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P163 Inhaled and oral corticosteroid treatment highlights differential effects in blood and airway compartments in type-2 high asthma

2023· article· en· W4388424003 on OpenAlexaff
J. Mark Melhorn, C Pelaia, G Hynes, M Mahdi, Rahul Shrimanker, Catherine Borg, E. Gamlen, Laura Bermejo-Sanchez, John F. Seymour, Simon Couillard, Ian Pavord, TSC Hinks

Bibliographic record

Venuenot available
Typearticle
Languageen
FieldMedicine
TopicAsthma and respiratory diseases
Canadian institutionsUniversité de Sherbrooke
Fundersnot available
KeywordsExhaled nitric oxideMedicineAsthmaEosinophilEosinophiliaEosinophilicCorticosteroidImmunologyGastroenterologyInflammationAirwayInternal medicineAnesthesiaPathologyBronchoconstriction

Abstract

fetched live from OpenAlex

Exhaled nitric oxide (FeNO) and blood eosinophilia are important biomarkers of type-2 inflammation with additive predictive value in asthma. We have shown that high FeNO correlates with chemokines and cytokines involved in epithelial signalling whilst blood eosinophil levels correlate with serum interleukin-5 only.1 This suggests that FeNO more accurately reflects inflammation in the airway ‘compartment’ and blood eosinophil count reflects the systemic ‘compartment’ in eosinophilic asthma. We now test the hypothesis that the effect of low dose inhaled corticosteroids and oral corticosteroids, both effective treatments for eosinophilic airway inflammation, have differential effects on the airway (reflected by FeNO) and systemic compartment (reflected by blood eosinophils) in patients with eosinophilic asthma. Corticosteroid-naïve patients were assessed before and after 8 weeks of 200 mcg twice daily beclomethasone via aero-chamber. Patients with eosinophilic asthma established on inhaled treatment were assessed before and after 10 days of 30 mg prednisolone daily. Patients were at steady state and had evidence of type-2 airway inflammation reflected by either baseline FeNO >45ppb and/or blood eosinophils >0.30x109/L. 11 patients were recruited to the ICS group and 13 to the OCS group. Groups were matched for age but not baseline FEV1. Low-dose ICS produced a large median decrease in FeNO of 53.5%, p < 0.002, 95% CI [36.1, 71.0] and a small decrease in blood eosinophilia of 18.8% p < 0.005, 95% CI [6.5, 42.8] (figure 1). By contrast, OCS resulted in a comparatively smaller reduction in FeNO of 34.8%, p < 0.001, 95% CI [18.0, 51.5] but a large decrease in blood eosinophils of 80.3%, p < 0.001, 95% CI [64.3, 92.3]. These results suggest inhaled and oral steroids act differentially in the airway and blood compartments. The relative resistance to inhaled corticosteroids identified in some patients with type-2 high asthma, and the comparative success of oral therapy in this group, may reflect a greater contribution from the systemic reservoir of blood eosinophils. Reference Couillard S, Shrimanker R, Chaudhuri R, et al. Fractional Exhaled Nitric Oxide Non-suppression Identifies Corticosteroid-Resistant Type 2 Signaling in Severe Asthma. Am J Respir Crit Care Med. 2021;204(6):731–734.

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)0.000
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 score0.002
Threshold uncertainty score0.007

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0020.000

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 head0.013
GPT teacher head0.266
Teacher spread0.253 · 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
Published2023
Admission routes1
Has abstractyes

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