色甘酸钠单独及与孟鲁司特联合应用对哮喘患者气道对甘露醇反应的影响
Sodium cromoglycate alone and in combination with montelukast on the airway response to mannitol in asthmatic subjects.
作者信息
Anderson Sandra D, Brannan John D, Perry Clare P, Caillaud Corinne, Seale J Paul
机构信息
Department of Respiratory and Sleep Medicine, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.
出版信息
J Asthma. 2010 May;47(4):429-33. doi: 10.3109/02770900903584043.
BACKGROUND
Mannitol, inhaled as a dry powder, is used for bronchial provocation to identify bronchial hyperresponsiveness. Bronchoconstriction is associated with an increase in urinary excretion of the metabolites of prostaglandin D(2) and leukotriene E(4). Sodium cromoglycate provides about 60% protection against the fall in forced expiratory volume in one second (FEV(1)) provoked by inhaled mannitol and appears to do so by inhibiting the release of prostaglandin D(2) but not leukotriene E(4).The leukotriene receptor antagonist montelukast does not alter sensitivity to mannitol, as measured by the provoking dose to cause a 15% fall in FEV(1) to mannitol, but it significantly enhances recovery from the bronchoconstriction provoked by mannitol.
OBJECTIVE
The authors proposed that the combination of these two drugs would be superior to sodium cromoglycate alone and result in greater protection from the bronchoconstriction provoked by mannitol.
METHODS
The % fall in FEV(1) from baseline and the area under the 30-min FEV(1) time curve and time to recover to 95% baseline FEV(1) were used to express protection from 40 mg sodium cromoglycate alone, and in combination with 10 mg montelukast, in subjects with asthma. Mannitol was inhaled in the dose that caused a 20% fall in FEV(1) on the screening day. The prechallenge medications were randomised on the 3 treatment days and were (1) placebo sodium cromoglycate and placebo montelukast; (2) sodium cromoglycate and placebo montelukast; and (3) sodium cromoglycate and montelukast.
RESULTS
The protection by sodium cromoglycate alone on the % fall in FEV(1) was 64.4% +/- 21.0% versus 65.8% +/- 62.8% (p = NS) on the combination. The protection on the area under the 30-min FEV(1) time curve for sodium cromoglycate was 81.8% +/- 14.0% (p <.04) and 89.3% +/- 9.8% for the combination (p <.001) compared with placebo. Recovery to 95% baseline FEV(1) by 5/10 min occurred in 58%/66% of subjects on sodium cromoglycate and 66%/83% on the combination compared with 0%/0% on placebo.
CONCLUSION
The addition of montelukast to sodium cromoglycate provided only a small additional benefit against the airway response to mannitol.
背景
吸入干粉状的甘露醇用于支气管激发试验以确定支气管高反应性。支气管收缩与前列腺素D₂和白三烯E₄代谢产物的尿排泄增加有关。色甘酸钠可对吸入甘露醇诱发的一秒用力呼气量（FEV₁）下降提供约60%的保护，其作用机制似乎是抑制前列腺素D₂的释放，而非白三烯E₄的释放。白三烯受体拮抗剂孟鲁司特并不改变对甘露醇的敏感性（以导致FEV₁下降15%的甘露醇激发剂量来衡量），但它能显著促进甘露醇诱发的支气管收缩后的恢复。
目的
作者提出这两种药物联合使用将优于单独使用色甘酸钠，能为甘露醇诱发的支气管收缩提供更好的保护。
方法
在哮喘患者中，使用FEV₁较基线下降的百分比、30分钟FEV₁时间曲线下面积以及恢复至基线FEV₁的95%所需时间来表示单独使用40mg色甘酸钠以及与10mg孟鲁司特联合使用时的保护作用。在筛查日吸入能使FEV₁下降20%的甘露醇剂量。在3个治疗日对激发前用药进行随机分组，分别为：（1）安慰剂色甘酸钠和安慰剂孟鲁司特；（2）色甘酸钠和安慰剂孟鲁司特；（3）色甘酸钠和孟鲁司特。
结果
单独使用色甘酸钠对FEV₁下降百分比的保护作用为64.4%±21.0%，联合用药时为65.8%±62.8%（p=无统计学差异）。与安慰剂相比，色甘酸钠对30分钟FEV₁时间曲线下面积的保护作用为81.8%±14.0%（p<0.04），联合用药时为89.3%±9.8%（p<0.001）。使用色甘酸钠时，5/10分钟内恢复至基线FEV₁的95%的受试者比例分别为58%/66%，联合用药时为66%/83%，而安慰剂组为0%/0%。
结论
在色甘酸钠基础上加用孟鲁司特对气道对甘露醇的反应仅提供了少量额外益处。
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