Azithromycin for prevention of exacerbations of COPD.
Azithromycin for prevention of exacerbations of COPD.
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DOI：
10.1056/nejmoa1104623
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发表时间：
2011-08-25
期刊：
影响因子：
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通讯作者：
COPD Clinical Research Network
中科院分区：
文献类型：
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作者：
Albert RK;Connett J;Bailey WC;Casaburi R;Cooper JA Jr;Criner GJ;Curtis JL;Dransfield MT;Han MK;Lazarus SC;Make B;Marchetti N;Martinez FJ;Madinger NE;McEvoy C;Niewoehner DE;Porsasz J;Price CS;Reilly J;Scanlon PD;Sciurba FC;Scharf SM;Washko GR;Woodruff PG;Anthonisen NR;COPD Clinical Research Network
急性加重对慢性阻塞性肺疾病(COPD)患者造成不利影响。大环内酯类抗生素使患有各种炎症性呼吸道疾病的患者受益。我们进行了一项随机试验，以确定阿奇霉素是否降低了COPD患者的恶化频率，这些患者病情恶化的风险增加，但没有听力障碍、静息性心动过速或校正的QT间期明显延长的风险。共有1577名受试者被筛选；1142名(72%)被随机分配接受阿奇霉素，每日剂量为250毫克(570名参与者)，或安慰剂(572名参与者)，在日常护理的基础上接受为期1年的治疗。阿奇霉素组1年随访率为%，安慰剂组为90%。在接受阿奇霉素治疗的参与者中，首次恶化的中位时间为266天(95%可信区间，227至313)，而在接受安慰剂的参与者中，中位时间为174天(95%可信区间，143至215)(P<；0.001)。阿奇霉素组的急性加重频率为1.48次/病人年，而安慰剂组为1.83次/病人年(P=0.01)；阿奇霉素组每病人年急性加重的风险比为0.73(95%可信区间为0.63；P<；0.001)。在圣乔治呼吸问卷上的得分(从0.004到100分，分数越低，表明功能更好)，阿奇霉素组比安慰剂组改善得更多(平均[±SD]下降2.8vs.0.6±11.4vs.0.6±11.4，P=0.004)；超过−4单位的最小临床重要差值的参与者比例在阿奇霉素组为43%，而安慰剂组为36%(P=0.03)。阿奇霉素组的听力下降比安慰剂组更常见(25%比20%，P=0.04)。在选定的COPD受试者中，每天服用阿奇霉素1年，在常规治疗的基础上，可以减少病情恶化的频率，改善生活质量，但会导致一小部分受试者听力下降。尽管这种干预可能会改变微生物的耐药性模式，但这种改变的效果尚不清楚。(由美国国立卫生研究院资助；ClinicalTrials.gov编号，NCT00325897。)
Acute exacerbations adversely affect patients with chronic obstructive pulmonary disease (COPD). Macrolide antibiotics benefit patients with a variety of inflammatory airway diseases. We performed a randomized trial to determine whether azithromycin decreased the frequency of exacerbations in participants with COPD who had an increased risk of exacerbations but no hearing impairment, resting tachycardia, or apparent risk of prolongation of the corrected QT interval. A total of 1577 subjects were screened; 1142 (72%) were randomly assigned to receive azithromycin, at a dose of 250 mg daily (570 participants), or placebo (572 participants) for 1 year in addition to their usual care. The rate of 1-year follow-up was 89% in the azithromycin group and 90% in the placebo group. The median time to the first exacerbation was 266 days (95% confidence interval [CI], 227 to 313) among participants receiving azithromycin, as compared with 174 days (95% CI, 143 to 215) among participants receiving placebo (P<0.001). The frequency of exacerbations was 1.48 exacerbations per patient-year in the azithromycin group, as compared with 1.83 per patient-year in the placebo group (P=0.01), and the hazard ratio for having an acute exacerbation of COPD per patient-year in the azithromycin group was 0.73 (95% CI, 0.63 to 0.84; P<0.001). The scores on the St. George’s Respiratory Questionnaire (on a scale of 0 to 100, with lower scores indicating better functioning) improved more in the azithromycin group than in the placebo group (a mean [±SD] decrease of 2.8±12.8 vs. 0.6±11.4, P=0.004); the percentage of participants with more than the minimal clinically important difference of −4 units was 43% in the azithromycin group, as compared with 36% in the placebo group (P=0.03). Hearing decrements were more common in the azithromycin group than in the placebo group (25% vs. 20%, P=0.04). Among selected subjects with COPD, azithromycin taken daily for 1 year, when added to usual treatment, decreased the frequency of exacerbations and improved quality of life but caused hearing decrements in a small percentage of subjects. Although this intervention could change microbial resistance patterns, the effect of this change is not known. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00325897.)