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Published on: November 4, 2010
Changes in Mucus Radiodensity and New Plug Formation Following Dupilumab Treatment in Asthma
Ekamdeep Sandhu1, Nandhitha Ragunayakam1, Anusha A Mappanasingam1
1Department of Medicine, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada.
Background:
Dupilumab, an IL-4 and IL-13 antagonist, has been shown to reduce 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:
Post-dupilumab reductions in mucus score, total mucus plug count, and total plug volume were greater than in the control group and were associated with improved FEV1, FEV1/FVC, and 129Xe 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 FLP (9% vs 42%; P < .0001) and new-onset (1 [0-5] vs 6 [0-18]; P = .0008) plugs. Radiodensity of FLP plugs decreased after 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:
Our results show that 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.
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