A Molecular Biomarker to Diagnose Community-acquired Pneumonia on Intensive Care Unit Admission

• Published in: American journal of respiratory and critical care medicine Vol. 192; no. 7; pp. 826 - 835
• Main Authors: Scicluna, Brendon P., Klein Klouwenberg, Peter M. C., van Vught, Lonneke A., Wiewel, Maryse A., Ong, David S. Y., Zwinderman, Aeilko H., Franitza, Marek, Toliat, Mohammad R., Nürnberg, Peter, Hoogendijk, Arie J., Horn, Janneke, Cremer, Olaf L., Schultz, Marcus J., Bonten, Marc J., van der Poll, Tom
• Format: Journal Article
• Language: English
• Published: United States American Thoracic Society 01.10.2015
• Subjects: 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; microarray; pneumonia; biomarker; blood; sepsis
• ISSN: 1073-449X; 1535-4970; 1535-4970
• DOI: 10.1164/rccm.201502-0355OC

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. 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. 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. 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. 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).