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Updated: Sep 25, 2026
Surfactant Depletion Combined with Injurious Ventilation Results in a Reproducible Model of the Acute Respiratory Distress Syndrome (ARDS)
Published on: April 7, 2021
Epithelial injury and inflammatory phenotypes for personalized ventilation in ARDS: Secondary analysis of the LIVE
Joris Pensier1, Laurent Renard-Triché2, Camille Theilliere3
1Anesthesiology and Intensive Care, Anesthesia and Critical Care Department B, Saint Eloi Teaching Hospital, University of Montpellier, Montpellier, France; PhyMedExp laboratory, University of Montpellier, INSERM U1046, CNRS, Montpellier, France; Department of Anesthesia, Critical Care and Pain Medicine, Center for Anesthesia Research Excellence Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA, 02215, USA; Department of Perioperative Medicine, CHU Clermont-Ferrand, Clermont-Ferrand, France; iGReD, CNRS, INSERM, Université Clermont Auvergne, Clermont-Ferrand, France.
Background:
Guidelines recommend against systematic lung recruitment strategies in acute respiratory distress syndrome (ARDS). sRAGE, an alveolar epithelial injury plasmatic biomarker, and inflammatory phenotypes may guide personalized approaches.
Research Question:
Does baseline sRAGE or inflammatory phenotype identify heterogeneity in the treatment effect of lung recruitment on mortality in ARDS?
Study Design And Methods:
This analysis included 259 patients with plasma sRAGE measurements from the original LIVE trial that compared lung recruitment with low-PEEP strategies in patients with focal or non-focal ARDS. Baseline sRAGE was dichotomized at 2,440 pg/mL into high and low groups. Inflammatory phenotypes were identified using a validated parsimonious model (IL-8, sTNFr-1, bicarbonate). The primary and secondary outcomes were 90-day mortality and sRAGE trajectory until day 6. Inverse probability weighting and weighted Cox models were used; sRAGE trajectories were assessed using joint models.
Results:
High plasma sRAGE (r=0.26, p<0.001), but not the inflammatory phenotype, was moderately correlated with non-focal ARDS. Treatment effect varied by baseline sRAGE (p-for-interaction=0.006), but not by inflammatory phenotype (p-for-interaction=0.56); however, the hyperinflammatory phenotype was associated with 90-day mortality (57% vs 26%, p<0.001). Among high-sRAGE patients, lung recruitment was associated with lower 90-day mortality (HR 0.41, 95%CI 0.18-0.93; p=0.033); among low-sRAGE patients it was associated with higher mortality (HR 3.27, 95%CI, 1.06-10.1; p=0.039). Lung recruitment was associated with different sRAGE slopes compared with low PEEP, with effect modification by baseline sRAGE. Lung recruitment was associated with a steeper decline in sRAGE among patients with high baseline sRAGE (p-for-interaction<0.001), and with a slower decline among patients with low baseline sRAGE (p-for-interaction=0.038). Inflammatory phenotypes did not identify heterogeneity of treatment effect. Sensitivity analyses without inverse probability weighting were directionally consistent.
Interpretation:
In ARDS, epithelial injury assessed by plasma sRAGE may identify heterogeneity of treatment effect with lung recruitment, whereas inflammatory phenotypes remained prognostic for mortality.
