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

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

Author information

1
1 Center for Experimental Molecular Medicine and Center for Infection and Immunity Amsterdam.
2
2 Department of Intensive Care Medicine.
3
3 Department of Medical Microbiology, and.
4
4 Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands; and.
5
5 Clinical Epidemiology Biostatistics and Bioinformatics.
6
6 Cologne Center for Genomics.
7
7 Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, and.
8
8 Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.
9
9 Department of Intensive Care Medicine, and.
10
10 Division of Infectious Diseases, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.

Abstract

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).

KEYWORDS:

biomarker; blood; microarray; pneumonia; sepsis

PMID:
26121490
DOI:
10.1164/rccm.201502-0355OC
[Indexed for MEDLINE]

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