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Original Research: CRITICAL CARE MEDICINE |

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

Raphael Briot, MD, PhD; James A. Frank, MD; Tokujiro Uchida, MD, PhD; Jae W. Lee, MD; Carolyn S. Calfee, MD; Michael A. Matthay, MD
Author and Funding Information

*From the Cardiovascular Research Institute (Dr. Briot) and Departments of Medicine (Drs. Frank, Calfee, and Matthay) and Anesthesia (Dr. Lee), University of California, San Francisco, CA; and Tokyo Medical and Dental University (Dr. Uchida), Department of Anesthesiology, Tokyo, Japan.

Correspondence to: Michael A. Matthay, MD, FCCP, University of California, San Francisco, Cardiovascular Research Institute, 505 Parnassus Ave, M-917, San Francisco, CA 94143-0624; e-mail: michael.matthay@ucsf.edu


This study was supported by National Heart, Lung, and Blood Institute HL51856 and HL088263 (Dr. Matthay), HL88440 (Dr. Frank), and Egide–Programme Lavoisier (Ministère Français des Affaires Etrangères) [Dr. Briot]. Dr. Calfee is supported by a National Heart, Lung, and Blood Institute K23 award (HL090833).

The authors have no conflicts of interest to disclose.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).


Chest. 2009;135(2):269-275. doi:10.1378/chest.08-0919
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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°C, the lungs were inflated with a continuous positive airway pressure of 10 cm H2O. 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 ≤ 14%/h, when compared with lungs with preserved AFC (median 0.82 vs 0.43 μg/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.

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