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Review
. 2022 Feb;66(2):137-145.
doi: 10.1165/rcmb.2021-0353PS.

Postnatal Sepsis and Bronchopulmonary Dysplasia in Premature Infants: Mechanistic Insights into "New BPD"

Umar Salimi  1 , Krishna Dummula  2 , Megan H Tucker  2 , Charles S Dela Cruz  3 , Venkatesh Sampath  2
Affiliations
Review

Postnatal Sepsis and Bronchopulmonary Dysplasia in Premature Infants: Mechanistic Insights into "New BPD"

Umar Salimi et al. Am J Respir Cell Mol Biol. 2022 Feb.

Abstract

Bronchopulmonary dysplasia (BPD) is a debilitating disease in premature infants resulting from lung injury that disrupts alveolar and pulmonary vascular development. Despite the use of lung-protective ventilation and _targeted oxygen therapy, BPD rates have not significantly changed over the last decade. Recent evidence suggests that sepsis and conditions initiating the systemic inflammatory response syndrome in preterm infants are key risk factors for BPD. However, the mechanisms by which sepsis-associated systemic inflammation and microbial dissemination program aberrant lung development are not fully understood. Progress has been made within the last 5 years with the inception of animal models allowing mechanistic investigations into neonatal acute lung injury and alveolar remodeling attributable to endotoxemia and necrotizing enterocolitis. These recent studies begin to unravel the pathophysiology of early endothelial immune activation via pattern recognition receptors such as Toll-like receptor 4 and disruption of critical lung developmental processes such as angiogenesis, extracellular matrix deposition, and ultimately alveologenesis. Here we review scientific evidence from preclinical models of neonatal sepsis-induced lung injury to new data emerging from clinical literature.

Keywords: Toll-like receptor 4; alveolar remodeling; bronchopulmonary dysplasia; pulmonary endothelium; sepsis.

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Figures

Figure 1.
Figure 1.
Pathogenesis of bronchopulmonary dysplasia following neonatal sepsis: schematic illustrating mechanisms by which bloodstream pathogens and systemic inflammation induce endothelial immune activation, dysregulated lung cell-specific molecular signaling, and dysmorphic lung development, resulting in bronchopulmonary dysplasia. Scale bars, 200 μm. ANGPT1 and 2 = Angiopoietin 1 and 2; AT1 and AT2 = type 1 and 2 alveolar epithelial cells; FGF2 and 7 = fibroblast growth factor 2 and 7; FGFR1 = fibroblast growth factor receptor 1; FOSL1 = FOS-like 1; FOXC2 = forkhead box C2; HDAC6 = histone deacetylase 6; HIF-1α = hypoxia-inducible factor 1-α; IL-1β = interleukin 1β; LPS = lipopolysaccharide; miRNAs =  micro-RNAs; MMP-9 = matrix metalloproteinase 9; NOX2 = nicotinamide adenine dinucleotide phosphate oxidase 2; PRRs = pattern recognition receptors; TGF-β = transforming growth factor-β; TIMP-1 = tissue inhibitor of metalloproteinase 1; TLR4 = Toll-like receptor 4; VEGF  = vascular endothelial growth factor. Created with Biorender.com.
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