title: Endothelin-1 precursor peptides correlate with severity of disease and outcome in patients with community acquired pneumonia.
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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  ISRCTN04176397.
authors.affiliation: Department of Internal Medicine, University Hospital Basel, Switzerland. SchuetzP@uhbs.ch
authors.forename: Philipp
authors.initials: P
authors.lastname: Schuetz
authors.forename: Daiana
authors.initials: D
authors.lastname: Stolz
authors.forename: Beat
authors.initials: B
authors.lastname: Mueller
authors.forename: Nils G
authors.initials: NG
authors.lastname: Morgenthaler
authors.forename: Joachim
authors.initials: J
authors.lastname: Struck
authors.forename: Christian
authors.initials: C
authors.lastname: Mueller
authors.forename: Roland
authors.initials: R
authors.lastname: Bingisser
authors.forename: Michael
authors.initials: M
authors.lastname: Tamm
authors.forename: Mirjam
authors.initials: M
authors.lastname: Christ-Crain
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016470:Bacteremia / Q000175:diagnosis; D017714:Community-Acquired Infections / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy / Q000401:mortality; D019332:Endothelin-1 / Q000097:blood*; D005260:Female; D006801:Humans; D007118:Immunoassay; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011014:Pneumonia / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy / Q000401:mortality; D011379:Prognosis; D011498:Protein Precursors / Q000097:blood*; D012372:ROC Curve; D016032:Randomized Controlled Trials as Topic; D012720:Severity of Illness Index; D013557:Switzerland; D016896:Treatment Outcome
chemical_list: D019332:Endothelin-1; D011498:Protein Precursors; C093240:proendothelin 1