BACKGROUND--Inhaled nebulised morphine may reduce breathlessness in patients with lung disease, although the results of controlled trials are conflicting. A direct action of morphine on the lung has been postulated. This study aimed to investigate whether nebulised morphine reduced exercise-induced breathlessness in patients with chronic obstructive pulmonary disease (COPD) and to determine if this was a local pulmonary effect or occurred after systemic morphine absorption. METHODS--A double blind, randomised, crossover study was performed in 12 men with COPD to compare the effects of nebulised morphine (10 and 25 mg), equivalent intravenous doses (1 and 2.5 mg), and placebo. Breathlessness (visual analogue scale), ventilation, gas exchange, and exercise endurance were measured during graded bicycle exercise. RESULTS--None of the treatments altered breathlessness, ventilation, or gas exchange at rest or at any time during exercise, and exercise endurance was unaffected. At peak exercise mean (95% CI) changes from placebo in ventilation were -0.8 (-0.57 to 1.1) l/min and -0.4 (-2.8 to 2.0) l/min for the highest intravenous and nebulised doses, respectively. For breathlessness equivalent values were +2 (-5 to 9) and +1 (-9 to 11) mm. The study was of sufficient power that it is unlikely that a clinically important effect was missed. CONCLUSIONS--Nebulised morphine in these doses has no effect on exercise-induced breathlessness. These findings do not support the hypothesis that intrapulmonary opiates modulate the sensation of breathlessness in patients with COPD.
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