This Article Full Text Full Text (PDF) All Versions of this Article: 200310-1434OCv1 170/7/766    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ware, L. B. Articles by Matthay, M. A. Search for Related Content PubMed PubMed Citation Articles by Ware, L. B. Articles by Matthay, M. A.

Significance of Von Willebrand Factor in Septic and Nonseptic Patients with Acute Lung Injury

Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee; Division of Pulmonary and Critical Care Medicine and Division of Occupational and Environmental Medicine, Department of Medicine, and Department of Anesthesia and Cardiovascular Research Institute, University of California, San Francisco; Pulmonary/Critical Care Unit and ARDS Network Clinical Coordinating Center, Department of Medicine, Massachusetts General Hospital, Massachusetts; and Division of Pulmonary and Critical Care Medicine, Department of Medicine, Fletcher Allen Health Care, University of Vermont, Burlington, Vermont

Correspondence and requests for reprints should be addressed to Lorraine B. Ware, M.D., Division of Allergy, Pulmonary and Critical Care Medicine, T1217 MCN, Vanderbilt University School of Medicine, Nashville, TN 37232–2650. E-mail: lorraine.ware{at}vanderbilt.edu

Systemic endothelial activation and injury are important causes of multiorgan system failure. We hypothesized that plasma levels of von Willebrand factor (VWF), a marker of endothelial activation and injury, would be associated with clinical outcomes in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). In 559 patients with ALI/ARDS enrolled in the National Heart, Lung, and Blood Institute ARDS Network trial of two VT strategies, plasma VWF levels were measured at randomization (mean 350 ± 265% of normal control plasma) and Day 3 (344 ± 207%). Baseline VWF levels were similar in patients with and without sepsis, and were significantly higher in nonsurvivors (435 ± 333%) versus survivors (306 ± 209%) even when controlling for severity of illness, sepsis, and ventilator strategy (increased odds ratio of death of 1.6 per SD size increase in VWF; 95% confidence interval, 1.4–2.1). Higher VWF levels were also significantly associated with fewer organ failure–free days. Ventilator strategy had no effect on VWF levels. In conclusion, the degree of endothelial activation and injury is strongly associated with outcomes in ALI/ARDS, regardless of the presence or absence of sepsis, and is not modulated by a protective ventilatory strategy. To improve outcomes further, new treatment strategies targeted at the endothelium should be investigated.

Key Words: acute respiratory distress syndrome • sepsis • von Willebrand factor

This article has been cited by other articles:

				J. E. Levitt, M. K. Gould, L. B. Ware, and M. A. Matthay Analytic Review: The Pathogenetic and Prognostic Value of Biologic Markers in Acute Lung Injury J Intensive Care Med, May 1, 2009; 24(3): 151 - 167. [Abstract] [PDF]

				J. E. Levitt, H. Bedi, C. S. Calfee, M. K. Gould, and M. A. Matthay Identification of Early Acute Lung Injury at Initial Evaluation in an Acute Care Setting Prior to the Onset of Respiratory Failure Chest, April 1, 2009; 135(4): 936 - 943. [Abstract] [Full Text] [PDF]

				S. X. L. Zhang, J. J. Miller, D. B. Stolz, L. D. Serpero, W. Zhao, D. Gozal, and Y. Wang Type I Epithelial Cells Are the Main Target of Whole-Body Hypoxic Preconditioning in the Lung Am. J. Respir. Cell Mol. Biol., March 1, 2009; 40(3): 332 - 339. [Abstract] [Full Text] [PDF]

				K. S. Farley, L. Wang, and S. Mehta Septic pulmonary microvascular endothelial cell injury: role of alveolar macrophage NADPH oxidase Am J Physiol Lung Cell Mol Physiol, March 1, 2009; 296(3): L480 - L488. [Abstract] [Full Text] [PDF]

				R. Briot, J. A. Frank, T. Uchida, J. W. Lee, C. S. Calfee, and M. A. Matthay Elevated Levels of the Receptor for Advanced Glycation End Products, a Marker of Alveolar Epithelial Type I Cell Injury, Predict Impaired Alveolar Fluid Clearance in Isolated Perfused Human Lungs Chest, February 1, 2009; 135(2): 269 - 275. [Abstract] [Full Text] [PDF]

				M van der Heijden, G P van Nieuw Amerongen, P Koolwijk, V W M van Hinsbergh, and A B J Groeneveld Angiopoietin-2, permeability oedema, occurrence and severity of ALI/ARDS in septic and non-septic critically ill patients Thorax, October 1, 2008; 63(10): 903 - 909. [Abstract] [Full Text] [PDF]

				K. D. Liu and M. A. Matthay Advances in Critical Care for the Nephrologist: Acute Lung Injury/ARDS Clin. J. Am. Soc. Nephrol., March 1, 2008; 3(2): 578 - 586. [Abstract] [Full Text] [PDF]

				J. A. Frank, P. E. Parsons, and M. A. Matthay Pathogenetic Significance of Biological Markers of Ventilator-Associated Lung Injury in Experimental and Clinical Studies Chest, December 1, 2006; 130(6): 1906 - 1914. [Abstract] [Full Text] [PDF]

				D. E. McClintock, B. Starcher, M. D. Eisner, B. T. Thompson, D. L. Hayden, G. D. Church, M. A. Matthay, and the National Heart, Lung, Blood Institute Acute Re Higher urine desmosine levels are associated with mortality in patients with acute lung injury Am J Physiol Lung Cell Mol Physiol, October 1, 2006; 291(4): L566 - L571. [Abstract] [Full Text] [PDF]

				S. M. Kawut, E. M. Horn, K. K. Berekashvili, A. C. Widlitz, E. B. Rosenzweig, and R. J. Barst von Willebrand Factor Independently Predicts Long-term Survival in Patients With Pulmonary Arterial Hypertension Chest, October 1, 2005; 128(4): 2355 - 2362. [Abstract] [Full Text] [PDF]

				G. R. Bernard Acute Respiratory Distress Syndrome: A Historical Perspective Am. J. Respir. Crit. Care Med., October 1, 2005; 172(7): 798 - 806. [Abstract] [Full Text] [PDF]

				D. Angus, A. Ishizaka, M. Matthay, F. Lemaire, W. MacNee, and E. Abraham Critical Care in AJRCCM 2004 Am. J. Respir. Crit. Care Med., March 15, 2005; 171(6): 537 - 544. [Full Text] [PDF]

				T. Nagasaki, M. Inaba, S. Jono, Y. Hiura, H. Tahara, K. Shirakawa, N. Onoda, T. Ishikawa, E. Ishimura, and Y. Nishizawa Increased levels of serum osteoprotegerin in hypothyroid patients and its normalization with restoration of normal thyroid function Eur. J. Endocrinol., March 1, 2005; 152(3): 347 - 353. [Abstract] [Full Text] [PDF]