Plasma Angiopoietin-2 Predicts the Onset of Acute Lung Injury in Critically III Patients

School of Medicine, UCSF, San Francisco, California, United States.
American Journal of Respiratory and Critical Care Medicine (Impact Factor: 13). 01/2013; 187(7). DOI: 10.1164/rccm.201208-1460OC
Source: PubMed


RATIONALE: Current clinical prediction scores for acute lung injury (ALI) have limited positive predictive value. No studies have evaluated predictive plasma biomarkers in a broad population of critically ill patients or as an adjunct to clinical prediction scores. OBJECTIVES: To determine whether plasma Angiopoietin-2 (Ang-2), von Willebrand factor (vWF), interleukin-8 (IL-8) and/or receptor for advanced glycation end-products (sRAGE) predict ALI in critically ill patients. METHODS: Plasma samples were drawn from critically ill patients (n=230) identified in the emergency department. Patients who had ALI at baseline or in the subsequent 6 hours were excluded, and the remaining patients were followed for development of ALI. MEASUREMENTS AND MAIN RESULTS: Nineteen patients developed ALI at least 6 hours after the sample draw. Higher levels of Ang-2 and IL-8 were significantly associated with increased development of ALI (p=0.0008, 0.004 respectively). The association between Ang-2 and subsequent development of ALI was robust to adjustment for sepsis and vasopressor use. Ang-2 and the Lung Injury Prediction Score each independently discriminated well between those who developed ALI and those who did not (AUROC 0.74 for each), and using the two together improved the AUC to 0.84 (vs 0.74, p=0.05). In contrast, plasma levels of sRAGE and vWF were not predictive of ALI. CONCLUSIONS: Plasma biomarkers such as Ang-2 can improve clinical prediction scores and identify patients at high risk for ALI. In addition, the early rise of Ang-2 emphasizes the importance of endothelial injury in the early pathogenesis of ALI.

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    • "As it remains challenging to identify patients who are at the highest risk of developing these syndromes and to differentiate these syndromes from other causes of acute respiratory failure, many studies have focused on biomarkers to identify patients with ARDS to predict those who are unlikely to have a positive outcome and create evidence-based therapies. Until now, four categories of biomarkers have been studied including inflammatory cytokines (IL-6, IL-8) [4, 5], coagulation proteins (PAI-1, protein C) [6, 7], epithelial proteins (KL-6, SP-D, RAGE) [8–10], and endothelial proteins (Ang-2, ICAM-1, vWF) [11–13]. Despite recent advances in our understanding of biomarkers associated with either diagnosis of ARDS in the at-risk population or ARDS-related mortality, researchers continue to explore a reliable ARDS biomarker. "
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    ABSTRACT: Purpose: To investigate the prognostic significance of endocan, compared with procalcitonin (PCT), C-reactive protein (CRP),white blood cells (WBC), neutrophils (N), and clinical severity scores in patients with ARDS. Methods: A total of 42 patients with ARDS were initially enrolled, and there were 20 nonsurvivors and 22 survivors based on hospital mortality. Plasma levels of biomarkers were measured and the acute physiology and chronic health evaluation II (APACHE II) was calculated on day 1 after the patient met the defining criteria of ARDS. Results: Endocan levels significantly correlated with the APACHE II score in the ARDS group (r = 0.676, P = 0.000, n = 42). Of 42 individuals with ARDS, 20 were dead, and endocan was significantly higher in nonsurvivors than in survivors (median (IQR) 5.01 (2.98-8.44) versus 3.01 (2.36-4.36) ng/mL, P = 0.017). According to the results of the ROC-curve analysis and COX proportional hazards models, endocan can predict mortality of ARDS independently with a hazard ratio of 1.374 (95% CI, 1.150-1.641) and an area of receiver operator characteristic curve (AUROC) of 0.715 (P = 0.017). Moreover, endocan can predict the multiple-organ dysfunction of ARDS. Conclusion: Endocan is a promising biomarker to predict the disease severity and mortality in patients with ARDS.
    Mediators of Inflammation 07/2014; 2014(1):625180. DOI:10.1155/2014/625180 · 3.24 Impact Factor
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    • "Use of biological markers could improve the diagnostic process of ARDS since such markers may change before the clinical criteria of ARDS are met [5]. It can be argued that biological markers from lung tissue contain more relevant biochemical information for ARDS diagnosis than plasma markers [6-9]. "
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    ABSTRACT: The acute respiratory distress syndrome (ARDS) is a common, devastating complication of critical illness that is characterized by pulmonary injury and inflammation. The clinical diagnosis may be improved by means of objective biological markers. Electronic nose (eNose) technology can rapidly and non-invasively provide breath prints, which are profiles of volatile metabolites in the exhaled breath. We hypothesized that breath prints could facilitate accurate diagnosis of ARDS in intubated and ventilated intensive care unit (ICU) patients. Prospective single-center cohort study with training and temporal external validation cohort. Breath of newly intubated and mechanically ventilated ICU-patients was analyzed using an electronic nose within 24 hours after admission. ARDS was diagnosed and classified by the Berlin clinical consensus definition. The eNose was trained to recognize ARDS in a training cohort and the diagnostic performance was evaluated in a temporal external validation cohort. In the training cohort (40 patients with ARDS versus 66 controls) the diagnostic model for ARDS showed a moderate discrimination, with an area under the receiver-operator characteristic curve (AUC-ROC) of 0.72 (95%-confidence interval (CI): 0.63-0.82). In the external validation cohort (18 patients with ARDS versus 26 controls) the AUC-ROC was 0.71 [95%-CI: 0.54 - 0.87]. Restricting discrimination to patients with moderate or severe ARDS versus controls resulted in an AUC-ROC of 0.80 [95%-CI: 0.70 - 0.90]. The exhaled breath profile from patients with cardiopulmonary edema and pneumonia was different from that of patients with moderate/severe ARDS. An electronic nose can rapidly and non-invasively discriminate between patients with and without ARDS with modest accuracy. Diagnostic accuracy increased when only moderate and severe ARDS patients were considered. This implicates that breath analysis may allow for rapid, bedside detection of ARDS, especially if our findings are reproduced using continuous exhaled breath profiling.Trial registration: NTR2750, registered 11 February 2011.
    BMC Pulmonary Medicine 04/2014; 14(1):72. DOI:10.1186/1471-2466-14-72 · 2.40 Impact Factor
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    • "The higher plasma sRAGE levels were associated with a more elevated PLI, which is an established early marker of increased capillary permeability in the lung [15], so that the elevated plasma sRAGE and PLI may both reflect endothelial injury in the lungs occurring during cardiac surgery, even before the clinical criteria of ALI are met [19]. The possible diagnostic value of sRAGE in lung injury found in our study may be specific for cardiac surgery patients, since sRAGE was recently found not to be predictive of lung injury in other critically ill patients [20]. However, our results are in line with a previous study in children which found plasma sRAGE to enable prediction of acute lung injury after cardiac surgery [21]. "
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    ABSTRACT: Cardiac surgery is frequently complicated by an acute vascular lung injury and this may be mediated, at least in part, by the (soluble) receptor for advanced glycation end products (sRAGE). In two university hospital intensive care units, circulating sRAGE was measured together with the 68Gallium-transferrin pulmonary leak index (PLI), a measure of pulmonary vascular permeabiliy, in 60 consecutive cardiac surgery patients stratified by the amount of blood transfusion, within 3 hours of admission to the intensive care. Cardiac surgery resulted in elevated plasma sRAGE levels compared to baseline (315 +/- 181 vs 110 +/- 55 pg/ml, P = 0.001). In 37 patients the PLI was elevated 50% above normal. The PLI correlated with sRAGE (r2 = 0.11, P = 0.018). Plasma sRAGE discriminated well between those with an elevated PLI and those with a normal PLI (area under the operator curve 0.75; P = 0.035; 95% CI 0.55-0.95), with 91% sensitivity but low specificity of 36% at a cutoff value of 200 pg/mL. Blood transfusion did not influence sRAGE levels. sRAGE is elevated in plasma after cardiac surgery and indicates increased pulmonary vascular permeability. The level of sRAGE is not affected by transfusion.
    BMC Pulmonary Medicine 12/2013; 13(1):76. DOI:10.1186/1471-2466-13-76 · 2.40 Impact Factor
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