Airway Mucus Plugs in Asthma and COPD: Pathobiology, Imaging, and Implications for Clinical Trials

Mucus plugs have been previously recognized as an important pathological feature in asthma and chronic obstructive pulmonary disease (COPD), but their clinical role in these diseases has not been explored in depth until recently. Mucus plug formation is driven by mucus hyperconcentration, changes in mucus viscoelastic properties, impaired clearance, and mucociliary collapse. Scoring systems, such as the bronchopulmonary segment mucus plug score, have been used to associate greater mucus plug burden with poor clinical outcomes. Additional scoring methods obtained through quantitative image processing are currently under development. Mucus plug burden has been associated with greater exacerbations and spirometric decline in both asthma and COPD, as well as greater mortality in COPD. Recently, mucus plug burden has been used as an endpoint in clinical trials to evaluate the effectiveness of biologic therapies in asthma; multiple biologic therapies demonstrated decreases in mucus plug burden and associated improvements in spirometry with treatment. Together, these data suggest that mucus plugs may be a treatable trait in asthma and COPD. Mucus plug burden has current clinical, phenotypic, and predictive utility and shows promise as a future biomarker. Increased incorporation into clinical trials, expanded evidence of treatment effect, and standardization of methodology and imaging protocols will be needed. Computed tomographic detection of mucus plug burden is ready for greater incorporation into both research outcomes and clinical care.