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

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.