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

Abstract：

OBJECTIVE: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.

journal_name

Cytokine

journal_title

Cytokine

authors

Zhang R,Rai U,Ibrahim NBM,Amazouz Y,Soo J,Conroy AL,Namasopo S,Opoka RO,Bhargava R,Hawkes MT

doi

10.1016/j.cyto.2020.155175

subject

Has Abstract

pub_date

2020-09-01 00:00:00

pages

155175

eissn

1043-4666

issn

1096-0023

pii

S1043-4666(20)30191-5

journal_volume

133

pub_type

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