Background <p>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.</p> Methods <p>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.</p> Results <p>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.</p> Conclusion <p>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.</p> Impact <p><UnorderedList Mark="Bullet"> <ItemContent> <p>The asthma-related transcriptomic signature predicts the severity of bronchopulmonary dysplasia (BPD) as early as day five of life, providing a potential early biomarker</p> </ItemContent> <ItemContent> <p>Elevated Th2-eosinophil inflammatory markers suggest a shared pathophysiology between BPD and asthma.</p> </ItemContent> <ItemContent> <p>This study highlights the potential for early diagnosis and targeted interventions to improve long-term respiratory outcomes in preterm infants.</p> </ItemContent> </UnorderedList></p>