title: Does nebulized fentanyl relieve dyspnea during exercise in healthy man?
abstract: Few therapies exist for the relief of dyspnea in restrictive lung disorders. Accumulating evidence suggests that nebulized opioids selective for the mu-receptor subtype may relieve dyspnea by modulating intrapulmonary opioid receptor activity. Our respective primary and secondary objectives were to test the hypothesis that nebulized fentanyl (a mu-opioid receptor agonist) relieves dyspnea during exercise in the presence of abnormal restrictive ventilatory constraints and to identify the physiological mechanisms of this improvement. In a randomized, double-blind, placebo-controlled crossover study, we examined the effect of 250 μg nebulized fentanyl, chest wall strapping (CWS), and their interaction on detailed physiological and perceptual responses to constant work rate cycle exercise (85% of maximum incremental work rate) in 14 healthy, fit young men. By design, CWS decreased vital capacity by ∼20% and mimicked the negative consequences of a mild restrictive lung disorder on exercise endurance time and on dyspnea, breathing pattern, dynamic operating lung volumes, and diaphragmatic electromyographic and respiratory muscle function during exercise. Compared with placebo under both unrestricted control and CWS conditions, nebulized fentanyl had no effect on exercise endurance time, integrated physiological response to exercise, sensory intensity, unpleasantness ratings of exertional dyspnea. Our results do not support a role for intrapulmonary opioids in the neuromodulation of exertional dyspnea in health nor do they provide a physiological rationale for the use of nebulized fentanyl in the management of dyspnea due to mild restrictive lung disorders, specifically those arising from abnormalities of the chest wall and not affiliated with airway inflammation.
authors.affiliation: Clinical Exercise & Respiratory Physiology Laboratory, Department of Kinesiology & Physical Education, McGill University, Montréal, Quebec, Canada;
authors.forename: Houssam G
authors.initials: HG
authors.lastname: Kotrach
authors.affiliation: Respiratory Epidemiology and Clinical Research Unit, Montréal Chest Institute, McGill University Health Centre, Montréal, Quebec, Canada; and.
authors.forename: Jean
authors.initials: J
authors.lastname: Bourbeau
authors.affiliation: Clinical Exercise & Respiratory Physiology Laboratory, Department of Kinesiology & Physical Education, McGill University, Montréal, Quebec, Canada; Respiratory Epidemiology and Clinical Research Unit, Montréal Chest Institute, McGill University Health Centre, Montréal, Quebec, Canada; and Research Centre for Physical Activity and Health, McGill University, Montréal, Quebec, Canada dennis.jensen@mcgill.ca.
authors.forename: Dennis
authors.initials: D
authors.lastname: Jensen
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage*; D001642:Bicycling; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004417:Dyspnea / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D004576:Electromyography; D015444:Exercise; D005080:Exercise Test; D005283:Fentanyl / Q000008:administration & dosage*; D064368:Healthy Volunteers; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008176:Lung Volume Measurements; D008297:Male; D009330:Nebulizers and Vaporizers; D012123:Pulmonary Ventilation / Q000187:drug effects; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000378:metabolism; D015656:Respiratory Mechanics / Q000187:drug effects; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D017450:Receptors, Opioid, mu; D005283:Fentanyl
keywords: chest wall strapping; dyspnea; exercise; fentanyl; opioid