Plasma angiopoietin-2 in clinical acute lung injury
Top Cited Papers
- 1 June 2012
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Critical Care Medicine
- Vol. 40 (6), 1731-1737
- https://doi.org/10.1097/ccm.0b013e3182451c87
Abstract
Background: Angiopoietin-2 is a proinflammatory mediator of endothelial injury in animal models, and increased plasma angiopoietin-2 levels are associated with poor outcomes in patients with sepsis-associated acute lung injury. Whether angiopoietin-2 levels are modified by treatment strategies in patients with acute lung injury is unknown. Objectives: To determine whether plasma angiopoietin-2 levels are associated with clinical outcomes and affected by fluid management strategy in a broad cohort of patients with acute lung injury. Design, Setting, and Participants: Plasma levels of angiopoietin-2 and von Willebrand factor (a traditional marker of endothelial injury) were measured in 931 subjects with acute lung injury enrolled in a randomized trial of fluid liberal vs. fluid conservative management. Measurements and Main Results: The presence of infection (sepsis or pneumonia) as the primary acute lung injury risk factor significantly modified the relationship between baseline angiopoietin-2 levels and mortality (p = .01 for interaction). In noninfection-related acute lung injury, higher baseline angiopoietin-2 levels were strongly associated with increased mortality (odds ratio, 2.43 per 1-log increase in angiopoietin-2; 95% confidence interval, 1.57-3.75; p < .001). In infection-related acute lung injury, baseline angiopoietin-2 levels were similarly elevated in survivors and nonsurvivors; however, patients whose plasma angiopoietin-2 levels increased from day 0 to day 3 had more than double the odds of death compared with patients whose angiopoietin-2 levels declined over the same period of time (odds ratio, 2.29; 95% confidence interval, 1.54-3.43; p < .001). Fluid-conservative therapy led to a 15% greater decline in angiopoietin-2 levels from day 0 to day 3 (95% confidence interval, 4.6-24.8%; p = .006) compared with fluid-liberal therapy in patients with infection-related acute lung injury. In contrast, plasma levels of von Willebrand factor were significantly associated with mortality in both infection-related and noninfection-related acute lung injury and were not affected by fluid therapy. Conclusions: Unlike von Willebrand factor, plasma angiopoietin-2 has differential prognostic value for mortality depending on the presence or absence of infection as an acute lung injury risk factor. Fluid conservative therapy preferentially lowers plasma angiopoietin-2 levels over time and thus may be beneficial in part by decreasing endothelial inflammation.This publication has 20 references indexed in Scilit:
- ANGPT2 Genetic Variant Is Associated with Trauma-associated Acute Lung Injury and Altered Plasma Angiopoietin-2 Isoform RatioAmerican Journal of Respiratory and Critical Care Medicine, 2011
- Angiopoietin-1 and angiopoietin-2 as clinically informative prognostic biomarkers of morbidity and mortality in severe sepsis*Critical Care Medicine, 2011
- Ratio of angiopoietin-2 to angiopoietin-1 as a predictor of mortality in acute lung injury patientsCritical Care Medicine, 2010
- New Developments in Lung Endothelial Heterogeneity: von Willebrand Factor, P-Selectin, and the Weibel-Palade BodySeminars in Thrombosis and Hemostasis, 2010
- Circulating angiopoietin-2 levels in the course of septic shock: relation with fluid balance, pulmonary dysfunction and mortalityIntensive Care Medicine, 2009
- Angiopoietin-2, permeability oedema, occurrence and severity of ALI/ARDS in septic and non-septic critically ill patientsThorax, 2008
- CIRCULATING ANGIOPOIETIN 2 CORRELATES WITH MORTALITY IN A SURGICAL POPULATION WITH ACUTE LUNG INJURY/ADULT RESPIRATORY DISTRESS SYNDROMEShock, 2008
- Early elevation of plasma von Willebrand factor antigen in pediatric acute lung injury is associated with an increased risk of death and prolonged mechanical ventilation*Pediatric Critical Care Medicine, 2007
- Excess Circulating Angiopoietin-2 May Contribute to Pulmonary Vascular Leak in Sepsis in HumansPLoS Medicine, 2006
- The Acute Respiratory Distress SyndromeThe New England Journal of Medicine, 2000