Long-term azithromycin for bronchiolitis obliterans syndrome after lung transplantation
Long-term azithromycin for bronchiolitis obliterans syndrome after lung transplantation
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DOI：
10.1097/01.tp.0000295981.84633.bc
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发表时间：
2008-01-15
期刊：
影响因子：
6.2
通讯作者：
Welte, Tobias
中科院分区：
文献类型：
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作者：
Gottlieb, Jens;Szangolies, Jennifer;Welte, Tobias
背景闭塞性细支气管炎综合征（BOS）是肺移植（LTx）后发病和死亡的主要原因。大环内酯类药物是治疗BOS的一种有前途的选择。本研究的目的是确定阿奇霉素治疗BOS患者的长期结果。评估了预测治疗反应的变量。在单中心进行了一项观察性研究。纳入了81例至少BOS 0 p期（1秒内平均用力呼气量[FEV 1] 55 +/- 19%）的成人LTx接受者（单次、双次、联合和再次）。治疗时，口服阿奇霉素250 mg，每周3次。81例患者中有24例（30%）在治疗6个月后显示FEV 1改善，22/24例在治疗3个月后已改善。通过单变量分析，6个月时的应答者具有较高的治疗前支气管肺泡灌洗（BAL）中性粒细胞（51 +/- 29 vs. 21 +/- 24%）。治疗前BAL中< 20%的截止值对治疗反应的阴性预测值为0.91。33例患者（40%）在随访期间（491 ± 165天）显示疾病进展。考克斯回归分析确定了治疗前FEV 1快速下降和哺乳动物雷帕霉素靶点抑制剂联合用药作为阳性预测因子，质子泵抑制剂联合用药和3个月时的治疗反应作为疾病进展的阴性预测因子（FEV 1 < 90%基线）。阿奇霉素可以改善大部分长期存在BOS的患者的气流限制。大多数应答者在治疗3个月后确定。结果表明，BAL嗜中性粒细胞对治疗反应的预测价值和治疗前病程的FEV 1作为一个变量的疾病进展。对胃食管反流病的有益作用可能是一种作用机制。
Background. Bronchiolitis obliterans syndrome (BOS) is a major cause of morbidity and mortality after lung transplantation (LTx). Macrolides are a promising treatment option for BOS. The objective of this study was to determine long-term results of azithromycin treatment in patients with BOS. Variables to predict treatment response were evaluated.Methods. An observational study in a single center was performed. Eighty-one adult LTx-recipients (single, double, combined, and re-do) with at least BOS stage 0p (mean forced expired volume in I second [FEV1] 55 +/- 19%) were included. For treatment, 250 mg of oral azithromycin was administered three times per week.Results. Twenty-four of 81 (30%) patients showed improvement in FEV1 after 6 months, 22/24 already after 3 months of treatment. By univariate analysis, responders at 6 months had higher pretreatment bronchoalveolar lavage (BAL) neutrophils (51 +/- 29 vs. 21 +/- 24%). A cutoff value of < 20% in pretreatment BAL had a negative predictive value of 0.91 for treatment response. Thirty-three patients (40%) showed disease progression during follow-up (491 +/- 165 days). Cox regression analysis identified a rapid pretreatment decline in FEV1 and comedication of an mammalian target of rapamycin inhibitor as positive predictors and proton pump inhibitor comedication and a treatment response at 3 months as negative predictors for disease progression (FEV1 < 90% baseline).Conclusions. Azithromycin can improve airflow limitation in a significant proportion of patients with even long-standing BOS. The majority of responders were identified after 3 months of treatment. Results indicate the predictive value of BAL neutrophilia for treatment response and pretreatment course of FEV1 as a variable for disease progression. Beneficial effects on gastroesophageal reflux disease may be a mechanism of action.