Pavord I D, Wisniewski A, Tattersfield A E
Respiratory Medicine Unit, City Hospital, Nottingham.
Thorax. 1992 Oct;47(10):797-800. doi: 10.1136/thx.47.10.797.
Inhaled frusemide protects subjects with asthma against a wide range of bronchoconstrictor challenges, including allergen, exercise and inhaled sodium metabisulphite. An investigation was designed to determine whether this protection is related to the production of inhibitory prostaglandins, such as prostaglandin E2 (PGE2), by studying the effect of the cyclooxygenase inhibitor indomethacin on the protection afforded by inhaled frusemide against exercise induced asthma.
In a double blind crossover study 10 subjects with mild asthma were pretreated with indomethacin (50 mg thrice daily) or placebo capsules for three days; they then inhaled frusemide (40 mg) or placebo 10 minutes before an exercise test previously shown to cause a 20-30% fall in forced expiratory volume in one second (FEV1).
After inhalation of placebo exercise caused a similar maximum fall in FEV1 whether pretreatment was with placebo (26%) or indomethacin (25.2%). After inhalation of frusemide the maximum fall in FEV1 was reduced to 14.3% after placebo pretreatment and to 21.8% after indomethacin pretreatment; the difference between placebo and indomethacin pretreatment was significant (mean difference 7.5%, 95% limits 0.6%, 14.4%). The inhibitory effect of frusemide on the response to exercise, assessed as change in FEV1 over 30 minutes, was significantly greater with placebo (62%) than indomethacin (13%) pretreatment.
These findings support a role for inhibitory prostanoids, such as PGE2, in the beneficial effects of frusemide as a protection against exercise induced asthma.
吸入速尿可保护哮喘患者免受多种支气管收缩刺激，包括过敏原、运动和吸入焦亚硫酸钠。本研究旨在通过研究环氧化酶抑制剂吲哚美辛对吸入速尿预防运动诱发性哮喘的保护作用的影响，来确定这种保护作用是否与抑制性前列腺素如前列腺素E2（PGE2）的产生有关。
在一项双盲交叉研究中，10名轻度哮喘患者接受吲哚美辛（每日三次，每次50mg）或安慰剂胶囊预处理三天；然后在一项先前显示会导致一秒用力呼气量（FEV1）下降20%-30%的运动试验前10分钟，他们吸入速尿（40mg）或安慰剂。
吸入安慰剂后，无论预处理是使用安慰剂（26%）还是吲哚美辛（25.2%），运动引起的FEV1最大下降相似。吸入速尿后，安慰剂预处理后FEV1的最大下降降至14.3%，吲哚美辛预处理后降至21.8%；安慰剂和吲哚美辛预处理之间的差异显著（平均差异7.5%，95%置信区间0.6%，14.4%）。以30分钟内FEV1的变化评估，速尿对运动反应的抑制作用在安慰剂预处理（62%）时显著大于吲哚美辛预处理（13%）时。
这些发现支持抑制性前列腺素如PGE2在速尿预防运动诱发性哮喘的有益作用中发挥作用。
