Pulmonary rehabilitation for interstitial lung disease

Leona Dowman; Catherine J Hill; Anthony May; Anne E Holland

doi:10.1002/14651858.CD006322.pub4

Cochrane Database of Systematic Reviews

Rehabilitación pulmonar para la enfermedad pulmonar intersticial

Información

DOI:

https://doi.org/10.1002/14651858.CD006322.pub4 Copiar DOI

Base de datos:

Cochrane Database of Systematic Reviews

Versión publicada:

01 febrero 2021see what's new

Tipo:

Intervention

Etapa:

Review

Grupo Editorial Cochrane:

Grupo Cochrane de Vías respiratorias

Copyright:

Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Autores

Leona Dowman

Department of Physiotherapy, Austin Health, Melbourne, Australia

Institute for Breathing and Sleep, Melbourne, Australia

Department of Allergy, Clinical Immunology and Respiratory Medicine, Monash University, Melbourne, Australia

Department of Respiratory Medicine, Austin Health, Melbourne, Australia
Catherine J Hill

Institute for Breathing and Sleep, Melbourne, Australia

Department of Physiotherapy, Austin Hospital, Melbourne, Australia
Anthony May

Department of Allergy, Clinical Immunology and Respiratory Medicine, Monash University, Melbourne, Australia

Institute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition Sciences, Deakin University, Geelong, Australia
Anne E Holland

Correspondencia a: Institute for Breathing and Sleep, Melbourne, Australia

[email protected]

Department of Allergy, Clinical Immunology and Respiratory Medicine, Monash University, Melbourne, Australia

Physiotherapy, Alfred Health, Melbourne, Australia

Contributions of authors

Initiated the protocol: AH.

Developed the protocol: AH and CH.

Undertook literature search for the original version: AH and CH; for the first update: AH and LD; for the current updated version: LD and AM.

Retrieved papers for the original version: AH; for the first and current updated version: LD.

Screened retrieved papers against eligibility criteria for the original version: AH and CH; for the first update: AH and LD; for the current updated version: LD and AM.

Appraised quality for the original version: AH and CH; for the first update: AH and LD; for the current updated version: LD and AM.

Extracted data for the original version: AH and CH; for the first update: AH and LD; for the current updated version: LD and AM.

Wrote to study authors for additional information for the original version: AH; for the 1st and current updated version: LD.

Entered data into Review Manager 5 for the original version: AH; for the first and current updated version: LD.

Performed analysis for the original version: AH and CH; for the first and current updated version: LD.

Wrote review for the original version: AH and CH; amended manuscript for the first and current updated version: LD; reviewed the first updated version of the manuscript: AH and CH; reviewed the current updated version of the manuscript: AH, CH and AM.

Served as guarantor of the review: AH.

Contributions of editorial team

Chris Cates (Co‐ordinating Editor) checked the data entry prior to the full write up of the review, edited the protocol; advised on methodology; approved the protocol prior to publication.

John White (Contact Editor): edited the review; advised on methodology, interpretation and content.

Emma Dennett (Managing Editor): co‐ordinated the editorial process; advised on interpretation and content; edited the review.

Emma Jackson (Assistant Managing Editor): conducted peer review; obtained translations; edited the reference and other sections of the review.

Elizabeth Stovold (Information Specialist): designed the search strategy; ran the searches; edited the search methods section.

Sources of support

Internal sources

No sources of support supplied

External sources

Victorian Tuberculosis and Lung Association, Australia
National Health and Medical Research Council, Australia

PhD stipend for Ms Dowman

Declarations of interest

AEH: none. Conducted two studies included in the review (Dowman 2017; Holland 2008).

LD: none. Conducted one study included in the review (Dowman 2017).

CJH: none. Conducted two studies included in the review (Dowman 2017; Holland 2008).

AM: none. Undertook the assessment of risk of bias for Holland 2008.

LD and AM undertook the assessment of risk of bias for all the studies except for Dowman 2017. AM undertook the assessment of risks of bias for this study.

Acknowledgements

We would like to thank the Cochrane Airways Group for support and guidance. We would like to thank Chao Liu, Tianqi Yu and Yuan Chi for the translation of the Chinese articles into English. We also thank all investigators who provided further information about existing studies.

We thank Tianqi Yu and Yuan Chi for their valuable assistance in translating and extracting the data for one of the included studies.

The authors and Airways Editorial Team are grateful to the following peer reviewers for their time and comments on this review: Philip L Molyneaux (UK), Dr NG Raghavan (Canada) and Dr Inga Jarosch (Germany).

The Background and Methods sections of this review are based on a standard template used by Cochrane Airways.

This project was supported by the National Institute for Health Research (NIHR), via Cochrane Infrastructure funding to the Cochrane Airways Group. The views and opinions expressed herein are those of the review authors and do not necessarily reflect those of the Systematic Reviews Programme, NIHR, National Health Service or the Department of Health.

Version history

Published

Title

Stage

Authors

Version

2021 Feb 01

Pulmonary rehabilitation for interstitial lung disease

Review

Leona Dowman, Catherine J Hill, Anthony May, Anne E Holland

https://doi.org/10.1002/14651858.CD006322.pub4

2014 Oct 06

Pulmonary rehabilitation for interstitial lung disease

Review

Leona Dowman, Catherine J Hill, Anne E Holland

https://doi.org/10.1002/14651858.CD006322.pub3

2008 Oct 08

Physical training for interstitial lung disease

Review

Anne E Holland, Catherine Hill

https://doi.org/10.1002/14651858.CD006322.pub2

2007 Jan 24

Physical training for interstitial lung disease

Protocol

Anne Holland, Catherine Hill

https://doi.org/10.1002/14651858.CD006322

Differences between protocol and review

We specified two subgroup analyses for this update. Subgroup analysis for exercise type could not be conducted, as we identified no trials on resistance training.

Keywords

MeSH

Medical Subject Headings (MeSH) Keywords

Medical Subject Headings Check Words

Adult; Aged; Humans; Middle Aged;

PICO

Population

Intervention

Comparison

Outcome

El uso y la enseñanza del modelo PICO están muy extendidos en el ámbito de la atención sanitaria basada en la evidencia para formular preguntas y estrategias de búsqueda y para caracterizar estudios o metanálisis clínicos. PICO son las siglas en inglés de cuatro posibles componentes de una pregunta de investigación: paciente, población o problema; intervención; comparación; desenlace (outcome).

Para saber más sobre el uso del modelo PICO, puede consultar el Manual Cochrane.

Figure 1

Study flow diagram for 2014–2020 literature searches. HRQoL: health‐related quality of life.

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Figure 2

Methodological quality summary: review authors' judgements about each methodological quality item for each included study.

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Figure 3

Forest plot of comparison: 1 Pulmonary rehabilitation versus no pulmonary rehabilitation, outcome: 1.1 Change in six‐minute walk test immediately following pulmonary rehabilitation.

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Figure 4

Funnel plot of comparison: 1 Pulmonary rehabilitation versus no pulmonary rehabilitation, outcome: 1.1 Change in six‐minute walk distance immediately following pulmonary rehabilitation. Mean change from baseline, metres.

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Figure 5

Forest plot of comparison: 1 Pulmonary rehabilitation versus no pulmonary rehabilitation, outcome: 1.3 Change in peak work rate immediately following pulmonary rehabilitation, watts.

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Figure 6

Forest plot of comparison: 1 Pulmonary rehabilitation versus no pulmonary rehabilitation, outcome: 1.6 Dyspnoea score immediately following pulmonary rehabilitation.

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Figure 7

Forest plot of comparison: 1 Pulmonary rehabilitation versus no pulmonary rehabilitation, outcome: 1.12 Change in quality of life (SGRQ Total) immediately following pulmonary rehabilitation.

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Figure 8

Funnel plot of comparison: 1 Pulmonary rehabilitation versus no pulmonary rehabilitation, outcome: 1.12 Change in quality of life (SGRQ Total) immediately following pulmonary rehabilitation.

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Figure 9

Forest plot of comparison: 1 Pulmonary rehabilitation versus no pulmonary rehabilitation, outcome: 1.17 Change in quality of life (Chronic Respiratory Disease Questionnaire (CRQ) Dyspnoea) immediately following pulmonary rehabilitation.

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Analysis 1.1

Comparison 1: Pulmonary rehabilitation versus no pulmonary rehabilitation, Outcome 1: Change in 6‐minute walk distance immediately following pulmonary rehabilitation. Mean change from baseline, metres

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Analysis 1.2

Comparison 1: Pulmonary rehabilitation versus no pulmonary rehabilitation, Outcome 2: Change in 6‐minute walk test at long‐term follow‐up. Mean change from baseline, metres

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Analysis 1.3

Comparison 1: Pulmonary rehabilitation versus no pulmonary rehabilitation, Outcome 3: Change in peak work rate immediately following pulmonary rehabilitation, watts

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Comparison 1: Pulmonary rehabilitation versus no pulmonary rehabilitation, Outcome 4: Change in VO 2 peak immediately following pulmonary rehabilitation, mL/kg/minute

Analysis 1.4

Comparison 1: Pulmonary rehabilitation versus no pulmonary rehabilitation, Outcome 4: Change in VO ₂ peak immediately following pulmonary rehabilitation, mL/kg/minute

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Analysis 1.5

Comparison 1: Pulmonary rehabilitation versus no pulmonary rehabilitation, Outcome 5: Change in maximum ventilation (Ve max ) immediately following pulmonary rehabilitation, L/minute

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Analysis 1.6

Comparison 1: Pulmonary rehabilitation versus no pulmonary rehabilitation, Outcome 6: Change in maximum heart rate immediately following pulmonary rehabilitation, beats/minute

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Analysis 1.7

Comparison 1: Pulmonary rehabilitation versus no pulmonary rehabilitation, Outcome 7: Change in dyspnoea score immediately following pulmonary rehabilitation

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Analysis 1.8

Comparison 1: Pulmonary rehabilitation versus no pulmonary rehabilitation, Outcome 8: Change in dyspnoea score at long‐term follow‐up

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Analysis 1.9

Comparison 1: Pulmonary rehabilitation versus no pulmonary rehabilitation, Outcome 9: Change in quality of life (St George's Respiratory Questionnaire (SGRQ) Symptoms) immediately following pulmonary rehabilitation

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Analysis 1.10

Comparison 1: Pulmonary rehabilitation versus no pulmonary rehabilitation, Outcome 10: Change in quality of life (SGRQ Activity) immediately following pulmonary rehabilitation

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Analysis 1.11

Comparison 1: Pulmonary rehabilitation versus no pulmonary rehabilitation, Outcome 11: Change in quality of life (SGRQ Impact) immediately following pulmonary rehabilitation

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Analysis 1.12

Comparison 1: Pulmonary rehabilitation versus no pulmonary rehabilitation, Outcome 12: Change in quality of life (SGRQ Total) immediately following pulmonary rehabilitation

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Analysis 1.13

Comparison 1: Pulmonary rehabilitation versus no pulmonary rehabilitation, Outcome 13: Change in quality of life (SGRQ Symptoms) at long‐term follow‐up

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Analysis 1.14

Comparison 1: Pulmonary rehabilitation versus no pulmonary rehabilitation, Outcome 14: Change in quality of life (SGRQ Activity) at long‐term follow‐up

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Analysis 1.15

Comparison 1: Pulmonary rehabilitation versus no pulmonary rehabilitation, Outcome 15: Change in quality of life (SGRQ Impact) at long‐term follow‐up

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Analysis 1.16

Comparison 1: Pulmonary rehabilitation versus no pulmonary rehabilitation, Outcome 16: Change in quality of life (SGRQ Total) at long‐term follow‐up

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Analysis 1.17

Comparison 1: Pulmonary rehabilitation versus no pulmonary rehabilitation, Outcome 17: Change in quality of life (Chronic Respiratory Disease Questionnaire (CRQ) Dyspnoea) immediately following pulmonary rehabilitation

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Analysis 1.18

Comparison 1: Pulmonary rehabilitation versus no pulmonary rehabilitation, Outcome 18: Change in quality of life (CRQ Fatigue) immediately following pulmonary rehabilitation.

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Analysis 1.19

Comparison 1: Pulmonary rehabilitation versus no pulmonary rehabilitation, Outcome 19: Change in quality of life (CRQ Emotion) immediately following pulmonary rehabilitation

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Analysis 1.20

Comparison 1: Pulmonary rehabilitation versus no pulmonary rehabilitation, Outcome 20: Change in quality of life (CRQ Mastery) immediately following pulmonary rehabilitation

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Analysis 1.21

Comparison 1: Pulmonary rehabilitation versus no pulmonary rehabilitation, Outcome 21: Change in quality of life (CRQ Dyspnoea) at long‐term follow‐up

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Analysis 1.22

Comparison 1: Pulmonary rehabilitation versus no pulmonary rehabilitation, Outcome 22: Change in quality of life (CRQ Fatigue) at long‐term follow‐up

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Analysis 1.23

Comparison 1: Pulmonary rehabilitation versus no pulmonary rehabilitation, Outcome 23: Change in quality of life (CRQ Emotion) at long‐term follow‐up

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Analysis 1.24

Comparison 1: Pulmonary rehabilitation versus no pulmonary rehabilitation, Outcome 24: Change in quality of life (CRQ Mastery) at long‐term follow‐up

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Analysis 1.25

Comparison 1: Pulmonary rehabilitation versus no pulmonary rehabilitation, Outcome 25: Long‐term survival

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Summary of findings 1. Pulmonary rehabilitation compared to no pulmonary rehabilitation for interstitial lung disease

Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Pulmonary rehabilitation compared to no pulmonary rehabilitation for interstitial lung disease
Patient or population: interstitial lung disease Setting: pulmonary rehabilitation centres Intervention: pulmonary rehabilitation Comparison: no pulmonary rehabilitation
Outcomes	Risk with no pulmonary rehabilitation	Risk with pulmonary rehabilitation	Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Change in 6MWD assessed with: 6MWT Follow‐up: range 3–48 weeks	The mean change in 6MWD ranged from –35 metres to 26 metres	MD 40.07 metres higher (32.70 higher to 47.44 higher)	—	585 (13 RCTs)	⊕⊕⊕⊝ Moderate^a	Sensitivity analysis from studies at lower risk of bias was similar (MD 41.22 metres, 95% CI 26.80 to 55.64; 5 RCTs, 288 participants; I² = 35%).
Change in 6MWD at long‐term follow‐up assessed with: 6MWT Follow‐up: range 6–11 months	The mean change in 6MWD at long‐term follow‐up ranged from –49 metres to –6 metres	MD 32.43 metres higher (15.58 higher to 49.28 higher)	—	321 (6 RCTs)	⊕⊕⊕⊝ Moderate^b	—
Change in peak work capacity assessed with: cardiopulmonary exercise test Follow‐up: range 8 weeks to 6 months	The mean change in peak work capacity ranged from –10 watts to 0.6 watts	MD 9.04 watts higher (6.07 higher to 12.0 higher)	—	159 (4 RCTs)	⊕⊕⊝⊝ Low^c,d	—
Change in dyspnoea score Follow‐up: range 8 weeks to 6 months	The mean change in dyspnoea score ranged from –0.2 to 0.4	SMD 0.36 SD lower (0.58 lower to 0.14 lower)	—	348 (7 RCTs)	⊕⊕⊝⊝ Low^e,f	Lower value post intervention is favourable, indicating improvement in dyspnoea. Sensitivity analysis from studies at lower risk of bias was similar (SMD –0.28, 95% CI –0.51 to –0.04; 5 RCTs, 288 participants; I² = 70%). SMD of –0.36 corresponds to MD of –0.32 points when re‐expressed on the modified Medical Research Dyspnoea Scale (0–4, 5‐point score, 0 indicates no dyspnoea).
Change in quality of life assessed with: SGRQ Total score Follow‐up: range 8–48 weeks	The mean change in quality of life ranged from –7 to 6 points	MD 9.29 points lower (11.06 lower to 7.52 lower)	—	478 (11 RCTs)	⊕⊕⊕⊝ Moderate^a	Lower value post intervention is favourable, indicating improvement in quality of life. Sensitivity analysis from studies at lower risk of bias was similar (MD –8.13, 95% CI –11.24 to –5.02; 4 RCTs, 231 participants; I² = 21%).
Change in quality of life at long‐term assessed with: SGRQ Total score Follow‐up: 6–11 months	The mean change in quality of life at long‐term follow‐up ranged from –1 to 5 points	MD 4.93 points lower (7.81 lower to 2.06 lower)	—	240 (4 RCTs)	⊕⊕⊝⊝ Low^c,f	Lower value post intervention is favourable, indicating improvement in quality of life.
Long‐term survival (incidence of mortality) Follow‐up: range 6–11 months	Study population		OR 0.40 (0.14 to 1.12)	291 (4 RCTs)	⊕⊕⊝⊝ Low^c,g	Lower OR represents improved survival at long‐term follow‐up.
	85 per 1000	36 per 1000 (13 to 94)	OR 0.40 (0.14 to 1.12)	291 (4 RCTs)	⊕⊕⊝⊝ Low^c,g
*The risk in the intervention group (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). 6MWD: 6‐minute walk distance; 6MWT: 6‐minute walk test; CI: confidence interval; MD: mean difference; OR: odds ratio; RCT: randomised controlled trial; SD: standard deviation; SGRQ: St George's Respiratory Questionnaire; SMD: standardised mean difference.
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.
^aDowngraded one level for detection bias (nine to 11 studies), attrition bias (five to eight studies) and selection bias (seven studies). ^bDowngraded one level for detection bias (two studies) and attrition bias (one study). ^cDowngraded one level for detection bias (two studies), attrition bias (one study) and small numbers of studies/participants in meta‐analysis. ^dDowngraded one level for inconsistency – high statistical heterogeneity detected (I² > 75%). ^eDowngraded one level for detection detection performance bias (four studies) and attrition bias (two studies). ^fDowngraded one level for inconsistency – substantial statistical heterogeneity detected (I² = 50% to 75%). ^gDowngraded one level for imprecision (wide CIs).

Summary of findings 1. Pulmonary rehabilitation compared to no pulmonary rehabilitation for interstitial lung disease

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Summary of findings 2. Pulmonary rehabilitation compared to no pulmonary rehabilitation for idiopathic pulmonary fibrosis

Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Pulmonary rehabilitation compared to no pulmonary rehabilitation for idiopathic pulmonary fibrosis
Patient or population: idiopathic pulmonary fibrosis Setting: pulmonary rehabilitation centres Intervention: pulmonary rehabilitation Comparison: no pulmonary rehabilitation
Outcomes	Risk with no pulmonary rehabilitation	Risk with pulmonary rehabilitation	Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Change in 6MWD assessed with: 6MWT Follow‐up: range 3–12 weeks	The mean change in 6MWD ranged from –35 metres to 26 metres	MD 37.25 metres higher (26.16 higher to 48.33 higher)	—	278 (8 RCTs)	⊕⊕⊕⊝ Moderate^a	—
Change in 6MWD at long‐term follow‐up assessed with: 6MWT Follow‐up: range 6–11 months	The mean change in 6MWD at long‐term follow‐up ranged from –49 metres to 4 metres	MD 1.64 metres higher (24.89 lower to 28.17 higher)	—	123 (3 RCTs)	⊕⊕⊝⊝ Low^b,c	—
Change in peak work capacity assessed with: cardiopulmonary exercise test Follow‐up: range 8–12 weeks	The mean change in peak work capacity ranged from –7 watts to –0.8 watts	MD 9.94 watts higher (6.39 higher to 13.49 higher)	—	62 (2 RCTs)	⊕⊕⊝⊝ Low^b,d,e	—
Change in dyspnoea score Follow‐up: range 8–12 weeks	The mean change in dyspnoea score ranged from –0.06 to 0.4	SMD 0.41 lower (0.74 lower to 0.09 lower)	—	155 (4 RCTs)	⊕⊕⊝⊝ Low^b,f	Lower value post intervention is favourable, indicating improvement in dyspnoea. SMD of –0.41 corresponds to MD of –0.37 points when re‐expressed on the modified Medical Research Dyspnoea Scale (0–4, 5‐point score, 0 indicates no dyspnoea).
Change in quality of life assessed with: SGRQ Total Follow‐up: range 8 weeks to 6 months	The mean change in quality of life ranged from –3 to 3 points	MD 7.91 points lower (10.55 lower to 5.26 lower)	—	194 (6 RCTs)	⊕⊕⊕⊝ Moderate^a	Lower value post intervention is favourable, indicating improvement in quality of life.
Change in quality of life at long‐term assessed with: SGRQ Total score Follow‐up: range 6–11 months	The mean change in quality of life at long‐term follow‐up ranged from 1 to 4 points	MD 3.45 points lower (7.43 lower to 0.52 higher)	—	89 (2 RCTs)	⊕⊕⊝⊝ Low^b,e	Lower value post intervention is favourable, indicating improvement in quality of life.
Long‐term survival (incidence of mortality) Follow‐up: range 6–11 months	Study population		OR 0.32 (0.08 to 1.19)	127 (3 RCTs)	⊕⊕⊝⊝ Low^b^,^c	Lower OR represents improved survival at long‐term follow‐up.
	133 per 1000	47 per 1000 (12 to 155)	OR 0.32 (0.08 to 1.19)	127 (3 RCTs)	⊕⊕⊝⊝ Low^b^,^c
*The risk in the intervention group (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). 6MWD: 6‐minute walk distance; 6MWT: 6‐minute walk test; CI: confidence interval; OR: odds ratio; RCT: randomised controlled trial; SGRQ: St George's Respiratory Questionnaire.
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.
^aDowngraded one level for detection bias (four or five studies), attrition bias (three or four studies) and selection bias (five studies) ^bDowngraded one level for detection bias (one or two studies), attrition bias (one study) and meta‐analysis was limited to 3‐4 studies ^cDowngraded one level for imprecision (wide CIs) ^dDowngraded one level for inconsistency – high statistical heterogeneity detected (I² > 75%) ^eDowngraded one level for imprecision ‐ meta‐analysis was limited to 2 studies ^fDowngraded one level for inconsistency – substantial statistical heterogeneity detected (I² = 50% to 75%)

Summary of findings 2. Pulmonary rehabilitation compared to no pulmonary rehabilitation for idiopathic pulmonary fibrosis

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Table 1. Study design

Study	Follow‐up	Duration (weeks)	Sessions (per week)	Setting	Programme type
Baradzina 2005	5 weeks	5	5	Outpatient	Exercise + other
Dale 2014	8, 26 weeks	8	2	Outpatient	Exercise
De Las Heras 2019	12 weeks	12	5–7	Tele‐rehabilitation	Exercise
Dowman 2017	8 weeks, 6 months	8	2	Outpatient	Exercise + other
Gaunaurd 2014	12 weeks, 3 months	12	2	Outpatient	Exercise + other
He 2016	12 weeks	12	3–5	Outpatient	Exercise
Holland 2008	8, 26 weeks	8	2	Outpatient	Exercise
Jackson 2014	12 weeks, 3 months	12	2	Outpatient	Exercise + other
Jarosch 2020	3 weeks, 3 months	3	5–6	Inpatient	Exercise + other
Ku 2017	8 weeks	8	2	Outpatient	Exercise + other
Lanza 2019	12 weeks	12	2	Outpatient	Exercise
Mejia 2000	12 weeks	12	3	Outpatient	Exercise
Menon 2011	8 weeks	8	—	Outpatient	Exercise
Naz 2018	12 weeks	12	2	Outpatient	Exercise
Nishiyama 2008	9 weeks	9	2	Outpatient	Exercise
Perez Bogerd 2018	3, 6, 12 months	26	2–3	Outpatient	Exercise + other
Shen 2016	12 weeks	12	3	Outpatient	Exercise
Vainshelboim 2014	12 weeks	12	2	Outpatient	Exercise
Wallaert 2020	8 weeks	8	3	Outpatient	Exercise + other
Wewel 2005	6 months	26	7	Home	Exercise
Xiao 2019	48 weeks	48	4	Outpatient/home	Exercise + other

Table 1. Study design

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Table 2. Summary of sensitivity analysis for interstitial lung disease

Outcome	Subscale	Included studies	№ of participants	Heterogeneity	MD (95% CI)	Test of overall effect
6MWT	—	Dale 2014; Dowman 2017; Holland 2008; Naz 2018; Perez Bogerd 2018	288	I² = 35%, P = 0.19	41.22 metres (26.80 to 55.64)	P < 0.00001
Dyspnoea score	—	Dale 2014; Dowman 2017; Holland 2008; Naz 2018; Perez Bogerd 2018	288	I² = 70%, P = 0.01	–0.28 (–0.51 to –0.04)	P < 0.02
SGRQ	Symptoms	Dale 2014; Dowman 2017; Naz 2018; Perez Bogerd 2018	231	I² = 51%, P = 0.11	–13.76 (–18.49 to –9.04)	P < 0.00001
	Activity	Dale 2014; Dowman 2017; Naz 2018; Perez Bogerd 2018	231	I² = 21%, P = 0.28	–8.56 (–12.90 to –4.22)	P = 0.0001
	Impact	Dale 2014; Dowman 2017; Naz 2018; Perez Bogerd 2018	231	I² = 0%, P = 0.83	–7.91 (–11.54 to –4.29)	P < 0.0001
	Total	Dale 2014; Dowman 2017; Naz 2018; Perez Bogerd 2018	231	I² = 21%, P = 0.29	–8.13 (–11.24 to –5.02)	P < 0.00001
CRQ	Dyspnoea	Dale 2014; Dowman 2017; Holland 2008; Perez Bogerd 2018	270	I² = 41%, P = 0.18	0.61 (0.32 to 0.90)	P < 0.0001
	Fatigue	Dale 2014; Dowman 2017; Holland 2008; Perez Bogerd 2018	270	I² = 0%, P = 0.93	0.66 (0.40 to 0.92)	P < 0.00001
	Emotion	Dale 2014; Dowman 2017; Holland 2008; Perez Bogerd 2018	270	I² = 0%, P = 0.44	0.58 (0.35 to 0.81)	P < 0.00001
	Mastery	Dale 2014; Dowman 2017; Holland 2008; Perez Bogerd 2018	270	I² = 58%, P = 0.07	0.71 (0.44 to 0.98)	P < 0.00001
6MWT: six‐minute walk test; CI: confidence interval; CRQ: Chronic Respiratory Disease Questionnaire; MD: mean difference; SGRQ: St George's Respiratory Questionnaire.

Table 2. Summary of sensitivity analysis for interstitial lung disease

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Comparison 1. Pulmonary rehabilitation versus no pulmonary rehabilitation

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1.1 Change in 6‐minute walk distance immediately following pulmonary rehabilitation. Mean change from baseline, metres Show forest plot	13		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

1.1.1 All participants	13	585	Mean Difference (IV, Fixed, 95% CI)	40.07 [32.70, 47.44]
1.1.2 Idiopathic pulmonary fibrosis only	8	278	Mean Difference (IV, Fixed, 95% CI)	37.25 [26.16, 48.33]
1.1.3 Severe lung disease	2	84	Mean Difference (IV, Fixed, 95% CI)	15.37 [‐10.70, 41.43]
1.1.4 Desaturators	2	103	Mean Difference (IV, Fixed, 95% CI)	20.12 [‐2.62, 42.87]
1.2 Change in 6‐minute walk test at long‐term follow‐up. Mean change from baseline, metres Show forest plot	5		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

1.2.1 All participants	5	297	Mean Difference (IV, Fixed, 95% CI)	32.43 [15.58, 49.28]
1.2.2 Idiopathic pulmonary fibrosis only	3	123	Mean Difference (IV, Fixed, 95% CI)	1.64 [‐24.89, 28.17]
1.2.3 Severe lung disease	2	84	Mean Difference (IV, Fixed, 95% CI)	4.20 [‐28.99, 37.40]
1.2.4 Desaturators	2	103	Mean Difference (IV, Fixed, 95% CI)	1.76 [‐28.95, 32.47]
1.3 Change in peak work rate immediately following pulmonary rehabilitation, watts Show forest plot	4	274	Mean Difference (IV, Fixed, 95% CI)	7.55 [5.66, 9.44]

1.3.1 All participants	4	159	Mean Difference (IV, Fixed, 95% CI)	9.04 [6.07, 12.00]
1.3.2 Idiopathic pulmonary fibrosis only	2	62	Mean Difference (IV, Fixed, 95% CI)	9.94 [6.39, 13.49]
1.3.3 Severe lung disease	1	23	Mean Difference (IV, Fixed, 95% CI)	2.10 [‐2.29, 6.49]
1.3.4 Desaturators	1	30	Mean Difference (IV, Fixed, 95% CI)	5.40 [0.07, 10.73]
1.4 Change in VO ₂ peak immediately following pulmonary rehabilitation, mL/kg/minute Show forest plot	3		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

1.4.1 All participants	3	94	Mean Difference (IV, Fixed, 95% CI)	1.28 [0.51, 2.05]
1.4.2 Idiopathic pulmonary fibrosis only	2	62	Mean Difference (IV, Fixed, 95% CI)	1.45 [0.51, 2.40]
1.4.3 Severe lung disease	1	18	Mean Difference (IV, Fixed, 95% CI)	‐0.03 [‐1.36, 1.30]
1.4.4 Desaturators	1	27	Mean Difference (IV, Fixed, 95% CI)	0.84 [‐0.31, 1.99]
1.5 Change in maximum ventilation (Ve max ) immediately following pulmonary rehabilitation, L/minute Show forest plot	3		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

1.5.1 All participants	3	94	Mean Difference (IV, Fixed, 95% CI)	7.21 [4.10, 10.32]
1.5.2 Idiopathic pulmonary fibrosis only	2	62	Mean Difference (IV, Fixed, 95% CI)	9.80 [6.06, 13.53]
1.5.3 Severe lung disease	1	20	Mean Difference (IV, Fixed, 95% CI)	4.16 [‐3.34, 11.66]
1.5.4 Desaturators	1	27	Mean Difference (IV, Fixed, 95% CI)	6.95 [0.03, 13.87]
1.6 Change in maximum heart rate immediately following pulmonary rehabilitation, beats/minute Show forest plot	3		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

1.6.1 All participants	3	94	Mean Difference (IV, Fixed, 95% CI)	‐0.77 [‐4.25, 2.72]
1.6.2 Idiopathic pulmonary fibrosis only	2	62	Mean Difference (IV, Fixed, 95% CI)	‐0.38 [‐3.78, 3.01]
1.6.3 Severe lung disease	1	20	Mean Difference (IV, Fixed, 95% CI)	‐5.38 [‐11.46, 0.70]
1.6.4 Desaturators	1	27	Mean Difference (IV, Fixed, 95% CI)	‐0.45 [‐6.07, 5.17]
1.7 Change in dyspnoea score immediately following pulmonary rehabilitation Show forest plot	7		Std. Mean Difference (IV, Fixed, 95% CI)	Subtotals only

1.7.1 All participants	7	348	Std. Mean Difference (IV, Fixed, 95% CI)	‐0.36 [‐0.58, ‐0.14]
1.7.2 Idiopathic pulmonary fibrosis only	4	155	Std. Mean Difference (IV, Fixed, 95% CI)	‐0.41 [‐0.74, ‐0.09]
1.7.3 Severe lung disease	2	84	Std. Mean Difference (IV, Fixed, 95% CI)	‐0.25 [‐0.68, 0.19]
1.7.4 Desaturators	2	103	Std. Mean Difference (IV, Fixed, 95% CI)	‐0.39 [‐0.79, 0.00]
1.8 Change in dyspnoea score at long‐term follow‐up Show forest plot	6		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

1.8.1 All participants	6	335	Mean Difference (IV, Fixed, 95% CI)	‐0.29 [‐0.49, ‐0.10]
1.8.2 Idiopathic pulmonary fibrosis only	3	123	Mean Difference (IV, Fixed, 95% CI)	‐0.38 [‐0.72, ‐0.05]
1.8.3 Severe lung disease	2	84	Mean Difference (IV, Fixed, 95% CI)	0.14 [‐0.36, 0.63]
1.8.4 Desaturators	2	103	Mean Difference (IV, Fixed, 95% CI)	‐0.03 [‐0.42, 0.35]
1.9 Change in quality of life (St George's Respiratory Questionnaire (SGRQ) Symptoms) immediately following pulmonary rehabilitation Show forest plot	7	588	Mean Difference (IV, Fixed, 95% CI)	‐13.68 [‐16.59, ‐10.77]

1.9.1 All participants	7	312	Mean Difference (IV, Fixed, 95% CI)	‐15.58 [‐19.54, ‐11.62]
1.9.2 Idiopathic pulmonary fibrosis only	4	142	Mean Difference (IV, Fixed, 95% CI)	‐13.92 [‐19.68, ‐8.17]
1.9.3 Severe lung disease	1	61	Mean Difference (IV, Fixed, 95% CI)	‐9.20 [‐19.17, 0.77]
1.9.4 Desaturators	1	73	Mean Difference (IV, Fixed, 95% CI)	‐7.70 [‐16.17, 0.77]
1.10 Change in quality of life (SGRQ Activity) immediately following pulmonary rehabilitation Show forest plot	7	588	Mean Difference (IV, Fixed, 95% CI)	‐2.30 [‐3.46, ‐1.14]

1.10.1 All participants	7	312	Mean Difference (IV, Fixed, 95% CI)	‐2.47 [‐4.11, ‐0.83]
1.10.2 Idiopathic pulmonary fibrosis only	4	142	Mean Difference (IV, Fixed, 95% CI)	‐1.71 [‐3.44, 0.01]
1.10.3 Severe lung disease	1	61	Mean Difference (IV, Fixed, 95% CI)	‐3.60 [‐11.51, 4.31]
1.10.4 Desaturators	1	73	Mean Difference (IV, Fixed, 95% CI)	‐8.20 [‐15.55, ‐0.85]
1.11 Change in quality of life (SGRQ Impact) immediately following pulmonary rehabilitation Show forest plot	7	588	Mean Difference (IV, Fixed, 95% CI)	‐8.66 [‐10.37, ‐6.94]

1.11.1 All participants	7	312	Mean Difference (IV, Fixed, 95% CI)	‐8.81 [‐11.17, ‐6.46]
1.11.2 Idiopathic pulmonary fibrosis only	4	142	Mean Difference (IV, Fixed, 95% CI)	‐8.94 [‐11.76, ‐6.13]
1.11.3 Severe lung disease	1	61	Mean Difference (IV, Fixed, 95% CI)	‐8.00 [‐16.18, 0.18]
1.11.4 Desaturators	1	73	Mean Difference (IV, Fixed, 95% CI)	‐5.90 [‐12.99, 1.19]
1.12 Change in quality of life (SGRQ Total) immediately following pulmonary rehabilitation Show forest plot	11		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

1.12.1 All participants	11	478	Mean Difference (IV, Fixed, 95% CI)	‐9.29 [‐11.06, ‐7.52]
1.12.2 Idiopathic pulmonary fibrosis only	6	194	Mean Difference (IV, Fixed, 95% CI)	‐7.91 [‐10.55, ‐5.26]
1.12.3 Severe lung disease	1	61	Mean Difference (IV, Fixed, 95% CI)	‐6.40 [‐12.79, ‐0.01]
1.12.4 Desaturators	1	73	Mean Difference (IV, Fixed, 95% CI)	‐6.00 [‐11.56, ‐0.44]
1.13 Change in quality of life (SGRQ Symptoms) at long‐term follow‐up Show forest plot	4	463	Mean Difference (IV, Fixed, 95% CI)	‐9.14 [‐12.91, ‐5.37]

1.13.1 All participants	4	240	Mean Difference (IV, Fixed, 95% CI)	‐11.31 [‐16.58, ‐6.03]
1.13.2 Idiopathic pulmonary fibrosis only	2	89	Mean Difference (IV, Fixed, 95% CI)	‐6.84 [‐15.77, 2.10]
1.13.3 Severe lung disease	1	61	Mean Difference (IV, Fixed, 95% CI)	‐12.00 [‐22.41, ‐1.59]
1.13.4 Desaturators	1	73	Mean Difference (IV, Fixed, 95% CI)	‐3.20 [‐12.08, 5.68]
1.14 Change in quality of life (SGRQ Activity) at long‐term follow‐up Show forest plot	4	463	Mean Difference (IV, Fixed, 95% CI)	‐1.41 [‐2.51, ‐0.30]

1.14.1 All participants	4	240	Mean Difference (IV, Fixed, 95% CI)	‐1.54 [‐3.11, 0.02]
1.14.2 Idiopathic pulmonary fibrosis only	2	89	Mean Difference (IV, Fixed, 95% CI)	‐1.07 [‐2.70, 0.56]
1.14.3 Severe lung disease	1	61	Mean Difference (IV, Fixed, 95% CI)	‐1.80 [‐9.93, 6.33]
1.14.4 Desaturators	1	73	Mean Difference (IV, Fixed, 95% CI)	‐5.20 [‐12.82, 2.42]
1.15 Change in quality of life (SGRQ Impact) at long‐term follow‐up Show forest plot	4	463	Mean Difference (IV, Fixed, 95% CI)	‐3.57 [‐5.79, ‐1.35]

1.15.1 All participants	4	240	Mean Difference (IV, Fixed, 95% CI)	‐4.73 [‐7.76, ‐1.69]
1.15.2 Idiopathic pulmonary fibrosis only	2	89	Mean Difference (IV, Fixed, 95% CI)	‐4.59 [‐8.60, ‐0.57]
1.15.3 Severe lung disease	1	61	Mean Difference (IV, Fixed, 95% CI)	1.40 [‐7.05, 9.85]
1.15.4 Desaturators	1	73	Mean Difference (IV, Fixed, 95% CI)	2.90 [‐4.45, 10.25]
1.16 Change in quality of life (SGRQ Total) at long‐term follow‐up Show forest plot	4	463	Mean Difference (IV, Fixed, 95% CI)	‐3.60 [‐5.66, ‐1.55]

1.16.1 All participants	4	240	Mean Difference (IV, Fixed, 95% CI)	‐4.93 [‐7.81, ‐2.06]
1.16.2 Idiopathic pulmonary fibrosis only	2	89	Mean Difference (IV, Fixed, 95% CI)	‐3.45 [‐7.43, 0.52]
1.16.3 Severe lung disease	1	61	Mean Difference (IV, Fixed, 95% CI)	‐1.90 [‐8.57, 4.77]
1.16.4 Desaturators	1	73	Mean Difference (IV, Fixed, 95% CI)	0.10 [‐5.62, 5.82]
1.17 Change in quality of life (Chronic Respiratory Disease Questionnaire (CRQ) Dyspnoea) immediately following pulmonary rehabilitation Show forest plot	5	677	Mean Difference (IV, Fixed, 95% CI)	0.72 [0.55, 0.88]

1.17.1 All participants	5	321	Mean Difference (IV, Fixed, 95% CI)	0.68 [0.42, 0.93]
1.17.2 Idiopathic pulmona ry fibrosis only	3	169	Mean Difference (IV, Fixed, 95% CI)	0.81 [0.49, 1.14]
1.17.3 Severe lung disease	2	84	Mean Difference (IV, Fixed, 95% CI)	0.68 [0.21, 1.15]
1.17.4 Desaturators	2	103	Mean Difference (IV, Fixed, 95% CI)	0.69 [0.30, 1.08]
1.18 Change in quality of life (CRQ Fatigue) immediately following pulmonary rehabilitation. Show forest plot	5	677	Mean Difference (IV, Fixed, 95% CI)	0.66 [0.49, 0.82]

1.18.1 All participants	5	321	Mean Difference (IV, Fixed, 95% CI)	0.66 [0.43, 0.90]
1.18.2 Idiopathic pulmonary fibrosis only	3	169	Mean Difference (IV, Fixed, 95% CI)	0.67 [0.36, 0.98]
1.18.3 Severe lung disease	2	84	Mean Difference (IV, Fixed, 95% CI)	0.65 [0.17, 1.13]
1.18.4 Desaturators	2	103	Mean Difference (IV, Fixed, 95% CI)	0.60 [0.15, 1.06]
1.19 Change in quality of life (CRQ Emotion) immediately following pulmonary rehabilitation Show forest plot	5	677	Mean Difference (IV, Fixed, 95% CI)	0.55 [0.40, 0.70]

1.19.1 All participants	5	321	Mean Difference (IV, Fixed, 95% CI)	0.63 [0.42, 0.84]
1.19.2 Idiopathic pulmonary fibrosis only	3	169	Mean Difference (IV, Fixed, 95% CI)	0.64 [0.33, 0.95]
1.19.3 Severe lung disease	2	84	Mean Difference (IV, Fixed, 95% CI)	0.30 [‐0.15, 0.75]
1.19.4 Desaturators	2	103	Mean Difference (IV, Fixed, 95% CI)	0.30 [‐0.09, 0.70]
1.20 Change in quality of life (CRQ Mastery) immediately following pulmonary rehabilitation Show forest plot	5	677	Mean Difference (IV, Fixed, 95% CI)	0.62 [0.46, 0.79]

1.20.1 All participants	5	321	Mean Difference (IV, Fixed, 95% CI)	0.67 [0.44, 0.90]
1.20.2 Idiopathic pulmonary fibrosis only	3	169	Mean Difference (IV, Fixed, 95% CI)	0.63 [0.33, 0.94]
1.20.3 Severe lung disease	2	84	Mean Difference (IV, Fixed, 95% CI)	0.52 [‐0.04, 1.07]
1.20.4 Desaturators	2	103	Mean Difference (IV, Fixed, 95% CI)	0.49 [0.02, 0.96]
1.21 Change in quality of life (CRQ Dyspnoea) at long‐term follow‐up Show forest plot	4	551	Mean Difference (IV, Fixed, 95% CI)	0.25 [0.07, 0.44]

1.21.1 All participants	4	269	Mean Difference (IV, Fixed, 95% CI)	0.42 [0.17, 0.68]
1.21.2 Idiopathic pulmonary fibrosis only	2	95	Mean Difference (IV, Fixed, 95% CI)	0.23 [‐0.26, 0.72]
1.21.3 Severe lung disease	2	84	Mean Difference (IV, Fixed, 95% CI)	0.08 [‐0.42, 0.58]
1.21.4 Desaturators	2	103	Mean Difference (IV, Fixed, 95% CI)	‐0.10 [‐0.54, 0.34]
1.22 Change in quality of life (CRQ Fatigue) at long‐term follow‐up Show forest plot	4	551	Mean Difference (IV, Fixed, 95% CI)	0.26 [0.05, 0.48]

1.22.1 All participants	4	269	Mean Difference (IV, Fixed, 95% CI)	0.40 [0.09, 0.70]
1.22.2 Idiopathic pulmonary fibrosis only	2	95	Mean Difference (IV, Fixed, 95% CI)	0.31 [‐0.20, 0.83]
1.22.3 Severe lung disease	2	84	Mean Difference (IV, Fixed, 95% CI)	0.16 [‐0.37, 0.69]
1.22.4 Desaturators	2	103	Mean Difference (IV, Fixed, 95% CI)	‐0.04 [‐0.54, 0.46]
1.23 Change in quality of life (CRQ Emotion) at long‐term follow‐up Show forest plot	4	551	Mean Difference (IV, Fixed, 95% CI)	0.32 [0.13, 0.50]

1.23.1 All participants	4	269	Mean Difference (IV, Fixed, 95% CI)	0.51 [0.26, 0.77]
1.23.2 Idiopathic pulmonary fibrosis only	2	95	Mean Difference (IV, Fixed, 95% CI)	0.23 [‐0.23, 0.70]
1.23.3 Severe lung disease	2	84	Mean Difference (IV, Fixed, 95% CI)	0.16 [‐0.29, 0.61]
1.23.4 Desaturators	2	103	Mean Difference (IV, Fixed, 95% CI)	‐0.00 [‐0.42, 0.42]
1.24 Change in quality of life (CRQ Mastery) at long‐term follow‐up Show forest plot	4	551	Mean Difference (IV, Fixed, 95% CI)	0.27 [0.05, 0.50]

1.24.1 All participants	4	269	Mean Difference (IV, Fixed, 95% CI)	0.47 [0.17, 0.78]
1.24.2 Idiopathic pulmonary fibrosis only	2	95	Mean Difference (IV, Fixed, 95% CI)	0.10 [‐0.47, 0.67]
1.24.3 Severe lung disease	2	84	Mean Difference (IV, Fixed, 95% CI)	0.23 [‐0.37, 0.83]
1.24.4 Desaturators	2	103	Mean Difference (IV, Fixed, 95% CI)	‐0.15 [‐0.68, 0.38]
1.25 Long‐term survival Show forest plot	4		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only

1.25.1 All participants	4	291	Odds Ratio (M‐H, Fixed, 95% CI)	0.40 [0.14, 1.12]
1.25.2 Idiopathic pulmonary fibrosis only	3	127	Odds Ratio (M‐H, Fixed, 95% CI)	0.32 [0.08, 1.19]
1.25.3 Severe lung disease	2	84	Odds Ratio (M‐H, Fixed, 95% CI)	0.53 [0.14, 2.05]
1.25.4 Desaturators	2	103	Odds Ratio (M‐H, Fixed, 95% CI)	0.59 [0.15, 2.35]

Comparison 1. Pulmonary rehabilitation versus no pulmonary rehabilitation

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