Mucus plugs have emerged as an important therapeutic target in asthma management and severe asthma exacerbations. Mucus plugging has a known association with worse asthma outcomes, including severe fatal asthma exacerbations and chronic severe asthma. Extensive mucus plugs have been characterized in autopsy studies of patients with fatal asthma exacerbations, with notable luminal obstruction identified as a major factor in case fatality.1 In acute severe exacerbations, intraluminal mucus accumulation contributes to airflow limitation, worsened air trapping, and loss of airways.2
More recent studies have reviewed chronic changes from mucus plugs in airways disease for patients with severe asthma. The mucus plug score (MPS) derived from CT scan imaging, described by Dunican and colleagues in 2018, evaluated the presence of mucus plugs occluding an airway in each bronchopulmonary segment, assigning a total score of 0 to 20.3 Patients were stratified into low-burden and high-burden groups based on MPS. A higher MPS correlated with lower FEV1 as well as increased markers of type 2 inflammation, including sputum eosinophils, eosinophil peroxidase, and Feno.1–4 Using the MPS, Chan and colleagues also identified a correlation between asthma patients with any mucus plugs and worse obstruction, more frequent exacerbations, and worsened type 2 inflammation.5
Type 2 inflammatory pathways contribute to mucus production and impaired mucociliary clearance, making biologics an attractive therapeutic strategy.6 The VESTIGE trial, published last year, evaluated dupilumab in patients with type 2 asthma to characterize its role in reducing airway inflammation and mucus plug scores.7 Patients treated with dupilumab demonstrated significantly greater reductions in MPS compared with placebo after 24 weeks of therapy. Furthermore, the patients with a higher MPS at baseline (4 to 20), demonstrated greater improvement in FEV1/FVC ratio and airway resistance at the end of the trial compared with those with a lower MPS (0 to 3.5) at baseline.8 The CASCADE trial in 2023 previously had similar findings in tezepelumab, with an overall reduction in mucus plugs after treatment with tezepelumab compared with placebo.9
Additional trials have been performed to examine the impact of targeting the interleukin (IL)-5 pathway on mucus plugs given that IL-5 increases mucus viscosity and impairs mucociliary clearance through its effect on eosinophils. Earlier this year, Campisi and colleagues demonstrated that treatment of severe eosinophilic asthma over a 12-month period with mepolizumab resulted in significant reductions in MPS, improvements in FEV1, fewer exacerbations, and improvement in quality of life.10 A systematic review performed by Aegerter and colleagues similarly identified improvements in MPS across biologic targets including the IL-5, IL-4, IL-13, and thymic stromal lymphopoietin pathways. MPS improvement was additionally associated with improvements in lung function, including improved FEV1, decreased air trapping, and improved ventilation defects; clinically, patients also all demonstrated improvements in asthma control and health-related quality of life. However, all studies reviewed did demonstrate residual mucus plugs, which presents as an avenue for further research to better determine how to best characterize mucus plugs to personalize treatment strategies and predict response to treatment.6
Airway mucus burden is increasingly recognized as a marker of type 2 inflammation that identifies patients who are at high risk for worse asthma outcomes as well as patients who will likely benefit from advanced therapies, such as biologics. As image-based markers become increasingly integrated into severe asthma phenotyping, MPS may evolve further into a clinically actionable tool to help identify patients at high risk, predict biologic responsiveness, and monitor disease progression over time.
References
1. Kuyper LM, Paré PD, Hogg JC, et al. Characterization of airway plugging in fatal asthma. Am J Med. 2003;115(1):6-11. doi:10.1016/s0002-9343(03)00241-9
2. Dunican EM, Elicker BM, Gierada DS, et al. Mucus plugs in patients with asthma linked to eosinophilia and airflow obstruction. J Clin Invest. 2018;128(3):997-1009. doi:10.1172/JCI95693
3. Dunican EM, Watchorn DC, Fahy JV. Autopsy and imaging studies of mucus in asthma: lessons learned about disease mechanisms and the role of mucus in airflow obstruction. Ann Am Thorac Soc. 2018;15(Suppl 3):S184-S191. doi:10.1513/AnnalsATS.201807-485AW
4. Tang M, Elicker BM, Henry T, et al. Mucus plugs persist in asthma, and changes in mucus plugs associate with changes in airflow over time. Am J Respir Crit Care Med. 2022;205(9):1036-1045. doi:10.1164/rccm.202110-2265OC
5. Chan R, Duraikannu C, Lipworth B. Clinical associations of mucus plugging in moderate to severe asthma. J Allergy Clin Immunol Pract. 2023;11(1):195-199.e2. doi:10.1016/j.jaip.2022.09.008
6. Porsbjerg C, Dunican EM, Lugogo NL, et al. Effect of dupilumab on mucus burden in patients with moderate-to-severe asthma: the VESTIGE trial. Am J Respir Crit Care Med. 2026;212(2):241-252. doi:10.1164/rccm.202410-1894OC
7. Aegerter H, Brightling CE, Dunican EM, et al. Effectiveness of biologics for reducing occlusive mucus plugs in patients with severe asthma: a systematic review. Respir Res. 2026;27(1):69. doi:10.1186/s12931-026-03501-z
8. Nordenmark LH, Hellqvist Å, Emson C, et al. Tezepelumab and mucus plugs in patients with moderate-to-severe asthma. NEJM Evid. 2023;2(10):EVIDoa2300135. doi:10.1056/EVIDoa2300135
9. Campisi R, Nolasco S, Bonsignore M, et al. Effectiveness of mepolizumab on mucus plug reduction and clinical outcomes in severe eosinophilic asthma: a prospective observational study. J Allergy Clin Immunol Pract .2026;14(2):404-414.e1. doi:10.1016/j.jaip.2025.10.015
