Effect of Azithromycin on Pulmonary Function in Patients With Cystic Fibrosis Uninfected With Pseudomonas aeruginosa A Randomized Controlled Trial
Effect of Azithromycin on Pulmonary Function in Patients With Cystic Fibrosis Uninfected With Pseudomonas aeruginosa A Randomized Controlled Trial
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DOI：
10.1001/jama.2010.563
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发表时间：
2010-05-05
影响因子：
120.7
通讯作者：
Ratjen, Felix
中科院分区：
文献类型：
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作者：
Saiman, Lisa;Anstead, Michael;Ratjen, Felix
背景阿奇霉素被推荐作为慢性铜绿假单胞菌感染的囊性纤维化（CF）患者的治疗方法，但没有足够的证据支持阿奇霉素在其他CF患者中的益处。目的确定阿奇霉素治疗是否能改善未感染铜绿假单胞菌的儿童CF患者的肺功能并减少肺恶化。2007年2月至2009年7月在美国和加拿大的40个CF护理中心进行了一项双盲安慰剂对照试验。在筛选的324名受试者中，260名受试者被随机分配并接受研究药物。入选标准包括年龄6 - 18岁，第一秒用力呼气量（FEV 1）至少为预测值的50%，呼吸道铜绿假单胞菌培养阴性至少1年。干预活性组（n=131）接受250 mg（体重18-35.9 kg）或500 mg（体重≥ 36 kg）阿奇霉素，每周3天（周一、周三和周五），共168天。安慰剂组（n=129）接受相同包装的安慰剂片剂在相同的schedule.Main结果测量主要结果是FEV 1的变化。探索性结局包括额外的肺功能终点、肺部急性加重、体重和身高变化、新使用抗生素和住院治疗。结果参与者的平均（SD）年龄为10.7（3.17）岁。阿奇霉素组基线和168天时的平均（SD）FEV 1分别为2.13（0.85）L和2.22（0.86）L，安慰剂组分别为2.12（0.85）L和2.20（0.88）L。阿奇霉素组和安慰剂组之间FEV 1变化的差异为0.02 L（95%置信区间[CI]，-0.05至0.08; P= 0.61）。探索性肺功能终点均无统计学显著性。阿奇霉素组和安慰剂组分别有21%和39%的患者发生肺部疾病加重。与安慰剂组受试者相比，阿奇霉素组受试者的急性加重减少50%（95%CI，31%-79%），体重增加0.58 kg（95%CI，0.14-1.02）。两组之间在身高、静脉或吸入抗生素的使用或住院方面没有显著差异。阿奇霉素组的参与者没有增加不良事件的风险，但咳嗽较少（-23%治疗差异; 95% CI，-33%至-11%）和排痰性咳嗽减少（-11%的治疗差异;结论在未感染铜绿假单胞菌的CF儿童和青少年中，阿奇霉素治疗24周并没有改善肺功能。
Context Azithromycin is recommended as therapy for cystic fibrosis (CF) patients with chronic Pseudomonas aeruginosa infection, but there has not been sufficient evidence to support the benefit of azithromycin in other patients with CF.Objective To determine if azithromycin treatment improves lung function and reduces pulmonary exacerbations in pediatric CF patients uninfected with P aeruginosa.Design, Setting, and Participants A multicenter, randomized, double-blind placebo-controlled trial was conducted from February 2007 to July 2009 at 40 CF care centers in the United States and Canada. Of the 324 participants screened, 260 were randomized and received study drug. Eligibility criteria included age of 6 to 18 years, a forced expiratory volume in the first second of expiration (FEV1) of at least 50% predicted, and negative respiratory tract cultures for P aeruginosa for at least 1 year. Randomization was stratified by age of 6 to 12 years vs 13 to 18 years and by CF center.Intervention The active group (n=131) received 250 mg (weight 18-35.9 kg) or 500 mg (weight >= 36 kg) of azithromycin 3 days per week (Monday, Wednesday, and Friday) for 168 days. The placebo group (n=129) received identically packaged placebo tablets on the same schedule.Main Outcome Measures The primary outcome was change in FEV1. Exploratory outcomes included additional pulmonary function end points, pulmonary exacerbations, changes in weight and height, new use of antibiotics, and hospitalizations. Changes in microbiology and adverse events were monitored.Results The mean (SD) age of participants was 10.7 (3.17) years. The mean (SD) FEV1 at baseline and 168 days were 2.13 (0.85) L and 2.22 (0.86) L for the azithromycin group and 2.12 (0.85) L and 2.20 (0.88) L for the placebo group. The difference in the change in FEV1 between the azithromycin and placebo groups was 0.02 L (95% confidence interval [CI], -0.05 to 0.08; P=.61). None of the exploratory pulmonary function end points were statistically significant. Pulmonary exacerbations occurred in 21% of the azithromycin group and 39% of the placebo group. Participants in the azithromycin group had a 50% reduction in exacerbations (95% CI, 31%-79%) and an increase in body weight of 0.58 kg (95% CI, 0.14-1.02) compared with placebo participants. There were no significant differences between groups in height, use of intravenous or inhaled antibiotics, or hospitalizations. Participants in the azithromycin group had no increased risk of adverse events, but had less cough (-23% treatment difference; 95% CI, -33% to -11%) and less productive cough (-11% treatment difference; 95% CI, -19% to -3%) compared with placebo participants.Conclusion In children and adolescents with CF uninfected with P aeruginosa, treatment with azithromycin for 24 weeks did not result in improved pulmonary function.