Rehabilitación pulmonar para la enfermedad pulmonar intersticial
Resumen
Antecedentes
La enfermedad pulmonar intersticial (EPI) se caracteriza por la disminución de la capacidad funcional, la disnea y la hipoxia inducida por el ejercicio. La rehabilitación pulmonar se utiliza a menudo para mejorar los síntomas, la calidad de vida relacionada con la salud y el estado funcional en otras enfermedades pulmonares crónicas. Cada vez hay más evidencia de los efectos comparables de la rehabilitación pulmonar en personas con EPI. Sin embargo, se necesita más información para aclarar el beneficio a largo plazo y para reforzar el fundamento para incorporar la rehabilitación pulmonar en el tratamiento clínico estándar de las personas con EPI. Esta revisión actualiza los resultados publicados en 2014.
Objetivos
Determinar si la rehabilitación pulmonar en personas con EPI tiene efectos beneficiosos sobre la capacidad de ejercicio, los síntomas, la calidad de vida y la supervivencia, en comparación con ninguna rehabilitación pulmonar en personas con EPI.
Evaluar la seguridad de la rehabilitación pulmonar en personas con EPI.
Métodos de búsqueda
Se hicieron búsquedas en CENTRAL, MEDLINE (Ovid), EMBASE (Ovid), CINAHL (EBSCO) y PEDro desde su creación hasta abril de 2020. Se realizaron búsquedas en las listas de referencia de los estudios pertinentes, en registros de ensayos clínicos internacionales y resúmenes de congresos sobre salud respiratoria para buscar estudios aptos.
Criterios de selección
Se incluyeron los ensayos controlados aleatorizados y cuasialeatorizados en los que se comparó la rehabilitación pulmonar con ninguna rehabilitación pulmonar o con otro tratamiento en personas con EPI de cualquier origen.
Obtención y análisis de los datos
Dos autores de la revisión, de forma independiente, seleccionaron los ensayos para exclusión, extrajeron los datos y evaluaron el riesgo de sesgo. Se estableció contacto con los autores de los estudios para solicitar datos e información faltante sobre los efectos adversos. Se especificaron análisis de subgrupos a priori para los participantes con fibrosis pulmonar idiopática (FPI) y los participantes con enfermedad pulmonar grave (baja capacidad de difusión o desaturación durante el ejercicio). No hubo datos suficientes para realizar el análisis de subgrupos predefinido según la modalidad de entrenamiento con ejercicios.
Resultados principales
En esta actualización se incluyeron otros 12 estudios, lo cual dio un total de 21 estudios. Se incluyeron 16 estudios en el metanálisis (356 participantes realizaron la rehabilitación pulmonar y 319 fueron participantes control). La media de edad de los participantes osciló entre los 36 y los 72 años e incluyó a personas con EPI de distinta etiología, sarcoidosis o FPI (con un porcentaje del factor medio de transferencia de dióxido de carbono [TLCO] previsto que varió entre el 37% y el 63%). La mayoría de los programas de rehabilitación pulmonar se llevaron a cabo en un ámbito ambulatorio y un pequeño número de ellos se realizó en el domicilio, en ámbitos hospitalarios o por telerrehabilitación. La duración de la rehabilitación pulmonar varió de tres a 48 semanas. Hubo un riesgo moderado de sesgo debido a la ausencia de cegamiento de los evaluadores de desenlaces y análisis por intención de tratar, así como a la información insuficiente acerca de los procedimientos de aleatorización y asignación en el 60% de los estudios.
La rehabilitación pulmonar probablemente mejoró la distancia de caminata de seis minutos (six‐minute walk distance [6MWD]) con una diferencia de medias (DM) de 40,07 metros; intervalo de confianza (IC) del 95%: 32,70 a 47,44; 585 participantes; evidencia de certeza moderada. Podría haber mejorías en la capacidad máxima de trabajo (DM 9,04 vatios; IC del 95%: 6,07 a 12,0; 159 participantes; evidencia de certeza baja), el consumo máximo de oxígeno (DM 1,28 ml/kg/minuto; IC del 95%: 0,51 a 2,05; 94 participantes; evidencia de certeza baja) y la ventilación máxima (DM 7,21 l/minuto; IC del 95%: 4,10 a 10,32; 94 participantes; evidencia de certeza baja). En el subgrupo de participantes con FPI, hubo mejorías comparables en la 6MWD (DM 37,25 metros; IC del 95%: 26,16 a 48,33; 278 participantes; evidencia de certeza moderada), el máximo de trabajo (DM 9,94 vatios; IC del 95%: 6,39 a 13,49; evidencia de certeza baja) el VO2 (consumo de oxígeno) máximo (DM 1,45 ml/kg/minuto; IC del 95%: 0,51 a 2,40; evidencia de certeza baja) y la ventilación máxima (DM 9,80 l/minuto; IC del 95%: 6,06 a 13,53; 62 participantes; evidencia de certeza baja). Se desconoce el efecto de la rehabilitación pulmonar sobre la frecuencia cardíaca máxima.
La rehabilitación pulmonar podría reducir la disnea en participantes con EPI (diferencia de medias estandarizada [DME] ‐0,36; IC del 95%: ‐0,58 a ‐0,14; 348 participantes; evidencia de certeza baja) y en el subgrupo de FPI (DME ‐0,41; IC del 95%: ‐0,74 a ‐0,09; 155 participantes, evidencia de certeza baja). Es probable que la rehabilitación pulmonar mejore la calidad de vida relacionada con la salud: hubo mejorías en los cuatro dominios del Chronic Respiratory Disease Questionnaire (CRQ) y el St George's Respiratory Questionnaire (SGRQ) en los participantes con EPI y en el subgrupo de personas con FPI. La mejoría en la puntuación total del SGRQ fue ‐9,29 en los participantes con EPI (IC del 95%: ‐11,06 a ‐7,52; 478 participantes; evidencia de certeza moderada) y ‐7,91 en los participantes con FPI (IC del 95%: ‐10,55 a ‐5,26; 194 participantes; evidencia de certeza moderada). Cinco estudios informaron desenlaces a más largo plazo y las mejorías en la capacidad de ejercicio, la disnea y la calidad de vida relacionada con la salud se mantuvieron a los seis a 12 meses después del período de intervención (6MWD: DM 32,43; IC del 95%: 15,58 a 49,28; 297 participantes; evidencia de certeza moderada; disnea: DM ‐0,29; IC del 95%: ‐0,49 a ‐0,10; 335 participantes; puntuación total del SGRQ: DM ‐4,93; IC del 95%: ‐7,81 a ‐2,06, 240 participantes, evidencia de certeza baja). En el subgrupo de participantes con FPI, hubo mejorías a los seis y 12 meses siguientes a la intervención en la disnea y la puntuación de impacto del SGRQ. Se desconoce el efecto de la rehabilitación pulmonar sobre la supervivencia en el seguimiento a largo plazo. No hubo datos suficientes para examinar la repercusión de la intensidad de la enfermedad o la modalidad de entrenamiento con ejercicios.
Diez estudios proporcionaron información sobre los eventos adversos; sin embargo, no se informaron eventos adversos durante la rehabilitación. Cuatro estudios informaron de la muerte de un participante en la rehabilitación pulmonar; sin embargo, los cuatro estudios indicaron que esta muerte no estaba relacionada con la intervención recibida.
Conclusiones de los autores
La rehabilitación pulmonar se puede realizar con seguridad en personas con EPI. Es probable que la rehabilitación pulmonar mejore la capacidad de ejercicio funcional, la disnea y la calidad de vida a corto plazo, con beneficios probables también en la FPI. Las mejorías en la capacidad de ejercicio funcional, la disnea y la calidad de vida se mantuvieron a más largo plazo. Las mejorías en la disnea y la calidad de vida se podrían mantener en las personas con FPI. La certeza de la evidencia fue de baja a moderada, debido a información insuficiente acerca de la metodología, la falta de cegamiento de la evaluación de los desenlaces y la heterogeneidad de algunos resultados. Se necesitan más ensayos aleatorizados bien diseñados para determinar la prescripción óptima de ejercicios y para investigar maneras de favorecer mejorías más duraderas, especialmente para las personas con FPI.
PICO
Resumen en términos sencillos
Rehabilitación pulmonar para la enfermedad pulmonar intersticial
Pregunta de la revisión: se revisó la evidencia disponible sobre los efectos de la rehabilitación pulmonar en la capacidad de ejercicio, la dificultad para respirar y la calidad de vida de las personas con enfermedad pulmonar intersticial (EPI).
Antecedentes: las personas con EPI (una enfermedad en la que se produce la cicatrización de tejido en los pulmones y en la que la respiración es cada vez más difícil) a menudo tienen poca capacidad de ejercicio y dificultad para respirar durante el mismo. La rehabilitación pulmonar puede mejorar el bienestar de las personas con otras enfermedades pulmonares crónicas, pero se sabe poco sobre su efectividad en la EPI. Se deseaba determinar si la rehabilitación pulmonar proporcionó ventajas sobre ninguna rehabilitación pulmonar para las personas con EPI y si puede realizarse de manera segura. También se examinó si las personas con fibrosis pulmonar idiopática (FPI), un tipo de EPI que puede progresar rápidamente, se podrían beneficiar de la rehabilitación pulmonar.
Estudios encontrados: se incluyeron 21 estudios con 909 personas con EPI. Se combinaron y compararon los resultados de 16 estudios (356 participantes que recibían rehabilitación pulmonar y 319 participantes que no recibían rehabilitación pulmonar). Nueve estudios incluyeron solo a personas con FPI, tres estudios incluyeron solo a aquellos con sarcoidosis (pequeñas manchas de tejido rojo e inflamado dentro de los pulmones), dos estudios incluyeron solo a aquellos con EPI relacionada con la exposición laboral al polvo, y los otros ocho estudios incluyeron a personas con varias EPI. La media de la edad de los participantes varió entre 36 a 72 años. Todos los programas de rehabilitación pulmonar consistían en un entrenamiento de resistencia (subir escalones, caminar, montar en bicicleta o una combinación de modalidades) y algunos también incluían ejercicios de entrenamiento de fuerza adicionales. La mayoría de programas de rehabilitación pulmonar duró ocho a 12 semanas y los participantes asistieron a dos o tres sesiones por semana.
Resultados clave: inmediatamente después de la rehabilitación pulmonar, los participantes podían caminar más que los que no habían realizado la rehabilitación pulmonar (en promedio, 40 metros más en seis minutos). Los participantes también mejoraron su capacidad máxima de ejercicio y comunicaron una menor dificultad para respirar y una mejor calidad de vida. Las personas con FPI también experimentaron mejoras en la capacidad de ejercicio, la dificultad para respirar y la calidad de vida después de la rehabilitación pulmonar. Seis a 12 meses después de la rehabilitación pulmonar, los participantes podían caminar más que los que no habían realizado la rehabilitación pulmonar (en promedio, 37 metros más en seis minutos) y mantenían ciertas mejoras en la dificultad para respirar y la calidad de vida. En las personas con FPI está menos claro si las mejoras se mantienen a los seis a 12 meses después de la rehabilitación pulmonar. Ningún estudio describió efectos no deseados de la rehabilitación pulmonar.
Calidad de la evidencia: por lo general, la calidad de la evidencia fue de baja a moderada. Esto se debió principalmente a una información insuficiente acerca de la metodología, a que los evaluadores sabían qué tratamiento se había administrado y a la variabilidad de algunos resultados.
Conclusión: la rehabilitación pulmonar probablemente mejora la capacidad de ejercicio, los síntomas y la calidad de vida, y se puede realizar de forma segura en personas con EPI, incluidas las que presentan FPI. Estos resultados apoyan la inclusión de la rehabilitación pulmonar como parte del tratamiento de las personas con EPI. Los estudios futuros deberían explorar formas de promover mejoras más duraderas tras el entrenamiento con ejercicios, en particular para aquellos con FPI y en los que la estrategia de entrenamiento con ejercicios produce el mayor beneficio.
Esta revisión está actualizada hasta junio de 2020.
Authors' conclusions
Summary of findings
| Pulmonary rehabilitation compared to no pulmonary rehabilitation for interstitial lung disease | ||||||
| Patient or population: interstitial lung disease | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | № of participants | Certainty of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with no pulmonary rehabilitation | Risk with pulmonary rehabilitation | |||||
| Change in 6MWD | The mean change in 6MWD ranged from –35 metres to 26 metres | MD 40.07 metres higher | — | 585 | ⊕⊕⊕⊝ | 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 | The mean change in 6MWD at long‐term follow‐up ranged from –49 metres to –6 metres | MD 32.43 metres higher | — | 321 | ⊕⊕⊕⊝ | — |
| Change in peak work capacity | The mean change in peak work capacity ranged from –10 watts to 0.6 watts | MD 9.04 watts higher | — | 159 | ⊕⊕⊝⊝ | — |
| Change in dyspnoea score | The mean change in dyspnoea score ranged from –0.2 to 0.4 | SMD 0.36 SD lower | — | 348 | ⊕⊕⊝⊝ | 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 | The mean change in quality of life ranged from –7 to 6 points | MD 9.29 points lower | — | 478 | ⊕⊕⊕⊝ | 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 | The mean change in quality of life at long‐term follow‐up ranged from –1 to 5 points | MD 4.93 points lower | — | 240 | ⊕⊕⊝⊝ | Lower value post intervention is favourable, indicating improvement in quality of life. |
| Long‐term survival (incidence of mortality) | Study population | OR 0.40 | 291 | ⊕⊕⊝⊝ | Lower OR represents improved survival at long‐term follow‐up. | |
| 85 per 1000 | 36 per 1000 | |||||
| *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 | ||||||
| aDowngraded one level for detection bias (nine to 11 studies), attrition bias (five to eight studies) and selection bias (seven studies). | ||||||
| Pulmonary rehabilitation compared to no pulmonary rehabilitation for idiopathic pulmonary fibrosis | ||||||
| Patient or population: idiopathic pulmonary fibrosis | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | № of participants | Certainty of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with no pulmonary rehabilitation | Risk with pulmonary rehabilitation | |||||
| Change in 6MWD | The mean change in 6MWD ranged from –35 metres to 26 metres | MD 37.25 metres higher | — | 278 | ⊕⊕⊕⊝ | — |
| Change in 6MWD at long‐term follow‐up | The mean change in 6MWD at long‐term follow‐up ranged from –49 metres to 4 metres | MD 1.64 metres higher | — | 123 | ⊕⊕⊝⊝ | — |
| Change in peak work capacity | The mean change in peak work capacity ranged from –7 watts to –0.8 watts | MD 9.94 watts higher | — | 62 | ⊕⊕⊝⊝ | — |
| Change in dyspnoea score | The mean change in dyspnoea score ranged from –0.06 to 0.4 | SMD 0.41 lower | — | 155 | ⊕⊕⊝⊝ | 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 | The mean change in quality of life ranged from –3 to 3 points | MD 7.91 points lower | — | 194 | ⊕⊕⊕⊝ | Lower value post intervention is favourable, indicating improvement in quality of life. |
| Change in quality of life at long‐term | The mean change in quality of life at long‐term follow‐up ranged from 1 to 4 points | MD 3.45 points lower | — | 89 | ⊕⊕⊝⊝ | Lower value post intervention is favourable, indicating improvement in quality of life. |
| Long‐term survival (incidence of mortality) | Study population | OR 0.32 | 127 | ⊕⊕⊝⊝ | Lower OR represents improved survival at long‐term follow‐up. | |
| 133 per 1000 | 47 per 1000 | |||||
| *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 | ||||||
| aDowngraded one level for detection bias (four or five studies), attrition bias (three or four studies) and selection bias (five studies) | ||||||
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, hypersensitivity pneumonitis, asbestosis, silicosis, sarcoidosis and connective tissue disease‐related disorders such as rheumatoid arthritis and scleroderma. 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). Treatment options for people with ILD are generally limited. Two antifibrotic therapies, pirfenidone and nintedanib, slow disease progression and potentially improve survival in IPF (King 2014; Richeldi 2014), and may also be beneficial for people with other types of progressive fibrosing ILD (Flaherty 2019). In addition, there is limited evidence to suggest these treatments can provide convincing benefits for exercise tolerance, quality of life or symptoms (Graney 2018; Kreuter 2020; Nathan 2019).
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 as a result of physical deconditioning (Markovitz 1998). 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). Exercise training is a fundamental component of pulmonary rehabilitation (Spruit 2013), and includes aerobic training as a core component, often comprising of walking, cycling or a combination of both. Resistance training is an important additional component for optimising improvements in muscle strength (Bolton 2013). Pulmonary rehabilitation can occur in several different settings such as hospital outpatient departments and community health centres, typically the most widely available of settings, inpatient stays or a home‐based environment. 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). Individuals with ILD often present with similar symptoms to those seen in COPD, despite differences in underlying pathophysiology, such as dyspnoea, fatigue, reduced exercise tolerance and poor quality of life (Holland 2013). Given these similarities, and that many of these issues are modifiable in COPD, several authors have postulated that similar effects of pulmonary rehabilitation may be seen in people 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 less established. Despite this, guidelines for pulmonary rehabilitation have advocated its use in 'individuals with chronic respiratory disorders other than COPD' including ILD as 'there is now more robust evidence to support inclusion of some of these patient groups in pulmonary rehabilitation programs' (Bolton 2013; Spruit 2013). However, it has been suggested that the benefits of pulmonary rehabilitation in ILD are smaller than those generally seen in COPD, that it may not be suitable for some patients due to variability across the disease spectrum and that its ongoing effects are not sustained beyond six months (Bolton 2013; Spruit 2013). Guidelines for clinical management of both ILD (Bradley 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
The review authors undertook the original version of this Cochrane Review to establish the safety and efficacy of pulmonary rehabilitation in adults with ILD, and to determine the effects of pulmonary rehabilitation on exercise capacity, symptoms, quality of life and survival in this patient group. The original review and the second update in 2014 concluded that pulmonary rehabilitation resulted in significant improvements in exercise capacity, quality of life and symptoms. However, the number of RCTs was small (five to nine) and they were associated with methodological bias and the longer‐term benefit of pulmonary rehabilitation remained unclear. Poor exercise tolerance, dyspnoea and fatigue remain a major burden for people with ILD and interventions such as pulmonary rehabilitation can positively improve these aspects. This has led to a dramatic rise in the number of studies investigating the benefits of pulmonary rehabilitation in ILD, with some following strong methodological design. In addition, there has been increasing international acceptance that pulmonary rehabilitation can positively impact people with ILD, with the inclusion of ILD in pulmonary rehabilitation programmes recommended in international guidelines (Bolton 2013). This review aimed to provide more conclusive evidence of the benefit of pulmonary rehabilitation in ILD, as well as clarifying the longer‐term benefit and strengthening the rationale for the inclusion of pulmonary rehabilitation in standard care for people with ILD.
Objectives
To determine whether pulmonary rehabilitation in people with ILD has beneficial effects on exercise capacity, symptoms, quality of life and survival compared with no pulmonary rehabilitation in people with ILD.
To assess the safety of pulmonary rehabilitation in people with ILD.
Methods
Criteria for considering studies for this review
Types of studies
We included randomised controlled trials (RCTs) and quasi‐RCTs in which a prescribed regimen of pulmonary rehabilitation was compared with no pulmonary rehabilitation or with other therapy in study participants with ILD. We considered single‐blind and open studies for inclusion.
Types of participants
People with ILD of any origin, diagnosed according to investigator definitions. There were no exclusions 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
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Functional or maximal exercise capacity, measured during formal exercise tests (maximal oxygen uptake (VO2 max), peak oxygen uptake (VO2 peak), peak work capacity (peak watts), maximal ventilation (Ve max), maximum heart rate (HRmax)) or field exercise tests (increase in distance walked).
Secondary outcomes
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Dyspnoea: all measures of dyspnoea used.
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Quality of life: measured by generic or disease‐specific quality‐of‐life instruments. All quality‐of‐life instruments used.
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Adverse effects: adverse cardiovascular events during exercise training, musculoskeletal injuries and deaths.
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Survival.
Search methods for identification of studies
Electronic searches
We searched the Cochrane Airways Trials Register via the Cochrane Register of Studies, Cochrane Central Register of Controlled Trials (CENTRAL 2020, Issue 4) via the Cochrane Register of Studies, MEDLINE (OvidSP), Embase (OvidSP), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (EBSCO) and the Physiotherapy Evidence Database (PEDro) from inception to 16 April 2020. There were no language restrictions. The previously published version included searches up to June 2014. The search period for this update was June 2014 to April 2020.
The full database search strategies are listed in the appendices (Appendix 1; Appendix 2; Appendix 3; Appendix 4; Appendix 5).
Searching other resources
We handsearched the reference lists of relevant studies and related review papers for qualifying studies. We reviewed clinical trial registries (ClinicalTrials.gov: www.clinicaltrials.gov and the World Health Organization (WHO) trials portal: www.who.int/ictrp/en) to search for relevant planned, ongoing and unpublished trials. We reviewed 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) for relevant studies. In addition, we contacted the authors of RCTs to ask for information on other published and unpublished studies.
Data collection and analysis
Selection of studies
Two review authors (LD and AM) independently coded for relevant studies identified in the literature searches by examining titles, abstracts and keyword fields as follows.
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Include: study categorically met all review criteria.
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Unclear: study appeared to meet some review criteria, but available information was insufficient for review authors to categorically determine relevance.
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Exclude: study did not categorically meet all review criteria.
Two review authors (LD and AM) used full‐text copies of study papers categorised as 'include' and 'unclear' to decide on study inclusion. We resolved disagreements by consensus or involving a third review author (AH). We kept a full record of decisions, and calculated simple agreement and kappa statistics.
Data extraction and management
Two review authors (LD and AM) independently extracted data using a prepared checklist; one review author (LD) entered data into Review Manager 5 with random checks on accuracy. We resolved disagreements by consensus. Data included characteristics of included studies (methods, participants, interventions, outcomes) and results of included studies. We contacted authors of included studies to request details of missing data where applicable.
Assessment of risk of bias in included studies
Two review authors (LD and AM) independently assessed the risk of bias for all included studies. We assessed the risk of bias following the criteria provided by the Cochrane Handbook of Systematic Reviews of Interventions (Higgins 2020). The review authors assessed the internal validity of included studies using a component approach (including sequence generation for randomisation, allocation concealment, blinding of participants and personnel, incomplete outcome data, selective outcome reporting and other potential sources of bias). We judged the risk of bias for each study as 'low', 'high' or 'unclear' risk and resolved disagreements by consensus. We wrote to study authors to seek clarification when information was inadequate to judge the risk of bias.
Measures of treatment effect
For continuous variables, we recorded mean change from baseline or mean post intervention values and standard deviation (SD) for each group. We calculated SDs when 95% confidence intervals (CIs) or standard errors were reported using guidance in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2020). When SDs were missing and we were unable to obtain the results from study authors, we used a mean value for the SD of a similar study that reported the outcome to calculate the required SD using guidance in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2020). When measures of improvement had opposite directions of effect on different scales (e.g. dyspnoea), we recorded all improvements as negative values, and all deteriorations as positive values. We calculated mean differences (MDs) for outcomes measured with the same metrics or standardised mean differences (SMDs) for outcomes measured with different metrics with 95% CIs using Review Manager 5 and RevmanWeb. To facilitate interpretation of SMDs, we re‐expressed SMD estimates as MDs on more common measurement scales as described in Chapter 15 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2020). For binary outcome measures, we recorded the number of participants with each outcome event, by allocated treated group, to allow intention‐to‐treat analysis. We calculated odds ratios (ORs) with 95% CIs for each study.
Unit of analysis issues
The search identified no cluster RCTs that met the inclusion criteria for this systematic review. If future versions include cluster RCTs that have not been adjusted for clustering in their analysis, we will calculate the effective sample size for these studies based on the methods described in the Cochrane Handbook for Systematic Review of Interventions (Higgins 2020).
Dealing with missing data
Where possible, we contacted the trial authors if data were missing from included studies. When SDs were missing and we were unable to obtain the results from study authors, we used the SD of a similar study that reported the outcome to impute a SD using Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2020). We excluded studies that did not report mean change scores or enough data to calculate mean change scores from meta‐analyses. We considered studies that did not use intention‐to‐treat analysis and omitted data from participants due to withdrawal or incompleteness to have a high risk of bias.
Assessment of heterogeneity
We assessed statistical heterogeneity in each meta‐analysis using the Chi² test and the I² statistic (Higgins 2020). We used a P value of 0.10 to determine statistical significance. We regarded heterogeneity as low when the I² statistic was less than 30%, moderate when the I² statistic was 30% to 50%, as substantial when the I² statistic was 50% to 75% and of high statistical heterogeneity if the I² statistic was greater than 75%.
Assessment of reporting biases
We assessed relevant causes of bias on the analysis including publication bias, outcome reporting bias and methodological quality. When meta‐analyses included a minimum of 10 studies, we created funnel plots to investigate reporting biases (such as publication bias).
Data synthesis
We performed a pooled quantitative analysis when trials were clinically homogeneous. We used a fixed‐effect model or a random‐effects model depending on assessment of heterogeneity.
Subgroup analysis and investigation of heterogeneity
We conducted three subgroup analyses specified a priori to explore possible sources of heterogeneity.
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Type of ILD: 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: people 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 (transfer factor for carbon monoxide (TLCO)) was less than 45% predicted (Flaherty 2001). In addition, participants who desaturated during exercise testing (oxygen saturation (SpO2) 88% or less) 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
We performed sensitivity analyses according to trial quality by repeating our analysis among only those studies judged to be of 'high quality’. For the purposes of this review, 'high‐quality’ trials were defined as trials with low risk of bias due to allocation concealment, and intention‐to‐treat analysis. We performed the sensitivity analyses for the primary outcome of functional or maximal exercise capacity (six‐minute walk distance (6MWD)) and the secondary outcomes of dyspnoea and health‐related quality of life.
Summary of findings and assessment of the certainty of the evidence
We used GRADE to assess the evidence for the primary outcome of functional or maximal exercise capacity (peak oxygen update, peak work rate) plus the secondary outcomes of dyspnoea, quality of life (St George's Respiratory Questionnaire (SGRQ)) and survival. We performed these analyses and presented the results in a 'Summary of findings' table for ILD (summary of findings Table 1) and IPF (summary of findings Table 2) generated using GRADEpro GDT software.
Results
Description of studies
Details are available in the Characteristics of included studies, Characteristics of excluded studies, Characteristics of studies awaiting classification, and Characteristics of ongoing studies tables.
Results of the search
See Figure 1 for the study flow diagram.
Study flow diagram for 2014–2020 literature searches. HRQoL: health‐related quality of life.
The original version of the review identified 4783 records from the initial search of databases (Holland 2008). From the studies on this list, the review authors retrieved 15 full‐text articles for closer inspection. There were no additional studies identified upon handsearching of reference lists or contact with study authors. Review authors achieved agreement on 13/15 full‐text articles (87%) with kappa = 0.74, indicating substantial agreement. They resolved disagreement by consensus. Five articles met the inclusion criteria for the original review (Baradzina 2005; Holland 2008; Mejia 2000; Nishiyama 2008; Wewel 2005).
The 2014 updated search of databases returned 1901 potential studies (Dowman 2014). The review authors retrieved eight full‐text articles from this list for closer inspection. They identified six additional studies upon handsearching of reference lists and review of international clinical trial registries and annual international respiratory conference abstracts. The review authors achieved agreement on 13/14 full‐text articles (92%) with kappa = 0.81, indicating substantial agreement. They resolved disagreements by consensus. We included four additional studies in the review update (Jackson 2014; Menon 2011; Perez Bogerd 2018 (identified as Perez Bogerd 2011 in the 2014 update of this review as only preliminary results were available); Vainshelboim 2014). One article was awaiting classification and, therefore, was not included in the analysis (Dale 2014). Nine articles in total were included in the 2014 review update.
The search for the most recent and current update covered the period from June 2014 to April 2020. We identified 4453 references through the electronic database search and four additional studies upon handsearching of reference lists and review of international clinical trial registries and annual international respiratory conference abstracts. We retrieved 22 studies (36 references) from electronic databases for full‐text assessment. We achieved agreement between review authors on 19 of the full‐text articles (86%) with kappa = 0.70, indicating good agreement. We resolved disagreement by consensus or by involving a third review author. We included 12 additional studies (Dale 2014; De Las Heras 2019; Dowman 2017; Gaunaurd 2014; He 2016; Jarosch 2020; Ku 2017; Lanza 2019; Naz 2018; Shen 2016; Wallaert 2020; Xiao 2019). Figure 1 shows a study flow diagram.
Included studies
Twenty‐one studies met the inclusion criteria for this review; all were parallel RCTs. We included four studies in the previous version of the review as preliminary data (Dale 2014; Gaunaurd 2014; Perez Bogerd 2018; Vainshelboim 2014), but full published data for all four studies for for Vainshelboim 2014 were available for this update. Seven studies were in abstract form only (Baradzina 2005; De Las Heras 2019; Lanza 2019; Mejia 2000; Menon 2011; Shen 2016; Wewel 2005). Sample sizes ranged from 18 to 142 participants. Full details can be found in the Characteristics of included studies table.
Participants
Most studies included participants with a variety of ILDs (Dowman 2017; Holland 2008; Ku 2017; Mejia 2000; Menon 2011; Perez Bogerd 2018; Wewel 2005). One of these was stratified according to the three subgroups of IPF, dust‐related ILD and connective tissue disease‐related ILD (Dowman 2017) and one was stratified for IPF (Holland 2008). Nine studies included only participants with IPF (De Las Heras 2019; Gaunaurd 2014; He 2016; Jackson 2014; Jarosch 2020; Lanza 2019; Nishiyama 2008; Shen 2016; Vainshelboim 2014), whilst three studies included only participants with sarcoidosis (Baradzina 2005; Naz 2018; Wallaert 2020), and two studies included only participants with occupational dust‐related ILD (pneumoconiosis) (Dale 2014; Xiao 2019). All participants were adults with mean age ranging from 36 to 72 years. Three studies did not report mean age (Lanza 2019; Menon 2011; Shen 2016).
Interventions
All studies compared pulmonary rehabilitation versus no pulmonary rehabilitation or a sham training control group. Eighteen studies examined pulmonary rehabilitation programmes conducted in an outpatient setting (Baradzina 2005; Dale 2014; Dowman 2017; Gaunaurd 2014; He 2016; Holland 2008; Jackson 2014; Ku 2017; Lanza 2019; Mejia 2000; Menon 2011; Naz 2018; Nishiyama 2008; Perez Bogerd 2018; Shen 2016; Vainshelboim 2014; Wallaert 2020; Xiao 2019), one study evaluated pulmonary rehabilitation in an inpatient setting (Jarosch 2020), one study evaluated a home‐based pulmonary rehabilitation programme (Wewel 2005), and another study evaluated a tele‐rehabilitation model of pulmonary rehabilitation (De Las Heras 2019) (Table 1). The length of pulmonary rehabilitation programmes varied from five to 48 weeks for outpatient rehabilitation with 15 studies being eight to 12 weeks and the remaining three being five weeks, six months and 48 weeks. The length of pulmonary rehabilitation programmes were three weeks for inpatient rehabilitation, six months for home‐based rehabilitation and three months for tele‐rehabilitation (Table 1).
| Study | Follow‐up | Duration (weeks) | Sessions (per week) | Setting | Programme type |
|---|---|---|---|---|---|
| 5 weeks | 5 | 5 | Outpatient | Exercise + other | |
| 8, 26 weeks | 8 | 2 | Outpatient | Exercise | |
| 12 weeks | 12 | 5–7 | Tele‐rehabilitation | Exercise | |
| 8 weeks, 6 months | 8 | 2 | Outpatient | Exercise + other | |
| 12 weeks, 3 months | 12 | 2 | Outpatient | Exercise + other | |
| 12 weeks | 12 | 3–5 | Outpatient | Exercise | |
| 8, 26 weeks | 8 | 2 | Outpatient | Exercise | |
| 12 weeks, 3 months | 12 | 2 | Outpatient | Exercise + other | |
| 3 weeks, 3 months | 3 | 5–6 | Inpatient | Exercise + other | |
| 8 weeks | 8 | 2 | Outpatient | Exercise + other | |
| 12 weeks | 12 | 2 | Outpatient | Exercise | |
| 12 weeks | 12 | 3 | Outpatient | Exercise | |
| 8 weeks | 8 | — | Outpatient | Exercise | |
| 12 weeks | 12 | 2 | Outpatient | Exercise | |
| 9 weeks | 9 | 2 | Outpatient | Exercise | |
| 3, 6, 12 months | 26 | 2–3 | Outpatient | Exercise + other | |
| 12 weeks | 12 | 3 | Outpatient | Exercise | |
| 12 weeks | 12 | 2 | Outpatient | Exercise | |
| 8 weeks | 8 | 3 | Outpatient | Exercise + other | |
| 6 months | 26 | 7 | Home | Exercise | |
| 48 weeks | 48 | 4 | Outpatient/home | Exercise + other |
Five studies examined the effects of aerobic training (Baradzina 2005; Dale 2014; He 2016; Mejia 2000; Wewel 2005), 13 studies used a combination of aerobic and resistance training (De Las Heras 2019; Dowman 2017; Gaunaurd 2014; Holland 2008; Jackson 2014; Jarosch 2020; Ku 2017; Naz 2018; Nishiyama 2008; Perez Bogerd 2018; Vainshelboim 2014; Wallaert 2020; Xiao 2019), and the remaining studies did not specify the exercise modality used (Lanza 2019; Menon 2011; Shen 2016). No study evaluated resistance training alone; therefore, subgroup analyses for type of exercise were not possible. Nine studies comprised exercise training alone (Dale 2014; De Las Heras 2019; He 2016; Holland 2008; Mejia 2000; Naz 2018; Vainshelboim 2014; Wewel 2005; Xiao 2019), whereas nine studies added interventions to exercise training that were not offered to the control group (Table 1); these included educational lectures (Baradzina 2005; Dowman 2017; Gaunaurd 2014; Jackson 2014; Jarosch 2020; Ku 2017; Nishiyama 2008; Perez Bogerd 2018; Wallaert 2020), nutritional advice (Baradzina 2005; Gaunaurd 2014; Jarosch 2020; Ku 2017; Perez Bogerd 2018), stress management (Baradzina 2005), physiotherapy (Baradzina 2005), occupational therapy (Perez Bogerd 2018), and psychosocial support (Gaunaurd 2014; Jarosch 2020; Ku 2017; Perez Bogerd 2018; Wallaert 2020). Inclusion of additional interventions with exercise training was unclear in three studies (Lanza 2019; Menon 2011; Shen 2016).
Outcomes
All studies used a measure of functional exercise tolerance, most commonly the six‐minute walk test (Dale 2014; De Las Heras 2019; Dowman 2017; Gaunaurd 2014; He 2016; Holland 2008; Jackson 2014; Jarosch 2020; Ku 2017; Lanza 2019; Menon 2011; Naz 2018; Nishiyama 2008; Perez Bogerd 2018; Shen 2016; Vainshelboim 2014; Wewel 2005; Xiao 2019). Five studies also performed a cardiopulmonary exercise test (Dale 2014; Holland 2008; Perez Bogerd 2018; Vainshelboim 2014; Wewel 2005). Eighteen studies assessed quality of life, using the Chronic Respiratory Disease Questionnaire (CRQ) (Dale 2014; Dowman 2017; Holland 2008; Jarosch 2020; Mejia 2000; Perez Bogerd 2018), the SGRQ (Dale 2014; De Las Heras 2019; Ku 2017; Naz 2018; Nishiyama 2008; Perez Bogerd 2018; Shen 2016; Vainshelboim 2014; Wewel 2005; Xiao 2019), the St George's Respiratory Questionnaire IPF version (SGRQ‐I) (Dowman 2017; Gaunaurd 2014; Lanza 2019), the 36‐item Short Form Health Survey (SF‐36) (Jarosch 2020, Naz 2018), or the WHO questionnaire (Baradzina 2005). Twelve studies assessed dyspnoea using the modified Medical Research Council Scale (Dale 2014; Dowman 2017; Holland 2008; Ku 2017; Naz 2018; Perez Bogerd 2018; Vainshelboim 2014; Wallaert 2020), the Baseline Dyspnoea Index (Nishiyama 2008), and an unspecified measure (Baradzina 2005; Wewel 2005).
Excluded studies
Common reasons for exclusion were that eight studies were not RCTs, three studies included participants without lung disease, four studies included mixed disease groups, four studies did not include pulmonary rehabilitation and one study included an intervention‐based control group. Full details of 20 excluded studies, of studies that are ongoing and of studies awaiting classification can be found in the Characteristics of excluded studies, Characteristics of ongoing studies, and Characteristics of studies awaiting classification tables.
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
Sequence generation
All studies reported random allocation to groups. Twelve studies described the methods used for generation of the randomisation sequence and were at low risk of bias (Dale 2014; De Las Heras 2019; Dowman 2017; Gaunaurd 2014; Holland 2008; Jarosch 2020; Ku 2017; Naz 2018; Perez Bogerd 2018; Vainshelboim 2014; Wallaert 2020; Xiao 2019). Nine studies did not specify the method by which the randomisation sequence was generated and these were considered to have unclear risk of bias (Baradzina 2005; He 2016; Jackson 2014; Lanza 2019; Mejia 2000; Menon 2011; Nishiyama 2008; Shen 2016; Wewel 2005).
Allocation concealment
Ten studies reported that the allocation sequence was concealed using sealed envelopes (Dale 2014; Dowman 2017; Holland 2008; Jackson 2014; Jarosch 2020; Naz 2018; Nishiyama 2008; Perez Bogerd 2018; Vainshelboim 2014; Wallaert 2020). Of the remaining studies, four did not specify whether the allocation sequence was concealed (Gaunaurd 2014; He 2016; Ku 2017; Xiao 2019), and seven were available only in abstract form, and did not provide sufficient information to permit assessment of whether the allocation sequence was concealed (Baradzina 2005; De Las Heras 2019; Gaunaurd 2014; He 2016; Ku 2017; Lanza 2019; Mejia 2000; Menon 2011; Shen 2016; Wewel 2005).
Blinding
Performance bias
Blinding of participants or personnel was not possible for the majority of the studies due to the physical nature of the intervention. All included studies except two were at high risk of performance bias. Two studies were at unclear risk since they provided sham exercise training (Mejia 2000), or simple exercise in the form of free movement and hospital‐led gymnastics (Xiao 2019), to the control group. It is possible the participants could be blinded to the intervention received. However, neither study provided specific details to confirm this. No studies reported whether data analysts were blinded to treatment allocation.
Detection bias
Four studies reported use of a blinded assessor for all outcome measures and at low risk of detection bias (Dale 2014; De Las Heras 2019; Dowman 2017; Holland 2008). Seven studies indicated that the assessors were unblinded; these were at high risk of bias (Gaunaurd 2014; Jackson 2014; Jarosch 2020; Ku 2017; Perez Bogerd 2018; Vainshelboim 2014; Wallaert 2020). There were insufficient data to show whether assessors were blinded in the other studies and were considered at unclear risk of bias (Baradzina 2005; He 2016; Lanza 2019; Mejia 2000; Menon 2011; Naz 2018; Nishiyama 2008; Shen 2016; Wewel 2005; Xiao 2019).
Incomplete outcome data
Ten studies reported dropouts and loss to follow‐up (Dale 2014; Dowman 2017; Gaunaurd 2014; Holland 2008; Jackson 2014; Jarosch 2020; Nishiyama 2008; Perez Bogerd 2018; Vainshelboim 2014; Xiao 2019). One of these reported that two participants in the exercise group withdrew before baseline data had been collected and was considered to have low risk of bias (Nishiyama 2008). Six studies reported that participants in the exercise group (one to four) and in the control group (zero to six) did not complete the intervention period (De Las Heras 2019; Gaunaurd 2014; Jackson 2014; Jarosch 2020; Vainshelboim 2014; Xiao 2019). Data from these participants were not included in the analysis in either study (De Las Heras 2019; Gaunaurd 2014; Jackson 2014; Jarosch 2020; Vainshelboim 2014; Xiao 2019), therefore these studies were at high risk of bias.
Eight studies were at low risk of bias for incomplete outcome data. Three studies reported no dropouts with all participants completing the intervention and assessments (He 2016; Ku 2017; Naz 2018). One study reported minimal dropouts (Dale 2014, 5% of people dropped out), three studies reported a moderate number of dropouts (Dowman 2017, 12%; Holland 2008, 20%; Wallaert 2020, 18%) and one study reported a significant number of dropouts (Perez Bogerd 2018, 40%). These five studies performed the data analysis according to the intention‐to‐treat principle (Dale 2014; Dowman 2017; Holland 2008; Perez Bogerd 2018; Wallaert 2020). One study used the last observation carried forward method (Holland 2008), and the other four studies used maximum likelihood estimation to account for missing data in the statistical analysis (Dale 2014; Dowman 2017; Perez Bogerd 2018; Wallaert 2020).
The remaining studies, all of which were published only in abstract form, did not report whether dropouts or losses to follow‐up occurred and were rated as having an unclear risk of bias (Baradzina 2005; Lanza 2019; Mejia 2000; Menon 2011; Shen 2016; Wewel 2005).
Selective reporting
Ten studies were listed on a clinical trial registry (Dale 2014; De Las Heras 2019; Dowman 2017; Gaunaurd 2014; Holland 2008; Jackson 2014; Jarosch 2020; Perez Bogerd 2018; Vainshelboim 2014; Wallaert 2020). Eight studies reported results for all outcomes at all time points (Dale 2014; Dowman 2017; Holland 2008; Jackson 2014; Jarosch 2020; Perez Bogerd 2018; Vainshelboim 2014; Wallaert 2020). Two studies did not report all outcome measures mentioned in the clinical registry (De Las Heras 2019; Gaunaurd 2014). One study was in abstract form, and it is likely that not all data are currently available (De Las Heras 2019). The other study (Gaunaurd 2014) was the publication of the quality‐of‐life data from the original study (Jackson 2014). This study (Gaunaurd 2014) and two others (Ku 2017; Xiao 2019) were judged to have a high risk of reporting bias as they did not report all quality‐of‐life outcomes (Gaunaurd 2014; Ku 2017; Xiao 2019), or mMRC Dyspnoea Score (Ku 2017). Three studies reported the results for all time points for the outcomes detailed in the methods and were considered at low risk of bias (He 2016; Naz 2018; Nishiyama 2008). 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; Lanza 2019; Mejia 2000; Menon 2011; Shen 2016; Wewel 2005); therefore, these studies were considered at unclear risk of bias.
Other potential sources of bias
Other potential sources of bias may be present due to not all of the data being available in required format of mean change from baseline and SD. Change from baseline SDs were imputed using a correlation coefficient calculated from Nishiyama 2008 for three studies (He 2016; Shen 2016; Xiao 2019). In addition, there were some studies from which we could not obtain additional data, despite contacting the authors to request additional information and there were a number of studies that were provided in abstract form only.
Effects of interventions
See: Summary of findings 1 Pulmonary rehabilitation compared to no pulmonary rehabilitation for interstitial lung disease; Summary of findings 2 Pulmonary rehabilitation compared to 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. Sixteen studies provided sufficient data for pooling in a meta‐analysis (Dale 2014; De Las Heras 2019; Dowman 2017; Gaunaurd 2014; He 2016; Holland 2008; Jackson 2014; Jarosch 2020; Ku 2017; Naz 2018; Nishiyama 2008; Perez Bogerd 2018; Shen 2016; Vainshelboim 2014; Wallaert 2020; Xiao 2019). summary of findings Table 1 and summary of findings Table 2 summarise the certainty of the evidence. For functional exercise capacity, maximal exercise capacity and the CRQ domains (quality of life), positive values reflect improvement. For measures of dyspnoea and the SGRQ domains (quality of life), negative values reflect improvement.
Primary outcomes
Functional exercise capacity
Nineteen studies reported functional exercise capacity. Of these, 17 trials including 802 participants reported that pulmonary rehabilitation resulted in an improvement in functional exercise capacity immediately following the programme (Baradzina 2005; Dale 2014; De Las Heras 2019; Dowman 2017; He 2016; Holland 2008; Jarosch 2020; Ku 2017; Lanza 2019; Mejia 2000; Menon 2011; Naz 2018; Nishiyama 2008; Perez Bogerd 2018; Vainshelboim 2014; Wewel 2005; Xiao 2019). There was no change in 6MWD following pulmonary rehabilitation in one study (Jackson 2014), and it was unclear if there was an improvement in 6MWD in the remaining study (Shen 2016). Thirteen trials provided sufficient data on the six‐minute walk test for meta‐analysis, with 309 participants in the pulmonary rehabilitation group and 276 participants in the control group (Dale 2014; De Las Heras 2019; Dowman 2017; He 2016; Holland 2008; Jackson 2014; Jarosch 2020; Ku 2017; Naz 2018: Nishiyama 2008; Perez Bogerd 2018; Vainshelboim 2014; Xiao 2019). Results of the meta‐analysis are shown in Figure 3 (Analysis 1.1). The common effect (MD) for change in distance walked was 40.07 metres in favour of the pulmonary rehabilitation group (95% CI 32.70 to 47.44). This effect exceeded the minimal important difference (MID) for the 6MWD of 30 metres to 33 metres for people with ILD (Holland 2014). There was also an effect in favour of pulmonary rehabilitation in the subgroup of participants with IPF (8 trials, 151 participants in pulmonary rehabilitation group, 127 participants in control group) with an MD of 37.25 metres (95% CI 26.16 to 48.33). This effect also exceeded the MID for the 6MWD of 29 metres to 34 metres for people with IPF (Holland 2014). Two studies provided sufficient data to show the effects of pulmonary rehabilitation among 84 participants with severe lung disease or in 103 participants who desaturated (Dowman 2017; Holland 2008). The effect of pulmonary rehabilitation on 6MWD was less certain for participants who desaturated (MD 20.21 metres, 95% CI –2.62 to 42.87; Analysis 1.1) or for participants with severe lung disease (MD 15.37 metres, 95% CI –10.71 to 41.43; Analysis 1.1).
Forest plot of comparison: 1 Pulmonary rehabilitation versus no pulmonary rehabilitation, outcome: 1.1 Change in six‐minute walk test immediately following pulmonary rehabilitation.
Five studies reported results of the six‐minute walk test at long‐term (six to 12 months') follow‐up (Analysis 1.2) (Dale 2014; Dowman 2017; Holland 2008; Perez Bogerd 2018; Vainshelboim 2014). In those who participated in pulmonary rehabilitation, improvements in 6MWD were maintained six to 12 months following the intervention period with an MD of 32.43 metres (95% CI 15.58 to 49.28; 297 participants). This effect was within the MID range for 6MWD of 30 metres to 33 metres (Holland 2014). In the subgroup of participants with IPF, improvements in 6MWD were less evident at long‐term follow‐up with an MD of 1.64 metres (95% CI –24.89 to 28.17 metres; 3 studies, 123 participants; Analysis 1.2).
Sensitivity analysis using studies of high quality (low risk of bias) produced a similar estimate of the treatment effect for participants with ILD (MD 41.22 metres, 95% CI 26.80 to 55.64; 5 studies, 288 participants; Table 2). Tests of heterogeneity for all analyses of functional exercise capacity were not significant. A funnel plot of the complete data showed no evidence of asymmetry (Figure 4).
| 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 | — | 288 | I² = 70%, P = 0.01 | –0.28 (–0.51 to –0.04) | P < 0.02 | |
| SGRQ | Symptoms | 231 | I² = 51%, P = 0.11 | –13.76 (–18.49 to –9.04) | P < 0.00001 | |
| Activity | 231 | I² = 21%, P = 0.28 | –8.56 (–12.90 to –4.22) | P = 0.0001 | ||
| Impact | 231 | I² = 0%, P = 0.83 | –7.91 (–11.54 to –4.29) | P < 0.0001 | ||
| Total | 231 | I² = 21%, P = 0.29 | –8.13 (–11.24 to –5.02) | P < 0.00001 | ||
| CRQ | Dyspnoea | 270 | I² = 41%, P = 0.18 | 0.61 (0.32 to 0.90) | P < 0.0001 | |
| Fatigue | 270 | I² = 0%, P = 0.93 | 0.66 (0.40 to 0.92) | P < 0.00001 | ||
| Emotion | 270 | I² = 0%, P = 0.44 | 0.58 (0.35 to 0.81) | P < 0.00001 | ||
| Mastery | 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.
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.
Maximal exercise capacity
Four studies measured maximal exercise capacity using an incremental cycle ergometer test. Four studies provided sufficient data to conduct a meta‐analysis for peak work rate (Dale 2014; Holland 2008; Perez Bogerd 2018; Vainshelboim 2014), and three studies for VO2 peak, maximum ventilation and maximum heart rate (Dale 2014; Holland 2008; Vainshelboim 2014). Peak work rate increased following pulmonary rehabilitation with an MD of 9.04 watts (95% CI 6.07 to 12.0; 81 participants in pulmonary rehabilitation group, 78 participants in control group; Figure 5; Analysis 1.3). There was an increase in peak work rate following pulmonary rehabilitation in the subgroup of participants with IPF with an MD of 9.94 watts (95% CI 6.39 to 13.49; 2 studies, 32 participants in pulmonary rehabilitation group, 30 participants in control group). This effect exceeded the MID of 4 watts proposed by Puhan 2011 for people with COPD. There was an increase in VO2 peak between baseline and follow‐up with an MD of 1.28 mL/kg/minute in favour of the pulmonary rehabilitation group (95% CI 0.51 to 2.05; Analysis 1.4). There was a similar effect in the subgroup of participants with IPF with a common effect of 1.45 mL/kg/minute (95% CI 0.51 to 2.40; Analysis 1.4). Pulmonary rehabilitation resulted in an increase in maximum ventilation with an MD between groups of 7.21 L/minute in favour of the pulmonary rehabilitation group (95% CI 4.10 to 10.32; Analysis 1.5). The effect was more pronounced in the subgroup of participants with IPF (MD 9.80 L/minute, 95% CI 6.06 to 13.53; 2 studies, 62 participants; Analysis 1.5). There was an increase in peak watts (MD 5.4 watts, 95% CI 0.07 to 10.73; 1 study, 30 participants; Analysis 1.3) and in maximum ventilation (MD 6.95 L/minute, 95% CI 0.03 to 13.87; 1 study, 27 participants; Analysis 1.5) in favour of the pulmonary rehabilitation group in participants who desaturated. This effect on peak watts and maximum ventilation was not evident for participants with severe lung disease (Analysis 1.3; Analysis 1.4; Analysis 1.5). There was no evidence of an effect of pulmonary rehabilitation on VO2 peak for participants with severe lung disease and for participants who desaturated (Analysis 1.4). There was no evidence of an effect of pulmonary rehabilitation on maximum heart rate (Analysis 1.6). Neither study reported data on maximal exercise capacity at long‐term follow‐up. Tests of heterogeneity were statistically high for peak work rate for both participants with ILD (I² = 89%, P < 0.00001) and the subgroup of participants with IPF (I² = 94%, P < 0.0001). There was substantial heterogeneity present for maximum ventilation for participants with ILD (I² = 68%, P = 0.05) and VO2 peak for the IPF subgroup (I² = 73%, P = 0.05). The high heterogeneity within this analysis could have stemmed from the small number of studies and small number of participants.
Forest plot of comparison: 1 Pulmonary rehabilitation versus no pulmonary rehabilitation, outcome: 1.3 Change in peak work rate immediately following pulmonary rehabilitation, watts.
Secondary outcomes
Dyspnoea
Eleven studies (512 participants) measured dyspnoea, with four reporting reduced dyspnoea immediately following pulmonary rehabilitation (Baradzina 2005; Holland 2008; Naz 2018; Vainshelboim 2014), and six reporting no change (Dale 2014; Dowman 2017; Ku 2017; Nishiyama 2008; Perez Bogerd 2018; Wewel 2005). We pooled data from seven studies for meta‐analysis (178 participants in the pulmonary rehabilitation group and 170 participants in the control group) (Figure 6; Analysis 1.7). Six studies utilised the modified Medical Research Council Scale (Dale 2014; Dowman 2017; Holland 2008; Naz 2018; Perez Bogerd 2018; Vainshelboim 2014), and one used the Baseline Dyspnoea Index (Nishiyama 2008). The common effect (SMD) for change in dyspnoea was –0.36 in favour of the pulmonary rehabilitation group (95% CI –0.58 to –0.14). There was a greater reduction in dyspnoea among participants with IPF (80 participants in the pulmonary rehabilitation group and 75 participants in the control group), with an SMD of –0.41 (95% CI –0.74 to –0.09; 4 studies). If the pooled SMD estimate was re‐expressed on the modified Medical Research Council Scale (5‐point scale, 0 to 4), it corresponded to an MD of –0.32 points (95% CI –0.52 to –0.13) for ILD and an MD of –0.37 points (95% CI –0.67 to –0.08) for the IPF subgroup for the IPF subgroup. This effect was smaller than the MID of one point for the modified Medical Research Dyspnoea Scale (Jones 2013). There was a small effect of pulmonary rehabilitation on dyspnoea with an SMD of –0.39 in participants with severe disease (95% CI –0.79 to 0.00; 1 study, 103 participants; Analysis 1.7). This effect was less evident in participants who desaturated (Figure 6). Six studies reported dyspnoea at long‐term follow‐up (Dale 2014; Dowman 2017; Holland 2008; Perez Bogerd 2018; Vainshelboim 2014; Wallaert 2020) (Analysis 1.8). In participants who received pulmonary rehabilitation, there was a reduction in dyspnoea that was still evident at long‐term follow‐up with an MD of –0.29 (95% CI –0.49 to –0.10; 6 studies, 335 participants; Analysis 1.8). There was a greater reduction in dyspnoea in the subgroup of participants with IPF at long‐term follow‐up with an MD of –0.38 (95% CI –0.72 to –0.05; 3 studies, 123 participants; Analysis 1.8). There was no evidence of a difference at long‐term follow‐up of pulmonary rehabilitation on dyspnoea in participants with severe disease (MD 0.14, 95% CI –0.36 to 0.63; 2 studies, 84 participants) and in those who desaturated (MD –0.03, 95% CI –0.42 to 0.35; 2 studies, 103 participants) (Analysis 1.8). Tests of heterogeneity for all analyses of dyspnoea were statistically substantial for both the participants with ILD (I² = 71%, P = 0.002) and the IPF subgroup (I² = 67%, P = 0.03) immediately following pulmonary rehabilitation, although this was not significant at long‐term follow‐up. The reduction in heterogeneity at long‐term follow‐up could stem from results in the meta‐analysis including a majority of studies with low risk of bias.
Forest plot of comparison: 1 Pulmonary rehabilitation versus no pulmonary rehabilitation, outcome: 1.6 Dyspnoea score immediately following pulmonary rehabilitation.
Quality of life
Fifteen studies measured health‐related quality of life, with 11 studies reporting differences between groups immediately following pulmonary rehabilitation (Dale 2014; Dowman 2017; Gaunaurd 2014; Holland 2008; Jarosch 2020; Ku 2017; Lanza 2019; Naz 2018; Nishiyama 2008; Perez Bogerd 2018; Vainshelboim 2014). Two studies reported improvement in health‐related quality of life following pulmonary rehabilitation; however, it was unclear if this finding reached statistical significance (Shen 2016; Xiao 2019). In the remaining studies, there was no evidence of differences between groups (Baradzina 2005; Mejia 2000; Wewel 2005). Six studies utilised the CRQ (Dale 2014; Dowman 2017; Holland 2008; Jarosch 2020; Mejia 2000; Perez Bogerd 2018), 10 used the SGRQ (Dale 2014; De Las Heras 2019; Ku 2017; Naz 2018; Nishiyama 2008; Perez Bogerd 2018; Shen 2016; Vainshelboim 2014; Wewel 2005; Xiao 2019), three used the SGRQ‐I (Dowman 2017; Gaunaurd 2014; Lanza 2019), two used the SF‐36 (Jarosch 2020; Naz 2018), and one used the WHO questionnaire (Baradzina 2005). There were sufficient raw data to conduct meta‐analyses for all domains of the CRQ (Dyspnoea, Fatigue, Emotional Function and Mastery) and SGRQ (Symptoms, Activity, Impact and Total). We pooled the SGRQ and SGRQ‐I for the meta‐analyses since the SGRQ‐I and SGRQ have similar psychometric properties. The SGRQ‐I has been designed to be more responsive in people with IPF whereas the SGRQ was originally designed for people with COPD. Not all the studies provided the results for all four domains of the SGRQ questionnaire; therefore, the numbers of studies and participants varies per domain.
St George's Respiratory Questionnaire
Thirteen studies utilised either the SGRQ or SGRQ‐I to assess health‐related quality of life (Dale 2014; De Las Heras 2019; Dowman 2017; Gaunaurd 2014; Ku 2017; Lanza 2019; Naz 2018; Nishiyama 2008; Perez Bogerd 2018; Shen 2016; Vainshelboim 2014; Wewel 2005; Xiao 2019). Pulmonary rehabilitation improved SGRQ Symptoms (MD –15.58, 95% CI –19.54 to –11.62; 7 studies, 312 participants; Analysis 1.9), SGRQ Activity (MD –2.47, 95% CI –4.11 to –0.83; 7 studies, 312 participants; Analysis 1.10), SGRQ Impact (MD –8.81, 95% CI –11.17 to –6.46; 7 studies, 312 participants; Analysis 1.11) and SGRQ Total (MD –9.29, 95% CI –11.06 to –7.52; 11 studies, 478 participants; Figure 7; Analysis 1.12). There was a similar effect in favour of pulmonary rehabilitation in participants with IPF for SGRQ Symptoms (MD –13.92, 95% CI –19.68 to –8.17; 4 studies, 142 participants; Analysis 1.9), SGRQ Impact (MD –8.94, 95% CI –11.76 to –6.13; 4 studies, 142 participants; Analysis 1.11) and SGRQ Total (MD –7.91 95% CI –10.55 to –5.26; 6 studies, 194 participants; Figure 7; Analysis 1.12). Pulmonary rehabilitation had a smaller effect on SGRQ Activity for participants with IPF (MD –1.71, 95% CI –3.44 to 0.01; 4 studies, 142 participants; Analysis 1.10). The improvements in the SGRQ following rehabilitation exceeded the MID for Symptoms (MID = 8), Impact (MID = 7) and Total (MID = 7) score in participants with ILD and the subgroup of IPF (Swigris 2010). Data regarding effects on quality of life in participants with severe disease and in participants who desaturated were available from one study (Dowman 2017). There were improvements favouring pulmonary rehabilitation for SGRQ Activity (MD –8.20, 95% CI –15.55 to –0.85; Analysis 1.10) and Total score (MD of –6.00, 95% CI –11.56 to –0.44; Figure 7; Analysis 1.12) in participants who desaturated.
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.
Four studies provided data regarding longer‐term effects on quality of life for meta‐analysis (Dale 2014; Dowman 2017; Perez Bogerd 2018; Vainshelboim 2014). The effects of pulmonary rehabilitation were still evident at long‐term follow‐up for all SGRQ domains except the Activity score (SGRQ Symptoms: MD –11.31, 95% CI –16.58 to –6.03; 240 participants; Analysis 1.13; SGRQ Impact: MD –4.73, 95% CI –7.76 to –1.69; 240 participants; Analysis 1.15; SGRQ Total score: MD –4.93, 95% CI –7.81 to –2.06; 240 participants; Analysis 1.16). In participants with IPF, the effects of pulmonary rehabilitation were evident at long‐term follow‐up for SGRQ Impact (MD –4.59, 95% CI –8.60 to –0.57; 2 studies, 89 participants; Analysis 1.15). Those with severe disease had improved SGRQ Symptoms scores compared to controls at long‐term follow‐up (MD –12.0, 95% CI –22.41 to –1.59; 1 study, 61 participants; Analysis 1.13). Heterogeneity was statistically high for the symptom score in the subgroup of IPF immediately following pulmonary rehabilitation (I² = 74%, P = 0.01). There was substantial heterogeneity for participants with ILD for the Activity score immediately following pulmonary rehabilitation (I² = 54%, P = 0.04). A funnel plot of the SGRQ Total data showed a tendency towards asymmetry, suggesting potential publication bias (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.
Chronic Respiratory Disease Questionnaire
Five studies provided data for meta‐analysis with a total of 175 participants in the pulmonary rehabilitation group and 146 participants in the control group (Dale 2014; Dowman 2017; Holland 2008; Jarosch 2020; Perez Bogerd 2018). Pulmonary rehabilitation improved CRQ Dyspnoea (MD 0.68, 95% CI 0.42 to 0.93; Figure 9; Analysis 1.17), CRQ Fatigue (MD 0.66, 95% CI 0.43 to 0.90; Analysis 1.18), CRQ Emotion (MD 0.63, 95% CI 0.42 to 0.84; Analysis 1.19) and CRQ Mastery (MD 0.67, 95% CI 0.44 to 0.90; Analysis 1.20). These improvements exceeded the MID of 0.5 points (Jaeschke 1989; Redelmeier 1996). There was a similar effect in favour of pulmonary rehabilitation in participants with IPF (3 studies, 169 participants) for CRQ Dyspnoea (MD 0.81, 95% CI 0.49 to 1.14; Figure 9; Analysis 1.17), CRQ Fatigue (MD 0.67, 95% CI 0.36 to 0.98; Analysis 1.18), CRQ Emotion (MD 0.64, 95% CI 0.33 to 0.95; Analysis 1.19) and CRQ Mastery (MD 0.63, 95% CI 0.33 to 0.94; Analysis 1.20). These improvements also exceeded the MID of 0.5 points (Jaeschke 1989; Redelmeier 1996). Two studies provided data regarding effects on quality of life in participants with severe disease and in those who desaturated (Dowman 2017; Holland 2008). There were improvements in CRQ Dyspnoea and CRQ Fatigue, that exceeded the MID of 0.5 points (Jaeschke 1989; Redelmeier 1996), for participants with severe disease and for those who desaturated. There were improvements in CRQ Mastery for those who desaturated (Analysis 1.17; Analysis 1.18; Analysis 1.19; Analysis 1.20).
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.
Four studies provided data for meta‐analysis regarding longer‐term effects on quality of life (Dale 2014; Dowman 2017; Holland 2008; Perez Bogerd 2018). The effects of pulmonary rehabilitation were evident at long‐term follow‐up for CRQ Dyspnoea (MD 0.42, 95% CI 0.17 to 0.68; Analysis 1.21), CRQ Fatigue (MD 0.40 95% CI 0.09 to 0.70; Analysis 1.22), CRQ Emotion (MD 0.51, 95% CI 0.26 to 0.77; Analysis 1.23) and CRQ Mastery (MD 0.47, 95% CI 0.17 to 0.78; Analysis 1.24). The effects of pulmonary rehabilitation were no longer evident at long‐term follow‐up for any CRQ domain for the subgroup of participants with IPF (28 studies, 95 participants), for those with severe disease (2 studies, 84 participants) or those who desaturated (2 studies, 103 participants) (Analysis 1.21; Analysis 1.22; Analysis 1.23; Analysis 1.24). There was substantial heterogeneity only for participants with ILD for the CRQ Emotion domain at long‐term follow‐up (I² = 57%, P = 0.07). Sensitivity analysis using studies of high quality (low risk of bias) produced a similar estimate of the treatment effect for participants with ILD (Table 2).
Adverse effects
Ten studies provided information regarding adverse events (Dale 2014; Dowman 2017; Holland 2008; Jarosch 2020; Ku 2017; Naz 2018; Nishiyama 2008; Perez Bogerd 2018; Vainshelboim 2014; Wallaert 2020), none of which reported adverse events during the study period. Four studies reported the death of one pulmonary rehabilitation participant during the intervention period; however, this was believed to be unrelated to the intervention received (Jackson 2014; Jarosch 2020; Perez Bogerd 2018; Wallaert 2020).
Survival
Four studies (291 participants) reported long‐term (six to 12 months) survival (Dowman 2017; Holland 2008; Perez Bogerd 2018; Vainshelboim 2014). There were five deaths in the exercise training group and 12 deaths in the control group (Analysis 1.25).
Sensitivity analysis
We performed a sensitivity analysis including only studies of high quality, for which random sequence generation, allocation concealment and incomplete outcome data were rated as low risk (see 'Risk of bias' table in Figure 2). Five studies met the criteria for high quality (Dale 2014; Dowman 2017; Holland 2008; Naz 2018; Perez Bogerd 2018). Three of the five studies also had low risk of detection bias (blinded outcome assessment) (Dale 2014; Dowman 2017; Holland 2008). The sensitivity analysis effect estimates were consistent with the overall summary effect estimates for functional exercise capacity (MD 41.221.223.44, 95% CI 26.806.809.64 to 55.645.647.24, 288 participants, Table 2), dyspnoea score, SGRQ Activity, SGRQ Impact, SGRQ Total and all four domains of the CRQ questionnaire (Table 2). Any heterogeneity that was previously present (Dyspnoea and SGRQ Activity) was reduced or no longer apparent, and all outcomes continued to be statistically significant when restricted to studies of high quality (Table 2). Sensitivity analysis for the subgroup of participants with IPF was not performed for any outcome as the number of included studies in the sensitivity analysis was limited to one or two studies.
Discussion
Summary of main results
We identified 21 eligible studies comparing pulmonary rehabilitation versus no pulmonary rehabilitation or sham control among people with ILD. There were no adverse effects of this treatment identified. Pulmonary rehabilitation probably improves functional exercise capacity, as measured by the six‐minute walk test, and maximum exercise capacity, represented by peak work rate. Reduction in dyspnoea and improvement in quality of life probably occurs immediately following pulmonary rehabilitation. The effects of pulmonary rehabilitation were comparable in the subgroup of participants with IPF. There were insufficient data available to allow conclusions regarding the effects of pulmonary rehabilitation among those with severe disease and those who desaturated. Sustained benefits in functional exercise capacity and quality of life are probable and improvements in dyspnoea may also be sustained at long‐term follow‐up. Sustained benefits in functional exercise capacity are less certain at long‐term follow‐up in those with IPF but there may be lasting effects of pulmonary rehabilitation in dyspnoea and quality of life.
The results of the previous version of this review supported pulmonary rehabilitation in the management of ILD and results of this current update reconfirm these findings, and add new evidence of sustained benefits at six to 12 months following pulmonary rehabilitation. Mean improvement in the six‐minute walk test following pulmonary rehabilitation was 40.07 metres, which is similar to the mean improvement of 43.93 metres seen in people with COPD who have undergone pulmonary rehabilitation (McCarthy 2015). This suggests that people with ILD receive comparable benefit from pulmonary rehabilitation. This improvement exceeds the MID for 6MWD among people with ILD, which ranges from 30 metres to 33 metres (Holland 2014). 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. There were also improvements in dyspnoea and health‐related quality of life following pulmonary rehabilitation. In addition, the magnitude of improvement for health‐related quality of life exceeded the MID in three of the four domains for the SGRQ (Swigris 2010), and all four domains of the CRQ (Jaeschke 1989; Redelmeier 1996). This supports the view that the observed improvements are clinically important and meaningful for patients.
Overall completeness and applicability of evidence
The update of this systematic review was substantial in that it included 12 additional studies and an increase in total study participants from 365 to 675 and number of studies from five to 16 for inclusion in the meta‐analysis. Included studies involved participants with a range of ILDs, and studies often included samples of participants with mixed diagnoses (Dowman 2017; Holland 2008; Ku 2017; Lanza 2019; Mejia 2000; Menon 2011; Perez Bogerd 2018; 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 subsequently it has been hypothesised that pulmonary rehabilitation might be less effective in people with IPF. However, our earlier review indicated that pulmonary rehabilitation is equally effective in people with IPF and the results of this current update strengthens these findings. Participants with IPF did achieve improvements in six‐minute walk test results, maximum exercise capacity, dyspnoea and health‐related quality of life. Improvement in the six‐minute walk test was comparable among participants with IPF (37.25 metres in participants with IPF versus 40.07 metres in all participants) and this mean improvement exceeded the MID for the 6MWD in people with IPF, which is in the range of 29 metres to 34 metres (Holland 2014). Changes in quality of life, dyspnoea and maximum exercise capacity were also comparable in the subgroup of participants with IPF. The comparable benefits in ILD and IPF suggest the response to exercise may not vary across the disease spectrum, despite the known heterogeneity between ILD subgroups.
Participants with IPF may experience sustained benefits in dyspnoea and quality of life, although the sustained improvement in functional capacity is less certain. IPF is a chronic progressive fibrotic lung disease, although the extent and rate of progression of IPF can vary, with rapid decline in some people and more gradual disease progression and periods of stability in others. This progressive nature of IPF may impact the long‐term benefit in functional capacity in some people with IPF, and, therefore, establishing strategies to manage this functional decline are essential.
It should be noted, however, that of the 16 studies contributing to the meta‐analysis, five included only participants with IPF (He 2016; Jackson 2014; Jarosch 2020; Nishiyama 2008; Vainshelboim 2014), whilst two others included a majority of participants with IPF (Dowman 2017; Holland 2008); thus, overall results of the meta‐analysis are strongly 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 (three to 48 weeks) 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.
Pulmonary rehabilitation by definition should include both an exercise and education component. There was substantial heterogeneity in the amount and type of education provided between the included studies and there was limited detail about the nature of the education. Therefore, it is difficult to ascertain the impact the inclusion or exclusion or type of education had on the outcomes of pulmonary rehabilitation.
A limitation of this review is it did not include the evaluation of pulmonary rehabilitation on psychological health. Anxiety and depression commonly occur in people with ILD, often further impacting health‐related quality of life. Pulmonary rehabilitation may promote an improvement in anxiety and depression for people with ILD. Therefore, we will include the assessment of the impact of pulmonary rehabilitation on anxiety and depression in the next review update.
Quality of the evidence
This review had several potential sources of bias. Of the 21 study identified, seven were available only in abstract form (Baradzina 2005; De Las Heras 2019; Lanza 2019; Mejia 2000; Menon 2011; Shen 2016; 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 usually ranged from five to 13 studies; however, there were a number of meta‐analyses that were limited to two or three studies. These were often the subgroup analysis of participants with IPF, severe disease and those who desaturated and the analyses at long‐term follow‐up. Despite this limitation, there was consistency in most reported outcomes, with all but one study reporting improved functional exercise capacity immediately following pulmonary rehabilitation (Jackson 2014). Reasons for lack of improvement in functional exercise capacity in the study by 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. As pulmonary rehabilitation is a physical intervention, it can be assumed that no participants were blinded. Therefore, the blinding of outcome assessors is critical to limit bias for outcomes such as exercise capacity, however, only four studies reported blinding of the assessor (Dale 2014; De Las Heras 2019; Dowman 2017; Holland 2008). Five studies reported use of an intention‐to‐treat analysis (Dale 2014; Dowman 2017; Holland 2008; Perez Bogerd 2018; Wallaert 2020). Three studies reported that all participants completed the study and were included in the analysis (He 2016; Ku 2017; Naz 2018). 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.
Using the GRADE system, we rated the review outcomes as providing very low‐ to moderate‐certainty evidence. Review outcomes were rated as of moderate certainty (6MWD, quality of life assessed by SGRQ) and low certainty (maximum exercise capacity, dyspnoea and survival) for ILD and as moderate certainty (6MWD, quality of life assessed by SGRQ), low certainty (survival) and very low certainty (maximum exercise capacity, dyspnoea) for IPF. Risk of bias was increased by poor reporting of methods (selection bias), lack of assessor blinding (detection bias) and lack of intention‐to‐treat analyses (attrition bias). This may have overestimated the effect provided by the meta‐analyses, however, sensitivity analysis including only high‐quality studies revealed similar effects in favour of pulmonary rehabilitation. Imprecision was increased by the small numbers of included studies and participants for the subgroup analysis on participants with IPF with two to three studies and 62 to 169 participants contributing to some outcomes. Inconsistency was increased by the presence of heterogeneity in all CRQ domains and Dyspnoea score for participants with ILD and the subgroup with IPF.
Potential biases in the review process
One review author independently extracted data and a second review author thoroughly checked accuracy. We resolved any discrepancies through discussion. Two review authors independently assessed risk of bias ratings. Clarification on data extraction and risk of bias assessments was sought from other co‐authors as required.
We conducted a broad search, which included handsearching of reference lists, conference abstracts and trial registries. We included studies that were published only in abstract form to ensure that all available trials were included. We sought additional information from eight authors, six of whom provided information, to increase the accuracy of the data for inclusion. However, there were some studies from which we could not obtain additional data. This may have influenced assessment of trial quality and some estimates of effect.
Three of the review authors (AH, LD and CJH) conducted two of the studies in the review (Dowman 2017; Holland 2008). To limit the bias of the review process, LD and AM completed the risk of bias assessments for Holland 2008 and AM completed them for Dowman 2017.
Agreements and disagreements with other studies or reviews
This is the second update of this Cochrane Review, which was last published in 2014 (Dowman 2014). Data included in the previous review suggested that improvement in functional exercise capacity following pulmonary rehabilitation in ILD was comparable to that seen in people with COPD (Lacasse 2006; McCarthy 2015). The results of this update reconfirm these findings (McCarthy 2015), and extend the findings to show persistent benefits at six to 12 months following pulmonary rehabilitation. The earlier version found similar, clinically important effects of rehabilitation in both the overall ILD group and the subgroup of IPF. This review reconfirms these findings with equivalent or greater improvements in the subgroup for participants with IPF. In addition, this review found the improvements were similar for the CRQ and greater for the SGRQ, except for the Activity score, for both people with ILD and in the subgroup of IPF than those observed in people with COPD. These significant findings support the international pulmonary rehabilitation statement suggesting that people with ILD should be included in pulmonary rehabilitation programmes (Spruit 2013) and strongly indicates that pulmonary rehabilitation should be part of the standard of care in ILD, just as it has become in COPD. Compared with the earlier version of this Cochrane Review (Dowman 2014), the three‐fold increase in number of trials led to smaller CIs, providing a more precise estimate of treatment effect.
Study flow diagram for 2014–2020 literature searches. HRQoL: health‐related quality of life.
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 six‐minute walk test immediately following pulmonary rehabilitation.
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.
Forest plot of comparison: 1 Pulmonary rehabilitation versus no pulmonary rehabilitation, outcome: 1.3 Change in peak work rate immediately following pulmonary rehabilitation, watts.
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: 1.12 Change in quality of life (SGRQ Total) immediately following pulmonary rehabilitation.
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.
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.
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
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
Comparison 1: Pulmonary rehabilitation versus no pulmonary rehabilitation, Outcome 3: Change in peak work rate immediately following pulmonary rehabilitation, watts
Comparison 1: Pulmonary rehabilitation versus no pulmonary rehabilitation, Outcome 4: Change in VO 2 peak immediately following pulmonary rehabilitation, mL/kg/minute
Comparison 1: Pulmonary rehabilitation versus no pulmonary rehabilitation, Outcome 5: Change in maximum ventilation (Ve max ) immediately following pulmonary rehabilitation, L/minute
Comparison 1: Pulmonary rehabilitation versus no pulmonary rehabilitation, Outcome 6: Change in maximum heart rate immediately following pulmonary rehabilitation, beats/minute
Comparison 1: Pulmonary rehabilitation versus no pulmonary rehabilitation, Outcome 7: Change in dyspnoea score immediately following pulmonary rehabilitation
Comparison 1: Pulmonary rehabilitation versus no pulmonary rehabilitation, Outcome 8: Change in dyspnoea score at long‐term follow‐up
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
Comparison 1: Pulmonary rehabilitation versus no pulmonary rehabilitation, Outcome 10: Change in quality of life (SGRQ Activity) immediately following pulmonary rehabilitation
Comparison 1: Pulmonary rehabilitation versus no pulmonary rehabilitation, Outcome 11: Change in quality of life (SGRQ Impact) immediately following pulmonary rehabilitation
Comparison 1: Pulmonary rehabilitation versus no pulmonary rehabilitation, Outcome 12: Change in quality of life (SGRQ Total) immediately following pulmonary rehabilitation
Comparison 1: Pulmonary rehabilitation versus no pulmonary rehabilitation, Outcome 13: Change in quality of life (SGRQ Symptoms) at long‐term follow‐up
Comparison 1: Pulmonary rehabilitation versus no pulmonary rehabilitation, Outcome 14: Change in quality of life (SGRQ Activity) at long‐term follow‐up
Comparison 1: Pulmonary rehabilitation versus no pulmonary rehabilitation, Outcome 15: Change in quality of life (SGRQ Impact) at long‐term follow‐up
Comparison 1: Pulmonary rehabilitation versus no pulmonary rehabilitation, Outcome 16: Change in quality of life (SGRQ Total) at long‐term follow‐up
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
Comparison 1: Pulmonary rehabilitation versus no pulmonary rehabilitation, Outcome 18: Change in quality of life (CRQ Fatigue) immediately following pulmonary rehabilitation.
Comparison 1: Pulmonary rehabilitation versus no pulmonary rehabilitation, Outcome 19: Change in quality of life (CRQ Emotion) immediately following pulmonary rehabilitation
Comparison 1: Pulmonary rehabilitation versus no pulmonary rehabilitation, Outcome 20: Change in quality of life (CRQ Mastery) immediately following pulmonary rehabilitation
Comparison 1: Pulmonary rehabilitation versus no pulmonary rehabilitation, Outcome 21: Change in quality of life (CRQ Dyspnoea) at long‐term follow‐up
Comparison 1: Pulmonary rehabilitation versus no pulmonary rehabilitation, Outcome 22: Change in quality of life (CRQ Fatigue) at long‐term follow‐up
Comparison 1: Pulmonary rehabilitation versus no pulmonary rehabilitation, Outcome 23: Change in quality of life (CRQ Emotion) at long‐term follow‐up
Comparison 1: Pulmonary rehabilitation versus no pulmonary rehabilitation, Outcome 24: Change in quality of life (CRQ Mastery) at long‐term follow‐up
Comparison 1: Pulmonary rehabilitation versus no pulmonary rehabilitation, Outcome 25: Long‐term survival
| Pulmonary rehabilitation compared to no pulmonary rehabilitation for interstitial lung disease | ||||||
| Patient or population: interstitial lung disease | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | № of participants | Certainty of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with no pulmonary rehabilitation | Risk with pulmonary rehabilitation | |||||
| Change in 6MWD | The mean change in 6MWD ranged from –35 metres to 26 metres | MD 40.07 metres higher | — | 585 | ⊕⊕⊕⊝ | 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 | The mean change in 6MWD at long‐term follow‐up ranged from –49 metres to –6 metres | MD 32.43 metres higher | — | 321 | ⊕⊕⊕⊝ | — |
| Change in peak work capacity | The mean change in peak work capacity ranged from –10 watts to 0.6 watts | MD 9.04 watts higher | — | 159 | ⊕⊕⊝⊝ | — |
| Change in dyspnoea score | The mean change in dyspnoea score ranged from –0.2 to 0.4 | SMD 0.36 SD lower | — | 348 | ⊕⊕⊝⊝ | 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 | The mean change in quality of life ranged from –7 to 6 points | MD 9.29 points lower | — | 478 | ⊕⊕⊕⊝ | 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 | The mean change in quality of life at long‐term follow‐up ranged from –1 to 5 points | MD 4.93 points lower | — | 240 | ⊕⊕⊝⊝ | Lower value post intervention is favourable, indicating improvement in quality of life. |
| Long‐term survival (incidence of mortality) | Study population | OR 0.40 | 291 | ⊕⊕⊝⊝ | Lower OR represents improved survival at long‐term follow‐up. | |
| 85 per 1000 | 36 per 1000 | |||||
| *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 | ||||||
| aDowngraded one level for detection bias (nine to 11 studies), attrition bias (five to eight studies) and selection bias (seven studies). | ||||||
| Pulmonary rehabilitation compared to no pulmonary rehabilitation for idiopathic pulmonary fibrosis | ||||||
| Patient or population: idiopathic pulmonary fibrosis | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | № of participants | Certainty of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with no pulmonary rehabilitation | Risk with pulmonary rehabilitation | |||||
| Change in 6MWD | The mean change in 6MWD ranged from –35 metres to 26 metres | MD 37.25 metres higher | — | 278 | ⊕⊕⊕⊝ | — |
| Change in 6MWD at long‐term follow‐up | The mean change in 6MWD at long‐term follow‐up ranged from –49 metres to 4 metres | MD 1.64 metres higher | — | 123 | ⊕⊕⊝⊝ | — |
| Change in peak work capacity | The mean change in peak work capacity ranged from –7 watts to –0.8 watts | MD 9.94 watts higher | — | 62 | ⊕⊕⊝⊝ | — |
| Change in dyspnoea score | The mean change in dyspnoea score ranged from –0.06 to 0.4 | SMD 0.41 lower | — | 155 | ⊕⊕⊝⊝ | 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 | The mean change in quality of life ranged from –3 to 3 points | MD 7.91 points lower | — | 194 | ⊕⊕⊕⊝ | Lower value post intervention is favourable, indicating improvement in quality of life. |
| Change in quality of life at long‐term | The mean change in quality of life at long‐term follow‐up ranged from 1 to 4 points | MD 3.45 points lower | — | 89 | ⊕⊕⊝⊝ | Lower value post intervention is favourable, indicating improvement in quality of life. |
| Long‐term survival (incidence of mortality) | Study population | OR 0.32 | 127 | ⊕⊕⊝⊝ | Lower OR represents improved survival at long‐term follow‐up. | |
| 133 per 1000 | 47 per 1000 | |||||
| *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 | ||||||
| aDowngraded one level for detection bias (four or five studies), attrition bias (three or four studies) and selection bias (five studies) | ||||||
| Study | Follow‐up | Duration (weeks) | Sessions (per week) | Setting | Programme type |
|---|---|---|---|---|---|
| 5 weeks | 5 | 5 | Outpatient | Exercise + other | |
| 8, 26 weeks | 8 | 2 | Outpatient | Exercise | |
| 12 weeks | 12 | 5–7 | Tele‐rehabilitation | Exercise | |
| 8 weeks, 6 months | 8 | 2 | Outpatient | Exercise + other | |
| 12 weeks, 3 months | 12 | 2 | Outpatient | Exercise + other | |
| 12 weeks | 12 | 3–5 | Outpatient | Exercise | |
| 8, 26 weeks | 8 | 2 | Outpatient | Exercise | |
| 12 weeks, 3 months | 12 | 2 | Outpatient | Exercise + other | |
| 3 weeks, 3 months | 3 | 5–6 | Inpatient | Exercise + other | |
| 8 weeks | 8 | 2 | Outpatient | Exercise + other | |
| 12 weeks | 12 | 2 | Outpatient | Exercise | |
| 12 weeks | 12 | 3 | Outpatient | Exercise | |
| 8 weeks | 8 | — | Outpatient | Exercise | |
| 12 weeks | 12 | 2 | Outpatient | Exercise | |
| 9 weeks | 9 | 2 | Outpatient | Exercise | |
| 3, 6, 12 months | 26 | 2–3 | Outpatient | Exercise + other | |
| 12 weeks | 12 | 3 | Outpatient | Exercise | |
| 12 weeks | 12 | 2 | Outpatient | Exercise | |
| 8 weeks | 8 | 3 | Outpatient | Exercise + other | |
| 6 months | 26 | 7 | Home | Exercise | |
| 48 weeks | 48 | 4 | Outpatient/home | Exercise + other |
| 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 | — | 288 | I² = 70%, P = 0.01 | –0.28 (–0.51 to –0.04) | P < 0.02 | |
| SGRQ | Symptoms | 231 | I² = 51%, P = 0.11 | –13.76 (–18.49 to –9.04) | P < 0.00001 | |
| Activity | 231 | I² = 21%, P = 0.28 | –8.56 (–12.90 to –4.22) | P = 0.0001 | ||
| Impact | 231 | I² = 0%, P = 0.83 | –7.91 (–11.54 to –4.29) | P < 0.0001 | ||
| Total | 231 | I² = 21%, P = 0.29 | –8.13 (–11.24 to –5.02) | P < 0.00001 | ||
| CRQ | Dyspnoea | 270 | I² = 41%, P = 0.18 | 0.61 (0.32 to 0.90) | P < 0.0001 | |
| Fatigue | 270 | I² = 0%, P = 0.93 | 0.66 (0.40 to 0.92) | P < 0.00001 | ||
| Emotion | 270 | I² = 0%, P = 0.44 | 0.58 (0.35 to 0.81) | P < 0.00001 | ||
| Mastery | 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. | ||||||
| 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] |
