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 (MPs) are common in severe eosinophilic asthma (SEA) and are often associated with airflow limitation and poor asthma control. MP formation is driven by type 2 (T2) inflammation and may be worsened by coexisting bronchiectasis (BE), a condition characterised by irreversible bronchial dilatation and mucus retention. The effect of mepolizumab on MP burden in SEA, either with or without BE, remains unclear. The objective of the present study was to evaluate the 12-month 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 MPs treated with mepolizumab for 12 months. Patients were grouped into SEA+MP (n=26) and SEA+MP+BE (n=21). MPs were 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 and reduced blood eosinophils and the number of annual exacerbations. Forced expiratory volume in 1 s (FEV1) improved significantly only in the SEA+MP+BE group. Baseline BSI score correlated positively with MPS and exacerbations, and negatively with FEV1 and ACT score. CONCLUSION: Mepolizumab reduces MP burden and improves SEA outcomes; this is also the case when including patients with coexisting BE. MPs 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 MP assessment as a complementary biomarker to guide biologic therapy in SEA.