title: Significance of von Willebrand factor in septic and nonseptic patients with acute lung injury.
abstract: 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.
authors.affiliation: Division of Allergy, Pulmonary and Critical Care Medicine, T1217 MCN, Vanderbilt University School of Medicine, Nashville, TN 37232-2650, USA. lorraine.ware@vanderbilt.edu
authors.forename: Lorraine B
authors.initials: LB
authors.lastname: Ware
authors.forename: Mark D
authors.initials: MD
authors.lastname: Eisner
authors.forename: B Taylor
authors.initials: BT
authors.lastname: Thompson
authors.forename: Polly E
authors.initials: PE
authors.lastname: Parsons
authors.forename: Michael A
authors.initials: MA
authors.lastname: Matthay
mesh_terms: D018806:APACHE; D000368:Aged; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D016014:Linear Models; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D009102:Multiple Organ Failure / Q000209:etiology; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D012121:Respiration, Artificial / Q000379:methods; D012128:Respiratory Distress Syndrome / Q000097:blood* / Q000209:etiology* / Q000401:mortality / Q000628:therapy; D018805:Sepsis / Q000150:complications*; D016019:Survival Analysis; D018746:Systemic Inflammatory Response Syndrome / Q000209:etiology; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology; D014841:von Willebrand Factor / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D014841:von Willebrand Factor