title: The association between the neutrophil-to-lymphocyte ratio and mortality in critical illness: an observational cohort study.
abstract: BACKGROUND
  The neutrophil-to-lymphocyte ratio (NLR) is a biological marker that has been shown to be associated with outcomes in patients with a number of different malignancies. The objective of this study was to assess the relationship between NLR and mortality in a population of adult critically ill patients.
  
  
  METHODS
  We performed an observational cohort study of unselected intensive care unit (ICU) patients based on records in a large clinical database. We computed individual patient NLR and categorized patients by quartile of this ratio. The association of NLR quartiles and 28-day mortality was assessed using multivariable logistic regression. Secondary outcomes included mortality in the ICU, in-hospital mortality and 1-year mortality. An a priori subgroup analysis of patients with versus without sepsis was performed to assess any differences in the relationship between the NLR and outcomes in these cohorts.
  
  
  RESULTS
  A total of 5,056 patients were included. Their 28-day mortality rate was 19%. The median age of the cohort was 65 years, and 47% were female. The median NLR for the entire cohort was 8.9 (interquartile range, 4.99 to 16.21). Following multivariable adjustments, there was a stepwise increase in mortality with increasing quartiles of NLR (first quartile: reference category; second quartile odds ratio (OR) = 1.32; 95% confidence interval (CI), 1.03 to 1.71; third quartile OR = 1.43; 95% CI, 1.12 to 1.83; 4th quartile OR = 1.71; 95% CI, 1.35 to 2.16). A similar stepwise relationship was identified in the subgroup of patients who presented without sepsis. The NLR was not associated with 28-day mortality in patients with sepsis. Increasing quartile of NLR was statistically significantly associated with secondary outcome.
  
  
  CONCLUSIONS
  The NLR is associated with outcomes in unselected critically ill patients. In patients with sepsis, there was no statistically significant relationship between NLR and mortality. Further investigation is required to increase understanding of the pathophysiology of this relationship and to validate these findings with data collected prospectively.
authors.affiliation: Department of Medicine, Imperial College London, London, SW7 2AZ, UK. justin.salciccioli12@imperial.ac.uk.
authors.forename: Justin D
authors.initials: JD
authors.lastname: Salciccioli
authors.affiliation: Department of Medicine, Imperial College London, London, SW7 2AZ, UK. dominic.marshall12@imperial.ac.uk.
authors.forename: Dominic C
authors.initials: DC
authors.lastname: Marshall
authors.affiliation: Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Old Road Campus Research Building, Headington, Oxford, OX3 7DQ, UK. marco.pimentel@eng.ox.ac.uk.
authors.forename: Marco A F
authors.initials: MA
authors.lastname: Pimentel
authors.affiliation: Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Old Road Campus Research Building, Headington, Oxford, OX3 7DQ, UK. mauro.santos@eng.ox.ac.uk.
authors.forename: Mauro D
authors.initials: MD
authors.lastname: Santos
authors.affiliation: University College London, Mullard Space Science Laboratory, Gower Street, London, WC1E 6BT, UK. tom.pollard.11@ucl.ac.uk.|Department of Anaesthetics and Critical Care, University College Hospital, Podium 3, Maple Link corridor, University College Hospital, 235 Euston Road, London, NW1 2BU, UK. tom.pollard.11@ucl.ac.uk.
authors.forename: Tom
authors.initials: T
authors.lastname: Pollard
authors.affiliation: Institute for Medical Engineering & Science, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, 02139, MA, USA. lceli@mit.edu.|Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, 02215, MA, USA. lceli@mit.edu.
authors.forename: Leo Anthony
authors.initials: LA
authors.lastname: Celi
authors.affiliation: Division of Vascular Surgery, Department of Surgery and Cancer, Imperial College London, 4 North, Charing Cross Hospital, Fulham Palace Road, London, W6 8RF, UK. j.shalhoub@imperial.ac.uk.
authors.forename: Joseph
authors.initials: J
authors.lastname: Shalhoub
mesh_terms: D000368:Aged; D015331:Cohort Studies; D016638:Critical Illness / Q000401:mortality*; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D007362:Intensive Care Units; D007958:Leukocyte Count; D016015:Logistic Models; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D009504:Neutrophils; D011237:Predictive Value of Tests; D018570:Risk Assessment