Azithromycin reduces airway neutrophilia and interleukin-8 in patients with bronchiolitis obliterans syndrome
Azithromycin reduces airway neutrophilia and interleukin-8 in patients with bronchiolitis obliterans syndrome
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DOI：
10.1164/rccm.200601-071oc
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发表时间：
2006-09-01
影响因子：
24.7
通讯作者：
Van Raemdonck, Dirk E.
中科院分区：
文献类型：
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作者：
Verleden, Geert M.;Vanaudenaerde, Bart M.;Van Raemdonck, Dirk E.
理由：闭塞性细支气管炎综合征（BOS）仍然是肺移植术后死亡的主要原因。治疗是困难的，尽管阿奇霉素最近被证明可以改善FEV1。确切的作用机制尚不清楚。假设：(1)阿奇霉素降低气道中性粒细胞和白细胞介素(IL)-8;(2)气道中性粒细胞可预测FEV1的改善。方法：14例BOS （BOS 0-p ~ BOS 3）肺移植患者在目前免疫抑制治疗的基础上加用阿奇霉素治疗。给予阿奇霉素治疗前和治疗后3个月，行支气管镜支气管肺泡灌洗（BAL）观察细胞分化，并测定IL-8和IL-17 mRNA比值。结果：FEV由2.36 （+/- 0.82 L）上升至2.67 L (+/- 0.85 L, p = 0.007)， BAL中性粒细胞比例由35.1%（+/- 35.7%）下降至5.7% （+/- 6.5%,p = 0.0024）。阿奇霉素有应答者6例（FEV1升高10%），无应答者8例。通过分类单变量线性回归分析，反应者和无反应者之间的主要显著差异特征是初始BAL中性粒细胞（p < 0.0001）、IL-8 mRNA比值（p = 0.0009）和术后开始使用阿奇霉素的天数（p = 0.036）。3个月后BAL中性粒细胞初始百分比与FEV变化有显著相关性（r = 0.79, p = 0.0019）。结论：阿奇霉素可显著降低BOS患者气道中性粒细胞和IL-8 mRNA的表达。与无应答者相比，应答者有明显更高的BAL中性粒细胞和IL-8，并且在移植后较早开始治疗。BAIL嗜中性粒细胞可作为对阿奇霉素反应FEV的预测因子。
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 FEV1. 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 FEV1.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, 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 FEV1 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, 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. BAIL neutrophilia can be used as a predictor for the FEV, response to azithromycin.