Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
Thorax. 2013 Apr;68(4):322-9. doi: 10.1136/thoraxjnl-2012-202698. Epub 2013 Jan 3.
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.
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 β2 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).
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 ≤200/µl): 0.44 PEPs (95% CI 0.25 to 0.78) versus 1.03 PEPs (95% CI 0.72 to 1.48) (p=0.013). Azithromycin significantly improved the AQLQ score but there were no significant between-group differences in the ACQ score or lung function. Azithromycin was well tolerated, but was associated with increased oropharyngeal carriage of macrolide-resistant streptococci.
Azithromycin did not reduce the rate of severe exacerbations and LRTI in patients with severe asthma. However, the significant reduction in the PEP rate in azithromycin-treated patients with non-eosinophilic severe asthma warrants further study. CLINICALTRIALS.GOV NUMBER: NCT00760838.
患有严重哮喘的患者发生加重和下呼吸道感染（LRTI）的风险增加。严重哮喘是异质性的，包括嗜酸性粒细胞和非嗜酸性粒细胞（主要是中性粒细胞）表型。患有中性粒细胞气道疾病的患者可能受益于大环内酯类药物。
我们在易发生加重的严重哮喘患者中进行了一项随机、双盲、安慰剂对照试验。患者接受低剂量阿奇霉素（n=55）或安慰剂（n=54）作为吸入皮质激素和长效β2 激动剂联合治疗的附加治疗，治疗 6 个月。主要结局是在 26 周治疗期间需要抗生素治疗的严重加重和 LRTI 的发生率。次要疗效结局包括肺功能和哮喘控制问卷（ACQ）和哮喘生活质量问卷（AQLQ）评分。
两组治疗 6 个月时主要终点（PEP）发生率无显著差异：阿奇霉素组每个患者发生 0.75 次 PEP（95%CI 0.55 至 1.01），安慰剂组发生 0.81 次 PEP（95%CI 0.61 至 1.09）（p=0.682）。根据炎症表型进行的预设亚组分析中，与安慰剂相比，阿奇霉素与非嗜酸性粒细胞性严重哮喘（血嗜酸性粒细胞计数≤200/µl）患者的 PEP 率显著降低：0.44 次 PEP（95%CI 0.25 至 0.78）与 1.03 次 PEP（95%CI 0.72 至 1.48）（p=0.013）。阿奇霉素显著改善了 AQLQ 评分，但两组间 ACQ 评分或肺功能无显著差异。阿奇霉素耐受性良好，但与大环内酯类耐药链球菌的口咽部携带增加有关。
阿奇霉素不能降低严重哮喘患者严重加重和 LRTI 的发生率。然而，阿奇霉素治疗非嗜酸性粒细胞性严重哮喘患者 PEP 率的显著降低值得进一步研究。临床试验注册编号：NCT00760838。
