Research article

Endothelin-1 precursor peptides correlate with severity of disease and outcome in patients with community acquired pneumonia

Philipp Schuetz¹ , Daiana Stolz² , Beat Mueller¹ , Nils G Morgenthaler³ , Joachim Struck³ , Christian Mueller¹ , Roland Bingisser¹ , Michael Tamm² and Mirjam Christ-Crain¹

¹Department of Internal Medicine, University Hospital Basel, Switzerland

²Clinic of Pneumology and Pulmonary Cell Research, University Hospital Basel, Switzerland

³Research Department, B.R.A.H.M.S AG, Biotechnology Center Hennigsdorf/Berlin, Germany

author email corresponding author email

BMC Infectious Diseases 2008, 8:22doi:10.1186/1471-2334-8-22

Published:	28 February 2008

Abstract

Background

Circulating levels of endothelin-1 are increased in sepsis and correlate with severity of disease. A rapid and easy immunoassay has been developed to measure the more stable ET-1 precursor peptides proET-1. The objective of this study was to assess the diagnostic and prognostic value of proET-1 in a prospective cohort of mainly septic patients with community-acquired pneumonia.

Methods

We evaluated 281 consecutive patients with community acquired pneumonia. Serum proET-1 plasma levels were measured using a new sandwich immunoassay.

Results

ProET-1 levels exhibited a gradual increase depending on the clinical severity of pneumonia as assessed by the pneumonia severity index (PSI) and the CURB65 scores (p < 0.001 and p < 0.01). The diagnostic accuracy to predict bacteraemia of procalcitonin (AUC 0.84 [95% 0.74–0.93]) was superior than C-reactive protein (AUC 0.67 [95%CI 0.56–0.78]) and leukocyte count (AUC 0.66 [95%CI 0.55–0.78]) and in the range of proET-1(AUC of 0.77 [95%CI 0.67–0.86]). ProET-1 levels on admission were increased in patients with adverse medical outcomes including death and need for ICU admission. ROC curve analysis to predict the risk for mortality showed a prognostic accuracy of proET-1 (AUC 0.64 [95%CI 0.53–0.74]), which was higher than C-reactive protein (AUC 0.51 [95%CI 0.41–0.61]) and leukocyte count (AUC 0.55 [95%CI 0.44–0.65]) and within the range of the clinical severity scores (PSI AUC 0.69 [95%CI 0.61–0.76] and CURB65 0.67 [95%CI 0.57–0.77]) and procalcitonin (AUC 0.59 [95% 0.51–0.67]). ProET-1 determination improved significantly the prognostic accuracy of the CURB65 score (AUC of the combined model 0.69 [95%CI 0.59–0.79]). In a multivariate logistic regression model, only proET1 and the clinical severity scores were independent predictors for death and for the need for ICU admission.

Conclusion

In community-acquired pneumonia, ET-1 precursor peptides correlate with disease severity and are independent predictors for mortality and ICU admission. If confirmed in future studies, proET-1 levels may become another helpful tool for risk stratification and management of patients with community-acquired pneumonia.

Trial registration

ISRCTN04176397