O'Connor B J, Barnes P J, Chung K F
Department of Thoracic Medicine, National Heart and Lung Institute, Royal Brompton National Heart and Lung Hospitals, London.
Thorax. 1994 Apr;49(4):307-11. doi: 10.1136/thx.49.4.307.
Inhaled frusemide inhibits airway responses to sodium metabisulphite and other indirect bronchial challenges in asthma by undetermined mechanisms which may relate to its ability to stimulate prostaglandin release. Inhalation of sodium metabisulphite provokes indirect bronchoconstriction, possibly by activating sensory nerves. To investigate the role of cyclooxygenase products in the airway actions of frusemide and sodium metabisulphite, the effects of a potent cyclooxygenase inhibitor, flurbiprofen, alone and in combination with frusemide were investigated against airway responsiveness to sodium metabisulphite.
In a double blind double placebo controlled study, 12 mild asthmatic subjects attended on four occasions to undergo three inhalation challenges with sodium metabisulphite. A baseline challenge was performed one hour before oral intake of flurbiprofen 200 mg or matched placebo, and two hours before inhalation of frusemide 40 mg or matched placebo. A second challenge was performed immediately after inhalation of frusemide (two hours after flurbiprofen) with a further challenge three hours later. The log concentration provoking a 20% fall in FEV1 (log PC20) was used to assess airway responsiveness to sodium metabisulphite.
Frusemide caused an immediate 1.9 doubling dose protection and a lesser 0.7 doubling dose protection at three hours. This protection was enhanced by flurbiprofen at both time points to 2.7 (early) and 1.9 (late) doubling doses. In addition, flurbiprofen alone significantly reduced airway responsiveness to sodium metabisulphite by 1.1 doubling doses at both two and five hours.
The generation of bronchoprotective prostaglandins is unlikely to underlie the inhibitory action of frusemide against airway responsiveness to sodium metabisulphite. Endogenous contractile prostaglandins within the airways may be involved in the bronchoconstrictor response to sodium metabisulphite.
吸入速尿可抑制哮喘患者气道对亚硫酸氢钠及其他间接支气管激发物的反应，其作用机制尚不清楚，可能与其刺激前列腺素释放的能力有关。吸入亚硫酸氢钠可能通过激活感觉神经引发间接支气管收缩。为研究环氧化酶产物在速尿和亚硫酸氢钠气道作用中的作用，研究了强效环氧化酶抑制剂氟比洛芬单独及与速尿联合应用对气道对亚硫酸氢钠反应性的影响。
在一项双盲双安慰剂对照研究中，12名轻度哮喘患者分四次就诊，接受三次亚硫酸氢钠吸入激发试验。在口服200mg氟比洛芬或匹配安慰剂前1小时，以及吸入40mg速尿或匹配安慰剂前2小时进行基线激发试验。在吸入速尿后立即（氟比洛芬后2小时）进行第二次激发试验，并在3小时后进行进一步激发试验。用引起第一秒用力呼气容积（FEV1）下降20%的对数浓度（log PC20）评估气道对亚硫酸氢钠的反应性。
速尿在给药后立即产生1.9倍剂量的保护作用，3小时时产生较小的0.7倍剂量的保护作用。在两个时间点，氟比洛芬均增强了这种保护作用，分别为2.7倍（早期）和1.9倍（晚期）剂量。此外，氟比洛芬单独使用在2小时和5小时时均显著降低气道对亚硫酸氢钠的反应性，降低幅度为1.1倍剂量。
支气管保护性前列腺素的生成不太可能是速尿抑制气道对亚硫酸氢钠反应性的作用基础。气道内的内源性收缩性前列腺素可能参与了对亚硫酸氢钠的支气管收缩反应。
