Role of Pulmonary Neuroendocrine Cells in COPD

BACKGROUND: Pulmonary neuroendocrine cells (PNECs) are specialized airway epithelial cells with dual sensory and secretory functions. They release bioactive mediators --including neuropeptides such as calcitonin gene-related peptide (CGRP) and gastrin-releasing peptide (GRP), and neurotransmitters such as 5-hydroxytryptamine (5-HT) and γ-aminobutyric acid (GABA) --that regulate airway smooth-muscle tone, mucus production, and immune responses. In chronic obstructive pulmonary disease (COPD), these PNEC-derived mediators contribute to airway inflammation, remodeling, and smooth-muscle dysfunction. Chronic inflammation and oxidative stress in COPD are closely linked to PNEC activity. METHODS: We conducted a narrative review summarizing evidence on PNEC biology, their principal secretory mediators, and mechanistic links to key pathological processes in COPD, including inflammation, oxidative stress, and airway remodeling. RESULTS: PNEC-derived mediators (CGRP, GRP, 5-HT, GABA) participate in COPD-relevant processes by modulating airway tone, mucus production, and immune responses. In COPD, dysregulated PNEC activity is associated with persistent inflammation, heightened oxidative stress, airway remodeling, and smooth-muscle dysfunction. PNECs also contribute to epithelial repair and regeneration, indicating a role in maintaining -and, when perturbed, disrupting -airway homeostasis. CONCLUSION: PNECs integrate sensory inputs with secretory signaling to shape multiple COPD-related pathways. Clarifying the mechanisms and context dependence of PNEC activity may inform therapeutic strategies targeting PNEC-derived mediators and support the development of novel interventions for COPD.