title: Effectiveness of pulmonary rehabilitation in COPD with mild symptoms: a systematic review with meta-analyses.
abstract: OBJECTIVE
  Most guidelines recommend pulmonary rehabilitation (PR) for patients with chronic obstructive pulmonary disease (COPD) and modified Medical Research Council dyspnea scale (mMRC) levels ≥2, but the effectiveness of PR in patients with less advanced disease is not well established. Our aim was to investigate the effects of PR in patients with COPD and mMRC ≤1.
  
  
  METHODS
  The methodology was developed as a part of evidence-based guideline development and is in accordance with the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group. We identified randomized controlled trials (RCTs) through a systematic, multidatabase literature search and selected RCTs comparing the effects of PR with usual care in patients with COPD and mMRC ≤1. Predefined critical outcomes were health-related quality of life (HRQoL), adverse effects and mortality, while walking distance, maximal exercise capacity, muscle strength, and dropouts were important outcomes. Two authors independently extracted data, assessed trial eligibility and risk of bias, and graded the evidence. Meta-analyses were performed when deemed feasible.
  
  
  RESULTS
  Four RCTs (489 participants) were included. On the basis of moderate-quality evidence, we found a clinically and statistically significant improvement in short-term HRQoL of 4.2 units (95% confidence interval [CI]: [-4.51 to -3.89]) on St George's Respiratory Questionnaire, but not at the longest follow-up. We also found a statistically significant improvement of 25.71 m (95% CI: [15.76-35.65]) in the 6-minute walk test with PR; however, this improvement was not considered clinically relevant. No difference was found for mortality, and insufficient data prohibited meta-analysis for muscle strength and maximal exercise capacity. No adverse effects were reported.
  
  
  CONCLUSIONS
  We found a moderate quality of evidence suggesting a small, significant improvement in short-term HRQoL and a clinically nonsignificant improvement in walking distance following PR in patients with COPD and mild symptoms. This resulted in a weak recommendation of routine PR in these patients using the GRADE approach.
authors.affiliation: The Centre of Inflammation and Metabolism and The Centre for Physical Activity Research, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Mette
authors.initials: M
authors.lastname: Rugbjerg
authors.affiliation: The Centre of Inflammation and Metabolism and The Centre for Physical Activity Research, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Ulrik Winning
authors.initials: UW
authors.lastname: Iepsen
authors.affiliation: The Nordic Cochrane Centre, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Karsten Juhl
authors.initials: KJ
authors.lastname: Jørgensen
authors.affiliation: The Centre of Inflammation and Metabolism and The Centre for Physical Activity Research, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark ; Department of Respiratory Medicine, University Hospital Hvidovre, Copenhagen, Denmark ; Department of Public Health, Section of Social Medicine, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Lange
mesh_terms: D016009:Chi-Square Distribution; D019317:Evidence-Based Medicine; D005080:Exercise Test; D017079:Exercise Tolerance; D006801:Humans; D008168:Lung / Q000503:physiopathology*; D011237:Predictive Value of Tests; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000401:mortality / Q000503:physiopathology / Q000523:psychology / Q000628:therapy*; D011788:Quality of Life; D016032:Randomized Controlled Trials as Topic; D020127:Recovery of Function; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome; D016138:Walking
keywords: COPD; COPD with mild symptoms; health-related quality of life; physical activity; pulmonary disease; pulmonary rehabilitation