• Matthieu Jabaudon, Raiko Blondonnet, Laurence Roszyk, Damien Bouvier, Jules Audard, Gael Clairefond, Mathilde Fournier, Geoffroy Marceau, Pierre Déchelotte, Bruno Pereira, Vincent Sapin, and Jean-Michel Constantin.
• 1 Intensive Care Unit, Department of Anesthesiology, Critical Care and Perioperative Medicine, Estaing University Hospital.
• Am. J. Respir. Crit. Care Med. 2015 Jul 15;192(2):191-9.

RationaleLevels of the soluble form of the receptor for advanced glycation end-products (sRAGE) are elevated during acute respiratory distress syndrome (ARDS) and correlate with severity and prognosis. Alveolar fluid clearance (AFC) is necessary for the resolution of lung edema but is impaired in most patients with ARDS. No reliable marker of this process has been investigated to date.ObjectivesTo verify whether sRAGE could predict AFC during ARDS.MethodsAnesthetized CD-1 mice underwent orotracheal instillation of hydrochloric acid. At specified time points, lung injury was assessed by analysis of blood gases, alveolar permeability, lung histology, AFC, and plasma/bronchoalveolar fluid measurements of proinflammatory cytokines and sRAGE. Plasma sRAGE and AFC rates were also prospectively assessed in 30 patients with ARDS.Measurements And Main ResultsThe rate of AFC was inversely correlated with sRAGE levels in the plasma and the bronchoalveolar fluid of acid-injured mice (Spearman's ρ = -0.73 and -0.69, respectively; P < 10(-3)), and plasma sRAGE correlated with AFC in patients with ARDS (Spearman's ρ = -0.59; P < 10(-3)). Similarly, sRAGE levels were significantly associated with lung injury severity, and decreased over time in mice, whereas AFC was restored and lung injury resolved.ConclusionsOur results indicate that sRAGE levels could be a reliable predictor of impaired AFC during ARDS, and should stimulate further studies on the pathophysiologic implications of RAGE axis in the mechanisms leading to edema resolution. Clinical trial registered with www.clinicaltrials.gov (NCT 00811629).

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