Superiority of transcriptional profiling over procalcitonin for distinguishing bacterial from viral lower respiratory tract infections in hospitalized adults

J Infect Dis. 2015 Jul 15;212(2):213-22. doi: 10.1093/infdis/jiv047. Epub 2015 Jan 29.


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.

Keywords: bacterial infections; lower respiratory tract infection; microarrays; procalcitonin; viral infections.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood
  • Calcitonin / blood*
  • Calcitonin Gene-Related Peptide
  • Case-Control Studies
  • Diagnosis, Differential
  • Female
  • Gene Expression Profiling
  • Hospitalization
  • Humans
  • Influenza, Human / blood
  • Influenza, Human / diagnosis*
  • Male
  • Middle Aged
  • Pneumonia, Pneumococcal / blood
  • Pneumonia, Pneumococcal / diagnosis*
  • Prospective Studies
  • Protein Precursors / blood*
  • Sensitivity and Specificity
  • Transcriptome


  • Biomarkers
  • CALCA protein, human
  • Protein Precursors
  • Calcitonin
  • Calcitonin Gene-Related Peptide