Long term azithromycin in children with cystic fibrosis: a randomised, placebo-controlled crossover trial
Long term azithromycin in children with cystic fibrosis: a randomised, placebo-controlled crossover trial
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DOI：
10.1016/s0140-6736(02)11081-6
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发表时间：
2002-09-28
期刊：
影响因子：
168.9
通讯作者：
Rosenthal, M
中科院分区：
文献类型：
--
作者：
Equi, A;Balfour-Lynn, IM;Rosenthal, M
大环内酯类抗生素阿奇霉素具有抗炎特性，可能对囊性纤维化有益。由于开放的试点研究的结果似乎显示临床benefit，我们进行了正式trial.Method 41囊性纤维化，年龄8-18岁，并与中位数用力呼气容积在1秒（FEV 1）的61%（范围33-80%）参加了一项为期15个月的随机双盲，安慰剂对照的交叉试验。他们接受阿奇霉素（体重小于或等于40 kg：每日250 mg，>40 kg：每日500 mg）或安慰剂治疗6个月。洗脱2个月后，交叉治疗。主要结果是阿奇霉素和安慰剂治疗期间FEV 1的中位相对差异。痰培养、痰白细胞介素8和中性粒细胞弹性蛋白酶、运动试验、生活质量、抗生素使用和肺部恶化率是次要结局指标。通过纯音测听和肝功能检查评估副作用。结果阿奇霉素和安慰剂之间FEV 1的中位数相对差异为5.4%（95%CI 0.8-10.5）。41例患者中有13例改善超过13%，5例恶化超过13%（p=0.059）。用力肺活量和呼气中期流量总体上没有显著变化。41名患者中有17名服用阿奇霉素的患者比服用安慰剂的患者少24个口服抗生素疗程，5名患者多6个疗程（p=0.005）。痰菌密度、炎症标志物、运动耐量和主观幸福感没有变化。没有明显的副作用。解释阿奇霉素4-6个月的试验是合理的囊性纤维化儿童谁不响应常规治疗。其作用机制尚不清楚。
Background The macrolide antibiotic azithromycin has anti-inflammatory properties potentially beneficial in cystic fibrosis. Since findings of open pilot studies seemed to show clinical benefit, we undertook a formal trial.Method 41 children with cystic fibrosis, aged 8-18 years, and with a median forced expiratory volume in 1 s (FEV1) of 61% (range 33-80%) participated in a 15-month randomised double-blind, placebo-controlled crossover trial. They received either azithromycin (bodyweight less than or equal to40 kg: 250 mg daily, >40 kg: 500 mg daily) or placebo for 6 months. After 2 months of washout, the treatments were crossed over. The primary outcome was median relative difference in FEV1 between azithromycin and placebo treatment periods. Sputum cultures, sputum interleukin 8 and neutrophil elastase, exercise testing, quality of life, antibiotic use, and pulmonary exacerbation rates were secondary outcome measures. Side-effects were assessed by pure tone audiometry and liver function tests. Analysis was by intention-to-treat.Findings Median relative difference in FEV1 between azithromycin and placebo was 5.4% (95% CI 0.8-10.5). 13 of 41 patients improved by more than 13% and five of 41 deteriorated by more than 13% (p=0.059). Forced vital capacity and mid-expiratory flow did not significantly change overall. 17 of 41 patients had 24 fewer oral antibiotic courses when on azithromycin than when taking placebo, and five had six extra courses (p=0.005). Sputum bacterial densities, inflammatory markers, exercise tolerance, and subjective well-being did not change. There were no noticeable side-effects.Interpretation A 4-6-month trial of azithromycin is justified in children with cystic fibrosis who do not respond to conventional treatment. The mechanism of action remains unknown.