Research Progress on the Mechanisms of High Mucus Secretion in the Airway: A Scoping Review

Background: Excessive mucus production in the airways is a key pathogenic characteristic of chronic respiratory conditions, including bronchial asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF). The etiology is intricate, encompassing various factors such as aberrant activation of inflammatory signaling pathways, deregulation of mucin gene expression, modified rheological characteristics of mucus, and impairment of the ciliary clearance mechanism. Nonetheless, the current evidence is disjointed, and a thorough and systematic synthesis is still absent. Objective: This scoping review sought to systematically summarize and delineate the mechanisms of airway mucus hypersecretion, identify predominant research themes, and underscore significant knowledge gaps in existing studies. Methods: This research was performed as a scoping review using the PRISMA principles. A thorough literature search was conducted in PubMed and the China National Knowledge Infrastructure (CNKI) databases using predefined keywords, encompassing papers from January 2005 to September 2025. Studies employing various experimental models to examine the mechanisms of airway mucus hypersecretion were included. Data were obtained from all qualifying papers for further synthesis. Results: A total of 31 studies were incorporated. This paper methodically examines recent research developments in this domain, emphasizing fundamental inflammatory pathways exemplified by NF-κB, IL-13/STAT6, and EGFR; the function of transcription regulatory networks illustrated by SPDEF, Notch, and Wnt; modifications in mucus rheological characteristics, including hydration dysfunction and polymer surplus; and clearance deficiencies primarily driven by ciliary dysfunction in excessive mucus production. Conclusion: Airway mucus hypersecretion is regulated by multiple mechanisms at various levels. This review systematically integrates contemporary evidence to establish a conceptual framework and translational perspective for developing targeted therapeutic strategies. These strategies include interventions aimed at IL-13–related pathways, transcriptional networks like Notch, water transport channels and regulatory factors, and genes linked to ciliary dysfunction, thereby facilitating the progression of personalized precision medicine in chronic airway diseases.