title: Superiority of transcriptional profiling over procalcitonin for distinguishing bacterial from viral lower respiratory tract infections in hospitalized adults.
abstract: BACKGROUND
  Distinguishing between bacterial and viral lower respiratory tract infection (LRTI) remains challenging. Transcriptional profiling is a promising tool for improving diagnosis in LRTI.
  
  
  METHODS
  We performed whole blood transcriptional analysis in 118 patients (median age [interquartile range], 61 [50-76] years) hospitalized with LRTI and 40 age-matched healthy controls (median age, 60 [46-70] years). We applied class comparisons, modular analysis, and class prediction algorithms to identify and validate diagnostic biosignatures for bacterial and viral LRTI.
  
  
  RESULTS
  Patients were classified as having bacterial (n = 22), viral (n = 71), or bacterial-viral LRTI (n = 25) based on comprehensive microbiologic testing. Compared with healthy controls, statistical group comparisons (P < .01; multiple-test corrections) identified 3376 differentially expressed genes in patients with bacterial LRTI, 2391 in viral LRTI, and 2628 in bacterial-viral LRTI. Patients with bacterial LRTI showed significant overexpression of inflammation and neutrophil genes (bacterial > bacterial-viral > viral), and those with viral LRTI displayed significantly greater overexpression of interferon genes (viral > bacterial-viral > bacterial). The K-nearest neighbors algorithm identified 10 classifier genes that discriminated between bacterial and viral LRTI with a 95% sensitivity (95% confidence interval, 77%-100%) and 92% specificity (77%-98%), compared with a sensitivity of 38% (18%-62%) and a specificity of 91% (76%-98%) for procalcitonin.
  
  
  CONCLUSIONS
  Transcriptional profiling is a helpful tool for diagnosis of LRTI.
authors: Center for Vaccines and Immunity Division of Pediatric Infectious Diseases, The Research Institute at Nationwide Children's Hospital, The Ohio State University College of Medicine, Columbus.
authors: Nicolas M
authors: NM
authors: Suarez
authors: Center for Vaccines and Immunity Division of Pediatric Infectious Diseases, The Research Institute at Nationwide Children's Hospital, The Ohio State University College of Medicine, Columbus.
authors: Eleonora
authors: E
authors: Bunsow
authors: Department of Medicine, University of Rochester Rochester General Hospital, New York.
authors: Ann R
authors: AR
authors: Falsey
authors: Department of Medicine, University of Rochester Rochester General Hospital, New York.
authors: Edward E
authors: EE
authors: Walsh
authors: Center for Vaccines and Immunity Division of Pediatric Infectious Diseases, The Research Institute at Nationwide Children's Hospital, The Ohio State University College of Medicine, Columbus.
authors: Asuncion
authors: A
authors: Mejias
authors: Center for Vaccines and Immunity Division of Pediatric Infectious Diseases, The Research Institute at Nationwide Children's Hospital, The Ohio State University College of Medicine, Columbus.
authors: Octavio
authors: O
authors: Ramilo
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002116:Calcitonin / Q000097:blood*; D015740:Calcitonin Gene-Related Peptide; D016022:Case-Control Studies; D003937:Diagnosis, Differential; D005260:Female; D020869:Gene Expression Profiling; D006760:Hospitalization; D006801:Humans; D007251:Influenza, Human / Q000097:blood / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D011018:Pneumonia, Pneumococcal / Q000097:blood / Q000175:diagnosis*; D011446:Prospective Studies; D011498:Protein Precursors / Q000097:blood*; D012680:Sensitivity and Specificity; D059467:Transcriptome
chemical_list: D015415:Biomarkers; C000606589:CALCA protein, human; D011498:Protein Precursors; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide
keywords: bacterial infections; lower respiratory tract infection; microarrays; procalcitonin; viral infections
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