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.
Conflict of interest statement
Declaration of Interest: Mark Nicolls, is an inventor on a patent that is directly germane to the ideas that are proposed in this review. U.S. Application Serial No. 14/653,245 Entitled: Iron Chelators and Use Thereof for Reducing Transplant Failure During Rejection Episodes First Named Inventor: Nicolls, Mark R. Your Ref.: S11–300; C11657_P11657–03 Our Ref.: STAN-891 Patent No. 9763899. Although, only in its incipient stages, a company, which Mark Nicolls is involved with, is being formed around the concept of using iron chelators in lung transplant recipients, which is a concept referred to multiple times as a promising approach within the manuscript.
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