A dual Cys<scp>LT</scp><sub>1/2</sub> antagonist attenuates allergen‐induced airway responses in subjects with mild allergic asthma
Bibliographic record
Abstract
Abstract Background The cysteinyl leukotrienes (cys LT s) play a key role in the pathophysiology of asthma. In addition to functioning as potent bronchoconstrictors, cys LT s contribute to airway inflammation through eosinophil and neutrophil chemotaxis, plasma exudation, and mucus secretion. We tested the activity of the dual cys LT 1/2 antagonist, ONO ‐6950, against allergen‐induced airway responses. Methods Subjects with documented allergen‐induced early ( EAR ) and late asthmatic response ( LAR ) were randomized in a three‐way crossover study to receive ONO ‐6950 (200 mg) or montelukast (10 mg) or placebo q.d. on days 1–8 of the three treatment periods. Allergen was inhaled on day 7 two hours postdose, and forced expiratory volume in 1 s ( FEV 1 ) was measured for 7 h following challenge. Sputum eosinophils and airway hyperresponsiveness were measured before and after allergen challenge. The primary outcome was the effect of ONO ‐6950 vs placebo on the EAR and LAR . Results Twenty‐five nonsmoking subjects with mild allergic asthma were enrolled and 20 subjects completed all three treatment periods per protocol. ONO ‐6950 was well tolerated. Compared to placebo, ONO ‐6950 significantly attenuated the maximum % fall in FEV 1 and area under the % FEV 1 /time curve during the EAR and LAR asthmatic responses ( P < 0.05) and allergen‐induced sputum eosinophils. There were no significant differences between ONO ‐6950 and montelukast. Conclusions Attenuation of EAR , LAR , and airway inflammation is consistent with cys LT 1 blockade. Whether dual cys LT 1/2 antagonism offers additional benefit for treatment of asthma requires further study.
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 distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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.
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 teacher head, 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".