title: Elevated Plasma Levels of sRAGE Are Associated With Nonfocal CT-Based Lung Imaging in Patients With ARDS: A Prospective Multicenter Study.
abstract: 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.
authors.affiliation: Anesthesiology and Critical Care Department, University Hospital of Toulouse, Toulouse, France.
authors.forename: Segolene
authors.initials: S
authors.lastname: Mrozek
authors.affiliation: Department of Perioperative Medicine, University Hospital of Clermont-Ferrand, Clermont-Ferrand, France; Clermont Université, Université d'Auvergne, Clermont-Ferrand, France.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Jabaudon
authors.affiliation: Department of Anesthesiology and Critical Care Medicine B, Saint-Eloi Teaching Hospital, University Hospital of Montpellier, Inserm U-1046, Montpellier, France.
authors.forename: Samir
authors.initials: S
authors.lastname: Jaber
authors.affiliation: Assistance 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.
authors.forename: Catherine
authors.initials: C
authors.lastname: Paugam-Burtz
authors.affiliation: Service des Réanimations, Pôle Anesthésie Réanimation Douleur Urgence, CHU Nîmes, Faculté de Médecine de Nîmes, Université Montpellier 1, Nîmes, France.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Lefrant
authors.affiliation: Multidisciplinary 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.
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Rouby
authors.affiliation: Department of Anesthesiology and Critical Care, Hotel-Dieu, Nantes, France.
authors.forename: Karim
authors.initials: K
authors.lastname: Asehnoune
authors.affiliation: Hospices Civils de Lyon Service de Réanimation Médicale Centre Hospitalier Lyon-Sud, Pierre Bénite, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Allaouchiche
authors.affiliation: Réanimation, CH Aix-en-provence, Aix-en-provence, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Baldesi
authors.affiliation: Service d'Anesthésie et de Réanimation, Hôpital Nord, Assistance Publique-Hôpitaux de Marseille, Aix Marseille Université, Marseille, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Leone
authors.affiliation: Multidisciplinary 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.
authors.forename: Qin
authors.initials: Q
authors.lastname: Lu
authors.affiliation: Department of Perioperative Medicine, University Hospital of Clermont-Ferrand, Clermont-Ferrand, France.
authors.forename: Jean-Etienne
authors.initials: JE
authors.lastname: Bazin
authors.affiliation: Clermont Université, Université d'Auvergne, Clermont-Ferrand, France; Department of Biology, University Hospital of Clermont-ferrand, Clermont-ferrand, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Roszyk
authors.affiliation: Clermont Université, Université d'Auvergne, Clermont-Ferrand, France; Department of Biology, University Hospital of Clermont-ferrand, Clermont-ferrand, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Sapin
authors.affiliation: Department of Perioperative Medicine, University Hospital of Clermont-Ferrand, Clermont-Ferrand, France; Clermont Université, Université d'Auvergne, Clermont-Ferrand, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Futier
authors.affiliation: Biostatistics Unit (Department of Clinical Research and Innovation), University Hospital of Clermont-Ferrand, Clermont-Ferrand, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Pereira
authors.affiliation: Department of Perioperative Medicine, University Hospital of Clermont-Ferrand, Clermont-Ferrand, France; Clermont Université, Université d'Auvergne, Clermont-Ferrand, France. Electronic address: jmconstantin@chu-clermontferrand.fr.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Constantin
mesh_terms: D015415:Biomarkers / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D000067759:Receptor for Advanced Glycation End Products / Q000097:blood*; D012128:Respiratory Distress Syndrome / Q000097:blood* / Q000000981:diagnostic imaging*; D012680:Sensitivity and Specificity; D014057:Tomography, X-Ray Computed
chemical_list: D015415:Biomarkers; D000067759:Receptor for Advanced Glycation End Products
keywords: ARDS phenotype; alveolar fluid clearance; lung morphology; mechanical ventilation; rage