Effectiveness of pulmonary rehabilitation in COPD with mild symptoms: a systematic review with meta-analyses

Figures & data

Table 1 Pulmonary rehabilitation compared to usual care in COPD with mild symptoms

Outcomes	Illustrative comparative risksa (95% CI)		Relative effect (95% CI)	No of participants (studies, reference)	Quality of theevidence (GRADE)b
	Assumed risk	Corresponding risk
	Usual care	Rehabilitation
Quality of life (SGRQ) (mean change from baseline) Assessed directly after the intervention: 7–16 weeks		The mean SGRQ change from baseline after intervention in the intervention groups was 4.2 lower (4.51 to 3.89 lower)		207 (2 studies^Citation14,Citation15)	⊕⊕⊕⊖ Moderatec
Quality of life (SGRQ) (mean change from baseline) Assessed 18–24 months from baseline		The mean SGRQ change from baseline in the intervention groups was 1.65 lower (5.45 lower to 2.16 higher)		205 (2 studies^Citation14,Citation15)	⊕⊖⊖⊖ Very lowc–e
6MWD in meters Assessed directly after the intervention		The mean 6MWD in meters in the intervention groups was 25.71 higher (15.76 to 35.65 higher)		313 (4 studies^Citation14,Citation15,Citation17,Citation22)	⊕⊕⊕⊖ Moderatec
Mortality Assessed at the end of follow-up	42 per 1,000	56 per 1,000 (12–233)	OR 1.35 (0.27–6.84)	328 (4 studies^Citation14,Citation15,Citation17,Citation22)	⊕⊕⊕⊖ Moderatef

Notes: Patient or population: patients with COPD and mMRC ≤1; intervention: pulmonary rehabilitation; comparison: usual care.

a The basis for the assumed risk (eg, the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

b GRADE Working Group grades of evidence: high quality: further research is very unlikely to change our confidence in the estimate of effect; moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate; low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate; very low quality: we are very uncertain about the estimate.

c No blinding of participants.

d Wide 95% CI.

e Effect estimates point in opposite directions.

f Very few events.

Abbreviations: CI, confidence interval; COPD, chronic obstructive pulmonary disease; GRADE, Grading of Recommendations Assessment, Development and Evaluation; mMRC, modified Medical Research Council dyspnea scale; OR, odds ratio; SGRQ, St George’s Respiratory Questionnaire; 6MWD, 6-minute walking distance.

Figure 1 Flow diagram showing the selection process of material from identification to inclusion.

Abbreviations: AGREE, Appraisal of Guidelines for Research and Evaluation; AMSTAR, A Measurement Tool to Assess Systematic Reviews.

Table 2 Baseline characteristics of the included studies

Reference	Country	Study design	Setting, duration and frequency	Participants	Intervention	Control	Notes	Outcomes
Gottlieb et al^Citation14	Denmark	RCT	Setting: outpatient Frequency: 2/week	61 patients with COPD FEV1: 64%–67% of predicted; mean age: 73.2–74.1 years; 33% male	7-week PR program; physical training for 90 minutes twice a week; maintenance program of 90 minutes/month for 6 months.	Standard GP care	Follow-up: 6, 12, 18 months after randomization	STS, 6MWT, MRC grading following the 6MWT, SGRQ, LF
Liu et al^Citation22	People’s Republic of China	RCT	Setting: outpatient Frequency: 3/week	132 patients with COPD FEV1: 75% of predicted; mean age: 61.3–62.2 years; 71.9%–80% male	1 week of instruction in aerobic exercises and pursed-lip breathing, followed by 6 months of peer-led training: 1 hour, 3 times a week.	Medical treatment	3-armed study including PR group, CG, Health Qigong group Follow-up: 6 months after randomization	LF, 6MWT, QoL (Zhong Shan COPD Questionnaire), IL-6, IL-8, TNF-α, AECOPD
Román et al^Citation17	Spain	RCT	Setting: outpatient Frequency: 3/week	97 patients with COPD FEV1: 60%–61% of predicted; mean age: 63.4–64.9 years; 80.8%–82.6% male	3 months of exercise, 3 times a week, with 60 minutes of duration. Three types of interventions: educational program of 45 minutes, respiratory physiotherapy, and low intensity muscle training.	Standard GP care	3-armed study including CG, exercise group, and exercise + maintenance group (who had maintenance exercise once a week for 9 months. Follow-up: 3, 12 months after randomization	CRQ, forced spirometry and reversibility test, 6MWT, AECOPD
van Wetering et al^Citation15	the Netherlands	RCT	Setting: outpatient + patients’ home surroundings Frequency: 2/week	199 patients with COPD FEV1: 58%–60% of predicted; mean age: 65.9–67.2 years; 71% male	4-month exercise period: 2 times a week with 30 minutes of endurance training and four specific exercises. The four exercises were to be done twice a day in the home environment plus cycling and walking outside. 20-month maintenance program.	Medical treatment and a short smoking cessation advice	Follow-up: 4, 12, 24 months after randomization	SGRQ, total score and the total number of exacerbations, MRC, CET, 6MWT, HGF, isometric QPT, Pimax, BMI, body composition, caregivers perceived effectiveness Wmax, LF

Abbreviations: 6MWT, 6-minute walk test; AECOPD, hospital admissions due to acute exacerbation of COPD; BMI, body mass index; CET, cycle endurance test; CG, control group; COPD, chronic obstructive pulmonary disease; CRQ, Chronic Respiratory Questionnaire; FEV₁, forced expiratory volume in first second; GP, General Practitioner; HGF, hand grip force; IL, interleukin; LF, lung function; MRC, Medical Research Council dyspnea scale; Pimax, maximal inspiratory mouth pressure; PR, pulmonary rehabilitation; QoL, quality of life; QPT, isometric quadriceps peak torque; RCT, randomized controlled trial; SGRQ, St George’s Respiratory Questionnaire; STS, Sit-to-Stand test; TNF, tumor necrosis factor; Wmax, peak exercise capacity.

Table 3 Dropout characteristics

Reference	Participants, n	Dropouts, n	Analyzed participants, n	Dropouts, %	Notes
Gottlieb et al^Citation14	61	19	42	31.1	No significant differences in baseline characteristics after dropouts
Liu et al^Citation22	132	1	131	0.8
Román et al^Citation17	97	54	43	55.7	Dropouts being 82.5% men (average age: 62.1 years), FEV1 =60%. No significant changes in baseline characteristics after dropouts
van Wetering et al^Citation15	199	41	158	20.6	Difference in characteristics between dropouts was reported since the PR group lost more elderly, and dropouts in the CG were younger
Total	489	115	374

Abbreviations: CG, control group; FEV₁, forced expiratory volume in first second; PR, pulmonary rehabilitation.

Figure 2 Risk of bias summary: the review authors’ evaluations of each risk of bias item for each included study.

Notes: Green, low risk of bias; yellow, unclear risk of bias; red, high risk of bias.

Figure 3 PR versus usual care: short-term evaluation of health-related quality of life measured by St George’s Respiratory Questionnaire.

Abbreviations: CI, confidence interval; df, degrees of freedom; IV, independent variable; PR, pulmonary rehabilitation; SD, standard deviation;

, point estimate; ♦, pooled effect estimate.

Figure 4 PR versus usual care: evaluation of health-related quality of life measured on St George’s Respiratory Questionnaire at the longest follow-up (18–24 months from baseline).

Abbreviations: CI, confidence interval; df, degrees of freedom; IV, independent variable; PR, pulmonary rehabilitation; SD, standard deviation;

, point estimate; ♦, pooled effect estimate.

Figure 5 PR versus usual care: walking distance (6-minute walking distance).

Abbreviations: CI, confidence interval; df, degrees of freedom; IV, independent variable; PR, pulmonary rehabilitation; SD, standard deviation;

, point estimate; ♦, pooled effect estimate.

Figure 6 PR versus usual care: mortality, odds ratio.

Abbreviations: CI, confidence interval; df, degrees of freedom; M–H, Mantel–Haenszel test; PR, pulmonary rehabilitation;

, point estimate; ♦, pooled effect estimate.

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