naloxone and Asthma--Exercise-Induced

We wanted to determine whether 10 mg naloxone inhaled quantitatively could modulate the resting bronchial tone and respiratory response in exercise-induced asthma (EIA). In 11 asthmatic subjects, we measured specific airway conductance (SGaw) and forced expiratory flow (FEF) before and after the inhalation of naloxone or saline. In another 10 asthmatic subjects, we measured SGaw, FEF, and the ventilatory gas exchange, heart rate, and blood pressure responses produced by a treadmill exercise during 3 separate days: without any pretreatment (Day 1) or preceded by the inhalation of either 10 mg naloxone (Day 2) or saline (Day 3). We found that after 10 mg inhaled naloxone only one of 11 subjects bronchodilated, displaying an isolated, reproducible delta SGaw greater than 40% at 30 and 60 min. In the EIA protocol, the cardiopulmonary responses during exercise remained similar on all experimental days, but in seven of 10 subjects (all with %FEV1/FVC greater than or equal to 70% delta SGaw was -60 +/- 11%, + 1 +/- 40%, and -52 +/- 7% during no treatment, naloxone, and saline days, respectively (p less than 0.05). FEF changes were comparable on all days (p greater than 0.05).. (1) consistent with the general role of endogenous opioids, these neurotransmitter/neuromodulators can modulate a stress-related bronchoconstrictor response (EIA), but only very seldom the resting bronchial tone. (2) Naloxone does not blunt EIA through a decrease in the asthmogenic stimulus (i.e., ventilation) or airway caliber change, but presumably through competition with the endogenous opioids released during exercise.

Topics: Administration, Inhalation; Adolescent; Adult; Airway Resistance; Asthma; Asthma, Exercise-Induced; Bronchi; Humans; Naloxone; Pulmonary Ventilation; Rest

Concentrations of endogenous opioid peptides in the plasma are increased during exercise and these substances have been implicated in the pathogenesis of asthma induced by chloropropramide and alcohol in diabetic patients. This work was undertaken to determine whether exercise induced asthma might be mediated by endogenous opioids. Plasma beta endorphin, met-enkephalin, and adrenocorticotrophic hormone (ACTH) concentrations were measured in five asthmatic patients and five normal volunteers breathing cold air during exercise. In four of the patients the effect of an infusion of naloxone on FEV1 was also measured during exercise induced asthma. Exercise produced acute bronchoconstriction in all asthmatics, characterised by a fall in FEV1; whereas no change occurred in normal subjects. There was no difference in plasma met-enkephalin, beta endorphin, and ACTH concentration between the two groups. Infusion of naloxone neither prevented nor worsened exercise induced asthma. These data suggest that endogenous opioids probably do not play a part in the development of exercise induced asthma.

Topics: Adult; Asthma; Asthma, Exercise-Induced; beta-Endorphin; Double-Blind Method; Endorphins; Enkephalin, Methionine; Female; Humans; Male; Naloxone; Random Allocation