Elevated Levels of the Receptor for Advanced Glycation End Products, a Marker of Alveolar Epithelial Type I Cell Injury, Predict Impaired Alveolar Fluid Clearance in Isolated Perfused Human Lungs

Autor: Jae Won Lee, Carolyn S. Calfee, Raphael Briot, James A. Frank, Tokujiro Uchida, Michael A. Matthay
Rok vydání: 2009
Předmět:
Zdroj: Chest. 135:269-275
ISSN: 0012-3692
DOI: 10.1378/chest.08-0919
Popis: The scarcity of available grafts and the growing number of candidates waiting for lung transplantation have led to an increase of deaths in patients on waiting lists. Moreover, clinical criteria used to screen donor lungs for transplantation may be inadequate, resulting in the under-utilization of lungs for transplantation.1 Novel methods of selecting donor lungs are therefore urgently needed, particularly given recent trends in the utilization of lungs from marginal donors.2-4 An intact alveolar epithelial barrier with preserved alveolar fluid clearance (AFC) is associated with better clinical outcomes in patients with acute lung injury (ALI)5 and patients with post-transplant reperfusion pulmonary edema.6 Biomarkers that reflect alveolar epithelial injury may therefore be useful in selecting potentially viable lungs for donation. The receptor for advanced glycation end products (RAGE) is a recently described novel marker of alveolar type I epithelial cell injury with both prognostic and pathogenetic value in patients with ALI.7,8 In our recently developed ex vivo perfused human lung preparation, using human lungs declined for transplantation, we found that the airspace and perfusate levels of RAGE were elevated in donor lungs without measurable AFC (< 3%/h).9 However, the sample size for that study was small. Therefore, the primary objective of the present study was to prospectively determine if airspace or perfusate RAGE levels in potential donor lungs are associated with AFC rate. A secondary objective was to determine if levels of circulating von Willebrand Factor antigen (vWF:Ag), a previously identified biological marker of vascular endothelial injury, are associated with alveolar epithelial fluid transport.
Databáze: OpenAIRE