Nathan R A, Minkwitz M C, Bonuccelli C M
Asthma and Allergy Associates, PC, Colorado Springs, Colorado 80907, USA.
Ann Allergy Asthma Immunol. 1999 May;82(5):497-503. doi: 10.1016/S1081-1206(10)62728-7.
New drug evaluations in patients with mild asthma are sometimes complicated by enrollment of patients whose disease is too mild to show improvement with therapy. A peak expiratory flow (PEF) variability criterion may help to more clearly define a mild asthmatic population.
To evaluate the effectiveness of zafirlukast (20 mg twice daily) and cromolyn sodium (1600 microg four times daily) compared with placebo as first-line therapy for mild asthma using a retrospective analysis, which stratified patients by PEF variability (<10% or > or =10%).
Symptomatic patients (daytime asthma symptoms score > or =8) were randomized to 13 weeks of treatment in a double-blind, double-dummy, placebo-controlled, parallel-group, multicenter trial.
Patients (n = 287) were nonsmokers (age > or =12 years) with reversible airway disease, a forced expiratory volume in one second (FEV1) of > or = 55% of predicted, and previous treatment with beta2-agonist or theophylline only. Assessments included changes from baseline to endpoint in daytime and nocturnal asthma symptoms, beta2-agonist use, PEF, and FEV1. Response to treatment was assessed by predetermined diary card and FEV1 criteria. Safety was determined from adverse events and laboratory test results.
No significant treatment effects were seen across efficacy measures for patients with PEF variability < 10%. For patients with PEF variability > or = 10%, both active treatments significantly (P < .05) decreased the daytime asthma symptoms score, nighttime awakenings, and beta2-agonist use, and increased morning PEF and FEV1 compared with placebo. Response to diary card criteria was 70% and 75% for zafirlukast and cromolyn, respectively; response to FEV1 criteria was 47% for both treatments. All treatments were tolerated well by patients.
Zafirlukast and cromolyn are effective first-line therapies for mild asthma, with both therapies producing greater benefits in patients whose PEF variability was > or = 10%. In prospective trials to evaluate therapies in patients with mild asthma, it may be worthwhile to include PEF variability with a 10% cutoff either as an inclusion criteria or as a tool for subset analysis.
轻度哮喘患者的新药评估有时会因纳入病情过轻以至于治疗后无改善的患者而变得复杂。呼气峰值流速（PEF）变异性标准可能有助于更清晰地界定轻度哮喘人群。
采用回顾性分析方法，比较扎鲁司特（每日两次，每次20毫克）和色甘酸钠（每日四次，每次1600微克）与安慰剂作为轻度哮喘一线治疗的有效性，该分析根据PEF变异性（<10%或≥10%）对患者进行分层。
有症状的患者（日间哮喘症状评分≥8）在一项双盲、双模拟、安慰剂对照、平行组、多中心试验中被随机分配接受13周的治疗。
患者（n = 287）为不吸烟者（年龄≥12岁），患有可逆性气道疾病，一秒用力呼气量（FEV1）≥预测值的55%，且之前仅接受过β2受体激动剂或茶碱治疗。评估内容包括从基线到终点的日间和夜间哮喘症状、β2受体激动剂使用情况、PEF和FEV1的变化。通过预先确定的日记卡和FEV1标准评估治疗反应。根据不良事件和实验室检查结果确定安全性。
对于PEF变异性<10%的患者，各项疗效指标均未观察到显著的治疗效果。对于PEF变异性≥10%的患者，与安慰剂相比，两种活性治疗均显著（P <.05）降低了日间哮喘症状评分、夜间觉醒次数和β2受体激动剂的使用，并提高了晨间PEF和FEV1。扎鲁司特和色甘酸钠对日记卡标准的反应率分别为70%和75%；两种治疗对FEV1标准的反应率均为47%。所有治疗患者耐受性良好。
扎鲁司特和色甘酸钠是轻度哮喘有效的一线治疗药物，两种疗法对PEF变异性≥10%的患者疗效更佳。在评估轻度哮喘患者治疗方法的前瞻性试验中，将PEF变异性以10%为界值作为纳入标准或作为亚组分析工具可能是值得的。
