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

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 patie...

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Vydáno v:American journal of respiratory and critical care medicine Ročník 192; číslo 7; s. 826 - 835
Hlavní autoři: 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
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States American Thoracic Society 01.10.2015
Témata:
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
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Abstract 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).
AbstractList 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.RATIONALECommunity-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.OBJECTIVESTo 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.METHODSThe 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.MEASUREMENTS AND MAIN RESULTSBlood 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).CONCLUSIONSCAP 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).
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).
Author Zwinderman, Aeilko H.
Nürnberg, Peter
Wiewel, Maryse A.
Schultz, Marcus J.
van Vught, Lonneke A.
Scicluna, Brendon P.
Toliat, Mohammad R.
Cremer, Olaf L.
Horn, Janneke
Hoogendijk, Arie J.
van der Poll, Tom
Klein Klouwenberg, Peter M. C.
Bonten, Marc J.
Franitza, Marek
Ong, David S. Y.
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  organization: Center for Experimental Molecular Medicine and Center for Infection and Immunity Amsterdam
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  givenname: Peter M. C.
  surname: Klein Klouwenberg
  fullname: Klein Klouwenberg, Peter M. C.
  organization: Department of Intensive Care Medicine, Department of Medical Microbiology, and, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands; and
– sequence: 3
  givenname: Lonneke A.
  surname: van Vught
  fullname: van Vught, Lonneke A.
  organization: Center for Experimental Molecular Medicine and Center for Infection and Immunity Amsterdam
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  givenname: Maryse A.
  surname: Wiewel
  fullname: Wiewel, Maryse A.
  organization: Center for Experimental Molecular Medicine and Center for Infection and Immunity Amsterdam
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  givenname: David S. Y.
  surname: Ong
  fullname: Ong, David S. Y.
  organization: Department of Intensive Care Medicine, Department of Medical Microbiology, and, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands; and
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  givenname: Aeilko H.
  surname: Zwinderman
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  givenname: Marek
  surname: Franitza
  fullname: Franitza, Marek
  organization: Cologne Center for Genomics, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, and
– sequence: 8
  givenname: Mohammad R.
  surname: Toliat
  fullname: Toliat, Mohammad R.
  organization: Cologne Center for Genomics
– sequence: 9
  givenname: Peter
  surname: Nürnberg
  fullname: Nürnberg, Peter
  organization: Cologne Center for Genomics, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, and, Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany
– sequence: 10
  givenname: Arie J.
  surname: Hoogendijk
  fullname: Hoogendijk, Arie J.
  organization: Center for Experimental Molecular Medicine and Center for Infection and Immunity Amsterdam
– sequence: 11
  givenname: Janneke
  surname: Horn
  fullname: Horn, Janneke
  organization: Department of Intensive Care Medicine, and
– sequence: 12
  givenname: Olaf L.
  surname: Cremer
  fullname: Cremer, Olaf L.
  organization: Department of Intensive Care Medicine
– sequence: 13
  givenname: Marcus J.
  surname: Schultz
  fullname: Schultz, Marcus J.
  organization: Department of Intensive Care Medicine, and
– sequence: 14
  givenname: Marc J.
  surname: Bonten
  fullname: Bonten, Marc J.
  organization: Department of Medical Microbiology, and, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands; and
– sequence: 15
  givenname: Tom
  surname: van der Poll
  fullname: van der Poll, Tom
  organization: Center for Experimental Molecular Medicine and Center for Infection and Immunity Amsterdam, Division of Infectious Diseases, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
BackLink https://www.ncbi.nlm.nih.gov/pubmed/26121490$$D View this record in MEDLINE/PubMed
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ContentType Journal Article
Copyright Copyright American Thoracic Society Oct 1, 2015
Copyright_xml – notice: Copyright American Thoracic Society Oct 1, 2015
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SubjectTerms 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
Title A Molecular Biomarker to Diagnose Community-acquired Pneumonia on Intensive Care Unit Admission
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