O'Byrne P M, Israel E, Drazen J M
Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
Ann Intern Med. 1997 Sep 15;127(6):472-80. doi: 10.7326/0003-4819-127-6-199709150-00009.
To review the activity in clinical models, the efficacy, and the safety of antileukotrienes as a new class of antiasthma treatment.
English-language trials identified from the archival literature, including the MEDLINE database, through 1996; bibliographic references; and textbooks.
Reports from placebo-controlled, double-blind, randomized trials were selected.
Study designs and results were extracted from the clinical trial reports. Statistical evaluation of combined results was not attempted.
The various classes of antileukotrienes have shown activity in clinical models of asthma, including exercise-induced, cold air hyperventilation-induced, allergen-induced, and aspirin-induced bronchoconstriction. In addition, the antileukotrienes partially reverse spontaneous bronchoconstriction in asthmatic persons, an effect additive to that of inhaled beta 2-agonists. Clinical trials of the antileukotrienes have shown clinical benefit, as measured by reductions in asthma symptom scores, improvements in air flow obstruction, and reductions in the rescue use of inhaled beta 2-agonists. Some, but not all, of the antileukotrienes have been shown to cause liver microsomal activation with increases in hepatic aminotransferase levels.
Antileukotrienes are an important new therapy for asthma. Inhibition of leukotriene synthesis or action has a beneficial effect in the treatment of both induced and spontaneous asthma. These results show that leukotrienes are important mediators of the asthmatic response. In addition, encouraging results have been obtained from clinical trials of antileukotrienes; however, these results do not yet provide guidelines for the optimal clinical use of antileukotrienes in asthma treatment. Such recommendations await the results of further studies.
综述作为一类新型抗哮喘治疗药物的抗白三烯药物在临床模型中的活性、疗效及安全性。
从1996年以前的文献档案中检索到的英文试验,包括MEDLINE数据库;参考文献;以及教科书。
选取安慰剂对照、双盲、随机试验的报告。
从临床试验报告中提取研究设计和结果。未尝试对合并结果进行统计学评估。
各类抗白三烯药物已在哮喘临床模型中显示出活性,包括运动诱发、冷空气过度通气诱发、变应原诱发及阿司匹林诱发的支气管收缩。此外,抗白三烯药物可部分逆转哮喘患者的自发性支气管收缩,此效应与吸入β2激动剂的效应相加。抗白三烯药物的临床试验已显示出临床益处,表现为哮喘症状评分降低、气流阻塞改善以及吸入β2激动剂的急救使用减少。部分(但并非全部)抗白三烯药物已被证明可导致肝微粒体激活,伴肝转氨酶水平升高。
抗白三烯药物是哮喘的一种重要新疗法。抑制白三烯合成或作用对诱导性和自发性哮喘的治疗均有有益作用。这些结果表明白三烯是哮喘反应的重要介质。此外,抗白三烯药物的临床试验已取得令人鼓舞的结果;然而,这些结果尚未为抗白三烯药物在哮喘治疗中的最佳临床应用提供指导原则。此类建议有待进一步研究的结果。