Angiopoietin-2 Levels as Predictors of Outcome in Mechanically Ventilated Patients with Acute Respiratory Distress Syndrome

Abstract

Pulmonary endothelium dysfunction is a key characteristic of ARDS. The aim of this study was to investigate endothelium-derived markers, such as angiopoietin-2 (Ang-2) and endothelial cell-specific molecule-1 (endocan), at the vascular and alveolar compartments as outcome predictors in ARDS. Fifty-three consecutive ARDS patients were studied. The primary outcome was 28-day mortality. Secondary endpoints were days of unassisted ventilation and days with organ failure other than ARDS, during the 28-day study period. Nonsurvivors presented higher lung injury scores and epithelial lining fluid (ELF) Ang-2 levels compared to survivors, with no significant differences in plasma Ang-2, endocan, and protein C concentrations between the two groups. In logistic regression analysis, ELF Ang-2 levels > 705 pg/ml were the only independent variable for 28-day mortality among the previous four. Plasma endocan values > 13 ng/pg were the only parameter predictive against days of unassisted ventilation during the 28-day study period. Finally, lung injury score > 2.25 and ELF Ang-2 levels > 705 pg/ml were associated with increased number of days with organ failure, other than ARDS. Our findings suggest that Ang-2 levels are increased in the alveolar compartment of ARDS patients, and this may be associated both with increased mortality and organ failure besides lung.

Increased mobilization of mesenchymal stem cells in patients with acute respiratory distress syndrome undergoing extracorporeal membrane oxygenation

“…We have previously demonstrated that plasma levels of VEGF and Ang-2 are increased in septic patients and correlate with the number of EPC [28,29]. Similar findings were shown for Ang-2 in ARDS [30,31]. With regards to VEGF, a correlation between increased plasma VEGF levels and severity of Multi-Organ-Dysfunction-Syndrome (MODS) has been reported by several groups [32,33].…”

Endocan, sepsis, pneumonia, and acute respiratory distress syndrome

“…In another series of 90 patients with ARDS at admission, endocan concentrations on the day after ARDS diagnosis were significantly higher in patients with poor evolution than in those with good evolution, with the median (IQR) respectively observed as 12.0 (6.8–18.6) vs 7.2 (5.4–12.5) ( p < 0.01) [ 61 ]. Consistently, high endocan levels (> 13 ng/ml) in mechanically ventilated ARDS correlated with failure to withdraw from mechanical ventilation [ 62 ].…”

Novel Perspectives Regarding the Pathology, Inflammation, and Biomarkers of Acute Respiratory Distress Syndrome

“…Protein C predicted 28-day mortality in both a cohort study based on the PROWESS trial (a placebo-controlled, double-blind, RCT) with 840 patients with sepsis [ 43 ] and in a cohort of 440 patients with sepsis and an average PaO 2 /FiO 2 ratio consistent with ARDS [ 44 ]. The predictive quality of Protein C could not be verified in smaller studies [ 42 , 45 ], which was probably due to small sample size ( N = 50 and N = 53). Hence, the role of Protein C as a biomarker looks promising with the currently available data.…”

“…Endocan, also known as endothelial cell-specific molecule 1, is a proteoglycan expressed by pulmonary endothelium, which may weaken inflammatory responses by inhibiting leukocyte recruitment. Endocan has only been analysed in small studies of lung injury, and its potential as a biomarker remains unclear with the currently available evidence [ 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 ].…”