title: Neutropenic sepsis is associated with distinct clinical and biological characteristics: a cohort study of severe sepsis.
abstract: Immunocompromised patients who develop sepsis while neutropenic are at high risk for morbidity and mortality; however, it is unknown if neutropenic sepsis is associated with distinct clinical and biological characteristics.
  
  
  
  We conducted a prospective cohort study of patients admitted to the medical intensive care unit of an academic medical center with severe sepsis. Patients were followed for the development of acute respiratory distress syndrome (ARDS), acute kidney injury (AKI), and mortality. Plasma proteins, representing the host inflammatory response, anti-inflammatory response, and endothelial leak were measured in 30 % of subjects. Clinical characteristics and plasma protein concentrations of patients with neutropenia at enrollment were compared to patients without neutropenia.
  
  
  
  Of 797 subjects enrolled, 103 (13 %) were neutropenic at ICU admission. The neutropenic subjects were more often in shock, admitted from the hospital ward, had higher APACHE III scores, and more likely bacteremic. Neutropenia was an independent risk factor for AKI (RR 1.28; 95 % CI 1.04, 1.57; p = 0.03), but not ARDS (RR 0.90; 95 % CI 0.70, 1.17; p = 0.42) or 30-day mortality (RR 1.05; 95 % CI 0.85, 1.31; p = 0.65). Neutropenic subjects had higher plasma interleukin (IL)-6 (457 vs. 249 pg/ml; p = 0.03), IL-8 (581 vs. 94 pg/ml; p <0.001), and granulocyte colony-stimulating factor (G-CSF) (3624 vs. 99 pg/ml; p <0.001). Angiopoietin-2 and IL-1 receptor antagonist concentrations did not differ between groups.
  
  
  
  Neutropenic sepsis is associated with a higher AKI risk and concentrations of inflammatory mediators IL-6, IL-8, and G-CSF relative to non-neutropenic patients. These differences may have implications for future therapies targeting neutropenic sepsis.
authors.affiliation: Division of Pulmonary, Allergy, and Critical Care, University of Pennsylvania, Perelman School of Medicine, 3400 Spruce Street, Philadelphia, 19104, PA, USA. John.Reilly@uphs.upenn.edu.
authors.forename: John P
authors.initials: JP
authors.lastname: Reilly
authors.affiliation: Division of Pulmonary, Allergy, and Critical Care, University of Pennsylvania, Perelman School of Medicine, 3400 Spruce Street, Philadelphia, 19104, PA, USA.|Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Anderson
authors.affiliation: Division of Pulmonary, Allergy, and Critical Care, University of Pennsylvania, Perelman School of Medicine, 3400 Spruce Street, Philadelphia, 19104, PA, USA.|Division of Pulmonary, Critical Care, and Sleep Medicine, University of Cincinnati, Cincinnati, OH, USA.|Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: Kristin M
authors.initials: KM
authors.lastname: Hudock
authors.affiliation: Division of Pulmonary, Allergy, and Critical Care, University of Pennsylvania, Perelman School of Medicine, 3400 Spruce Street, Philadelphia, 19104, PA, USA.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Dunn
authors.affiliation: Division of Pulmonary, Allergy, and Critical Care, University of Pennsylvania, Perelman School of Medicine, 3400 Spruce Street, Philadelphia, 19104, PA, USA.
authors.forename: Altaf
authors.initials: A
authors.lastname: Kazi
authors.affiliation: Division of Pulmonary, Allergy, and Critical Care, University of Pennsylvania, Perelman School of Medicine, 3400 Spruce Street, Philadelphia, 19104, PA, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Tommasini
authors.affiliation: Division of Pulmonary, Allergy, and Critical Care, University of Pennsylvania, Perelman School of Medicine, 3400 Spruce Street, Philadelphia, 19104, PA, USA.
authors.forename: Dudley
authors.initials: D
authors.lastname: Charles
authors.affiliation: Division of Pulmonary, Allergy, and Critical Care, University of Pennsylvania, Perelman School of Medicine, 3400 Spruce Street, Philadelphia, 19104, PA, USA.|Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
authors.forename: Michael G S
authors.initials: MG
authors.lastname: Shashaty
authors.affiliation: Division of Pulmonary, Allergy, and Critical Care, University of Pennsylvania, Perelman School of Medicine, 3400 Spruce Street, Philadelphia, 19104, PA, USA.|Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Mikkelsen
authors.affiliation: Division of Pulmonary, Allergy, and Critical Care, University of Pennsylvania, Perelman School of Medicine, 3400 Spruce Street, Philadelphia, 19104, PA, USA.|Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
authors.forename: Jason D
authors.initials: JD
authors.lastname: Christie
authors.affiliation: Division of Pulmonary, Allergy, and Critical Care, University of Pennsylvania, Perelman School of Medicine, 3400 Spruce Street, Philadelphia, 19104, PA, USA.
authors.forename: Nuala J
authors.initials: NJ
authors.lastname: Meyer
mesh_terms: D018806:APACHE; D058186:Acute Kidney Injury / Q000453:epidemiology / Q000401:mortality; D000328:Adult; D000368:Aged; D042702:Angiopoietin-2 / Q000032:analysis / Q000097:blood; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D016009:Chi-Square Distribution; D015331:Cohort Studies; D016638:Critical Illness / Q000453:epidemiology; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000032:analysis / Q000097:blood; D006801:Humans; D007362:Intensive Care Units / Q000458:organization & administration / Q000706:statistics & numerical data; D015850:Interleukin-6 / Q000032:analysis / Q000097:blood; D016209:Interleukin-8 / Q000032:analysis / Q000097:blood; D007378:Interleukins / Q000032:analysis / Q000097:blood; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000145:classification* / Q000453:epidemiology / Q000401:mortality; D010414:Pennsylvania / Q000453:epidemiology; D011446:Prospective Studies; D017472:Receptors, Interleukin-1 / Q000032:analysis / Q000097:blood; D012128:Respiratory Distress Syndrome / Q000453:epidemiology / Q000401:mortality; D018805:Sepsis / Q000145:classification* / Q000453:epidemiology / Q000401:mortality*
chemical_list: D042702:Angiopoietin-2; D015415:Biomarkers; D015850:Interleukin-6; D016209:Interleukin-8; D007378:Interleukins; D017472:Receptors, Interleukin-1; D016179:Granulocyte Colony-Stimulating Factor
keywords: Critical illness; Immunocompromised host; Inflammation; Neutropenia; Sepsis; Septic shock