Effectiveness of Mepolizumab on Mucus Plugs and Clinical Outcomes in Severe Eosinophilic Asthma with and without Coexisting Bronchiectasis: A Prospective Pilot Study

Background Mucus plugs (MP) are common in severe eosinophilic asthma (SEA) and are often associated with airflow limitation and poor control. MP formation is driven by type 2 (T2) inflammation and may be worsened by coexisting bronchiectasis (BE), a condition characterized by irreversible bronchial dilation and mucus retention. The effect of mepolizumab on MP burden in SEA with or without BE remains unclear. Objective To evaluate the 12-months effectiveness of mepolizumab in reducing MP and improving clinical outcomes in SEA patients with high-resolution computed tomography (HRCT)-confirmed MP, stratified by the presence of BE. Methods We prospectively analysed 47 SEA patients with HRCT-confirmed MP treated with mepolizumab for 12 months. Patients were grouped into SEA+MP (n=26) and SEA+MP+BE (n=21). MP was assessed using the Mucus Plug Score (MPS) and BE severity using the Bronchiectasis Severity Index (BSI). Clinical, functional, and inflammatory parameters were evaluated pre- and post-treatment. Results Mepolizumab significantly reduced MPS in both groups [−3 in SEA+MP (p=0.0005); −5 in SEA+MP+BE (p<0.0001)], improved Asthma Control Test (ACT) scores, reduced blood eosinophils and annual exacerbations. Forced expiratory volume in 1 s (FEV 1 ) improved significantly only in the SEA+MP+BE group. Baseline BSI correlated positively with MPS and exacerbations, and negatively with FEV₁ and ACT. Conclusion Mepolizumab reduces MP burden and improves SEA outcomes, including those with BE. MP and BE may represent treatable, T2-driven traits that could serve as a therapeutic target in precision asthma care. These findings support the use of HRCT-derived mucus plug assessment as a complementary biomarker to guide biologic therapy in SEA.