A molecular biomarker to diagnose community-acquired pneumonia on intensive care unit admission.
Am J Respir Crit Care Med
; 192(7): 826-35, 2015 Oct 01.
Article
em En
| MEDLINE
| ID: mdl-26121490
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 MAINRESULTS:
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 FAIM3PLAC8 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 FAIM3PLAC8 ratio was ascertained by quantitative polymerase chain reaction in the validation cohort. The FAIM3PLAC8 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 FAIM3PLAC8 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).Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Pneumonia
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Biomarcadores
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Proteínas
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Infecções Comunitárias Adquiridas
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Proteínas Reguladoras de Apoptose
Tipo de estudo:
Clinical_trials
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Diagnostic_studies
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Prognostic_studies
Limite:
Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article