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根据发表于12月1日版美国呼吸暨重症照护期刊上的随机双盲安慰剂控制研究结果，长期使用红霉素(erythromycin)可以有效减少慢性阻塞性肺部疾病(chronic obstructive pulmonary disease，COPD)的恶化。
千里达West Indies大学的Terence A. R. Seemungal等人写道，频繁的COPD恶化是引起住院与死亡的重要原因，且与增加呼吸道发炎有关。Macrolides有呼吸道抗发炎作用，可减少COPD恶化的发生率。
本研究的目标是检视长期使用Macrolide是否可降低COPD恶化的频率；研究人员将COPD门诊病患随机指派接受红霉素250 mg或者安慰剂，每天两次，为期12个月；主要研究终点是中度和/或严重恶化的人数，定义是那些使用全身性类固醇或抗生素或是住院的恶化病例。
在这109名随机选取的门诊病患中，69(63%)人是男性，52 (48%)人目前有抽烟习惯，平均年纪是67.2 ± 8.6岁，平均一秒钟最大呼气量(FEV1)是1.32 ± 0.53，平均FEV1%预测值为50% ± 18%；在参与试验前一年，38(35%)名病患有至少三次复发，治疗组之间没有差异。
在研究期间，206名中度到重度恶化者中，125人属于安慰剂组，有10名病患从安慰剂组退出，从Macrolide组退出的有9人；根据一般线性模式，接受Macrolide者，相较于接受安慰剂者，其恶化比率为0.648 (95% 信心区间，0.489 – 0.859; P = .003)；相较于安慰剂组的病患，Macrolide的恶化期间比较短。
在这一年的研究中，Macrolide和安慰剂组的稳定期FEV1、痰中的介白质6 (IL-6)、 IL-8、骨髓过氧化酶(Myeloperoxidase)、菌落(bacterial flora)、血清C反应蛋白质或者血清IL-6、或者这些参数在第一次恶化时与开始时的改变并无差异。
研究作者写道，相较于安慰剂，Macrolide治疗与显著降低恶化有关，可以有效减少此类病患的过度疾病负担；在一年的研究期间，治疗的耐受性良好。
本研究的研究限制包括痰中发炎标记的明显变异、可能高估顺从性、无法侦测研究组之间的发炎标记和抗生素的差异，且缺乏生活品质资料； 在编辑评论中，荣民医学中心和明尼苏达大学的Ken M. Kunisaki医师和Dennis E. Niewoehner医师指出，需要确认研究发现。
Kunisaki医师和Niewoehner医师写道，假设Macrolide治疗以减少恶化是唯一的临床好处，想必只能用于少数恶化风险最高的COPD病患，但全球可能有数百万或上千万的病患。
他们结论表示，在此状况中，实际广泛出现的Macrolides细菌抗药性是注定的，因此需要减少此类药物的抗菌性；然而，权衡利益与伤害之间的两难，使得目前尚无明确答案。
英国肺脏基金会支持本研究。研究作者与 Kunisaki博士宣称没有相关资金上的往来。Niewoehner医师报告与Boehringer Ingelheim、Pfizer、Adams Respiratory Therapeutics、AstraZeneca、Schering Plough、Sanofi Aventis、Sepracor和GlaxoSmithKline等药厂有资金上的往来。
Long-Term Macrolide Use May Help Reduce COPD Exacerbations
By Laurie Barclay, MD
Medscape Medical News
Long-term use of erythromycin was effective in reducing exacerbations of chronic obstructive pulmonary disease (COPD), according to the results of a randomized, double-blind, placebo-controlled study reported in the December 1 issue of the American Journal of Respiratory and Critical Care Medicine.
"Frequent exacerbations are a major cause of hospital admission and mortality and are associated with increased airway inflammation," write Terence A. R. Seemungal, from University of the West Indies in Trinidad and Tobago, and colleagues. "Macrolides have airway anti-inflammatory actions and may reduce the incidence of COPD exacerbations."
The goal of this study was to examine whether chronic macrolide therapy reduces the frequency of COPD exacerbations. Outpatients with COPD were randomly assigned to receive either erythromycin 250 mg or placebo twice daily for a 12-month period. The main study endpoint was the number of moderate and/or severe exacerbations, defined as those exacerbations that were treated with systemic steroids or antibiotics or that led to hospitalizations.
Of 109 randomized outpatients, 69 (63%) were men, and 52 (48%) were current smokers. Mean age was 67.2 ± 8.6 years, mean forced expiratory volume in 1 second (FEV1) was 1.32 ± 0.53, and mean FEV1% predicted was 50% ± 18%. In the year before recruitment, 38 patients (35%) had at least 3 exacerbations, with no differences between treatment groups.
Of 206 moderate to severe exacerbations that occurred during the study, 125 were in the placebo group. Ten patients withdrew from the placebo group and 9 from the macrolide group. The rate ratio for exacerbations for the patients receiving macrolide vs the patients receiving placebo was 0.648 (95% confidence interval, 0.489 – 0.859; P = .003) based on generalized linear modeling. Compared with patients in the placebo group, those in the macrolide group had a shorter duration of exacerbations.
The macrolide and placebo groups did not differ in stable FEV1, sputum interleukin 6 (IL-6), IL-8, myeloperoxidase, bacterial flora, serum C-reactive protein, or serum IL-6 or in changes in these parameters from baseline to the first exacerbation during the 1-year study.
"Macrolide therapy was associated with a significant reduction in exacerbations compared with placebo and may be useful in decreasing the excessive disease burden in this important patient population," the study authors write. "The treatment was well tolerated over the 1-year study period."
Limitations of this study include significant variability of sputum inflammatory markers, possible overestimate of compliance, insufficient power to detect a difference between study groups in terms of inflammatory markers and bacterial agents, and lack of quality-of-life data.
In an accompanying editorial, Ken M. Kunisaki, MD, and Dennis E. Niewoehner, MD, from the Veterans Affairs Medical Center and the University of Minnesota in Minneapolis, note that the study findings require confirmation.
"Macrolide therapy for reduction of exacerbations, assuming that is the only clinical benefit, presumably would be indicated for only a small proportion of patients with COPD at highest risk for exacerbations," Dr. Kunisaki and Dr. Niewoehner write. "But this might still include millions or even tens of millions of patients on a global scale."
They conclude, "In this scenario, substantial, widespread emergence of macrolide bacterial resistance is virtually foreordained, with attendant reduction in the antimicrobial usefulness of this drug class. Balancing benefit against harm could pose a dilemma for which there might be no clear answers."
The British Lung Foundation supported this study. The study authors and Dr. Kunisaki have disclosed no relevant financial relationships. Dr. Niewoehner reports various financial relationships with Boehringer Ingelheim, Pfizer, Adams Respiratory Therapeutics, AstraZeneca, Schering Plough, Sanofi Aventis, Sepracor, and GlaxoSmithKline.
Am J Respir Crit Care Med. 2008;178:1098–1099, 1139–1147.