title: Outcome prediction in pneumonia induced ALI/ARDS by clinical features and peptide patterns of BALF determined by mass spectrometry.
abstract: BACKGROUND
  Peptide patterns of bronchoalveolar lavage fluid (BALF) were assumed to reflect the complex pathology of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) better than clinical and inflammatory parameters and may be superior for outcome prediction.
  
  
  RESULTS
  A training group of patients suffering from ALI/ARDS was compiled from equal numbers of survivors and nonsurvivors. Clinical history, ventilation parameters, Murray's lung injury severity score (Murray's LISS) and interleukins in BALF were gathered. In addition, samples of bronchoalveolar lavage fluid were analyzed by means of hydrophobic chromatography and MALDI-ToF mass spectrometry (MALDI-ToF MS). Receiver operating characteristic (ROC) analysis for each clinical and cytokine parameter revealed interleukin-6>interleukin-8>diabetes mellitus>Murray's LISS as the best outcome predictors. Outcome predicted on the basis of BALF levels of interleukin-6 resulted in 79.4% accuracy, 82.7% sensitivity and 76.1% specificity (area under the ROC curve, AUC, 0.853). Both clinical parameters and cytokines as well as peptide patterns determined by MALDI-ToF MS were analyzed by classification and regression tree (CART) analysis and support vector machine (SVM) algorithms. CART analysis including Murray's LISS, interleukin-6 and interleukin-8 in combination was correct in 78.0%. MALDI-ToF MS of BALF peptides did not reveal a single identifiable biomarker for ARDS. However, classification of patients was successfully achieved based on the entire peptide pattern analyzed using SVM. This method resulted in 90% accuracy, 93.3% sensitivity and 86.7% specificity following a 10-fold cross validation (AUC = 0.953). Subsequent validation of the optimized SVM algorithm with a test group of patients with unknown prognosis yielded 87.5% accuracy, 83.3% sensitivity and 90.0% specificity.
  
  
  CONCLUSIONS
  MALDI-ToF MS peptide patterns of BALF, evaluated by appropriate mathematical methods can be of value in predicting outcome in pneumonia induced ALI/ARDS.
authors: Institute of Biochemistry, University of Leipzig, Leipzig, Germany. Jochen.Frenzel@medizin.uni-leipzig.de
authors: Jochen
authors: J
authors: Frenzel
authors: Christian
authors: C
authors: Gessner
authors: Torsten
authors: T
authors: Sandvoss
authors: Stefan
authors: S
authors: Hammerschmidt
authors: Wolfgang
authors: W
authors: Schellenberger
authors: Ulrich
authors: U
authors: Sack
authors: Klaus
authors: K
authors: Eschrich
authors: Hubert
authors: H
authors: Wirtz
mesh_terms: D055371:Acute Lung Injury / Q000150:complications* / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D016207:Cytokines / Q000378:metabolism; D057225:Data Mining; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D011014:Pneumonia / Q000209:etiology* / Q000473:pathology; D011379:Prognosis; D012372:ROC Curve; D015203:Reproducibility of Results; D012128:Respiratory Distress Syndrome / Q000150:complications* / Q000473:pathology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*; D060388:Support Vector Machine; D016896:Treatment Outcome
chemical_list: D016207:Cytokines; D010455:Peptides