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Original Research: Critical Care |

Elevated Plasma Levels of sRAGE Are Associated With Nonfocal CT-Based Lung Imaging in Patients With ARDS: A Prospective Multicenter Study

Segolene Mrozek, MD; Matthieu Jabaudon, MD; Samir Jaber, MD, PhD; Catherine Paugam-Burtz, MD, PhD; Jean-Yves Lefrant, MD, PhD; Jean-Jacques Rouby, MD, PhD; Karim Asehnoune, MD, PhD; Bernard Allaouchiche, MD, PhD; Olivier Baldesi, MD; Marc Leone, MD, PhD; Qin Lu, MD, PhD; Jean-Etienne Bazin, MD, PhD; Laurence Roszyk, PharmD; Vincent Sapin, PharmD, PhD; Emmanuel Futier, MD, PhD; Bruno Pereira, PhD; Jean-Michel Constantin, MD, PhD
Author and Funding Information

FUNDING/SUPPORT: This work was supported by grants from the Auvergne Regional Council (Programme Nouveau Chercheur de la Region Auvergne 2013), the French Agence Nationale de la Recherche and the Direction Generale de l’Offre de Soins (Programme de Recherche Translationnelle en Sante, ANR-13-PRTS-0010), and Clermont-Ferrand University Hospital (Appel d’Offre Interne 2010, CHU Clermont-Ferrand).

aAnesthesiology and Critical Care Department, University Hospital of Toulouse, Toulouse, France

bDepartment of Perioperative Medicine, University Hospital of Clermont-Ferrand, Clermont-Ferrand, France

cClermont Université, Université d'Auvergne, Clermont-Ferrand, France

dDepartment of Anesthesiology and Critical Care Medicine B, Saint-Eloi Teaching Hospital, University Hospital of Montpellier, Inserm U-1046, Montpellier, France

eAssistance Publique–Hôpitaux de Paris, Département d’Anesthésie et Réanimation, Hôpital Beaujon, Hôpitaux Universitaires Paris Nord Val de Seine and Université Paris Diderot, Sorbonne Paris Cité, France

fService des Réanimations, Pôle Anesthésie Réanimation Douleur Urgence, CHU Nîmes, Faculté de Médecine de Nîmes, Université Montpellier 1, Nîmes, France

gMultidisciplinary Intensive Care Unit, Department of Anesthesiology and Critical Care Medicine, Assistance Publique Hôpitaux de Paris, Pitié-Salpêtrière Hospital, University Pierre and Marie Curie of Paris, France

hDepartment of Anesthesiology and Critical Care, Hotel-Dieu, Nantes, France

iHospices Civils de Lyon Service de Réanimation Médicale Centre Hospitalier Lyon-Sud, Pierre Bénite, France

jRéanimation, CH Aix-en-provence, Aix-en-provence, France

kService d’Anesthésie et de Réanimation, Hôpital Nord, Assistance Publique-Hôpitaux de Marseille, Aix Marseille Université, Marseille, France

lDepartment of Biology, University Hospital of Clermont-ferrand, Clermont-ferrand, France

mBiostatistics Unit (Department of Clinical Research and Innovation), University Hospital of Clermont-Ferrand, Clermont-Ferrand, France

CORRESPONDENCE TO: Jean-Michel Constantin, MD, PhD, Department of Perioperative Medicine, University Hospital of Clermont-Ferrand, 1 place Lucie Aubrac, 63000 Clermont-Ferrand Cedex, Clermont-Ferrand, France


Copyright 2016, American College of Chest Physicians. All Rights Reserved.


Chest. 2016;150(5):998-1007. doi:10.1016/j.chest.2016.03.016
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Background  During ARDS, CT can reveal two distinct lung imaging patterns, focal or nonfocal, with different responses to positive end-expiratory pressure, recruitment maneuvers, and prone position. Nevertheless, their association with plasma biomarkers and their distinct functional/pathobiological mechanisms are unknown. The objective of this study was to characterize focal and nonfocal patterns of lung CT-based imaging with plasma markers of lung injury.

Methods  A prospective multicenter cohort study involving 119 consecutive patients with ARDS. Plasma biomarkers (soluble form of the receptor for advanced glycation end product [sRAGE], plasminogen activator inhibitor-1, soluble intercellular adhesion molecule-1, and surfactant protein-D) were measured within 24 h of ARDS onset. Lung CT scan was performed within the first 48 h to assess lung morphology.

Results  Thirty-two (27%) and 87 (73%) patients had focal and nonfocal ARDS, respectively. Plasma levels of sRAGE were significantly higher in nonfocal ARDS, compared with focal ARDS. A cut-off of 1,188 pg/mL differentiated focal from nonfocal ARDS with a sensitivity of 94% and a specificity of 84%. Nonfocal patterns were associated with higher 28- and 90-day mortality than focal patterns (31% vs 12%, P = .038 and 46% vs 21%, P = .026, respectively). Plasma levels of plasminogen activator inhibitor-1 were significantly higher in nonfocal ARDS. There was no difference in other biomarkers.

Conclusions  Plasma sRAGE is associated with a nonfocal ARDS. Such novel findings may suggest a role for RAGE pathway in an underlying endotype of impaired alveolar fluid clearance and stimulate future research on the association between ARDS phenotypes and therapeutic responses.

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