Airway hypoxia in lung transplantation

Abstract

Lung transplantation is a life-saving operation for patients with advanced lung disease. Pulmonary allografts eventually fail because of infection, thromboembolism, malignancy, airway complications, and chronic rejection, otherwise known as chronic lung allograft dysfunction (CLAD). Emerging evidence suggests that a highly-compromised airway circulation contributes to the evolution of airway complications and CLAD. There are two significant causes of poor perfusion and airway hypoxia in lung transplantation: an abnormal bronchial circulation which causes airway complications and microvascular rejection which induces CLAD. At the time of transplantation, the bronchial artery circulation, a natural component of the airway circulatory anatomy, is not surgically connected, and bronchi distal to the anastomosis become hypoxic. Subsequently, the bronchial anastomosis is left to heal under ischemic conditions. Still later, the extant microvessels in transplant bronchi are subjected to alloimmune insults that can further negatively impact pulmonary function. This review describes how airway tissue hypoxia evolves in lung transplantation, why depriving oxygenation in the bronchi and more distal bronchioles contributes to disease pathology and what therapeutic interventions are currently emerging to address these vascular injuries. Improving anastomotic vascular healing at the time of transplantation and preventing microvascular loss during acute rejection episodes are two steps that could limit airway hypoxia and improve patient outcomes.

Keywords: anastomosis; hypoxia; hypoxia-inducible factors; lung transplantation; microvasculature.

Figure 1.. Airway hypoxia in lung transplantation: the bronchial anastomosis at the time of transplantation.

Airways are supplied with blood by a vascular plexus which receives blood from both bronchial and pulmonary circulatory systems. In the early post-transplant period, the anastomosis site is ischemic and hypoxic and becomes, over time, susceptible to airway complications.

Figure 2.. Airway hypoxia in lung transplantation: the airways during acute rejection episodes.

In the acute rejection phase, there is a loss of airway microvessels that may lead to the development of chronic rejection. The airway microvasculature is especially vulnerable during acute rejection and may be amenable to specific therapeutic interventions prior to airway remodeling in the post-ischemic and remodeling phases.