Abstract
Question addressed by the study Endogenous opioids (endorphins) have been reported to modulate exercise-induced breathlessness, but the relative contribution of peripheral opioid receptors has not been tested.
Materials, participants and methods This was a double-blind, randomised, three-arm, cross-over trial in outpatients with spirometry-verified moderate to severe chronic obstructive pulmonary disease. Participants undertook an incremental symptom-limited treadmill test followed by five endurance treadmill tests at 75% of their maximal work rate; two tests for familiarisation and three tests 30 min after intravenous injection of either methylnaltrexone 0.3 mg·kg−1 (blocking peripheral opioid receptors only) or naloxone 0.1 mg·kg−1 (blocking both central and peripheral opioid receptors) or normal saline, in randomised order. The primary end-point was the regression slope between breathlessness intensity (0–10 numerical rating scale) and oxygen consumption (V′O2) during the walk tests, comparing methylnaltrexone and placebo using a paired t-test.
Results 17 participants completed the trial: median (range) 66 (55–82) years; 15 males; mean±sd forced expiratory volume (FEV1) 53.8±17.6% predicted; FEV1/forced vital capacity ratio 0.55±15.9. There was no statistically or clinically significant difference in the primary end-point (regression slope of breathlessness intensity and V′O2) for methylnaltrexone (p=0.498) or naloxone (p=0.804), compared to placebo. Secondary outcomes were similar between the three treatment groups, including peak and mean breathlessness intensity and unpleasantness, exercise capacity, endurance time and leg fatigue.
Answer to the question Blocking peripheral opioid receptors (methylnaltrexone) or peripheral and central opioid receptors (naloxone) did not appear to modulate breathlessness intensity nor exercise capacity when compared with placebo (no blockade).
Abstract
A double-blind, placebo controlled, randomised, cross-over study using methylnaltrexone found no evidence for a contribution of peripheral opioid receptors to the modulation of breathlessness by endogenous endorphins. http://bit.ly/32DZv3I
Footnotes
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This study is registered at www.anzctr.org.au with identifier number ACTRN12611001182987. Data are available on request from bona fide researchers.
Support statement: Funding was provided for the study by the National Health and Medical Research Council (Australia) grant 1065572. The funder had no control over study design, conduct, analysis, interpretation or dissemination of results. M. Ekström was supported by an unrestricted grant from the Swedish Heart-Lung Foundation and the Swedish Society for Medical Research. Funding information for this article has been deposited with the Crossref Funder Registry.
Conflict of interest: D.C. Currow is an unpaid member of an advisory board for Helsinn Pharmaceuticals, is a consultant to Specialised Therapeutics and Mayne Pharma, and received intellectual property payments from Mayne Pharma.
Conflict of interest: T. Hunt reports paid employment independent of this work for Boehringer Ingelheim and Janssen-Cilag Pty Ltd.
Conflict of interest: S. Louw reports statistical consulting fees from McCloud Consulting Group during the conduct of the study.
Conflict of interest: D. Eckert reports research grants from and advisory board membership for Apnimed (a pharmaceutical company established to develop drug therapy for sleep apnoea), a research grant from and consultancy (sleep apnoea area) for Bayer, and a Cooperative Research Centre (CRC)-P grant, a collaboration between the Australian Government, academia and industry (industry partner Oventus Medical), outside the submitted work.
Conflict of interest: P. Allcroft has nothing to disclose.
Conflict of interest: T.H.M. To has nothing to disclose.
Conflict of interest: A. Greene has nothing to disclose.
Conflict of interest: M. Krajnik reports that she is the head (unpaid) of a foundation supported financially in its educational activities by Angellini, Stada, Takeda and Molteni, outside the submitted work.
Conflict of interest: D. Mahler has nothing to disclose.
Conflict of interest: M. Ekström has nothing to disclose.
- Received August 15, 2019.
- Accepted October 17, 2019.
- Copyright ©ERS 2019
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