Kemp J P, Minkwitz M C, Bonuccelli C M, Warren M S
University of California School of Medicine, San Diego, USA.
Chest. 1999 Feb;115(2):336-42. doi: 10.1378/chest.115.2.336.
We evaluated the efficacy of the leukotriene receptor antagonist zafirlukast (Accolate), 20 mg twice daily, as monotherapy in patients with severe persistent asthma (defined by an FEV1 < 60% of predicted before treatment and frequent night-time symptoms).
Data were analyzed from a subgroup of 261 steroid-naive patients (zafirlukast, n = 149; placebo, n = 112) from four randomized, double-blind, placebo-controlled, 13-week trials with similar experimental designs, entry criteria, and clinical assessments.
These patients were mostly men (57%) older than 30 years (56%) with pulmonary obstruction, ie, FEV1/FVC ratio < 0.7 (79%), and reversible airway disease demonstrated by a 15% increase in FEV1 after inhaled bronchodilator use.
At end point, patients who received zafirlukast monotherapy had significant (p < 0.05) improvements from baseline, and compared with placebo, in FEV1, morning and evening peak expiratory flow (PEF), daytime asthma symptoms, nighttime awakenings, and beta2-agonist use. A stratified analysis based on the FEV1/FVC ratio showed an interaction between treatment and the amount of airflow obstruction for nighttime awakenings and mornings with asthma. Moreover, 37% of patients in both treatment groups had PEF variability > or = 20% (an indirect measure of airway inflammation). Zafirlukast patients with PEF variability > or = 20% had increases from baseline in the morning and evening PEF of approximately 40 and 11 L/min, respectively. For patients who take zafirlukast and who have a PEF variability of < 20%, the morning and evening PEF increased by 25 and 30 L/min, respectively. Regardless of the degree of PEF variability, zafirlukast significantly (p < 0.05) increased morning and evening PEF compared with placebo.
Patients with severe persistent asthma who received zafirlukast as monotherapy had clinically significant improvements across all efficacy measures compared with placebo and significant reductions in PEF variability.
我们评估了白三烯受体拮抗剂扎鲁司特（Accolate）每日两次、每次20毫克作为单一疗法治疗重度持续性哮喘患者（定义为治疗前FEV1<预测值的60%且有频繁夜间症状）的疗效。
对来自四项随机、双盲、安慰剂对照、为期13周试验的261名未使用过类固醇的患者亚组（扎鲁司特组，n = 149；安慰剂组，n = 112）的数据进行分析，这些试验具有相似的实验设计、纳入标准和临床评估。
这些患者大多为男性（57%），年龄大于30岁（56%），存在肺阻塞，即FEV1/FVC比值<0.7（79%），且吸入支气管扩张剂后FEV1增加15%证明存在可逆性气道疾病。
在研究终点，接受扎鲁司特单一疗法的患者与基线相比，在FEV1、早晚呼气峰值流速（PEF）、白天哮喘症状、夜间觉醒次数和β2受体激动剂使用方面有显著（p<0.05）改善。基于FEV1/FVC比值的分层分析显示，治疗与夜间觉醒和哮喘发作早晨的气流阻塞程度之间存在交互作用。此外，两个治疗组中37%的患者PEF变异性≥20%（气道炎症的间接指标）。PEF变异性≥20%的扎鲁司特患者早晚PEF较基线分别增加约40和11升/分钟。对于服用扎鲁司特且PEF变异性<20%的患者，早晚PEF分别增加25和30升/分钟。无论PEF变异性程度如何，与安慰剂相比，扎鲁司特显著（p<0.05）增加了早晚PEF。
与安慰剂相比，接受扎鲁司特单一疗法的重度持续性哮喘患者在所有疗效指标上均有临床显著改善，且PEF变异性显著降低。
