title: Increased plasminogen activator inhibitor-1 concentrations in bronchoalveolar lavage fluids are associated with increased mortality in a cohort of patients with Pseudomonas aeruginosa.
abstract: BACKGROUND
  Increased plasminogen activator inhibitor-1 (PAI-1) concentrations are found in bronchoalveolar lavage (BAL) fluids from patients with ventilator-associated pneumonia or acute respiratory distress syndrome. The authors hypothesized that PAI-1 concentrations were associated with increased mortality in patients with either Pseudomonas aeruginosa-induced ventilator-associated pneumonia or tracheobronchial colonization.
  
  
  METHODS
  In a prospective cohort study, daily aspirates from intubated patients were cultured for P. aeruginosa. Positive patients had blind BAL (bBAL) that was processed for biomarker concentrations. Secretion of type III secretion cytotoxins were also analyzed from the P. aeruginosa strains.
  
  
  RESULTS
  Thirty-three patients were enrolled. Ten of the 33 patients died. bBAL PAI-1 concentrations were significantly increased in nonsurvivors compared with survivors (31.7 vs. 3.4 ng/ml, P = 0.001 for hospital mortality; 35.9 vs. 4.7 ng/ml, P = 0.02 for 28-day mortality). Even when acute respiratory distress syndrome patients were excluded, there was a significant difference between the survivors and nonsurvivors for bBAL PAI-1 concentrations (P = 0.005). Eighty-three percent of P. aeruginosa strains isolated from patients with high concentrations of bBAL PAI-1 also had strains that secreted cytotoxins.
  
  
  CONCLUSIONS
  PAI-1 concentrations in bBALs correlated with mortality in ventilated patients with positive cultures for P. aeruginosa. Elevated bBAL PAI-1 concentrations also correlated with the secretion of type III exotoxins by P. aeruginosa.
authors.affiliation: Department of Anesthesia and Perioperative Care, University of California, San Francisco, USA.
authors.forename: Yuanlin
authors.initials: Y
authors.lastname: Song
authors.forename: Susan V
authors.initials: SV
authors.lastname: Lynch
authors.forename: Judith
authors.initials: J
authors.lastname: Flanagan
authors.forename: Hanjing
authors.initials: H
authors.lastname: Zhuo
authors.forename: Wynnson
authors.initials: W
authors.lastname: Tom
authors.forename: Rachel H
authors.initials: RH
authors.lastname: Dotson
authors.forename: Marshall S
authors.initials: MS
authors.lastname: Baek
authors.forename: Amua
authors.initials: A
authors.lastname: Rubio-Mills
authors.forename: Gaurav
authors.initials: G
authors.lastname: Singh
authors.forename: Eric
authors.initials: E
authors.lastname: Kipnis
authors.forename: David
authors.initials: D
authors.lastname: Glidden
authors.forename: Ron
authors.initials: R
authors.lastname: Brown
authors.forename: Oscar
authors.initials: O
authors.lastname: Garcia
authors.forename: Jeanine P
authors.initials: JP
authors.lastname: Wiener-Kronish
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D015415:Biomarkers; D001980:Bronchi / Q000382:microbiology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis*; D053717:Pneumonia, Ventilator-Associated / Q000401:mortality*; D011552:Pseudomonas Infections / Q000378:metabolism / Q000401:mortality*; D011550:Pseudomonas aeruginosa / Q000472:pathogenicity*; D011971:Receptors, Immunologic / Q000032:analysis; D014132:Trachea / Q000382:microbiology*; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D014774:Virulence
chemical_list: D000900:Anti-Bacterial Agents; D015415:Biomarkers; D008562:Membrane Glycoproteins; D017395:Plasminogen Activator Inhibitor 1; D011971:Receptors, Immunologic; C408842:TREM1 protein, human; D000073871:Triggering Receptor Expressed on Myeloid Cells-1