eprintid: 1456514
rev_number: 29
eprint_status: archive
userid: 608
dir: disk0/01/45/65/14
datestamp: 2014-11-21 20:38:56
lastmod: 2021-09-26 22:43:41
status_changed: 2014-11-21 20:38:56
type: article
metadata_visibility: show
item_issues_count: 0
creators_name: Shrikrishna, D
creators_name: Tanner, RJ
creators_name: Lee, JY
creators_name: Natanek, A
creators_name: Lewis, A
creators_name: Murphy, PB
creators_name: Hart, N
creators_name: Moxham, J
creators_name: Montgomery, HE
creators_name: Kemp, PR
creators_name: Polkey, MI
creators_name: Hopkinson, NS
title: A Randomized Controlled Trial of Angiotensin-Converting Enzyme Inhibition for Skeletal Muscle Dysfunction in COPD
ispublished: pub
divisions: UCL
divisions: B02
divisions: C10
divisions: D17
divisions: G94
note: PubMed ID: 24556825
© 2014 AMERICAN COLLEGE OF CHEST PHYSICIANS. This is a Wellcome-Trust-compliant open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/).
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.
date: 2014-10-01
official_url: http://dx.doi.org/10.1378/chest.13-2483
vfaculties: VGHCSCI
oa_status: green
full_text_type: pub
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_source: WoS-Lite
elements_id: 994147
doi: 10.1378/chest.13-2483
lyricists_name: Montgomery, Hugh
lyricists_id: HEMON01
full_text_status: public
publication: CHEST
volume: 146
number: 4
pagerange: 932 - 940
issn: 0012-3692
citation:        Shrikrishna, D;    Tanner, RJ;    Lee, JY;    Natanek, A;    Lewis, A;    Murphy, PB;    Hart, N;                     ... Hopkinson, NS; + view all <#>        Shrikrishna, D;  Tanner, RJ;  Lee, JY;  Natanek, A;  Lewis, A;  Murphy, PB;  Hart, N;  Moxham, J;  Montgomery, HE;  Kemp, PR;  Polkey, MI;  Hopkinson, NS;   - view fewer <#>    (2014)    A Randomized Controlled Trial of Angiotensin-Converting Enzyme Inhibition for Skeletal Muscle Dysfunction in COPD.                   CHEST , 146  (4)   932 - 940.    10.1378/chest.13-2483 <https://doi.org/10.1378/chest.13-2483>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/1456514/1/chest_146_4_932.pdf