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A dichotomy in bronchiolitis obliterans syndrome after lung transplantation revealed by azithromycin therapy

Laboratories of ¹ Pneumology, and ² Experimental Thoracic Surgery, Katholieke Universiteit Leuven, Depts of ³ Paediatrics, ⁴ Radiology, ⁵ Histology, ⁶ Thoracic Surgery, and ⁸ Respiratory Disease, and ⁷ Lung Transplantation Unit, University Hospital Gasthuisberg, Leuven, Belgium.

CORRESPONDENCE: G. M. Verleden, Dept of Respiratory Disease and Lung Transplantation Unit, University Hospital Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium. Fax: 32 16346803. E-mail: geert.verleden{at}uz.kuleuven.be

Keywords: Azithromycin, bronchiolitis obliterans syndrome, dichotomy, lung transplantation, neutrophils, phenotypes

Received: October 12, 2007
Accepted March 27, 2008

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 (FEV₁), 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, FEV₁ 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.

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