Vanaudenaerde B M, Meyts I, Vos R, Geudens N, De Wever W, Verbeken E K, Van Raemdonck D E, Dupont L J, Verleden G M
Laboratory of Pneumology, Katholieke Universiteit Leuven, Leuven, Belgium.
Eur Respir J. 2008 Oct;32(4):832-43. doi: 10.1183/09031936.00134307.
Bronchiolitis obliterans syndrome (BOS) is the most important cause of late mortality following lung transplantation, resulting in major morbidity and a huge burden on healthcare resources. Treatment options are limited, resulting in a mere stabilisation of the lung function decline. Recent introduction of the macrolide antibiotic azithromycin raised new hope after demonstrating lung function improvement in subsets of patients. The present study aimed to provide an overview of the clinical effects on azithromycin in the setting of BOS after lung transplantation, with special emphasis on the anti-inflammatory actions. Moreover, the authors proposed a new frame of thinking centred on a dichotomy in the pathogenesis and clinical phenotype of BOS. Subsets of BOS patients were identified who do or do not respond to azithromycin (regarding forced expiratory volume in one second (FEV(1)), bronchoalveolar lavage (BAL) neutrophilia/interleukin-8). These observations have shed new light on the current belief that BOS represents a homogenous clinical entity in which the neutrophil is the main culprit. Recent clinical observations, supported by research findings, have revealed a dichotomy in the clinical spectrum of BOS with neutrophilic (partially) reversible allograft dysfunction (responding to azithromycin) and fibroproliferative BOS (not responding to azithromycin). This concept is reinforced by unique data obtained in BOS patients, consisting of histology specimens, physical and radiological examination, FEV(1 )and BAL examination. The acceptance of this dichotomy can improve understanding of the heterogeneous pathological condition that constitutes bronchiolitis obliterans syndrome, thus encouraging a more accurate diagnosis and, ultimately, better tailored treatment for each bronchiolitis obliterans syndrome patient.
闭塞性细支气管炎综合征（BOS）是肺移植术后晚期死亡的最重要原因，会导致严重的发病率并给医疗资源带来巨大负担。治疗选择有限，只能使肺功能下降仅得到稳定。大环内酯类抗生素阿奇霉素的近期应用在部分患者中显示出肺功能改善后带来了新的希望。本研究旨在概述阿奇霉素在肺移植后BOS情况下的临床效果，特别强调其抗炎作用。此外，作者提出了一种新的思维框架，其核心是BOS发病机制和临床表型的二分法。确定了对阿奇霉素有或无反应的BOS患者亚组（根据一秒用力呼气容积（FEV₁）、支气管肺泡灌洗（BAL）中性粒细胞增多/白细胞介素-8）。这些观察结果为目前认为BOS是一种以中性粒细胞为主要罪魁祸首的同质临床实体的观点提供了新的线索。近期的临床观察结果，在研究发现的支持下，揭示了BOS临床谱中的二分法，即嗜中性粒细胞性（部分）可逆性同种异体移植功能障碍（对阿奇霉素有反应）和纤维增殖性BOS（对阿奇霉素无反应）。BOS患者获得的独特数据，包括组织学标本、体格检查和影像学检查、FEV₁和BAL检查，强化了这一概念。接受这种二分法可以增进对构成闭塞性细支气管炎综合征的异质性病理状况的理解，从而鼓励更准确的诊断，并最终为每个闭塞性细支气管炎综合征患者提供更有针对性的治疗。
