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Effect of Dupilumab on the Temporospatial Characteristics of Mucus Plugs in Patients With Moderate-to-Severe Asthma

2025· article· en· W4410268742 on OpenAlexaff
Eleanor Sandhu, Nandhitha Ragunayakam, Anittha Mappanasingam, C. Venegas Garrido, A. Thakar, Nisarg Radadia, Y. Friedlander, M. Jegatheeswaran, Melanie Kjarsgaard, Manali Mukherjee, P. Nair, Sarah Svenningsen

Bibliographic record

VenueAmerican Journal of Respiratory and Critical Care Medicine · 2025
Typearticle
Languageen
FieldMedicine
TopicAsthma and respiratory diseases
Canadian institutionsSt. Joseph’s Healthcare HamiltonMcMaster University
Fundersnot available
KeywordsMedicineDupilumabAsthmaMucusImmunology

Abstract

fetched live from OpenAlex

Abstract RATIONALE: Mucus plugs play a critical role in asthma pathophysiology, contributing to airflow obstruction and adverse clinical outcomes.1 Dupilumab, an interleukin-4 and interleukin-13 pathway blocker, has been shown to reduce airway mucus burden, as quantified by the computed tomography (CT) mucus score.2,3 However, the resolution of mucus plugs after treatment with dupilumab has not been fully investigated. Here, we characterized the effect of dupilumab on the spatial and temporal behaviour of mucus plugs. METHODS: This retrospective analysis included 28 adults with uncontrolled moderate-to-severe asthma; 20 received dupilumab, while 8 received placebo every 2-weeks for 16-weeks. At week-0 and week-16, full-inspiration chest CT scans were acquired as previously described.2 CT scans were reviewed and annotated for all mucus plugs using VIDA|vision software (VIDA Diagnostics) to determine the total mucus plug count (TMPC) and the temporospatial behaviour of individual mucus plugs. Subsequently, patients were classified into the following groups: complete resolution of plugs (all plugs resolved at week-16), persistent plugs (≥1 plug resolved at week-16, but not all), persistently no plugs (no plugs at week-0 and week-16), and new-onset plugs (no plugs at week-0 and ≥1 plug at week-16). Individual mucus plugs were characterized as resolved, fixed-location persistent (FLP), or new-onset. RESULTS: Figure 1 summarizes the effect of dupilumab (13F/7M, age=50±14 years, week-0 TMPC=6[0-23]) in comparison to placebo (3F/5M, age=60±9 years, week-0 TMPC=9[0-31]) on the total mucus burden and temporospatial behaviour of mucus plugs. At week-16, the TMPC was decreased following dupilumab but not placebo (Figure 1A). Figure 1B shows that 40% of patients treated with dupilumab had complete resolution of mucus plugs (13% in placebo), 55% had persistent plugs (75% in placebo), and 5% had persistently no plugs (0% in placebo). Considering the temporospatial behaviour of individual mucus plugs, the proportion of resolved plugs was greater (92%, 141 of 154 plugs vs. 62%, 59 of 95 plugs; p<0.0001) and FLPs was lower (8%, 13 of 154 plugs vs. 38%, 36 of 95 plugs; p<0.0001) following dupilumab compared to placebo (Figure 1C). The number of new-onset plugs was lower following dupilumab compared to placebo (0[0-4] vs. 9[0-18], p=0.001 (Figure 1D)). CONCLUSIONS: Treatment with dupilumab can reduce persistent plugs, decrease the formation of new plugs and completely resolve CT-evaluated mucus plugging in a subset of patients with asthma over a 16-week period. 1C Venegas et al. Allergol Int (2024); 2S Svenningsen et al. AJRCCM (2023); 3E Dunican et al. JCI (2018).

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.003

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.005
GPT teacher head0.274
Teacher spread0.269 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

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Citations0
Published2025
Admission routes1
Has abstractyes

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