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.
BACKGROUND
Although alveolar epithelial injury is a major determinant of outcome in patients with acute lung injury, there is no reliable biological marker of alveolar epithelial injury. The primary objective was to determine whether elevated levels of the receptor for advanced glycation end products (RAGE), a marker of alveolar epithelial injury, reflect impaired alveolar fluid clearance (AFC) in an ex vivo perfused human lung preparation. A second objective was to determine whether levels of a marker of endothelial injury, von Willebrand factor antigen (vWF:Ag), are associated with impaired AFC.


METHODS
Human lungs (N = 30) declined for transplantation by the California Transplant Donor Network were perfused at a constant pulmonary artery pressure of 12 mm Hg. Following rewarming to 36 degrees C, the lungs were inflated with a continuous positive airway pressure of 10 cm H(2)O. RAGE and vWF:Ag levels and AFC rates were then measured.


RESULTS
The rate of AFC was inversely correlated with RAGE levels in the alveolar fluid (p < 0.005). Similarly, the concentration of RAGE in the alveolar fluid was significantly higher in lungs with submaximal AFC, defined in a prespecified analysis as <or= 14%/h, when compared with lungs with preserved AFC (median 0.82 vs 0.43 microg/mL; p < 0.05). In contrast, vWF:Ag levels did not correlate with the rate of AFC.


CONCLUSIONS
RAGE may be a useful biological marker of alveolar epithelial injury and impaired AFC in donor lungs prior to transplant and perhaps in patients with acute lung injury.
Briot
Raphael
R
Cardiovascular Research Institute, University of California, San Francisco, CA.
Frank
James A
JA
Department of Medicine, University of California, San Francisco, CA.
Uchida
Tokujiro
T
Tokyo Medical and Dental University, Department of Anesthesiology, Tokyo, Japan.
Lee
Jae W
JW
Department of Anesthesia, University of California, San Francisco, CA.
Calfee
Carolyn S
CS
Department of Medicine, University of California, San Francisco, CA.
Matthay
Michael A
MA
Department of Medicine, University of California, San Francisco, CA. Electronic address: michael.matthay@ucsf.edu.
D055371:Acute Lung Injury / Q000378:metabolism* / Q000473:pathology*; D015415:Biomarkers / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004797:Enzyme-Linked Immunosorbent Assay; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D016014:Linear Models; D008168:Lung / Q000473:pathology; D016040:Lung Transplantation; D010477:Perfusion; D011237:Predictive Value of Tests; D011650:Pulmonary Alveoli / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000473:pathology; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D014019:Tissue Donors; D014841:von Willebrand Factor / Q000032:analysis
D015415:Biomarkers; D017127:Glycation End Products, Advanced; D014841:von Willebrand Factor