Soluble Receptor for Advanced Glycation End-Products Predicts Impaired Alveolar Fluid Clearance in Acute Respiratory Distress Syndrome.
BACKGROUND
Levels 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.


OBJECTIVE
To verify whether sRAGE could predict AFC during ARDS.


METHODS
Anesthetized 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.


RESULTS
The 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.


CONCLUSIONS
Our 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).
1 Intensive Care Unit, Department of Anesthesiology, Critical Care and Perioperative Medicine, Estaing University Hospital.|2 Clermont Université, Université d'Auvergne, Clermont-Ferrand, France.
Matthieu
http://orcid.org/0000-0002-8121-1680
M
Jabaudon
1 Intensive Care Unit, Department of Anesthesiology, Critical Care and Perioperative Medicine, Estaing University Hospital.|2 Clermont Université, Université d'Auvergne, Clermont-Ferrand, France.
Raiko
R
Blondonnet
3 Department of Medical Biochemistry and Molecular Biology.|2 Clermont Université, Université d'Auvergne, Clermont-Ferrand, France.
Laurence
L
Roszyk
3 Department of Medical Biochemistry and Molecular Biology.|2 Clermont Université, Université d'Auvergne, Clermont-Ferrand, France.
Damien
D
Bouvier
1 Intensive Care Unit, Department of Anesthesiology, Critical Care and Perioperative Medicine, Estaing University Hospital.
Jules
J
Audard
2 Clermont Université, Université d'Auvergne, Clermont-Ferrand, France.
Gael
G
Clairefond
4 Department of Microbiology.
Mathilde
M
Fournier
3 Department of Medical Biochemistry and Molecular Biology.|2 Clermont Université, Université d'Auvergne, Clermont-Ferrand, France.
Geoffroy
G
Marceau
5 Department of Pathology, Estaing University Hospital, and.
Pierre
P
Déchelotte
6 Department of Clinical Research and Innovation, CHU Clermont-Ferrand, Clermont-Ferrand, France; and.
Bruno
B
Pereira
3 Department of Medical Biochemistry and Molecular Biology.|2 Clermont Université, Université d'Auvergne, Clermont-Ferrand, France.
Vincent
V
Sapin
1 Intensive Care Unit, Department of Anesthesiology, Critical Care and Perioperative Medicine, Estaing University Hospital.|2 Clermont Université, Université d'Auvergne, Clermont-Ferrand, France.
Jean-Michel
JM
Constantin
D000818:Animals; D015415:Biomarkers / Q000097:blood; D001992:Bronchoalveolar Lavage Fluid; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008168:Lung / Q000503:physiopathology; D008297:Male; D051379:Mice; D008875:Middle Aged; D011446:Prospective Studies; D011650:Pulmonary Alveoli / Q000503:physiopathology*; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood*; D012128:Respiratory Distress Syndrome / Q000097:blood* / Q000503:physiopathology*
D015415:Biomarkers; D016207:Cytokines; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic
acid aspiration; alveolar epithelium; animal model; lung injury resolution; pulmonary edema