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

Chest. 2016 Nov;150(5):998-1007. doi: 10.1016/j.chest.2016.03.016. Epub 2016 Mar 23.

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.

Keywords: ARDS phenotype; alveolar fluid clearance; lung morphology; mechanical ventilation; rage.

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Biomarkers / blood
  • Female
  • Humans
  • Male
  • Middle Aged
  • Prospective Studies
  • Receptor for Advanced Glycation End Products / blood*
  • Respiratory Distress Syndrome / blood*
  • Respiratory Distress Syndrome / diagnostic imaging*
  • Sensitivity and Specificity
  • Tomography, X-Ray Computed*

Substances

  • Biomarkers
  • Receptor for Advanced Glycation End Products