Beyond Hypersecretion: Mucus Plugs as structural and biological determinants of Airway Obstruction

Mucus plugs represent a muco-obstructive endophenotype across the spectrum of chronic obstructive airway diseases. Beyond reflecting mucus hypersecretion alone, they constitute a structural and biological manifestation of altered mucus biophysics, impaired mucociliary clearance, epithelial dysfunction, and inflammatory signaling. Their presence contributes to regional airflow limitation, ventilation heterogeneity, hypoxemia, and adverse clinical outcomes, even when conventional pulmonary function tests underestimate their impact. Advances in imaging have enabled the transition of mucus plugs from a descriptive radiologic finding to a potentially actionable biomarker for risk stratification and therapeutic response assessment, particularly in severe asthma and chronic obstructive pulmonary disease, where muco-obstruction has been associated with increased exacerbation risk and mortality. This narrative review integrates current evidence on the mechanisms underlying plug formation and persistence, their clinical expression, imaging strategies, and therapeutic implications across asthma and chronic obstructive pulmonary disease.