S11 The different mechanisms of inhaled and oral corticosteroids in T2-high asthma. For those established on inhaled steroids additional effects from oral steroids may lie in access to the small airways
Bibliographic record
Abstract
Introduction Inhaled and oral corticosteroids are cornerstone treatments of eosinophilic asthma but their differential mechanisms of action are incompletely understood. Methods We conducted a prospective observational study to examine the effects of inhaled and oral corticosteroids [REC18/SC/0361]. Participants with FeNO >45 ppb and/or blood eosinophils >0.30x109/L were selected. Cohorts comprised: (i) inhaled corticosteroid-naïve patients before/after 8 weeks beclomethasone 200 mcg twice daily (ICS group, n=21); (ii) participants with confirmed adherence to ICS treatment (geomean daily BDP equivalent dose ±SEM 949±130mcg) and abstinent of oral corticosteroids for >3 months before/after 10 days of prednisolone 30 mg daily (OCS group, n=21); (iii) healthy controls (n=31). Outcomes included lung function, symptoms, blood and sputum cell counts and levels of 12 canonical markers of type-2 inflammation assayed via ELISA. Between and within group comparisons were made using mixed effects ANOVA. Results ICS and OCS groups were matched at baseline for age, gender, atopy, bronchodilator reversibility and FeNO. Both ICS and OCS treatments resulted in significant improvements in FEV1 (figure 1A) and reduction of symptom scores (mean ACQ5 difference 1.1 with OCS and 1.5 with ICS, both p<0.001). FeNO was reduced by both ICS (mean reduction 62%, p<0.0001) and OCS (mean reduction 42%, p<0.001) with no significant between-group treatment effect (figure 1B). Introducing OCS treatment resulted in a greater reduction of blood eosinophils (76%) than initiating ICS treatment (31%) (p<0.001) and OCS reduced sputum eosinophil% by a greater margin than ICS (28.5% points vs 6.8% points, p=0.02, figure 1D). ICS treatment had no significant effect on serum mediators while OCS treatment reduced serum IL-5 only (figure 1F). Both ICS and OCS treatment reduced sputum levels of IL-5, eotaxin-3 and TSLP (all p<0.01). Sputum eotaxin was reduced uniquely by ICS (p=0.02, figure 1G) while the addition of OCS uniquely reduced sputum levels of IL-4, IL-13 and LTE4 (all p<0.04). Conclusion Our findings are consistent with an important role for the small airways in FeNO non-suppression and a site of OCS treatment response in T2-high patients. This effect might result through greater tissue bioavailability of OCS and/or in providing enhanced access for inhaled therapies.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.086 | 0.009 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".