A molecular biomarker to diagnose community-acquired pneumonia on intensive care unit admission

Am J Respir Crit Care Med. 2015 Oct 1;192(7):826-35. doi: 10.1164/rccm.201502-0355OC.


Rationale: Community-acquired pneumonia (CAP) accounts for a major proportion of intensive care unit (ICU) admissions for respiratory failure and sepsis. Diagnostic uncertainty complicates case management, which may delay appropriate cause-specific treatment.

Objectives: To characterize the blood genomic response in patients with suspected CAP and identify a candidate biomarker for the rapid diagnosis of CAP on ICU admission.

Methods: The study comprised two cohorts of consecutively enrolled patients treated for suspected CAP on ICU admission. Patients were designated CAP (cases) and no-CAP patients (control subjects) by post hoc assessment. The first (discovery) cohort (101 CAP and 33 no-CAP patients) was enrolled between January 2011 and July 2012; the second (validation) cohort (70 CAP and 30 no-CAP patients) between July 2012 and June 2013. Blood was collected within 24 hours of ICU admission.

Measurements and main results: Blood microarray analysis of CAP and no-CAP patients revealed shared and distinct gene expression patterns. A 78-gene signature was defined for CAP, from which a FAIM3:PLAC8 gene expression ratio was derived with area under curve of 0.845 (95% confidence interval, 0.764-0.917) and positive and negative predictive values of 83% and 81%, respectively. Robustness of the FAIM3:PLAC8 ratio was ascertained by quantitative polymerase chain reaction in the validation cohort. The FAIM3:PLAC8 ratio outperformed plasma procalcitonin and IL-8 and IL-6 in discriminating between CAP and no-CAP patients.

Conclusions: CAP and no-CAP patients presented shared and distinct blood genomic responses. We propose the FAIM3:PLAC8 ratio as a candidate biomarker to assist in the rapid diagnosis of CAP on ICU admission. Clinical trial registered with www.clinicaltrials.gov (NCT 01905033).

Trial registration: ClinicalTrials.gov NCT01905033.

Keywords: biomarker; blood; microarray; pneumonia; sepsis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Apoptosis Regulatory Proteins / genetics*
  • Biomarkers / blood*
  • Calcitonin / blood
  • Calcitonin Gene-Related Peptide
  • Community-Acquired Infections / diagnosis*
  • Female
  • Gene Expression Profiling
  • Humans
  • Intensive Care Units
  • Interleukin-6 / blood
  • Interleukin-8 / blood
  • Male
  • Middle Aged
  • Pneumonia / diagnosis*
  • Protein Precursors / blood
  • Proteins / genetics*
  • Tissue Array Analysis


  • Apoptosis Regulatory Proteins
  • Biomarkers
  • CALCA protein, human
  • FAIM protein, human
  • Interleukin-6
  • Interleukin-8
  • PLAC8 protein, human
  • Protein Precursors
  • Proteins
  • Calcitonin
  • Calcitonin Gene-Related Peptide

Associated data

  • ClinicalTrials.gov/NCT01905033