Mucus plug formation is associated with eosinophilic activation in chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is the fourth greatest cause of death worldwide. Airway mucus plugs (MP) are a novel biomarker of disease activity and are identified in 27% to 67% of patients with COPD. High MP score has been associated with greater airflow obstruction, increased risk of exacerbations, and mortality. However, the mechanisms underlying MP formation and composition have not been fully elucidated. In asthma, mucus plugging has been linked to eosinophil peroxidase (EPX), a cationic hemoprotein that promotes disulphide crosslinking between mucins validated as a biomarker of eosinophil activation. Blood eosinophil count (BEC) is a well-established biomarker in COPD, predicting response to inhaled corticosteroids and biologics targeting type 2 inflammation. Although an association between BEC values and MP score has been shown, the relationship between the activation state of airway eosinophils and MPs is unknown. We hypothesized that, in COPD, mucus plugging is associated with airway eosinophil activation, reflected by elevated sputum EPX (sEPX).