title: A randomized controlled trial of angiotensin-converting enzyme inhibition for skeletal muscle dysfunction in COPD.
abstract: BACKGROUND
  Skeletal muscle impairment is a recognized complication of COPD, predicting mortality in severe disease. Increasing evidence implicates the renin-angiotensin system in control of muscle phenotype. We hypothesized that angiotensin-converting enzyme (ACE) inhibition would improve quadriceps function and exercise performance in COPD.
  
  
  METHODS
  This double-blind, randomized placebo-controlled trial investigated the effect of the ACE inhibitor, fosinopril, on quadriceps function in patients with COPD with quadriceps weakness. Primary outcomes were change in quadriceps endurance and atrophy signaling at 3 months. Quadriceps maximum voluntary contraction (QMVC), mid-thigh CT scan of the cross-sectional area (MTCSA), and incremental shuttle walk distance (ISWD) were secondary outcomes.
  
  
  RESULTS
  Eighty patients were enrolled (mean [SD], 65 [8] years, FEV1 43% [21%] predicted, 53% men). Sixty-seven patients (31 fosinopril, 36 placebo) completed the trial. The treatment group demonstrated a significant reduction in systolic BP (Δ-10.5 mm Hg; 95% CI, -19.9 to -1.1; P = .03) and serum ACE activity (Δ-20.4 IU/L; 95% CI, -31.0 to -9.8; P < .001) compared with placebo. No significant between-group differences were observed in the primary end points of quadriceps endurance half-time (Δ0.5 s; 95% CI, -13.3-14.3; P = .94) or atrogin-1 messenger RNA expression (Δ-0.03 arbitrary units; 95% CI, -0.32-0.26; P = .84). QMVC improved in both groups (fosinopril: Δ1.1 kg; 95% CI, 0.03-2.2; P = .045 vs placebo: Δ3.6 kg; 95% CI, 2.1-5.0; P < .0001) with a greater increase in the placebo arm (between-group, P = .009). No change was shown in the MTCSA (P = .09) or ISWD (P = .51).
  
  
  CONCLUSIONS
  This randomized controlled trial found that ACE inhibition, using fosinopril for 3 months, did not improve quadriceps function or exercise performance in patients with COPD with quadriceps weakness.
  
  
  BACKGROUND
  Current Controlled Trials; No.: ISRCTN05581879; URL: www.controlled-trials.com.
authors.affiliation: National Heart & Lung Institute (NHLI), NIHR Respiratory Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust and Imperial College London, University College London, London, England; Molecular Medicine Section, National Heart & Lung Institute (NHLI), Imperial College London, University College London, London, England.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Shrikrishna
authors.affiliation: National Heart & Lung Institute (NHLI), NIHR Respiratory Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust and Imperial College London, University College London, London, England.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Tanner
authors.affiliation: Molecular Medicine Section, National Heart & Lung Institute (NHLI), Imperial College London, University College London, London, England.
authors.forename: Jen Y
authors.initials: JY
authors.lastname: Lee
authors.affiliation: National Heart & Lung Institute (NHLI), NIHR Respiratory Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust and Imperial College London, University College London, London, England; Molecular Medicine Section, National Heart & Lung Institute (NHLI), Imperial College London, University College London, London, England.
authors.forename: Amanda
authors.initials: A
authors.lastname: Natanek
authors.affiliation: Molecular Medicine Section, National Heart & Lung Institute (NHLI), Imperial College London, University College London, London, England.
authors.forename: Amy
authors.initials: A
authors.lastname: Lewis
authors.affiliation: Guy's and St. Thomas' NHS Foundation Trust and NIHR Comprehensive Biomedical Research Centre and Department of Asthma, Allergy &, University College London, London, England.
authors.forename: Patrick B
authors.initials: PB
authors.lastname: Murphy
authors.affiliation: Guy's and St. Thomas' NHS Foundation Trust and NIHR Comprehensive Biomedical Research Centre and Department of Asthma, Allergy &, University College London, London, England.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Hart
authors.affiliation: Respiratory Science, Division of Asthma, Allergy and Lung Biology, King's College London, University College London, London, England.
authors.forename: John
authors.initials: J
authors.lastname: Moxham
authors.affiliation: Institute for Human Health and Performance, University College London, London, England.
authors.forename: Hugh E
authors.initials: HE
authors.lastname: Montgomery
authors.affiliation: Molecular Medicine Section, National Heart & Lung Institute (NHLI), Imperial College London, University College London, London, England.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Kemp
authors.affiliation: National Heart & Lung Institute (NHLI), NIHR Respiratory Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust and Imperial College London, University College London, London, England.
authors.forename: Michael I
authors.initials: MI
authors.lastname: Polkey
authors.affiliation: National Heart & Lung Institute (NHLI), NIHR Respiratory Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust and Imperial College London, University College London, London, England. Electronic address: n.hopkinson@ic.ac.uk.
authors.forename: Nicholas S
authors.initials: NS
authors.lastname: Hopkinson
mesh_terms: D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001794:Blood Pressure; D004311:Double-Blind Method; D015444:Exercise / Q000502:physiology; D005260:Female; D017328:Fosinopril / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018908:Muscle Weakness / Q000503:physiopathology; D010807:Physical Endurance; D029424:Pulmonary Disease, Chronic Obstructive / Q000503:physiopathology*; D052097:Quadriceps Muscle / Q000187:drug effects* / Q000503:physiopathology
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D017328:Fosinopril