mL/kg/min.
Forest plot of comparison: 1 Pulmonary rehabilitation versus no pulmonary rehabilitation, outcome: 1.6 Dyspnoea score immediately following pulmonary rehabilitation.
Forest plot of comparison: 1 Pulmonary rehabilitation versus no pulmonary rehabilitation, outcome: 1.8 Change in quality of life immediately following pulmonary rehabilitation.
Comparison 1 Pulmonary rehabilitation vs no pulmonary rehabilitation, Outcome 1 Change in 6‐minute walk distance immediately following pulmonary rehabilitation. Mean change from baseline, metres.
Comparison 1 Pulmonary rehabilitation vs no pulmonary rehabilitation, Outcome 2 Change in 6‐minute walk test at long‐term follow‐up. Mean change from baseline, metres.
Comparison 1 Pulmonary rehabilitation vs no pulmonary rehabilitation, Outcome 3 Change in VO2 peak immediately following pulmonary rehabilitation, mL/kg/min.
Comparison 1 Pulmonary rehabilitation vs no pulmonary rehabilitation, Outcome 4 Change in VEmax immediately following pulmonary rehabilitation, L/min.
Comparison 1 Pulmonary rehabilitation vs no pulmonary rehabilitation, Outcome 5 Change in maximum heart rate immediately following pulmonary rehabilitation, beats per minute.
Comparison 1 Pulmonary rehabilitation vs no pulmonary rehabilitation, Outcome 6 6‐Month survival.
Comparison 1 Pulmonary rehabilitation vs no pulmonary rehabilitation, Outcome 7 Change in dyspnoea score at long‐term follow‐up.
Comparison 1 Pulmonary rehabilitation vs no pulmonary rehabilitation, Outcome 8 Change in quality of life immediately following pulmonary rehabilitation.
Comparison 1 Pulmonary rehabilitation vs no pulmonary rehabilitation, Outcome 9 Change in quality of life at long‐term follow‐up.
Comparison 1 Pulmonary rehabilitation vs no pulmonary rehabilitation, Outcome 10 Change in dyspnoea score immediately following pulmonary rehabilitation.
| Pulmonary rehabilitation compared with no pulmonary rehabilitation for interstitial lung disease | ||||||
| Patient or population: people with interstitial lung disease | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | Number of participants | Quality of the evidence | Comments | |
| Assumed risk | Corresponding risk | |||||
| No pulmonary rehabilitation | Pulmonary rehabilitation | |||||
| Change in 6‐minute walk distance Follow‐up: end of rehabilitation (8‐12 weeks) | Mean change in 6‐minute walk distance ranged across control groups from | Mean change in 6‐minute walk distance in the intervention groups was | MD 44.34 (26.04 to 62.64) | 168 | ⊕⊕⊕⊝ | |
| Change in peak oxygen uptake Follow‐up: end of rehabilitation (8‐12 weeks) | Mean change in peak oxygen uptake ranged across control groups from | Mean change in peak oxygen uptake in the intervention groups was | MD 1.24 (0.46 to 2.13) | 80 | ⊕⊕⊝⊝ | |
| Change in maximum ventilation Follow‐up: end of rehabilitation (8 weeks) | Mean change in maximum ventilation in control groups was | Mean change in maximum ventilation in the intervention groups was | MD 4.71 (0.10 to 9.32) | 52 | ⊕⊕⊝⊝ | |
| Change in dyspnoea score Follow‐up: end of rehabilitation (8‐12 weeks) | Mean change in dyspnoea score ranged across control groups from | Mean change in dyspnoea score in the intervention groups was | SMD ‐0.66 (‐1.05 to ‐0.28) | 113 | ⊕⊕⊝⊝ | Scores estimated using SMD ‐0.66 (‐1.05 to ‐0.28) Lower value post intervention is favourable, indicating improvement in dyspnoea |
| Change in quality of life Follow‐up: end of rehabilitation (8‐12 weeks) | Mean change in quality of life in control groups was | Mean change in quality of life in the intervention groups was | SMD 0.59 (0.2 to 0.98) | 106 | ⊕⊕⊝⊝ | Scores estimated using SMD 0.59 (0.2 to 0.98) Higher value post intervention is favourable, indicating improvement in quality of life |
| 6‐Month survival | 74 per 1000 | 67 per 1000 | RR 0.9 | 57 | ⊕⊕⊝⊝ | |
| Adverse events Follow‐up: 6 months | See comment | See comment | Not estimable | 85 | See comment | No adverse events were reported during the study period |
| *The basis for the assumed risk (e.g. median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence. | ||||||
| aMethods of randomisation were not described for most studies, and only 1 study reported blinding of the assessor (risk of bias ‐1). | ||||||
| Pulmonary rehabilitation compared with no pulmonary rehabilitation for idiopathic pulmonary fibrosis | ||||||
| Patient or population: people with idiopathic pulmonary fibrosis | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | Number of participants | Quality of the evidence | Comments | |
| Assumed risk | Corresponding risk | |||||
| No pulmonary rehabilitation | Pulmonary rehabilitation | |||||
| Change in 6‐minute walk distance Follow‐up: end of rehabilitation (8‐12 weeks) | Mean change in 6‐minute walk distance ranged across control groups from | Mean change in 6‐minute walk distance in the intervention groups was | MD 35.63 (16.02 to 55.23) | 111 | ⊕⊕⊕⊝ | |
| Change in peak oxygen uptake Follow‐up: end of rehabilitation (8‐12 weeks) | Mean change in peak oxygen uptake ranged across control groups from | Mean change in peak oxygen uptake in the intervention groups was | MD 1.46 (0.54 to 2.39) | 58 | ⊕⊕⊝⊝ | |
| Change in maximum ventilation Follow‐up: end of rehabilitation (8 weeks) | Mean change in maximum ventilation in the control groups was | Mean change in maximum ventilation in the intervention groups was | MD 6.97 (0.87 to 13.07) | 30 | ⊕⊕⊝⊝ | |
| Change in dyspnoea Follow‐up: end of rehabilitation (8‐12 weeks) | Mean change in dyspnoea ranged across control groups from | Mean change in dyspnoea in the intervention groups was | SMD ‐0.68 (‐1.12 to ‐0.25) | 90 | ⊕⊕⊝⊝ | Scores estimated using SMD ‐0.68 (‐1.12 to ‐0.25) Lower value post intervention is favourable, indicating improvement in dyspnoea |
| Change in quality of life Follow‐up: end of rehabilitation (8‐12 weeks) | Mean change in quality of life in the control groups was | Mean change in quality of life in the intervention groups was | SMD 0.59 (0.14 to 1.03) | 83 | ⊕⊕⊝⊝ | Scores estimated using SMD 0.59 (0.14 to 1.03) Higher value post intervention is favourable, indicating improvement in quality of life |
| 6‐Month survival | 143 per 1000 | 100 per 1000 | OR 0.67 | 34 | ⊕⊕⊝⊝ | |
| Adverse events Follow‐up: 6 months | See comment | See comment | Not estimable | 62 | See comment | No adverse events were reported during the study period |
| *The basis for the assumed risk (e.g. median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence. | ||||||
| aMethods of randomisation were not described for most studies, and only 1 study reported blinding of the assessor (risk of bias ‐1). | ||||||
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Change in 6‐minute walk distance immediately following pulmonary rehabilitation. Mean change from baseline, metres Show forest plot | 5 | Mean Difference (IV, Fixed, 95% CI) | Subtotals only | |
| 1.1 All participants | 5 | 168 | Mean Difference (IV, Fixed, 95% CI) | 44.34 [26.04, 62.64] |
| 1.2 Idiopathic pulmonary fibrosis only | 4 | 111 | Mean Difference (IV, Fixed, 95% CI) | 35.63 [16.02, 55.23] |
| 1.3 Severe lung disease | 1 | 23 | Mean Difference (IV, Fixed, 95% CI) | 9.61 [‐29.43, 48.65] |
| 1.4 Desaturators | 1 | 30 | Mean Difference (IV, Fixed, 95% CI) | 15.62 [‐15.93, 47.17] |
| 2 Change in 6‐minute walk test at long‐term follow‐up. Mean change from baseline, metres Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Subtotals only | |
| 2.1 All participants | 1 | 57 | Mean Difference (IV, Fixed, 95% CI) | 7.40 [‐36.42, 51.22] |
| 2.2 Idiopathic pulmonary fibrosis only | 1 | 34 | Mean Difference (IV, Fixed, 95% CI) | ‐23.08 [‐70.59, 24.43] |
| 2.3 Severe lung disease | 1 | 23 | Mean Difference (IV, Fixed, 95% CI) | 13.49 [‐62.30, 89.28] |
| 2.4 Desaturators | 1 | 30 | Mean Difference (IV, Fixed, 95% CI) | ‐22.24 [‐89.85, 45.37] |
| 3 Change in VO2 peak immediately following pulmonary rehabilitation, mL/kg/min Show forest plot | 2 | Mean Difference (IV, Fixed, 95% CI) | Subtotals only | |
| 3.1 All participants | 2 | 80 | Mean Difference (IV, Fixed, 95% CI) | 1.24 [0.46, 2.03] |
| 3.2 Idiopathic pulmonary fibrosis only | 2 | 58 | Mean Difference (IV, Fixed, 95% CI) | 1.46 [0.54, 2.39] |
| 3.3 Severe lung disease | 1 | 18 | Mean Difference (IV, Fixed, 95% CI) | ‐0.03 [‐1.36, 1.30] |
| 3.4 Desaturators | 1 | 27 | Mean Difference (IV, Fixed, 95% CI) | 0.84 [‐0.31, 1.99] |
| 4 Change in VEmax immediately following pulmonary rehabilitation, L/min Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Subtotals only | |
| 4.1 All participants | 1 | 52 | Mean Difference (IV, Fixed, 95% CI) | 4.71 [0.10, 9.32] |
| 4.2 Idiopathic pulmonary fibrosis only | 1 | 30 | Mean Difference (IV, Fixed, 95% CI) | 6.97 [0.87, 13.07] |
| 4.3 Severe lung disease | 1 | 20 | Mean Difference (IV, Fixed, 95% CI) | 4.16 [‐3.34, 11.66] |
| 4.4 Desaturators | 1 | 27 | Mean Difference (IV, Fixed, 95% CI) | 6.95 [0.03, 13.87] |
| 5 Change in maximum heart rate immediately following pulmonary rehabilitation, beats per minute Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Subtotals only | |
| 5.1 All participants | 1 | 52 | Mean Difference (IV, Fixed, 95% CI) | ‐1.84 [‐6.26, 2.58] |
| 5.2 Idiopathic pulmonary fibrosis only | 1 | 30 | Mean Difference (IV, Fixed, 95% CI) | ‐1.91 [‐5.92, 2.10] |
| 5.3 Severe lung disease | 1 | 20 | Mean Difference (IV, Fixed, 95% CI) | ‐5.38 [‐11.46, 0.70] |
| 5.4 Desaturators | 1 | 27 | Mean Difference (IV, Fixed, 95% CI) | ‐0.45 [‐6.07, 5.17] |
| 6 6‐Month survival Show forest plot | 1 | Odds Ratio (M‐H, Fixed, 95% CI) | Subtotals only | |
| 6.1 All participants | 1 | 57 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.89 [0.12, 6.82] |
| 6.2 Idiopathic pulmonary fibrosis only | 1 | 34 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.67 [0.08, 5.40] |
| 6.3 Severe lung disease | 1 | 23 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.64 [0.13, 21.10] |
| 6.4 Desaturators | 1 | 30 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.6 [0.13, 19.84] |
| 7 Change in dyspnoea score at long‐term follow‐up Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Subtotals only | |
| 7.1 All participants | 1 | 57 | Mean Difference (IV, Fixed, 95% CI) | ‐0.13 [‐0.81, 0.55] |
| 7.2 Idiopathic pulmonary fibrosis only | 1 | 34 | Mean Difference (IV, Fixed, 95% CI) | 0.01 [‐0.79, 0.81] |
| 7.3 Severe lung disease | 1 | 23 | Mean Difference (IV, Fixed, 95% CI) | ‐0.12 [‐1.23, 0.99] |
| 7.4 Desaturators | 1 | 30 | Mean Difference (IV, Fixed, 95% CI) | 0.20 [‐0.84, 1.24] |
| 8 Change in quality of life immediately following pulmonary rehabilitation Show forest plot | 3 | Std. Mean Difference (IV, Fixed, 95% CI) | Subtotals only | |
| 8.1 All participants | 3 | 106 | Std. Mean Difference (IV, Fixed, 95% CI) | 0.59 [0.20, 0.98] |
| 8.2 Idiopathic pulmonary fibrosis only | 3 | 83 | Std. Mean Difference (IV, Fixed, 95% CI) | 0.59 [0.14, 1.03] |
| 8.3 Severe lung disease | 1 | 23 | Std. Mean Difference (IV, Fixed, 95% CI) | 0.86 [‐0.00, 1.73] |
| 8.4 Desaturators | 1 | 30 | Std. Mean Difference (IV, Fixed, 95% CI) | 0.42 [‐0.31, 1.15] |
| 9 Change in quality of life at long‐term follow‐up Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Subtotals only | |
| 9.1 All participants | 1 | 57 | Mean Difference (IV, Fixed, 95% CI) | 8.78 [‐2.18, 19.74] |
| 9.2 Idiopathic pulmonary fibrosis only | 1 | 34 | Mean Difference (IV, Fixed, 95% CI) | 7.05 [‐8.29, 22.39] |
| 9.3 Severe lung disease | 1 | 23 | Mean Difference (IV, Fixed, 95% CI) | 14.93 [0.54, 29.32] |
| 9.4 Desaturators | 1 | 30 | Mean Difference (IV, Fixed, 95% CI) | 3.66 [‐13.35, 20.67] |
| 10 Change in dyspnoea score immediately following pulmonary rehabilitation Show forest plot | 3 | Std. Mean Difference (IV, Fixed, 95% CI) | Subtotals only | |
| 10.1 All participants | 3 | 113 | Std. Mean Difference (IV, Fixed, 95% CI) | ‐0.66 [‐1.05, ‐0.28] |
| 10.2 Idiopathic pulmonary fibrosis only | 3 | 90 | Std. Mean Difference (IV, Fixed, 95% CI) | ‐0.68 [‐1.12, ‐0.25] |
| 10.3 Severe lung disease | 1 | 23 | Std. Mean Difference (IV, Fixed, 95% CI) | ‐0.70 [‐1.56, 0.15] |
| 10.4 Desaturators | 1 | 30 | Std. Mean Difference (IV, Fixed, 95% CI) | ‐0.85 [‐1.61, ‐0.09] |
