Brendon P Scicluna1, Peter M C Klein Klouwenberg2,3,4, Lonneke A van Vught1, Maryse A Wiewel1, David S Y Ong2,3,4, Aeilko H Zwinderman5, Marek Franitza6,7, Mohammad R Toliat6, Peter Nürnberg6,7,8, Arie J Hoogendijk1, Janneke Horn9, Olaf L Cremer2, Marcus J Schultz9, Marc J Bonten3,4, Tom van der Poll1,10. 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).
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).
Authors: Giorgia Purcaro; Christiaan A Rees; Jeffrey A Melvin; Jennifer M Bomberger; Jane E Hill Journal: J Breath Res Date: 2018-07-03 Impact factor: 3.262
Authors: Timothy E Sweeney; Tej D Azad; Michele Donato; Winston A Haynes; Thanneer M Perumal; Ricardo Henao; Jesús F Bermejo-Martin; Raquel Almansa; Eduardo Tamayo; Judith A Howrylak; Augustine Choi; Grant P Parnell; Benjamin Tang; Marshall Nichols; Christopher W Woods; Geoffrey S Ginsburg; Stephen F Kingsmore; Larsson Omberg; Lara M Mangravite; Hector R Wong; Ephraim L Tsalik; Raymond J Langley; Purvesh Khatri Journal: Crit Care Med Date: 2018-06 Impact factor: 7.598