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Advances in Understanding Bronchiolitis Obliterans After Lung Transplantation

Stijn E. Verleden, PhD; Annelore Sacreas, MSc; Robin Vos, MD, PhD; Bart M. Vanaudenaerde, PhD; Geert M. Verleden, MD, PhD
Author and Funding Information

FUNDING/SUPPORT: Drs S. E. Verleden and Vos were sponsored by grants [FWO12G8715N, 1515816N and 1803516N] from the Research Foundation Flanders. Dr Vos was supported by a grant [KAN20141.5.139.14] from the FWO and the start fund of UZLeuven. Drs G. M. Verleden and Vanaudenaerde were supported by research funding [C24/15/030] from KULeuven.

Department of Clinical and Experimental Medicine, Lung Transplant Unit, KU Leuven, Leuven, Belgium

CORRESPONDENCE TO: Geert M. Verleden, MD, PhD, Department of Clinical and Experimental Medicine, Laboratory of Respiratory Diseases, Lung Transplantation Unit, KU Leuven, Herestraat 49, B-3000 Leuven, Belgium


Copyright 2016, American College of Chest Physicians. All Rights Reserved.


Chest. 2016;150(1):219-225. doi:10.1016/j.chest.2016.04.014
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Bronchiolitis obliterans syndrome (BOS) remains a major complication after lung transplantation, causing significant morbidity and mortality in a majority of recipients. BOS is believed to be the clinical correlate of chronic allograft dysfunction, and is defined as an obstructive pulmonary function defect in the absence of other identifiable causes, mostly not amenable to treatment. Recently, it has become clear that BOS is not the only form of chronic allograft dysfunction and that other clinical phenotypes exist; however, we focus exclusively on BOS. Radiologic findings typically demonstrate air trapping, mosaic attenuation, and hyperinflation. Pathologic examination reveals obliterative bronchiolitis lesions and a pure obliteration of the small airways (< 2 mm), with a relatively normal surrounding parenchyma. In this review, we highlight recent advances in diagnosis, pathologic examination, and risk factors, such as microbes, viruses, and antibodies. Although the pathophysiological mechanisms remain largely unknown, we review the role of the airway epithelium and inflammation and the various experimental animal models. We also clarify the clinical and therapeutic implications of these findings. Although significant progress has been made, the exact pathophysiological mechanisms and adequate therapy for posttransplantation BOS remain unknown, highlighting the need for further research to improve long-term posttransplantation BOS-free and overall survival.

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