Azithromycin for prevention of exacerbations in severe asthma (AZISAST): a multicentre randomised double-blind placebo-controlled trial
Azithromycin for prevention of exacerbations in severe asthma (AZISAST): a multicentre randomised double-blind placebo-controlled trial
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DOI：
10.1136/thoraxjnl-2012-202698
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发表时间：
2013-04-01
期刊：
影响因子：
10
通讯作者：
Joos, Guy F. P.
中科院分区：
文献类型：
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作者：
Brusselle, Guy G.;VanderStichele, Christine;Joos, Guy F. P.
背景重度哮喘患者病情加重和下呼吸道感染的风险增加。重症哮喘是异质性的，包括嗜酸性和非嗜酸性(主要是中性粒细胞)表型。中性粒细胞呼吸道疾病的患者可能受益于大环内酯类药物。方法我们对易加重的严重哮喘患者进行了一项随机、双盲、安慰剂对照试验。受试者接受小剂量阿奇霉素(n=55)或安慰剂(n=54)，作为吸入皮质类固醇和长效β-受体激动剂联合治疗的补充治疗，为期6个月。主要结果是在26周的治疗阶段，严重恶化和需要使用抗生素治疗的下呼吸道感染的比率。结果阿奇霉素组和安慰剂组6个月内主要终点(PEP)发生率分别为0.75PEPS(95%可信区间0.55~1.01)和0.81PEPS(95%可信区间0.61~1.09PEPS)(P=0.682)。在根据炎症表型进行的预定义亚组分析中，在非嗜酸性重度哮喘(血嗜酸性粒细胞增多症)受试者中，阿奇霉素的PEP发生率显著低于安慰剂
Background Patients with severe asthma are at increased risk of exacerbations and lower respiratory tract infections (LRTI). Severe asthma is heterogeneous, encompassing eosinophilic and non-eosinophilic (mainly neutrophilic) phenotypes. Patients with neutropilic airway diseases may benefit from macrolides.Methods We performed a randomised double-blind placebo-controlled trial in subjects with exacerbation-prone severe asthma. Subjects received low-dose azithromycin (n=55) or placebo (n=54) as add-on treatment to combination therapy of inhaled corticosteroids and long-acting beta(2) agonists for 6 months. The primary outcome was the rate of severe exacerbations and LRTI requiring treatment with antibiotics during the 26-week treatment phase. Secondary efficacy outcomes included lung function and scores on the Asthma Control Questionnaire (ACQ) and Asthma Quality of Life Questionnaire (AQLQ).Results The rate of primary endpoints (PEPs) during 6 months was not significantly different between the two treatment groups: 0.75 PEPs (95% CI 0.55 to 1.01) per subject in the azithromycin group versus 0.81 PEPs (95% CI 0.61 to 1.09) in the placebo group (p=0.682). In a predefined subgroup analysis according to the inflammatory phenotype, azithromycin was associated with a significantly lower PEP rate than placebo in subjects with non-eosinophilic severe asthma (blood eosinophilia