title: Combined dysfunctions of immune cells predict nosocomial infection in critically ill patients.
abstract: BACKGROUND
  Nosocomial infection occurs commonly in intensive care units (ICUs). Although critical illness is associated with immune activation, the prevalence of nosocomial infections suggests concomitant immune suppression. This study examined the temporal occurrence of immune dysfunction across three immune cell types, and their relationship with the development of nosocomial infection.
  
  
  METHODS
  A prospective observational cohort study was undertaken in a teaching hospital general ICU. Critically ill patients were recruited and underwent serial examination of immune status, namely percentage regulatory T-cells (Tregs), monocyte deactivation (by expression) and neutrophil dysfunction (by CD88 expression). The occurrence of nosocomial infection was determined using pre-defined, objective criteria.
  
  
  RESULTS
  Ninety-six patients were recruited, of whom 95 had data available for analysis. Relative to healthy controls, percentage Tregs were elevated 6-10 days after admission, while monocyte HLA-DR and neutrophil CD88 showed broader depression across time points measured. Thirty-three patients (35%) developed nosocomial infection, and patients developing nosocomial infection showed significantly greater immune dysfunction by the measures used. Tregs and neutrophil dysfunction remained significantly predictive of infection in a Cox hazards model correcting for time effects and clinical confounders {hazard ratio (HR) 2.4 [95% confidence interval (CI) 1.1-5.4] and 6.9 (95% CI 1.6-30), respectively, P=0.001}. Cumulative immune dysfunction resulted in a progressive risk of infection, rising from no cases in patients with no dysfunction to 75% of patients with dysfunction of all three cell types (P=0.0004).
  
  
  CONCLUSIONS
  Dysfunctions of T-cells, monocytes, and neutrophils predict acquisition of nosocomial infection, and combine additively to stratify risk of nosocomial infection in the critically ill.
authors.affiliation: MRC/University Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
authors.forename: A
authors.initials: A
authors.lastname: Conway Morris
authors.forename: N
authors.initials: N
authors.lastname: Anderson
authors.forename: M
authors.initials: M
authors.lastname: Brittan
authors.forename: T S
authors.initials: TS
authors.lastname: Wilkinson
authors.forename: D F
authors.initials: DF
authors.lastname: McAuley
authors.forename: J
authors.initials: J
authors.lastname: Antonelli
authors.forename: C
authors.initials: C
authors.lastname: McCulloch
authors.forename: L C
authors.initials: LC
authors.lastname: Barr
authors.forename: K
authors.initials: K
authors.lastname: Dhaliwal
authors.forename: R O
authors.initials: RO
authors.lastname: Jones
authors.forename: C
authors.initials: C
authors.lastname: Haslett
authors.forename: A W
authors.initials: AW
authors.lastname: Hay
authors.forename: D G
authors.initials: DG
authors.lastname: Swann
authors.forename: I F
authors.initials: IF
authors.lastname: Laurenson
authors.forename: D J
authors.initials: DJ
authors.lastname: Davidson
authors.forename: A G
authors.initials: AG
authors.lastname: Rossi
authors.forename: T S
authors.initials: TS
authors.lastname: Walsh
authors.forename: A J
authors.initials: AJ
authors.lastname: Simpson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D015936:Complement C5a / Q000502:physiology; D016638:Critical Illness / Q000453:epidemiology*; D003428:Cross Infection / Q000453:epidemiology* / Q000382:microbiology; D005260:Female; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D011379:Prognosis; D011446:Prospective Studies; D044087:Receptor, Anaphylatoxin C5a / Q000096:biosynthesis; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D055815:Young Adult
chemical_list: D006684:HLA-DR Antigens; D044087:Receptor, Anaphylatoxin C5a; D015936:Complement C5a
keywords: cross infection; intensive care; lymphocytes; neutrophils