Scicluna, Brendon P., Klouwenberg, Peter M. C. Klein, van Vught, Lonneke A., Wiewel, Maryse A., Ong, David S. Y., Zwinderman, Aeilko H., Franitza, Marek, Toliat, Mohammad R., Nuernberg, Peter, Hoogendijk, Arie J., Horn, Janneke, Cremer, Olaf L., Schultz, Marcus J., Bonten, Marc J. and van der Poll, Tom (2015). A Molecular Biomarker to Diagnose Community-acquired Pneumonia on Intensive Care Unit Admission. Am. J. Respir. Crit. Care Med., 192 (7). S. 826 - 836. NEW YORK: AMER THORACIC SOC. ISSN 1535-4970

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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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Scicluna, Brendon P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klouwenberg, Peter M. C. KleinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van Vught, Lonneke A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wiewel, Maryse A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ong, David S. Y.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zwinderman, Aeilko H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Franitza, MarekUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Toliat, Mohammad R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nuernberg, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hoogendijk, Arie J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Horn, JannekeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cremer, Olaf L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schultz, Marcus J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bonten, Marc J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van der Poll, TomUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-391841
DOI: 10.1164/rccm.201502-0355OC
Journal or Publication Title: Am. J. Respir. Crit. Care Med.
Volume: 192
Number: 7
Page Range: S. 826 - 836
Date: 2015
Publisher: AMER THORACIC SOC
Place of Publication: NEW YORK
ISSN: 1535-4970
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
CRITICALLY-ILL PATIENTS; C-REACTIVE PROTEIN; GENE-EXPRESSION; SEPTIC SHOCK; SEPSIS DIAGNOSIS; SYSTEMIC INFLAMMATION; PROCALCITONIN; METAANALYSIS; BLOOD; INFECTIONSMultiple languages
Critical Care Medicine; Respiratory SystemMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/39184

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