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  CHEST Nov 2016; 150(5): 998-1007

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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