The contribution of airway ischemia and vascular remodelling to the pathophysiology of bronchiolitis obliterans syndrome and chronic lung allograft dysfunction

Abstract

Purpose of review: Chronic allograft dysfunction continues to limit the enduring success of lung transplantation. Increasingly it is recognized that events very early post-transplant such as primary graft dysfunction can be linked to poor clinical outcomes at much later time points. In this article we review a number of the different processes that predispose the allograft to ischemia early post-transplant and explore how these events may contribute to obliterative bronchiolitis, the histological correlate of chronic lung allograft dysfunction.

Recent findings: Allograft ischemia may arise during explantation (warm ischemia), at implantation (in the absence of bronchial arterial reanastomosis) or at later time points (small airway microvascular damage). We describe how allograft ischemia may result in a hypoxic inflammatory milieu within the lung allograft that is conducive to vascular remodelling and angiogenesis.

Summary: Whilst the published literature for vascular remodelling in post-transplant obliterative bronchiolitis is not as extensive as that for asthma, a disease also characterized by airway pathology, there are clear parallels and shared pathophysiological pathways between the two diseases. An understanding of the complex interaction between ischemia, vascular remodelling and chronic lung allograft dysfunction may lead to the future development of therapeutic strategies that can unravel this association.