Abstract
BackgroundPeptide 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.Methodology/Principal FindingsA 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/SignificanceMALDI-ToF MS peptide patterns of BALF, evaluated by appropriate mathematical methods can be of value in predicting outcome in pneumonia induced ALI/ARDS.
Highlights
Patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are at increased risk of death within 28 days [1,2,3]
We started with predicting outcome of pneumonia induced ALI/ARDS patients on the basis of clinical data including Murray’s LIS score, ventilation parameters, i.e. peak inspiratory pressure (PIP), positive end-expiratory airway pressure (PEEP), risk factors and bronchoalveolar lavage fluid (BALF) interleukins
Outcome Prediction Based on Clinical Features Individual risk factors, Murray’s LIS score, ventilatory variables and inflammatory parameters in BALF were gathered from 30 patients with pneumonia induced ALI/ARDS
Summary
Patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are at increased risk of death within 28 days [1,2,3]. In some studies MS spectra of complex samples from lung patients were recorded and the peptide/protein patterns were analyzed by means of mathematical algorithms without peak identification. We started with predicting outcome of pneumonia induced ALI/ARDS patients on the basis of clinical data including Murray’s LIS score, ventilation parameters, i.e. peak inspiratory pressure (PIP), positive end-expiratory airway pressure (PEEP), risk factors (diabetes mellitus, smoking habit) and BALF interleukins. A new approach was developed to predict outcome of patients from BALF peptide patterns captured by mass spectrometric determination and analyzed by sophisticated mathematical methods. This peptide profiling approach is fast and proved superior following cross validation, calculation of receiver. Operating characteristic (ROC) curves and the area under the ROC curve (AUC) and validation by analyzing a test group of patients [7,33,34,35]
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