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Browsing by Author "Soo, Jeremy"
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Item Biomarkers of Systemic Inflammation in Ugandan Infants and Children Hospitalized With Respiratory Syncytial Virus Infection(Wolters Kluwer, 2019-08) Sawatzky, Julia; Soo, Jeremy; Conroy, Andrea L.; Bhargava, Ravi; Namasopo, Sophie; Opoka, Robert O.; Hawkes, Michael T.; Pediatrics, School of MedicineBackground: Optimizing outcomes in respiratory syncytial virus (RSV) pneumonia requires accurate diagnosis and determination of severity that, in resource-limited settings, is often based on clinical assessment alone. We describe host inflammatory biomarkers and clinical outcomes among children hospitalized with RSV lower respiratory tract infection (LRTI) in Uganda and controls with rhinovirus and pneumococcal pneumonia. Methods: 58 children hospitalized with LRTI were included. We compared 37 patients with RSV, 10 control patients with rhinovirus and 11 control patients with suspected pneumococcal pneumonia. Results: Patients in the RSV group had significantly lower levels of C-reactive protein (CRP) and chitinase-3-like protein 1 (CHI3L1) than the pneumococcal pneumonia group (P < 0.05 for both). Among children with RSV, higher admission levels of CRP predicted prolonged time to resolution of tachypnea, tachycardia and fever. Higher levels of CHI3L1 were associated with higher composite clinical severity scores and predicted prolonged time to resolution of tachypnea and tachycardia, time to wean oxygen and time to sit. Higher levels of lipocalin-2 (LCN2) predicted prolonged time to resolution of tachypnea, tachycardia and time to feed. Higher admission levels of all 3 biomarkers were predictive of a higher total volume of oxygen administered during hospitalization (P < 0.05 for all comparisons). Of note, CHI3L1 and LCN2 appeared to predict clinical outcomes more accurately than CRP, the inflammatory biomarker most widely used in clinical practice. Conclusions: Our findings suggest that CHI3L1 and LCN2 may be clinically informative biomarkers in childhood RSV LRTI in low-resource settings.Item Circulating markers of neutrophil activation and lung injury in pediatric pneumonia in low-resource settings(Taylor & Francis, 2022) Konrad, Emily R.; Soo, Jeremy; Conroy, Andrea L.; Namasopo, Sophie; Opoka, Robert O.; Hawkes, Michael T.; Pediatrics, School of MedicineDiagnostic biomarkers for childhood pneumonia could guide management and improve antibiotic stewardship in low-resource settings where chest x-ray (CXR) is not always available. In this cross-sectional study, we measured chitinase 3-like protein 1 (CHI3L1), surfactant protein D (SP-D), lipocalin-2 (LCN2), and tissue inhibitor of metalloproteinases-1 (TIMP-1) in Ugandan children under the age of five hospitalized with acute lower respiratory tract infection. We determined the association between biomarker levels and primary end-point pneumonia, indicated by CXR consolidation. We included 89 children (median age 11 months, 39% female). Primary endpoint pneumonia was present in 22 (25%). Clinical signs were similar in children with and without CXR consolidation. Broad-spectrum antibiotics (ceftriaxone) were administered in 83 (93%). Levels of CHI3L1, SP-D, LCN2 and TIMP-1 were higher in patients with primary end-point pneumonia compared to patients with normal CXR or other infiltrates. All markers were moderately accurate predictors of primary end-point pneumonia, with area under receiver operator characteristic curves of 0.66-0.70 (<0.05 for all markers). The probability of CXR consolidation increased monotonically with the number of markers above cut-off. Among 28 patients (31%) in whom all four markers were below the cut-off, the likelihood ratio of CXR consolidation was 0.11 (95%CI 0.015 to 0.73). CHI3L1, SP-D, LCN2 and TIMP-1 were associated with CXR consolidation in children with clinical pneumonia in a low-resource setting. Combinations of quantitative biomarkers may be useful to safely withhold antibiotics in children with a low probability of bacterial infection.Item Dysregulation of angiopoietin-Tie-2 axis in ugandan children hospitalized with pneumonia(Elsevier, 2020-09) Zhang, Ran; Rai, Urvi; Ibrahim, Nafeesah Bte Mohamed; Amazouz, Yanni; Soo, Jeremy; Conroy, Andrea L.; Namasopo, Sophie; Opoka, Robert O.; Bhargava, Ravi; Hawkes, Michael T.; Pediatrics, School of MedicineObjective Pneumonia is the leading cause of death in children under 5, with the highest burden in resource-limited countries. Endothelial activation occurs in pneumonia and can be assessed using quantitative levels of biomarkers angiopoietin (Ang)-1 and Ang-2. We examined admission levels of Ang-1 and Ang-2 in pediatric pneumonia and their association with disease severity and outcome. Methods Prospective cohort study of children with hypoxemic pneumonia admitted to two hospitals in Uganda. Clinical, radiographic, and microbiologic characteristics were measured at admission. Disease severity was assessed using the Respiratory Index of Severity in Children (RISC). Plasma levels of Ang-1 and Ang-2 were quantified by enzyme-linked immunosorbent assay. Vital signs, oxygen supplementation, and mortality were assessed prospectively. Results We included 65 patients (43% female) with median age 19 months (IQR 8–24). Admission Ang-2/Ang-1 ratio directly correlated with RISC (ρ = 0.32, p = 0.008) and lactate level (ρ = 0.48, p < 0.001). Ang-2/Ang-1 ratio was higher in pneumococcal pneumonia than viral RTI (0.19 [IQR: 0.076–0.54] vs. 0.078 [IQR: 0.027–0.11]; p = 0.03). Elevated Ang-2/Ang-1 ratio (>0.084) was associated with prolonged tachypnea (HR 0.50 (95%CI 0.29–0.87), p = 0.02), fever (HR 0.56 (95%CI 0.33 to 0.96), p = 0.02), longer duration of oxygen therapy (HR 0.59 (95%CI 0.35–0.99), p = 0.04), and hospital stay (HR 0.43 (95%CI 0.25–0.74), p = 0.001). The Ang-2/Ang-1 ratio at admission was higher in fatal cases relative to survivors (0.36 [IQR: 0.17–0.58] vs. 0.077 [IQR: 0.025–0.19]; p = 0.05) Conclusion Endothelial activation in hypoxemic pediatric pneumonia, reflected by high plasma Ang-2/Ang-1 ratio, is associated with disease severity, prolonged recovery time, and mortality.