Gottlieb Jens, Szangolies Jennifer, Koehnlein Thomas, Golpon Heiko, Simon André, Welte Tobias
Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany.
Transplantation. 2008 Jan 15;85(1):36-41. doi: 10.1097/01.tp.0000295981.84633.bc.
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.
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 1 second [FEV1] 55+/-19%) were included. For treatment, 250 mg of oral azithromycin was administered three times per week.
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).
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.
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的一种有前景的选择。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。
在单一中心进行了一项观察性研究。纳入了81例成年LTx受者（单肺、双肺、联合及再次移植），其至少处于BOS 0p期（第1秒用力呼气容积[FEV1]平均为55±19%）。治疗时，每周口服250 mg阿奇霉素，每日3次。
81例患者中有24例（30%）在6个月后FEV1有所改善，其中22/24例在治疗3个月后即有改善。单因素分析显示，6个月时的反应者预处理支气管肺泡灌洗（BAL）中性粒细胞比例较高（51±29%对21±24%）。预处理BAL中<20%的临界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）病情进展。Cox回归分析确定，预处理时FEV1快速下降以及联合使用雷帕霉素哺乳动物靶点抑制剂是疾病进展（FEV1<90%基线）的阳性预测因素，联合使用质子泵抑制剂以及3个月时的治疗反应是阴性预测因素。
阿奇霉素可使相当一部分即使是患有长期BOS的患者的气流受限得到改善。大多数反应者在治疗3个月后即可确定。结果表明BAL中性粒细胞增多对治疗反应的预测价值以及预处理时FEV1的变化过程作为疾病进展的一个变量。对胃食管反流病的有益作用可能是一种作用机制。
