Evidence for opioid modulation and generation of prostaglandins in sulphur dioxide (SO)2-induced bronchoconstriction.

BACKGROUND: Inhalation of sulphur dioxide (SO2) provokes bronchoconstriction in asthmatic subjects. Cholinergic mechanisms contribute, but other mechanisms remain undefined. The effect of morphine, an opioid agonist, on the cholinergic component of SO2-induced bronchoconstriction was investigated, and the effect of indomethacin, a cyclooxygenase inhibitor, on SO2-induced bronchoconstriction and tachyphylaxis was studied. METHODS: In the first study 16 asthmatic subjects inhaled either ipratropium bromide or placebo 60 minutes before an SO2 challenge on days 1 and 2. On day 3 an SO2 challenge was performed immediately after intravenous morphine. In the second study 15 asthmatic subjects took either placebo or indomethacin for three days before each study day when two SO2 challenges were performed 30 minutes apart. The response was measured as the cumulative dose causing a 35% fall in specific airways conductance (sGaw; PDsGaw35). RESULTS: Ipratropium bromide significantly inhibited SO2 responsiveness, reducing PDsGaw35 by 0.89 (95% CI 0.46 to 1.31) doubling doses. This effect persisted after correction for bronchodilatation induced by ipratropium bromide. The effect of ipratropium bromide and morphine on SO2 responsiveness also correlated (r2 = 0.71). In the second study SO2 tachyphylaxis developed with PDsGaw35 on repeated testing, being reduced by 0.62 (95% CI 0.17 to 1.07) doubling doses. Indomethacin attenuated baseline SO2 responsiveness, increasing PDsGaw35 by 0.5 (95% CI 0.06 to 0.93) doubling doses. CONCLUSIONS: These results suggest that opioids modulate the cholinergic component of SO2 responsiveness and that cyclooxygenase products contribute to the immediate response to SO2

Cross refractoriness between sodium metabisulphite and exercise induced asthma.

BACKGROUND--Exercise and inhaled sodium metabisulphite are thought to cause bronchoconstriction in asthma through different mechanisms. The response to both stimuli becomes refractory with repeat challenge. The mechanism of refractoriness is unclear, although depletion of mast cell derived mediators or neurotransmitters has been suggested. Recent studies suggest a common mechanism involving release of inhibitory prostaglandins. If this is true, exercise and sodium metabisulphite induced bronchoconstriction should show cross refractoriness. METHODS--Thirteen subjects with mild asthma and previously established exercise and sodium metabisulphite induced bronchoconstriction performed two sodium metabisulphite challenges (giving a single dose previously shown to cause a 20% fall in FEV1) on one study day, and two exercise tests on another. The second challenge proceeded after recovery (FEV1 > 95% baseline) from the first. Subjects then attended on two further occasions when an exercise test was performed after sodium metabisulphite and a sodium metabisulphite challenge after exercise. RESULTS--When expressed as the percentage reduction in the area under the change in percentage FEV1 curve over 20 minutes (AUC) the response to exercise was reduced by a mean 62.3% (95% CI 46.5% to 78.1%) following a first exercise challenge, and by 50.7% (95% CI 27.8% to 73.6%) following a sodium metabisulphite challenge. The response to a sodium metabisulphite challenge was reduced by a mean of 80.2% (95% CI 68.9% to 91.5%) when it followed a sodium metabisulphite challenge, and by 37.3% (95% CI 15.1% to 59.5%) following an exercise challenge. CONCLUSION--This study shows some cross refractoriness between exercise and sodium metabisulphite induced bronchoconstriction, in keeping with a partially shared mechanism of refractoriness