Understanding the Impact of Infection, Inflammation, and Their Persistence in the Pathogenesis of Bronchopulmonary Dysplasia

Abstract

The concerted interaction of genetic and environmental factors acts on the preterm human immature lung with inflammation being the common denominator leading to the multifactorial origin of the most common chronic lung disease in infants - -bronchopulmonary dysplasia (BPD). Adverse perinatal exposure to infection/inflammation with added insults like invasive mecha nical ventilation, exposure to hyperoxia, and sepsis causes persistent immune dysregulation. In this review article, we have attempted to analyze and consolidate current knowledge about the role played by persistent prenatal and postnatal inflammation in the pathogenesis of BPD. While some parameters of the early inflammatory response (neutrophils, cytokines, etc.) may not be detectable after days to weeks of exposure to noxious stimuli, they have already initiated the signaling pathways of the inflammatory process/immune cascade and have affected permanent defects structurally and functionally in the BPD lungs. Hence, translational research aimed at prevention/amelioration of BPD needs to focus on dampening the inflammatory response at an early stage to prevent the cascade of events leading to lung injury with impaired healing resulting in the pathologic pulmonary phenotype of alveolar simplification and dysregulated vascularization characteristic of BPD.

Keywords: chronic lung disease; cytokines; hyperoxia; mechanical ventilation; premature newborn; sepsis.

Figure 1

Genetic predisposition and persistent inflammation due to environmental factors (sepsis, invasive mechanical ventilation, and hyperoxia) acting on the foundation of immature lung underlie the pathogenesis of BPD.

Figure 2

Photomicrographs (×10, upper panel; ×20 lower panel; hematoxylin and eosin stain) of neonatal lung injury noted in newborn mice at postnatal day 2, after 100% O₂ exposure since birth. Note the alveolar exudates and presence of inflammatory cells in the hyperoxia-exposed lungs compared with litter-mate controls in room air. RA, room air; HYP, hyperoxia [with permission from Semin Fetal Neonatal Med (2010) 15(4):223–9].