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.

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.

• Authors: Philipp Schuetz, Daiana Stolz, Beat Mueller, Nils G Morgenthaler, Joachim Struck, Christian Mueller, Roland Bingisser, Michael Tamm, Mirjam Christ-Crain
• Journal: BMC infectious diseases (BMC Infect Dis) Vol. 8 Pg. 22 (Feb 28 2008) ISSN: 1471-2334 [Electronic] England
• PMID: 18304365 (Publication Type: Journal Article)

Chemical References

• Endothelin-1
• Protein Precursors
• proendothelin 1

Topics

• Aged
• Aged, 80 and over
• Bacteremia (diagnosis)
• Community-Acquired Infections (blood, diagnosis, drug therapy, mortality)
• Endothelin-1 (blood)
• Female
• Humans
• Immunoassay
• Logistic Models
• Male
• Middle Aged
• Multivariate Analysis
• Pneumonia (blood, diagnosis, drug therapy, mortality)
• Prognosis
• Protein Precursors (blood)
• ROC Curve
• Randomized Controlled Trials as Topic
• Severity of Illness Index
• Switzerland
• Treatment Outcome