title: Diagnostic importance of pulmonary interleukin-1beta and interleukin-8 in ventilator-associated pneumonia.
abstract: BACKGROUND
  Ventilator-associated pneumonia (VAP) is the most commonly fatal nosocomial infection. Clinical diagnosis of VAP remains notoriously inaccurate. The hypothesis was tested that significantly augmented inflammatory markers distinguish VAP from conditions closely mimicking VAP.
  
  
  METHODS
  A prospective, observational cohort study was carried out in two university hospital intensive care units recruiting 73 patients with clinically suspected VAP, and a semi-urban primary care practice recruiting a reference group of 21 age- and sex-matched volunteers. Growth of pathogens at >10(4) colony-forming units (cfu)/ml of bronchoalveolar lavage fluid (BALF) distinguished VAP from "non-VAP". Inflammatory mediators were quantified in BALF and serum. Mediators showing significant differences between patients with and without VAP were analysed for diagnostic utility by receiver operator characteristic (ROC) curves.
  
  
  RESULTS
  Seventy-two patients had recoverable lavage-24% had VAP. BALF interleukin-1beta (IL-1beta), IL-8, granulocyte colony-stimulating factor and macrophage inflammatory protein-1alpha were significantly higher in the VAP group (all p<0.005). Using a cut-off of 10 pg/ml, BALF IL-1beta generated negative likelihood ratios for VAP of 0.09. In patients with BALF IL-1beta <10 pg/ml the post-test probability of VAP was 2.8%. Using a cut-off value for IL-8 of 2 ng/ml, the positive likelihood ratio was 5.03. There was no difference in cytokine levels between patients with sterile BALF and those with growth of <10(4) cfu/ml.
  
  
  CONCLUSIONS
  BALF IL-1beta and IL-8 are amongst the strongest markers yet identified for accurately demarcating VAP within the larger population of patients with suspected VAP. These findings have potential implications for reduction in unnecessary antibiotic use but require further validation in larger populations.
authors.affiliation: MRC Centre for Inflammation Research, Room C2.17, University of Edinburgh, Edinburgh EH16 4TJ, UK. mozza@doctors.org.uk
authors.forename: Andrew
authors.initials: A
authors.lastname: Conway Morris
authors.forename: Kallirroi
authors.initials: K
authors.lastname: Kefala
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Wilkinson
authors.forename: Olga Lucia
authors.initials: OL
authors.lastname: Moncayo-Nieto
authors.forename: Kevin
authors.initials: K
authors.lastname: Dhaliwal
authors.forename: Lesley
authors.initials: L
authors.lastname: Farrell
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Walsh
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Mackenzie
authors.forename: David G
authors.initials: DG
authors.lastname: Swann
authors.forename: Peter J D
authors.initials: PJ
authors.lastname: Andrews
authors.forename: Niall
authors.initials: N
authors.lastname: Anderson
authors.forename: John R W
authors.initials: JR
authors.lastname: Govan
authors.forename: Ian F
authors.initials: IF
authors.lastname: Laurenson
authors.forename: Hamish
authors.initials: H
authors.lastname: Reid
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Davidson
authors.forename: Christopher
authors.initials: C
authors.lastname: Haslett
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Sallenave
authors.forename: A John
authors.initials: AJ
authors.lastname: Simpson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000032:analysis; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000382:microbiology; D004812:Epidemiologic Methods; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000032:analysis; D053583:Interleukin-1beta / Q000032:analysis*; D016209:Interleukin-8 / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D053717:Pneumonia, Ventilator-Associated / Q000175:diagnosis* / Q000382:microbiology; D055815:Young Adult
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D016209:Interleukin-8