Bronchopulmonary dysplasia in preterm neonates: Th2-Eosinophilic inflammation and asthma-like features.

Abstract

Asthma is the most prevalent pediatric lung disease, characterized by T-helper 2 (Th2) cell activation and associated eosinophilic inflammation. Mounting evidence suggests a similar Th2 skewing in premature neonates who develop bronchopulmonary dysplasia (BPD), a chronic lung disease with overlapping features of asthma. Given that a substantial proportion of neonates with BPD later develop asthma, our study aimed to investigate the association between an asthma-related transcriptomic signature and BPD. Using a previously established 10-gene asthma transcriptomic signature, we analyzed data from 111 very-low-birth-weight (VLBW) neonates over the first month of life. Meta-analysis across seven independent datasets confirmed the association of the asthma gene signature with BPD during the first week of life. The transcriptomic signature predicted BPD severity as early as day of life 5 and stratified disease progression. Validation in an extremely preterm baboon model of BPD revealed elevated plasma concentrations of interleukin (IL)-5 and IL-6, along with increased expression of Th2-driven inflammatory cytokines in lung tissue. Our findings provide evidence of a shared genetic and immunologic framework between asthma and BPD, offering potential biomarkers for early diagnosis and avenues for targeted therapy. The asthma-related transcriptomic signature predicts the severity of bronchopulmonary dysplasia (BPD) as early as day five of life, providing a potential early biomarker Elevated Th2-eosinophil inflammatory markers suggest a shared pathophysiology between BPD and asthma. This study highlights the potential for early diagnosis and targeted interventions to improve long-term respiratory outcomes in preterm infants.