Inhaled Pitavastatin Inhibits Bronchoconstriction in an Experimental Sheep Lung Model
Bibliographic record
Abstract
Abstract RATIONALE: The 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) inhibitor, Pitavastatin, reduces airway smooth muscle (ASM) contraction and causes bronchodilation by both mevalonate (MA)-dependent and MA-independent mechanisms of action. This testing has been previously done in submerged media (e.g., cell culture, or precision-cut lung slices). To test the relevance of these effects via aerosol airway delivery, we hypothesized that inhaled Pitavastatin improves lung function in a non-inflammatory model of bronchoconstriction. METHODS: The sheep lung model develops spontaneous bronchoconstriction as is measured ex vivo. A “lung-in-a-box” apparatus housed living fresh whole lung explants which models tidal volume (TV) breaths. During the incubation period, the lung was ventilated at a TV of 120 mL for 60 min during which a deep inspiration (DI) was imposed once every 10 min. During this period the lung was constantly exposed to nebulized Pitavastatin aerosol (Pit, 9.47 mM), Salbutamol aerosol (Salb, 10.4 mM), or drug vehicle control aerosols. After the incubation period, the lung was ventilated at the same TV for 60 min during which no DI was imposed until the end of this period. Lung resistance or elastance was measured at various frequencies (0.25-2 Hz) every 10 min throughout the whole experiment. RESULTS: Inhalation of nebulized Salb or Pit aerosols independently caused a significant reduction in lung resistance and lung elastance at all measured frequencies, as compared to negative controls (Krebs solution, drug vehicle). Inhaled Pit caused a ∼80-95% reduction in both lung resistance and lung elastance (i.e., increased lung compliance) as compared to negative controls. This beneficial Pit effect was significant and appears on par with Salb with respect to both parameters (see Figure). CONCLUSIONS: Inhaled Pitavastatin aerosol improves lung function by reducing lung resistance and improving lung compliance in a sheep model of spontaneous bronchoconstriction. The efficacy of inhaled Pitavastatin rivals that of Salbutamol, a beta2-agonist, but aditional research is warranted in inflammatory allergic models of asthma. Inhaled statins have the potential to be a novel class of inhaled bronchodilators for the treatment of bronchoconstriction in obstructive airway diseases such as asthma or chronic obstructive pulmonary disease.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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.
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".