The Role of Neurotrophic Modulation in COPD and Its Influence on Airway Pathophysiology: A Systematic Review and Meta-Analysis

Background: Chronic obstructive pulmonary disease (COPD) is a chronic pulmonary disorder that is characterized by inflammation in the airways and their remodeling. Neurotrophic factors, such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), are seen to potentially contribute to this disease progression. This review synthesized evidence on the potential function of neurotrophic regulation in COPD pathophysiology. Methods: A systematic review was undertaken by searching PubMed, Scopus, Web of Science, and Embase up to March 2025 for studies that examined neurotrophic factors in COPD. Studies that assessed neurotrophin expression, signaling, or its influence on airway function in COPD patients or animal models were included in this study. Studies that focused on unrelated respiratory disorders, non-neurotrophic biomarkers, or lacked primary data were excluded. Data on the study design, sample size, neurotrophin levels, and major findings were gathered. Meta-analysis was performed using RevMan 5.0.0, and risk of bias was assessed using a modified form of the Evidence Project Risk of Bias Tool. Results: Of 10 studies included, mixed findings were seen: some reported a rise in NGF and BDNF levels linked to airway inflammation and remodeling, while some found decreased neurotrophin associated with skeletal muscle dysfunction. A pooled effect size of 0.711 [0.553, 0.869] was observed for neurotropic procurement, -0.32 [-0.58, -0.05] for airway remodeling, and 4.26 [2.21, 6.31] for airway inflammation. Discussion: Neurotrophic factors may contribute to COPD pathophysiology because they influence airway inflammation, remodeling, and muscle dysfunction. Future research should validate the mechanisms that underlie these associations and explore therapeutic targets within neurotrophic pathways.