Serum Lipopolysaccharide Binding Protein Levels Predict Severity of Lung Injury and Mortality in Patients with Severe Sepsis

Jesús Villar,Lina Pérez-Méndez,Arturo Muriel,Mercedes Muros,Santiago Basaldúa,Elena Espinosa,Carlos Flores,Antonio Artigas,Lluis Blanch,Jesús Blanco,Robert M Kacmarek,Rory Edward Morty

doi:10.1371/journal.pone.0006818

Abstract

BackgroundThere is a need for biomarkers insuring identification of septic patients at high-risk for death. We performed a prospective, multicenter, observational study to investigate the time-course of lipopolysaccharide binding protein (LBP) serum levels in patients with severe sepsis and examined whether serial serum levels of LBP could be used as a marker of outcome.Methodology/Principal FindingsLBP serum levels at study entry, at 48 hours and at day-7 were measured in 180 patients with severe sepsis. Data regarding the nature of infections, disease severity, development of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), and intensive care unit (ICU) outcome were recorded. LBP serum levels were similar in survivors and non-survivors at study entry (117.4±75.7 µg/mL vs. 129.8±71.3 µg/mL, P = 0.249) but there were significant differences at 48 hours (77.2±57.0 vs. 121.2±73.4 µg/mL, P<0.0001) and at day-7 (64.7±45.8 vs. 89.7±61.1 µg/ml, p = 0.017). At 48 hours, LBP levels were significantly higher in ARDS patients than in ALI patients (112.5±71.8 µg/ml vs. 76.6±55.9 µg/ml, P = 0.0001). An increase of LBP levels at 48 hours was associated with higher mortality (odds ratio 3.97; 95%CI: 1.84–8.56; P<0.001).Conclusions/SignificanceSerial LBP serum measurements may offer a clinically useful biomarker for identification of patients with severe sepsis having the worst outcomes and the highest probability of developing sepsis-induced ARDS.

Highlights

Sepsis remains a major challenge in critical care medicine
An explosion of information regarding the inflammatory response to sepsis has prompted a search for biomarkers that help elucidate molecular pathways that are important in the pathogenesis of the septic process and acute lung injury, that predict outcome, and that may serve as surrogate indicators of potential benefits of therapies [3,4,5,6,7,8]
Patients had been hospitalized a median of 1 day (IQR: 0–7 days) prior to intensive care unit (ICU) admission and 54.4% had severe sepsis on ICU admission

Summary

Introduction

Sepsis remains a major challenge in critical care medicine It is the leading cause of death and its mortality has not decreased substantially in the past decade [1,2]. Lipopolysaccharide binding protein (LBP), a key participant in the inflammatory response to infection, may be a useful marker for diagnosis and prognosis of patients with bacterial infections [9]. Binding of LPS activates monocyte/macrophage system cells via Toll-like receptors [14], resulting in the production of proinflammatory cytokines that aggravate the clinical presentation of sepsis. Multicenter, observational study to investigate the time-course of lipopolysaccharide binding protein (LBP) serum levels in patients with severe sepsis and examined whether serial serum levels of LBP could be used as a marker of outcome

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