RATIONALE:Bronchiolitis obliterans syndrome (BOS) remains the leading cause of death after lung transplantation. Treatment is difficult, although azithromycin has recently been shown to improve FEV(1). The exact mechanism of action is unclear. HYPOTHESES:(1) Azithromycin reduces airway neutrophilia and interleukin (IL)-8 and (2) airway neutrophilia predicts the improvement in FEV(1). METHODS:Fourteen lung transplant patients with BOS (between BOS 0-p and BOS 3) were treated with azithromycin, in addition to their current immunosuppressive treatment. Before and 3 mo after azithromycin was introduced, bronchoscopy with bronchoalveolar lavage (BAL) was performed for cell differentiation and to measure IL-8 and IL-17 mRNA ratios. RESULTS:The FEV(1) increased from 2.36 (+/- 0.82 L) to 2.67 L (+/- 0.85 L; p = 0.007), whereas the percentage of BAL neutrophilia decreased from 35.1 (+/- 35.7%) to 5.7% (+/- 6.5%; p = 0.0024). There were six responders to azithromycin (with an FEV(1) increase of > 10%) and eight nonresponders. Using categorical univariate linear regression analysis, the main significant differences in characteristics between responders and nonresponders were the initial BAL neutrophilia (p < 0.0001), IL-8 mRNA ratio (p = 0.0009), and the postoperative day at which azithromycin was started (p = 0.036). There was a significant correlation between the initial percentage of BAL neutrophilia and the changes in FEV(1) after 3 mo (r = 0.79, p = 0.0019). CONCLUSION:Azithromycin significantly reduces airway neutrophilia and IL-8 mRNA in patients with BOS. Responders have a significantly higher BAL neutrophilia and IL-8 compared with nonresponders and had commenced treatment earlier after transplantation. BAL neutrophilia can be used as a predictor for the FEV(1) response to azithromycin.

译文

理由:闭塞性细支气管炎综合征(BOS)仍然是肺移植后死亡的主要原因。尽管最近已证明阿奇霉素可改善FEV(1),但治疗困难。确切的作用机理尚不清楚。
假设:(1)阿奇霉素可减少气道中性粒细胞增多和白介素(IL)-8,(2)气道中性粒细胞减少可预测FEV(1)。
方法:除了目前的免疫抑制治疗外,还用阿奇霉素治疗了14例BOS 0-p和BOS 3之间的BOS肺移植患者。在引入阿奇霉素之前和之后3个月,用支气管肺泡灌洗液(BAL)进行支气管镜检查以区分细胞并测量IL-8和IL-17 mRNA的比例。
结果:FEV(1)从2.36(/-0.82 L)增加到2.67 L(/-0.85 L; p = 0.007),而BAL中性粒细胞的百分比从35.1(/-35.7%)降低到5.7%(/ -6.5%; p = 0.0024)。阿奇霉素有6名反应者(FEV(1)升高> 10%)和8名无反应者。使用分类单变量线性回归分析,反应者和非反应者之间的主要特征差异是初始BAL中性粒细胞增多(p <0.0001),IL-8 mRNA比(p = 0.0009)和阿奇霉素开始的术后天数(p = 0.036)。 BAL中性粒细胞的初始百分比与3个月后FEV(1)的变化之间存在显着相关性(r = 0.79,p = 0.0019)。
结论:阿奇霉素可显着降低BOS患者气道中性粒细胞和IL-8 mRNA的表达。与无反应者相比,有反应者的BAL中性粒细胞和IL-8明显更高,并且在移植后更早开始治疗。 BAL中性粒细胞增多症可用作FEV(1)对阿奇霉素反应的预测因子。

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