Systematic Review and Meta-Analysis of Diagnostic Biomarkers for Pediatric Pneumonia

BACKGROUND: Pneumonia causes significant morbidity and mortality in children worldwide, especially in resource-poor settings. Accurate identification of bacterial etiology leads to timely antibiotic initiation, minimizing overuse, and development of resistance. Host biomarkers may improve diagnostic sensitivity and specificity. We assessed the ability of biomarkers to correctly identify bacterial pneumonia in children who present with respiratory distress. METHODS: A librarian-directed search was conducted of MEDLINE, EMBASE, CENTRAL, Global Health, the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov to May 2020 with no language restriction. Included studies compared a diagnostic biomarker in children with bacterial pneumonia to those with nonbacterial respiratory distress. RESULTS: There were 31 observational studies of 23 different biomarkers. C-reactive protein (CRP), procalcitonin (PCT), white blood cell (WBC) count, and erythrocyte sedimentation rate (ESR) were the biomarkers with sufficient data for meta-analysis. Meta-analysis revealed that CRP and PCT best differentiated bacterial from viral pneumonia with CRP summary AUROC (area under the receiver operating characteristic curve) 0.71 (0.69-0.73), Youden index 53 mg/L, sensitivity 0.70 (0.68-0.78), and specificity 0.64 (0.58-0.68) and PCT summary AUROC 0.70 (0.67-0.74), Youden index 0.59 ng/mL, sensitivity 0.69 (0.65-0.77), and specificity 0.64 (0.60-0.68). WBC and ESR did not perform as well. Nineteen other inflammatory and immunologic biomarkers were identified including CRP/mean platelet value, neutrophil/leukocyte ratio, interleukin 6, and interferon-alpha, with sensitivities from 60% to 85% and specificities from 76% to 83%. CONCLUSION: CRP and PCT performed better than WBC and ESR but had suboptimal sensitivity. Some less well-studied novel biomarkers appear to have promise particularly in combination.