Field P I, Simmul R, Bell S C, Allen D H, Berend N
Department of Thoracic Medicine, Royal North Shore Hospital, New South Wales, Australia.
Thorax. 1996 Feb;51(2):159-63. doi: 10.1136/thx.51.2.159.
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.
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).
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.
These results suggest that opioids modulate the cholinergic component of SO2 responsiveness and that cyclooxygenase products contribute to the immediate response to SO2.
吸入二氧化硫（SO₂）可诱发哮喘患者的支气管收缩。胆碱能机制起作用，但其他机制尚不清楚。研究了阿片类激动剂吗啡对SO₂诱导的支气管收缩的胆碱能成分的影响，并研究了环氧化酶抑制剂吲哚美辛对SO₂诱导的支气管收缩和快速减敏的影响。
在第一项研究中，16名哮喘患者在第1天和第2天接受SO₂激发试验前60分钟吸入异丙托溴铵或安慰剂。在第3天，静脉注射吗啡后立即进行SO₂激发试验。在第二项研究中，15名哮喘患者在每个研究日前三天服用安慰剂或吲哚美辛，然后进行两次间隔30分钟的SO₂激发试验。以引起特定气道传导率（sGaw；PDsGaw35）下降35%的累积剂量作为反应指标。
异丙托溴铵显著抑制SO₂反应性，使PDsGaw35降低0.89（95%可信区间0.46至1.31）倍剂量。在校正异丙托溴铵引起的支气管扩张后，该效应仍然存在。异丙托溴铵和吗啡对SO₂反应性的影响也具有相关性（r² = 0.71）。在第二项研究中，重复试验时SO₂快速减敏出现，PDsGaw35降低0.62（95%可信区间0.17至1.07）倍剂量。吲哚美辛减弱了基线SO₂反应性，使PDsGaw35增加0.5（95%可信区间0.06至0.93）倍剂量。
这些结果表明，阿片类药物调节SO₂反应性的胆碱能成分，环氧化酶产物参与对SO₂的即时反应。
