Dysregulation of angiopoietin-Tie-2 axis in Ugandan children hospitalized with pneumonia

Ran Zhang, University of Alberta, Canada
Urvi Rai, University of Alberta, Canada
Nafeesah Bte Mohamed Ibrahim, University of Alberta, Canada
Yanni Amazouz, University of Alberta, Canada
Jeremy Soo, University of Alberta, Canada
Andrea Conroy, Indiana University School of Medicine, USA
Sophie Namasopo, Jinja Regional Referral Hospital, Uganda
Robert Opoka, Aga Khan University
Ravi Bhargava, University of Alberta, Canada
Michael Hawkes, University of Alberta, Canada

This work was published before the author joined Aga Khan University.


Objective: Pneumonia is the leading cause of death in children under 5, with the highest burden in resourcelimited 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