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Abstract
The plasma soluble receptor for advanced glycation end-products (sRAGE) is a marker of lung epithelial injury with prognostic value when measured at baseline in acute respiratory distress syndrome (ARDS). However, whether changes in plasma sRAGE could inform prognosis in ARDS remains unknown. In this secondary analysis of the Lung Imaging for Ventilator Setting in ARDS (LIVE) multicenter randomized controlled trial, which evaluated a personalized ventilation strategy tailored to lung morphology, plasma sRAGE was measured upon study entry (baseline) and on days one, two, three, four and six. The association between changes in plasma sRAGE over time and 90-day survival was evaluated. Higher baseline plasma sRAGE (HR per-one log increment, 1.53; 95% CI, 1.16–2.03; p = 0.003) and an increase in sRAGE over time (HR for each one-log increment in plasma sRAGE per time unit, 1.01; 95% CI, 1.01–1.02; p < 10−3) were both associated with increased 90-day mortality. Each 100-unit increase in the plasma sRAGE level per unit of time increased the risk of death at day 90 by 1% in joint modeling. Plasma sRAGE increased over time when a strategy of maximal alveolar recruitment was applied in patients with focal ARDS. Current findings suggest that the rate of change in plasma sRAGE over time is associated with 90-day survival and could be helpful as a surrogate outcome in ARDS.
Highlights
Acute respiratory distress syndrome (ARDS), as clinically defined [1], includes patients with a wide range of underlying biologic processes
The baseline characteristics and clinical outcomes of patients with available soluble receptor for advanced glycation end-products (sRAGE) measurements randomized to the intervention group or to the control group are reported in Table S1 (Supplementary Materials)
These analyses included joint modeling of longitudinal and time-to-event data, which is considered to be the best method for evaluating the relationship between a biomarker trajectory and clinical outcomes such as survival because it accounts for immortal time bias and, allows for informative dropouts such as death
Summary
Acute respiratory distress syndrome (ARDS), as clinically defined [1], includes patients with a wide range of underlying biologic processes. Elevated plasma levels of soluble receptor for advanced glycation end-products (sRAGE) may reflect the severity of lung epithelial injury [7,8] and are associated with mortality in acute respiratory distress syndrome (ARDS) when measured at baseline [9]. This hypothesis has been supported by studies in ex vivo human lungs [10] and in patients with ARDS [8]. Single measurements of plasma sRAGE could improve our ability to forecast prognosis and identify lung imaging phenotypes within ARDS [9,11], whether changes in plasma sRAGE, which may indicate ongoing alveolar epithelial injury, can inform prognosis and be influenced by some interventions, such as mechanical ventilation, remains unknown
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