The Inflammatory Nexus of Bronchopulmonary Dysplasia: From Molecular Pathways to Precision Therapeutics

Bronchopulmonary dysplasia (BPD) is a common and serious complication among preterm infants, particularly those born at extremely low gestational ages. It is primarily characterized by impaired alveolar and vascular development. Inflammation is increasingly recognized as a central mechanism in its pathogenesis. Both prenatal factors, such as intrauterine infection, and postnatal insults, including mechanical ventilation, oxygen toxicity, and infection, can trigger and sustain a dysregulated inflammatory response in the immature lung. This response involves the activation of inflammatory cells, such as neutrophils and macrophages, and the release of pro-inflammatory mediators, reactive oxygen species (ROS), and proteases. These factors disrupt critical developmental signaling pathways and contribute to alveolar simplification and abnormal vascular growth, which are the hallmark features of BPD. Current therapeutic strategies aim to limit these inflammatory processes and support lung development. Established interventions like caffeine and corticosteroids have demonstrated varying levels of effectiveness and safety. Emerging therapies-including anti-cytokine agents, inflammasome inhibitors, and stem cell-based approaches-offer promising avenues by specifically targeting the inflammatory cascade. Additionally, supportive strategies such as non-invasive ventilation, careful oxygen titration, and optimal nutrition play essential roles in reducing initial injury and facilitating recovery. Inflammation is a key mediator linking diverse perinatal insults to the disrupted lung development seen in BPD. A deeper understanding of the inflammatory mechanisms and timely, targeted interventions may offer improved outcomes for this vulnerable population.