A recent study has found that dupilumab significantly decreased the mucus plug score and improved lung function in patients with moderate-to-severe asthma, mainly in those with a high burden of mucus plugs at baseline. Chronic mucus hypersecretion plays an important role in airway obstruction and persistent inflammation, thus it is a key target for therapy in asthma management. VESTIGE was a study aimed at assessing how dupilumab affects airway mucus plugs, FeNO, and lung function, stratified by baseline scores. The study was conducted by Celeste P. and colleagues published in theAmerican Journal of Respiratory and Critical Care Medicine. The VESTIGE study (NCT04400318) enrolled 109 adults with moderate-to-severe asthma, baseline blood eosinophils ≥300 cells/μL, and FeNO ≥25 ppb. Patients were randomized to receive dupilumab 300 mg (n = 72) or placebo (n = 37) every 2 weeks for 24 weeks. Baseline mucus plug scores were derived from HRCT scans, with a high score ≥4 and low score 0–3.5. Post hoc analyses examined changes in mucus plug score, proportion of patients achieving FeNO <25 ppb, and changes in percent predicted FEV1 and FVC stratified by baseline mucus plug burden. Mucus Plug Discharge Compared with baseline, fewer dupilumab-treated patients had high mucus plug scores at Week 24 (32.8% vs 67.2%), whereas proportions remained largely unchanged in placebo recipients (76.7% vs 73.3%). FeNO Achievement Dupilumab recipients were more likely than placebo recipients to achieve FeNO <25 ppb in both high and low-mucus plug subgroups: High mucus plug score: odds ratio 6.64; P = 0.003 Low mucus plug score: odds ratio 8.54; P = 0.024 Improving Lung Function In patients with high baseline mucus plug scores, dupilumab significantly improved: Pre- and post-bronchodilator FEV1: LSMD 16.77 percentage points [95% CI: 9.81–23.73; P <0.0001] and 12.70 [3.87–21.52; P = 0.0055], respectively Pre-bronchodilator FVC: LSMD 0.42 mL [95% CI: 0.17–0.66; P = 0.001] Post-bronchodilator FVC: LSMD 0.30 mL [95% CI: 0.01–0.59; P = 0.0399] In adults with moderate-to-severe asthma, dupilumab significantly reduced mucus plug scores, improved lung function, and increased the probability of achieving FeNO <25 ppb, which underlines its efficacy for airway obstruction and inflammation, particularly in patients with a high baseline mucus plug burden. Porsbjerg, C., Dunican, E. M., Lugogo, N. L., Castro, M., Papi, A., Backer, V., Brightling, C. E., Bourdin, A., Virchow, J. C., Zhang, M., Soler, X., Rowe, P. J., Deniz, Y., de Prado Gómez, L., Sacks, H. J., & Jacob-Nara, J. A. (2025). Effect of dupilumab on mucus burden in patients with moderate-to-severe asthma: The VESTIGE trial. American Journal of Respiratory and Critical Care Medicine, rccm.202410-1894OC.https://doi.org/10.1164/rccm.202410-1894OC