title: Proteomic profiling of bronchoalveolar lavage fluid in critically ill patients with ventilator-associated pneumonia.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicinal Chemistry, University of Washington, Seattle, Washington, United States of America.
authors.forename: Elizabeth V
authors.initials: EV
authors.lastname: Nguyen
authors.forename: Sina A
authors.initials: SA
authors.lastname: Gharib
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Palazzo
authors.forename: Yu-hua
authors.initials: YH
authors.lastname: Chow
authors.forename: David R
authors.initials: DR
authors.lastname: Goodlett
authors.forename: Lynn M
authors.initials: LM
authors.lastname: Schnapp
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D016022:Case-Control Studies; D016000:Cluster Analysis; D016638:Critical Illness; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008875:Middle Aged; D053717:Pneumonia, Ventilator-Associated / Q000235:genetics / Q000378:metabolism*; D025941:Protein Interaction Mapping; D060066:Protein Interaction Maps; D020543:Proteome; D040901:Proteomics; D015203:Reproducibility of Results; D055815:Young Adult
chemical_list: D020543:Proteome