title: Distinct inflammatory mediator patterns characterize infectious and sterile systemic inflammation in febrile neutropenic hematology patients.
abstract: BACKGROUND
  Invasive infections and sterile tissue damage can both give rise to systemic inflammation with fever and production of inflammatory mediators. This makes it difficult to diagnose infections in patients who are already inflamed, e.g. due to cell and tissue damage. For example, fever in patients with hematological malignancies may depend on infection, lysis of malignant cells, and/or chemotherapy-induced mucosal damage. We hypothesized that it would be possible to distinguish patterns of inflammatory mediators characterizing infectious and non-infectious causes of inflammation, respectively. Analysis of a broad range of parameters using a multivariate method of pattern recognition was done for this purpose.
  
  
  METHODS
  In this prospective study, febrile (>38°C) neutropenic patients (n = 42) with hematologic malignancies were classified as having or not having a microbiologically defined infection by an infectious disease specialist. In parallel, blood was analyzed for 116 biomarkers, and 23 clinical variables were recorded for each patient. Using O-PLS (orthogonal projection to latent structures), a model was constructed based on these 139 variables that could separate the infected from the non-infected patients. Non-discriminatory variables were discarded until a final model was reached. Finally, the capacity of this model to accurately classify a validation set of febrile neutropenic patients (n = 10) as infected or non-infected was tested.
  
  
  RESULTS
  A model that could segregate infected from non-infected patients was achieved based on discrete differences in the levels of 40 variables. These variables included acute phase proteins, cytokines, measures of coagulation, metabolism, organ stress and iron turn-over. The model correctly identified the infectious status of nine out of ten subsequently recruited febrile neutropenic hematology patients.
  
  
  CONCLUSIONS
  It is possible to separate patients with infectious inflammation from those with sterile inflammation based on inflammatory mediator patterns. This strategy could be developed into a decision-making tool for diverse clinical applications.
authors.affiliation: Department of Hematology and Coagulation, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden; Department of Infectious Diseases, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.
authors.forename: Christine
authors.initials: C
authors.lastname: Wennerås
authors.affiliation: Department of Infectious Diseases, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Hagberg
authors.affiliation: Department of Infectious Diseases, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.
authors.forename: Rune
authors.initials: R
authors.lastname: Andersson
authors.affiliation: Department of Clinical Chemistry, Sahlgrenska University Hospital, Göteborg, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Hynsjö
authors.affiliation: Department of Clinical Chemistry, Sahlgrenska University Hospital, Göteborg, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Lindahl
authors.affiliation: Department of Laboratory Medicine, Lund University, Malmö, Sweden.
authors.forename: Marcin
authors.initials: M
authors.lastname: Okroj
authors.affiliation: Department of Laboratory Medicine, Lund University, Malmö, Sweden.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Blom
authors.affiliation: Department of Hematology and Coagulation, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden; Department of Internal Medicine, Uddevalla Hospital, Uddevalla, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Johansson
authors.affiliation: Department of Hematology and Coagulation, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden; Department of Internal Medicine, Uddevalla Hospital, Uddevalla, Sweden.
authors.forename: Björn
authors.initials: B
authors.lastname: Andreasson
authors.affiliation: Department of Chemistry and Molecular Biology, University of Gothenburg, Göteborg, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Gottfries
authors.affiliation: Department of Infectious Diseases, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.
authors.forename: Agnes E
authors.initials: AE
authors.lastname: Wold
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D003937:Diagnosis, Differential; D064147:Febrile Neutropenia / Q000097:blood* / Q000175:diagnosis; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D007938:Leukemia / Q000097:blood; D008297:Male; D008875:Middle Aged; D010363:Pattern Recognition, Automated; D011446:Prospective Studies; D018805:Sepsis / Q000097:blood* / Q000175:diagnosis; D055815:Young Adult
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators