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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    • "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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    • "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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