Pulmonary neuroendocrine cells in pediatric asthma and bronchopulmonary dysplasia: neuroimmune-developmental mechanisms and translational implications.

Pediatric asthma, bronchopulmonary dysplasia (BPD), and viral-induced wheeze arise from distinct clinical settings, but all occur in the context of a maturing pediatric lung, where epithelial injury, inflammation, neural inputs, and repair or remodeling programs are closely interconnected. This intersection between pediatric lung maturation and inflammatory injury provides a rationale for focusing on pulmonary neuroendocrine cells (PNECs), developmentally enriched airway epithelial sensor cells that translate environmental and injury-related cues into local neuroimmune, repair, and remodeling responses. In pediatric asthma, PNEC-derived calcitonin gene-related peptide (CGRP) has been implicated in ILC2-associated type 2 inflammation, although CGRP-ILC2 signaling appears context-dependent and should be interpreted alongside epithelial alarmins such as IL-33, IL-25, and TSLP. PNEC-derived γ-aminobutyric acid (GABA) further links neuroendocrine signaling to IL-13-associated mucus remodeling and goblet cell responses. In neonatal lung injury and BPD, gastrin-releasing peptide and bombesin-like peptides have been linked to oxygen-associated stress, inflammatory remodeling, and impaired alveolar or vascular development; recent biomarker studies extend the relevance of this pathway to contemporary preterm lung disease and motivate further mechanistic investigation. Viral-induced wheeze is discussed as a related extension of epithelial alarmin-neuroimmune crosstalk. Overall, this review positions PNECs as cellular nodes linking pediatric lung maturation, environmental sensing, neuroimmune regulation, and epithelial repair or remodeling, with implications for mechanistic phenotyping, biomarker exploration, disease stratification, and future human-centered studies in pediatric respiratory disease.