Dupilumab Reduces Mucus Radiodensity and New Plug Formation in Asthma

BACKGROUND: Dupilumab, an IL-4 and IL-13 antagonist, reduces the burden of mucus plugs visualized by CT imaging in asthma. RESEARCH QUESTION: Does dupilumab modify the volume, radiodensity, and temporospatial behavior of individual CT-visible mucus plugs in patients with moderate to severe asthma? STUDY DESIGN AND METHODS: Thirty-two adults with moderate to severe asthma were evaluated; 22 received dupilumab every 2 weeks for at least 16 weeks, and 10 were in the control group. All mucus plugs visible on CT scans acquired at baseline and follow-up were annotated to evaluate plug count, volume, and radiodensity. Individual plugs were assessed longitudinally and classified as resolved, fixed-location persistent (FLP), or new onset. RESULTS: Xe MRI ventilation defect percent (all, P < .05). Thirty-six percent of dupilumab-treated participants had complete resolution (control, 10%), and 59% had incomplete resolution of mucus plugs (control, 80%). Compared with control participants, dupilumab-treated participants had more resolved plugs (91% vs 58%; P < .0001) and fewer (9% vs 42%; P < .0001) FLP and new-onset (1 [0-5] vs 6 [0-18]; P = .0008) plugs. Radiodensity of FLP plugs decreased post-dupilumab treatment (-422 Hounsfield unit [HU] [-759 to -5] to -569 HU [-738 to -258]; P = .009), and new-onset plugs had lower radiodensity in dupilumab-treated participants compared with control participants (-573 HU [-765 to -320] vs -387 HU [-662 to -26]; P = .0006). Participants with incomplete resolution had persistently higher ventilation defect percent compared with those with complete resolution (P < .05). INTERPRETATION: Dupilumab reduces mucus burden in asthma by resolving persistent plugs and decreasing the formation of new plugs. Despite complete resolution in a subset of participants, residual low-radiodensity persistent and new-onset plugs are functionally relevant.