Anti-leukotriene agents compared to inhaled corticosteroids in the management of recurrent and/or chronic asthma in adults and children.
Anti-leukotriene agents compared to inhaled corticosteroids in the management of recurrent and/or chronic asthma in adults and children.
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DOI：
10.1002/14651858.cd002314.pub3
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发表时间：
2012-05-16
影响因子：
8.4
通讯作者：
Ducharmc, Francine M.
中科院分区：
文献类型：
--
作者：
Chauhan, Bhupendrasinh F.;Ducharmc, Francine M.
关键词：
抗白三烯（5-脂氧合酶抑制剂和白三烯受体拮抗剂）可作为吸入皮质类固醇 (ICS) 的替代单一疗法，用于治疗成人和儿童的复发性和/或慢性哮喘。确定抗白三烯类药物与吸入皮质类固醇作为单一疗法治疗成人和儿童哮喘的安全性和有效性，并更好地了解患者和治疗特征对效果程度的影响。我们检索了 MEDLINE（1966 年至 2010 年 12 月）、EMBASE（1980 年至 2010 年 12 月）、CINAHL（1982 年至 2010 年 12 月）、Cochrane Airways Group 试验登记册和 Cochrane 对照试验中央登记册（2010 年 12 月）、摘要书籍以及综述文章和试验的参考文献列表。我们联系了同事和抗白三烯生产商的国际总部。我们纳入了随机试验，比较抗白三烯与吸入皮质类固醇作为单一疗法对两岁及以上哮喘患者至少四个星期的治疗。两位综述作者独立评估试验的方法学质量并提取数据。主要结局是至少有一次病情加重且需要全身皮质类固醇治疗的患者数量。次要结局包括至少有一次恶化需要入院的患者、肺功能测试、慢性哮喘控制指数、不良反应、戒断率和生物炎症标志物。 65 项试验符合本次审查的纳入标准。 56 项试验（19 项儿科试验）提供了数据（总共 10,005 名成人和 3,333 名儿童）； 21 项试验具有较高的方法学质量；全文发表44篇。所有试验均涉及轻度或中度持续性哮喘患者。试验持续时间从 4 周到 52 周不等。吸入皮质类固醇的中位剂量相当均匀，为 200 μg/天的微细氢氟烷驱动的倍氯米松或等效物 (HFABDP eq)。使用抗白三烯类药物治疗的患者更有可能出现需要全身皮质类固醇治疗的病情加重（N = 6077 名参与者；风险比 (RR) 1.51，95% 置信区间 (CI) 1.17、1.96）。每 28 名（95% CI 15 至 82）名接受抗白三烯类药物而非吸入性皮质类固醇治疗的患者中，就会有一名病情加重的患者需要全身性皮质类固醇的救援。与轻度气道阻塞患者相比，中度气道阻塞患者的效果显着更大（RR 2.03，95% CI 1.41，2.91 vs RR 1.25，95% CI 0.97，1.61），但不受年龄组（儿童占体重的 23% 与成人相比）、使用的抗白三烯药物、干预持续时间、方法学质量和资金来源的显着影响。在大多数次要结局中，注意到有利于吸入皮质类固醇的显着组间差异，包括至少有一次病情加重需要入院的患者（N = 2715 名受试者；RR 3.33；95% CI 1.02 至 10.94），相对于基线 FEV1 的变化（N = 7128 名受试者；平均组间差异 (MD) 110 mL，95% CI 140 至 80）其他肺功能参数、哮喘症状、夜间觉醒、急救药物使用、无症状天数、生活质量、父母和医生的满意度。抗白三烯治疗与哮喘控制不良导致的戒断风险增加相关（N = 7669 名受试者；RR 2.56；95% CI 2.01 至 3.27）。每 31 名（95% CI 22 至 47）名接受抗白三烯类药物而非吸入皮质类固醇治疗的患者中，就会有 1 名患者因控制不良而额外停药。两组之间的副作用风险没有显着差异。作为单一疗法，吸入皮质类固醇对患有持续性哮喘的成人和儿童显示出优于抗白三烯类药物的疗效。对于中度气道阻塞的患者，其优越性尤其明显。根据疗效，结果支持当前指南的建议，即吸入皮质类固醇仍然是首选的单一疗法。
Anti-leukotrienes (5-lipoxygenase inhibitors and leukotriene receptors antagonists) serve as alternative monotherapy to inhaled corticosteroids (ICS) in the management of recurrent and/or chronic asthma in adults and children. To determine the safety and efficacy of anti-leukotrienes compared to inhaled corticosteroids as monotherapy in adults and children with asthma and to provide better insight into the influence of patient and treatment characteristics on the magnitude of effects. We searched MEDLINE (1966 to Dec 2010), EMBASE (1980 to Dec 2010), CINAHL (1982 to Dec 2010), the Cochrane Airways Group trials register, and the Cochrane Central Register of Controlled Trials (Dec 2010), abstract books, and reference lists of review articles and trials. We contacted colleagues and the international headquarters of anti-leukotrienes producers. We included randomised trials that compared anti-leukotrienes with inhaled corticosteroids as monotherapy for a minimum period of four weeks in patients with asthma aged two years and older. Two review authors independently assessed the methodological quality of trials and extracted data. The primary outcome was the number of patients with at least one exacerbation requiring systemic corticosteroids. Secondary outcomes included patients with at least one exacerbation requiring hospital admission, lung function tests, indices of chronic asthma control, adverse effects, withdrawal rates and biological inflammatory markers. Sixty-five trials met the inclusion criteria for this review. Fifty-six trials (19 paediatric trials) contributed data (representing total of 10,005 adults and 3,333 children); 21 trials were of high methodological quality; 44 were published in full-text. All trials pertained to patients with mild or moderate persistent asthma. Trial durations varied from four to 52 weeks. The median dose of inhaled corticosteroids was quite homogeneous at 200 μg/day of microfine hydrofluoroalkane-propelled beclomethasone or equivalent (HFABDP eq). Patients treated with anti-leukotrienes were more likely to suffer an exacerbation requiring systemic corticosteroids (N = 6077 participants; risk ratio (RR) 1.51, 95% confidence interval (CI) 1.17, 1.96). For every 28 (95% CI 15 to 82) patients treated with anti-leukotrienes instead of inhaled corticosteroids, there was one additional patient with an exacerbation requiring rescue systemic corticosteroids. The magnitude of effect was significantly greater in patients with moderate compared with those with mild airway obstruction (RR 2.03, 95% CI 1.41, 2.91 versus RR 1.25, 95% CI 0.97, 1.61), but was not significantly influenced by age group (children representing 23% of the weight versus adults), anti-leukotriene used, duration of intervention, methodological quality, and funding source. Significant group differences favouring inhaled corticosteroids were noted in most secondary outcomes including patients with at least one exacerbation requiring hospital admission (N = 2715 participants; RR 3.33; 95% CI 1.02 to 10.94), the change from baseline FEV1 (N = 7128 participants; mean group difference (MD) 110 mL, 95% CI 140 to 80) as well as other lung function parameters, asthma symptoms, nocturnal awakenings, rescue medication use, symptom-free days, the quality of life, parents’ and physicians’ satisfaction. Anti-leukotriene therapy was associated with increased risk of withdrawals due to poor asthma control (N = 7669 participants; RR 2.56; 95% CI 2.01 to 3.27). For every thirty one (95% CI 22 to 47) patients treated with anti-leukotrienes instead of inhaled corticosteroids, there was one additional withdrawal due to poor control. Risk of side effects was not significantly different between both groups. As monotherapy, inhaled corticosteroids display superior efficacy to anti-leukotrienes in adults and children with persistent asthma; the superiority is particularly marked in patients with moderate airway obstruction. On the basis of efficacy, the results support the current guidelines’ recommendation that inhaled corticosteroids remain the preferred monotherapy.