Segolene Mrozek1, Matthieu Jabaudon2, Samir Jaber3, Catherine Paugam-Burtz4, Jean-Yves Lefrant5, Jean-Jacques Rouby6, Karim Asehnoune7, Bernard Allaouchiche8, Olivier Baldesi9, Marc Leone10, Qin Lu6, Jean-Etienne Bazin11, Laurence Roszyk12, Vincent Sapin12, Emmanuel Futier2, Bruno Pereira13, Jean-Michel Constantin14. 1. Anesthesiology and Critical Care Department, University Hospital of Toulouse, Toulouse, France. 2. Department of Perioperative Medicine, University Hospital of Clermont-Ferrand, Clermont-Ferrand, France; Clermont Université, Université d'Auvergne, Clermont-Ferrand, France. 3. Department of Anesthesiology and Critical Care Medicine B, Saint-Eloi Teaching Hospital, University Hospital of Montpellier, Inserm U-1046, Montpellier, France. 4. 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. 5. Service des Réanimations, Pôle Anesthésie Réanimation Douleur Urgence, CHU Nîmes, Faculté de Médecine de Nîmes, Université Montpellier 1, Nîmes, France. 6. 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. 7. Department of Anesthesiology and Critical Care, Hotel-Dieu, Nantes, France. 8. Hospices Civils de Lyon Service de Réanimation Médicale Centre Hospitalier Lyon-Sud, Pierre Bénite, France. 9. Réanimation, CH Aix-en-provence, Aix-en-provence, France. 10. Service d'Anesthésie et de Réanimation, Hôpital Nord, Assistance Publique-Hôpitaux de Marseille, Aix Marseille Université, Marseille, France. 11. Department of Perioperative Medicine, University Hospital of Clermont-Ferrand, Clermont-Ferrand, France. 12. Clermont Université, Université d'Auvergne, Clermont-Ferrand, France; Department of Biology, University Hospital of Clermont-ferrand, Clermont-ferrand, France. 13. Biostatistics Unit (Department of Clinical Research and Innovation), University Hospital of Clermont-Ferrand, Clermont-Ferrand, France. 14. 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.
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.
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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