Institute of Biochemistry, University of Leipzig, Leipzig, Germany.
PLoS One. 2011;6(10):e25544. doi: 10.1371/journal.pone.0025544. Epub 2011 Oct 3.
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.
METHODOLOGY/PRINCIPAL FINDINGS: 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/SIGNIFICANCE: MALDI-ToF MS peptide patterns of BALF, evaluated by appropriate mathematical methods can be of value in predicting outcome in pneumonia induced ALI/ARDS.
支气管肺泡灌洗液（BALF）的肽模式被认为比临床和炎症参数更好地反映急性肺损伤（ALI）/急性呼吸窘迫综合征（ARDS）的复杂病理，并且可能更适合预后预测。
方法/主要发现：从ALI/ARDS 患者中编译了一个训练组，其中包括相同数量的幸存者和非幸存者。收集了临床病史、通气参数、Murray 的肺损伤严重程度评分（Murray 的 LISS）和 BALF 中的白细胞介素。此外，还通过疏水色谱和 MALDI-ToF 质谱（MALDI-ToF MS）分析了支气管肺泡灌洗液样本。对每个临床和细胞因子参数进行的接收者操作特征（ROC）分析显示，白细胞介素-6>白细胞介素-8>糖尿病>Murray 的 LISS 是最佳的预后预测因子。基于 BALF 白细胞介素-6 水平预测的结果准确率为 79.4%，灵敏度为 82.7%，特异性为 76.1%（ROC 曲线下面积，AUC，0.853）。MALDI-ToF MS 确定的临床参数、细胞因子和肽模式均通过分类和回归树（CART）分析和支持向量机（SVM）算法进行分析。包括 Murray 的 LISS、白细胞介素-6 和白细胞介素-8 在内的 CART 分析的准确率为 78.0%。MALDI-ToF MS 对 BALF 肽未发现任何可识别的 ARDS 生物标志物。然而，使用 SVM 分析整个肽模式成功地对患者进行了分类。该方法在 10 倍交叉验证后准确率为 90%，灵敏度为 93.3%，特异性为 86.7%（AUC=0.953）。随后，对一组预后未知的患者进行了优化 SVM 算法的验证，准确率为 87.5%，灵敏度为 83.3%，特异性为 90.0%。
结论/意义：通过适当的数学方法评估 BALF 的 MALDI-ToF MS 肽模式可用于预测肺炎引起的 ALI/ARDS 的预后。
