title: Pre-analytic factors and initial biomarker levels in community-acquired pneumonia patients.
abstract: BACKGROUND
  Blood biomarkers are increasingly used to diagnose, guide therapy in, and risk-stratify community-acquired pneumonia (CAP) patients in emergency departments (EDs). How pre-analytic factors affect these markers' initial levels in this population is unknown.
  
  
  METHODS
  In this secondary analysis of consecutive ED patients with CAP from a large multicentre antibiotic stewardship trial, we used adjusted multivariate regression models to determine the magnitude and statistical significance of differences in mean baseline concentrations of five biomarkers (procalcitonin [PCT], C-reactive protein [CRP], white blood cells count [WBC], proadrenomedullin [ProADM], copeptin) associated with six pre-analytic factors (antibiotic or corticosteroid pretreatment, age, gender, chronic renal failure or chronic liver insufficiency).
  
  
  RESULTS
  Of 925 CAP patients (median age 73 years, 58.8% male), 25.5% had antibiotic pretreatment, 2.4%, corticosteroid pretreatment, 22.3%, chronic renal failure, 2.4% chronic liver insufficiency. Differences associated with pre-analytic factors averaged 6.1% ± 4.6%; the three largest statistically significant changes (95% confidence interval) were: PCT, +14.2% (+2.1% to +26.4%, p = 0.02) with liver insufficiency; ProADM, +13.2% (+10.2% to +16.1%, p < 0.01) with age above median; CRP, -12.8% (-25.4% to -0.2%, p = 0.05) with steroid pretreatment. In post hoc sensitivity analyses, reclassification statistics showed that these factors did not result in significant changes of biomarker levels across clinically used cut-off ranges.
  
  
  CONCLUSIONS
  Despite statistically significant associations of some pre-analytic factors and biomarker levels, a clinically relevant influence seems unlikely. Our observations reinforce the concept of using biomarkers in algorithms with widely-separated cut-offs and overruling criteria considering the entire clinical picture.
  
  
  BACKGROUND
  Identifier ISRCTN95122877.
authors.affiliation: University Department of Medicine, Tellstrasse, CH-5001 Kantonsspital Aarau, Switzerland.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kutz
authors.affiliation: University Department of Medicine, Tellstrasse, CH-5001 Kantonsspital Aarau, Switzerland.
authors.forename: Eva
authors.initials: E
authors.lastname: Grolimund
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Diabetes and Clinical Nutrition, University Hospital Basel, Basel, Switzerland.
authors.forename: Mirjam
authors.initials: M
authors.lastname: Christ-Crain
authors.affiliation: Department of Internal Medicine, Bürgerspital Solothurn, Solothurn, Switzerland.
authors.forename: Robert
authors.initials: R
authors.lastname: Thomann
authors.affiliation: Basel University Medical Clinic Liestal, Liestal, Switzerland.
authors.forename: Claudine
authors.initials: C
authors.lastname: Falconnier
authors.affiliation: Department of Internal Medicine, Kantonsspital Münsterlingen, Münsterlingen, Switzerland.
authors.forename: Claus
authors.initials: C
authors.lastname: Hoess
authors.affiliation: Department of Internal Medicine, Kantonsspital Lucerne, Lucerne, Switzerland.
authors.forename: Christoph
authors.initials: C
authors.lastname: Henzen
authors.affiliation: Basel University Medical Clinic Liestal, Liestal, Switzerland.
authors.forename: Werner
authors.initials: W
authors.lastname: Zimmerli
authors.affiliation: University Department of Medicine, Tellstrasse, CH-5001 Kantonsspital Aarau, Switzerland.
authors.forename: Beat
authors.initials: B
authors.lastname: Mueller
authors.affiliation: University Department of Medicine, Tellstrasse, CH-5001 Kantonsspital Aarau, Switzerland.
authors.forename: Philipp
authors.initials: P
authors.lastname: Schuetz
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D017714:Community-Acquired Infections / Q000097:blood* / Q000188:drug therapy; D004636:Emergency Service, Hospital; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011014:Pneumonia / Q000097:blood* / Q000188:drug therapy; D011446:Prospective Studies; D012044:Regression Analysis
chemical_list: D000900:Anti-Bacterial Agents; D015415:Biomarkers; D005938:Glucocorticoids
keywords: Blood biomarkers; C-reactive protein; Community-acquired pneumonia; Copeptin; Pre-analytic factors; Pretreatment; Proadrenomedullin; Procalcitonin; White blood cells count