Circulating markers of neutrophil activation and lung injury in pediatric pneumonia in low-resource settings

• Published in: Pathogens and global health Vol. ahead-of-print; no. ahead-of-print; pp. 1 - 9
• Main Authors: Konrad, Emily R., Soo, Jeremy, Conroy, Andrea L., Namasopo, Sophie, Opoka, Robert O., Hawkes, Michael T.
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 01.12.2023
• Subjects: Africa; Anti-Bacterial Agents; Biomarkers; Child; Cross-Sectional Studies; Female; Humans; Infant; Lung; Lung Injury; Male; Neutrophil Activation; Pediatric pneumonia; Pneumonia - diagnosis; Pneumonia - drug therapy; Pulmonary Surfactant-Associated Protein D; Tissue Inhibitor of Metalloproteinase-1; Pediatric pneumonia; biomarkers; Africa
• ISSN: 2047-7724; 2047-7732
• DOI: 10.1080/20477724.2022.2160885

Diagnostic 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 (p<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.