RT Journal Article SR Electronic T1 Isolating peripheral effects of endogenous opioids in modulating exertional breathlessness in people with moderate or severe COPD: a randomised controlled trial JF ERJ Open Research JO erjor FD European Respiratory Society SP 00153-2019 DO 10.1183/23120541.00153-2019 VO 5 IS 4 A1 David C. Currow A1 Toby Hunt A1 Sandra Louw A1 Danny Eckert A1 Peter Allcroft A1 Tim H.M. To A1 Aine Greene A1 Malgorzata Krajnik A1 Don Mahler A1 Magnus Ekström YR 2019 UL http://openres.ersjournals.com/content/5/4/00153-2019.abstract AB 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).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