Clinical relevance of the relaxant effects of roflumilast on human bronchus: potentiation by a long‐acting beta‐2‐agonist
Bibliographic record
Abstract
Abstract Roflumilast is an oral, add‐on option for treating patients with severe COPD and frequent exacerbations despite optimal therapy with inhaled drugs. The present study focused on whether this phosphodiesterase 4 inhibitor and its active metabolite roflumilast N‐oxide affect the tone of human bronchial rings. We also investigated the interactions between roflumilast, roflumilast N‐oxide and the long‐acting β 2 ‐agonist formoterol with regard to the relaxation of isolated human bronchial rings at basal tone or pre‐contracted with histamine. Our results demonstrated for the first time that at a clinically relevant concentration (1 n m ), roflumilast N‐oxide and roflumilast induce a weak relaxation of the isolated human bronchus either at resting tone (22% and 16%, respectively) or even weaker on pre‐contracted bronchus with histamine (7% and 5%, respectively). In addition, the combination of formoterol with roflumilast or roflumilast N‐oxide is more potent than each component alone for relaxing pre‐contracted isolated bronchi ‐ the apparent pD2 of formoterol was significantly reduced for the threshold concentration of 1 n m of the phosphodiesterase 4 inhibitors by a factor of 2.4 for roflumilast N‐oxide and 1.9 for roflumilast. The full inhibition of phosphodiesterase 4 activity is achieved at 100 n m but this high concentration only caused partial relaxations of the human bronchi. At a clinically relevant concentration, these oral phosphodiesterase 4 inhibitors are not effective direct bronchodilators but could enhance the efficacy of inhaled long‐acting β2‐agonists.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| 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".