title: Inhaled fentanyl citrate improves exercise endurance during high-intensity constant work rate cycle exercise in chronic obstructive pulmonary disease.
abstract: BACKGROUND
  Activity limitation and dyspnea are the dominant symptoms of chronic obstructive pulmonary disease (COPD). Traditionally, efforts to alleviate these symptoms have focused on improving ventilatory mechanics, reducing ventilatory demand, or both of these in combination. Nevertheless, many patients with COPD remain incapacitated by dyspnea and exercise intolerance despite optimal therapy.
  
  
  OBJECTIVE
  To determine the effect of single-dose inhalation of nebulized fentanyl citrate (a μ-opioid agonist drug) on exercise tolerance and dyspnea in COPD.
  
  
  METHODS
  In a randomized, double-blind, placebo-controlled, crossover study, 12 stable patients with COPD (mean ± standard error of the mean post-β(2)-agonist forced expiratory volume in one second [FEV(1)] and FEV(1) to forced vital capacity ratio of 69% ± 4% predicted and 49% ± 3%, respectively) received either nebulized fentanyl citrate (50 mcg) or placebo on two separate days. After each treatment, patients performed pulmonary function tests and a symptom-limited constant work rate cycle exercise test at 75% of their maximum incremental work rate.
  
  
  RESULTS
  There were no significant postdose differences in spirometric parameters or plethysmographic lung volumes. Neither the intensity nor the unpleasantness of perceived dyspnea was, on average, significantly different at isotime (5.0 ± 0.6 minutes) or at peak exercise after treatment with fentanyl citrate vs. placebo. Compared with placebo, fentanyl citrate was associated with 1) increased exercise endurance time by 1.30 ± 0.43 minutes or 25% ± 8% (P=0.01); 2) small but consistent increases in dynamic inspiratory capacity by ∼0.10 L at isotime and at peak exercise (both P≤0.03); and 3) no concomitant change in ventilatory demand, breathing pattern, pulmonary gas exchange, and/or cardiometabolic function during exercise. The mean rate of increase in dyspnea intensity (1.2 ± 0.3 vs. 2.9 ± 0.8 Borg units/minute, P=0.03) and unpleasantness ratings (0.5 ± 0.2 vs. 2.9 ± 1.3 Borg units/minute, P=0.06) between isotime and peak exercise was less after treatment with fentanyl citrate vs. placebo.
  
  
  CONCLUSIONS
  Single-dose inhalation of fentanyl citrate was associated with significant and potentially clinically important improvements in exercise tolerance in COPD. These improvements were accompanied by a delay in the onset of intolerable dyspnea during exercise near the limits of tolerance.
authors.affiliation: Department of Kinesiology and Physical Education, McGill University, Montreal, Quebec, Canada. dennis.jensen@mcgill.ca
authors.forename: Dennis
authors.initials: D
authors.lastname: Jensen
authors.forename: Abdullah
authors.initials: A
authors.lastname: Alsuhail
authors.forename: Raymond
authors.initials: R
authors.lastname: Viola
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Dudgeon
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Webb
authors.forename: Denis E
authors.initials: DE
authors.lastname: O'Donnell
mesh_terms: D000280:Administration, Inhalation; D000368:Aged; D000701:Analgesics, Opioid / Q000008:administration & dosage; D018592:Cross-Over Studies; D004311:Double-Blind Method; D017079:Exercise Tolerance / Q000187:drug effects*; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D005082:Physical Exertion / Q000187:drug effects*; D015990:Placebo Effect; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology*; D016896:Treatment Outcome
chemical_list: D000701:Analgesics, Opioid; D005283:Fentanyl