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Original Research |

Elevated Plasma Levels of sRAGE are Associated with Non-Focal CT-Based Lung Imaging in ARDS patients.: A Prospective Multicenter Study

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

Authors contribution to the study

JMC takes responsibility for the content of the manuscript, was involved in the conception, hypotheses delineation, and design of the study, acquisition and analysis of the data, in writing the article and in its revision prior to submission.?

SM MJ EF were involved in the design of the study, hypotheses delineation, acquisition and analysis of the data, in writing the article and in its revision prior to submission.

LR VS were involved in the design of the study, performed the biological analysis, in writing the article and in its revision prior to submission.

JJR ML were involved in the design of the study, acquisition and analysis of the data, in writing the article and in the revision of this article prior to submission.

BP was involved in the hypotheses delineation and design of the study, was responsible for statistical analysis, take part in writing the article and in its revision prior to submission.

SJ CP KA OB JEB were involved in the design of the study, acquisition and analysis of the data, in the revision of this article prior to submission.

COI: SJ has received consulting fees from Maquet, Draeger, Hamilton Medical and Fisher Paykel. CPB has participated in speaking activities and industry advisory boards for Baxter Gambro Hospal and MSD. EF has received consulting fees from General Electric Medical System and Baxter, lecture fees from Baxter and Fresenius Kaki, and travel reimbursement from Fisher & Paykel Healthcare. All other authors declare they have no conflict of interest related to this manuscript.

Funding Sources

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 from Clermont-Ferrand University Hospital (“Appel d’Offre Interne 2010”, CHU Clermont-Ferrand).

Corresponding Author: Professor Jean-Michel Constantin, Department of perioperative medicine, Head of ICUs, University Hospital of Clermont-Ferrand, 1 place Lucie Aubrac, 63000 Clermont-Ferrand Cedex, France..


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


Chest. 2016. doi:10.1016/j.chest.2016.03.016
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Abstract

Background  During acute respiratory distress syndrome (ARDS), computed tomography (CT) can reveal two distinct lung imaging patterns, focal or non-focal, with different responses to PEEP, 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 non-focal patterns of lung CT-based imaging with plasma markers of lung injury.

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

Results  Thirty-two (27%) and 87 (73%) patients had focal and non-focal ARDS, respectively. Plasma levels of sRAGE were significantly higher in non-focal ARDS, compared to focal ARDS. A cut-off of 1188 pg/ml differentiated focal from non-focal ARDS with a sensitivity of 94% and a specificity of 84%. Non-focal patterns were associated with higher 28-day and 90-day mortality than focal patterns (31% vs 12%, p=0.038 and 46% vs 21%, p=0.026, respectively). Plasma levels of PAI-1 were significantly higher in non-focal ARDS. There was no difference in other biomarkers.

Conclusion  Plasma sRAGE is associated with a non-focal 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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