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Late Breaking Abstract - Up-dosing of reslizumab in severe asthmatics with persistent sputum eosinophilia

2024· article· en· W4404098903 on OpenAlexaff
Manali Mukherjee, Jaime Bernaola, Melanie Kjarsgaard, Yinglan Xie, Katherine Radford, Bashyr Alotaibi, Santi Nolasco, Carmen Venegas Garrido, Parameswaran Nair

Bibliographic record

Venuenot available
Typearticle
Languageen
FieldMedicine
TopicAsthma and respiratory diseases
Canadian institutionsSt. Joseph’s Healthcare HamiltonMcMaster UniversityMcMaster University Medical Centre
Fundersnot available
KeywordsEosinophiliaMedicineDosingSputumPulmonary EosinophiliaAsthmaImmunologyInternal medicineEosinophilPathologyTuberculosis

Abstract

fetched live from OpenAlex

Rationale: A subset of severe eosinophilic asthmatics (SEA) remains uncontrolled despite anti-IL-5 biologic which may be due to inadequate neutralisation of airway IL-5. Aim: To investigate whether sequential up-dosing of a weight-adjusted anti-IL-5 mAb (reslizumab) will decrease sputum eosinophils(sp-eos) and improve asthma control. Method: We conducted a prospective, single-centre, open-label, 52-weeks dose-escalation (DE) study ( NCT04710134 ). SEA with sp-eos>3% after 16 weeks of standard dose (3mg/kg, iv, Q4W) underwent DE to 4 mg/kg after V6 (4 infusions) or 5 mg/kg after V10 (4 infusions). Sp-eos, cytokines, anti-eosinophil peroxidase (EPX) IgG, FEV1, and ACQ-5 were examined. Results: Ten SEA (53±16 yrs; 6F) started reslizumab at 3 mg/kg (V1). After 4 infusions (V6), 4 (40%) had sp-eos>3% and ACQ-5<1.5, while n=5 (sp-eos 16±11%) were DE to 4 mg/kg, and one to 5 mg/kg. Reslizumab reduced sp-eos, EPX, IL-5 and improved FEV1 at V14 (p<0.05), irrespective of dosing. Despite reduced sp-IL-5 after DE, 2/10 patients (20%) had sp-eos at V14 (>3%, Fig 1A). Reslizumab did not reduce sp-IL-13 or anti-EPX levels. At V14, anti-EPX IgG were elevated in 5/6 DE patients and significantly correlated with IL-13 (r=0.7; P=0.02, Fig 1D). Conclusion: A proportion of SEA may benefit from higher doses of anti-IL-5 mAb that allow normalisation of sputum eosinophils and IL-5. A subset remains symptomatic with evidence of sp-eos, IL-13, and anti-EPX IgG. erj;64/suppl_68/PA3943/F1 F1 F1

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: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.011

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0030.001

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 head0.017
GPT teacher head0.269
Teacher spread0.252 · 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".

Quick stats

Citations0
Published2024
Admission routes1
Has abstractyes

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