Proteomic Profiling of Bronchoalveolar Lavage Fluid in Critically Ill Patients with Ventilator-Associated Pneumonia

• Published in: PloS one Vol. 8; no. 3; p. e58782
• Main Authors: Nguyen, Elizabeth V., Gharib, Sina A., Palazzo, Steven J., Chow, Yu-hua, Goodlett, David R., Schnapp, Lynn M.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 07.03.2013; Public Library of Science (PLoS)
• Subjects: Actinin; Adult; Adult respiratory distress syndrome; Aged; Aged, 80 and over; Algorithms; Alveoli; Analysis; Annotations; Biology; Biomarkers; Bronchoalveolar lavage; Bronchoalveolar Lavage Fluid - chemistry; Bronchus; Case-Control Studies; Cluster Analysis; Computer applications; Critical care; Critical Illness; Female; Functional analysis; Gene expression; Gene Expression Regulation; Health aspects; Humans; Identification methods; Inflammation; Lungs; Male; Mass spectrometry; Mass spectroscopy; Medicine; Middle Aged; Morbidity; Mortality; Network analysis; Neutrophils; Patients; Peptides; Pharmaceutical sciences; Pneumonia; Pneumonia, Ventilator-Associated - genetics; Pneumonia, Ventilator-Associated - metabolism; Protein Interaction Mapping; Protein Interaction Maps; Proteins; Proteome; Proteomics; Pulmonary arteries; Reproducibility of Results; Shotguns; Statistical methods; Target recognition; Ventilator-associated pneumonia; Ventilators; Young Adult; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0058782

Ventilator-associated pneumonia (VAP) is a common complication in patients with acute lung injury (ALI) and can lead to increased morbidity and mortality. Identifying protein profiles specific to VAP in bronchoalveolar lavage fluid (BALF) may aid in earlier diagnosis, elucidate mechanisms of disease, and identify putative targets for therapeutic intervention. BALF was obtained from 5 normal subjects and 30 ALI patients: 14 with VAP (VAP(+)) and 16 without VAP (VAP(-)). Each sample underwent shotgun proteomic analysis based on tandem mass spectrometry. Differentially expressed proteins between the groups were identified using statistical methods based on spectral counting. Mechanisms of disease were explored using functional annotation and protein interaction network analysis. Supervised classification algorithms were implemented to discover a proteomic classifier for identifying critically ill patients with VAP. ALI patients had distinct BALF proteomic profiles compared to normal controls. Within the ALI group, we identified 76 differentially expressed proteins between VAP(+) and VAP(-). Functional analysis of these proteins suggested activation of pro-inflammatory pathways during VAP. We identified and validated a limited proteomic signature that discriminated VAP(+) from VAP(-) patients comprised of three proteins: S100A8, lactotransferrin (LTF), and actinin 1 (ACTN1). Combining proteomic with computational analyses is a powerful approach to study the BALF proteome during lung injury and development of VAP. This integrative methodology is a promising strategy to differentiate clinically relevant subsets of ALI patients, including those suffering from VAP.