title: Neuromuscular electrical stimulation to improve exercise capacity in patients with severe COPD: a randomised double-blind, placebo-controlled trial.
abstract: BACKGROUND
  Skeletal muscle dysfunction and exercise intolerance are common in severe chronic obstructive pulmonary disease (COPD). We assessed the effectiveness of neuromuscular electrical stimulation (NMES) as a home-based exercise therapy.
  
  
  METHODS
  In this double-blind, placebo-controlled trial, undertaken across three UK National Health Service sites, we randomly assigned (1:1) adults with COPD, a forced expiratory volume in 1 s (FEV1) less than 50% predicted, and incapacitating breathlessness (Medical Research Council dyspnoea scale ≥4) to receive active or placebo NMES, daily over a 6-week period. Randomisation was by an independent system using minimisation to balance age, GOLD stage, and quadriceps strength. Participants and outcome assessors were masked to group allocation. The primary endpoint was change in 6-min walk test (6MWT) distance at 6 weeks. Analysis was by intention to treat. The trial was registered as ISRCTN15985261 and is now closed.
  
  
  RESULTS
  Between June 29, 2012, and July 4, 2014, we enrolled 73 participants, of whom 52 participants were randomly assigned; 25 to receive active NMES and 27 to placebo NMES. Change in 6MWT distance was greater in the active NMES group (mean 29·9 [95% CI 8·9 to 51·0]) compared with in the placebo group (-5·7 [-19·9 to 8·4]; mean difference at 6 weeks 35·7 m [95% CI 10·5 to 60·9]; p=0·005). Sensitivity analyses for complete-cases and adjustment for baseline values showed similar results. 6 weeks after stopping the intervention the effect waned (7·3 m [95% CI -32·5 to 47·0]; p=0·50). The proportion of participants who had adverse events was similar between groups (five [20%] in the active NMES group and nine [33%] in the placebo group). Two participants, one from each group, reported persistent erythema, which was considered to be possibly related to NMES and the use of adhesive electrodes.
  
  
  CONCLUSIONS
  NMES improves functional exercise capacity in patients with severe COPD by enhancing quadriceps muscle mass and function. These data support the use of NMES in the management of patients unable to engage with conventional pulmonary rehabilitation. More work is needed to study how to maintain the effect.
  
  
  BACKGROUND
  National Institute for Health Research.
authors.affiliation: King's College London, Cicely Saunders Institute, Division of Palliative Care, Policy & Rehabilitation, London, UK. Electronic address: matthew.maddocks@kcl.ac.uk.
authors.forename: Matthew
authors.initials: M
authors.lastname: Maddocks
authors.affiliation: NIHR Respiratory Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust and Imperial College, London, UK; Harefield Pulmonary Rehabilitation Team, Harefield Hospital, Harefield, Middlesex, UK.
authors.forename: Claire M
authors.initials: CM
authors.lastname: Nolan
authors.affiliation: NIHR Respiratory Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust and Imperial College, London, UK; Harefield Pulmonary Rehabilitation Team, Harefield Hospital, Harefield, Middlesex, UK.
authors.forename: William D-C
authors.initials: WD
authors.lastname: Man
authors.affiliation: NIHR Respiratory Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust and Imperial College, London, UK.
authors.forename: Michael I
authors.initials: MI
authors.lastname: Polkey
authors.affiliation: Lane Fox Unit, Guy's & St Thomas' NHS Foundation Trust, London, UK; King's College London, Respiratory Medicine, Division of Asthma, Allergy & Lung Biology, London, UK.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Hart
authors.affiliation: King's College London, Cicely Saunders Institute, Division of Palliative Care, Policy & Rehabilitation, London, UK.
authors.forename: Wei
authors.initials: W
authors.lastname: Gao
authors.affiliation: King's College London, Respiratory Medicine, Division of Asthma, Allergy & Lung Biology, London, UK.
authors.forename: Gerrard F
authors.initials: GF
authors.lastname: Rafferty
authors.affiliation: King's College London, Respiratory Medicine, Division of Asthma, Allergy & Lung Biology, London, UK.
authors.forename: John
authors.initials: J
authors.lastname: Moxham
authors.affiliation: King's College London, Cicely Saunders Institute, Division of Palliative Care, Policy & Rehabilitation, London, UK.
authors.forename: Irene J
authors.initials: IJ
authors.lastname: Higginson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D004311:Double-Blind Method; D004417:Dyspnea; D004599:Electric Stimulation Therapy / Q000379:methods*; D005080:Exercise Test; D005081:Exercise Therapy / Q000379:methods*; D017079:Exercise Tolerance; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000503:physiopathology / Q000628:therapy*; D052097:Quadriceps Muscle; D012720:Severity of Illness Index; D016896:Treatment Outcome