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- Title
A molecular biomarker to diagnose community-acquired pneumonia on intensive care unit admission.
- 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
- Abstract
<bold>Rationale: </bold>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.<bold>Objectives: </bold>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.<bold>Methods: </bold>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.<bold>Measurements and Main Results: </bold>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.<bold>Conclusions: </bold>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).
- Subjects
PNEUMONIA diagnosis; COMMUNITY-acquired infections; CALCITONIN; INTENSIVE care units; INTERLEUKINS; PROTEIN precursors; PROTEINS; TISSUE arrays; GENE expression profiling; DIAGNOSIS
- Publication
American Journal of Respiratory & Critical Care Medicine, 2015, Vol 192, Issue 7, p826
- ISSN
1073-449X
- Publication type
journal article
- DOI
10.1164/rccm.201502-0355OC