Host Inflammatory Biomarkers of Disease Severity in Pediatric Community-Acquired Pneumonia: A Systematic Review and Meta-analysis

BACKGROUND: Community-acquired pneumonia (CAP) is the leading cause of death in children. Identification of reliable biomarkers offers the potential to develop a severity quantitative score to assist in clinical decision-making and improve outcomes. METHODS: A systematic review and meta-analysis was performed in PubMed and EMBASE on November 13, 2018, to examine the association between host inflammatory biomarkers and CAP severity in children. The inclusion criteria were case–control, cross-sectional, and cohort studies that examined candidate serum biomarkers. We extracted outcomes of interest, means, and standardized mean differences (SMDs) of plasma and serum levels of biomarkers together with information on disease severity. Meta-analysis was performed. This review was registered in the PROSPERO international registry (CRD42019123351). RESULTS: Two hundred seventy-two abstracts were identified, and 17 studies were included. Among the biomarkers evaluated, levels of C-reactive protein (CRP; SMD, 0.63; 95% confidence interval [CI], 0.35 to 0.91), interleukin (IL)-6 (SMD, 0.46; 95% CI, 0.25 to 0.66), IL-8 (SMD, 0.72; 95% CI, 0.15 to 1.29), neutrophil count (SMD, 0.27; 95% CI, 0.07 to 0.47), and procalcitonin (SMD, 0.68; 95% CI, 0.20 to 1.15) were substantially increased in severe CAP. In contrast, IL-2 concentrations (SMD, –0.24; 95% CI, –0.45 to –0.03) were higher in nonsevere CAP. Study heterogeneity was reported to be high (I(2) > 75%), except for IL-2, IL-5, IL-6, and IL-12p70, which were classified as moderate (I(2) = 50%–74%). Only neutrophil and white blood cell counts were described by studies exhibiting a low level of heterogeneity. CONCLUSIONS: Our results suggest that host biomarkers, and especially CRP, IL-6, IL-8, and procalcitonin levels, have the potential to predict severe CAP in pediatric populations.