Abstract
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a complex respiratory disorder with heterogeneous pathological manifestations. Emerging evidence highlights that autonomic nervous system (ANS) dysregulation may play an promising role in COPD progression. This narrative review aims to summarize a current mechanistic insights into ANS-mediated pathophysiology and explore novel therapeutic strategies targeting autonomic dysfunction. METHODS: We conducted a narrative analysis of preclinical and clinical studies from PubMed and Web of Science, focusing on ANS-related pathways in COPD. Key mechanisms and therapeutic interventions were evaluated through integrative interpretation of published evidence. RESULTS: ANS imbalance, marked by diminished sympathetic tone and excessive parasympathetic activity, exacerbates core COPD pathologies. Mechanistically, cholinergic hyperactivity drives airway constriction and mucus hypersecretion, while sympathetic suppression impairs bronchodilation and immune responses. Neuroimmune crosstalk and systemic autonomic remodeling further link COPD to extrapulmonary comorbidities, including cardiovascular disorders and lung cancer. Emerging therapies, such as bioelectronic neuromodulation and phenotype-specific interventions, demonstrate potential in restoring autonomic equilibrium. For instance, vagus nerve stimulation attenuates inflammation, and targeted lung denervation reduces exacerbation risks in specific patient subgroups. Traditional approaches, including acupuncture, also show efficacy in improving functional outcomes. CONCLUSION: Precision modulation of ANS plasticity represents a transformative approach to COPD management, bridging molecular mechanisms with clinical applications. Future research should prioritize combinatorial therapies and biomarker-driven stratification to address the multifaceted nature of ANS dysfunction. This paradigm shift holds promise for personalized interventions that mitigate disease progression and systemic complications.