Lack of clinical efficacy of a phosphodiesterase-4 inhibitor for treatment of heaves in horses.

The research evaluates the effects of a drug, phosphodiesterase-4 (PDE-4) inhibitor L-826,141, on horses suffering from “heaves”, an equine respiratory disease, and finds that, despite some minor benefits, it does not significantly improve their airway function or inflammation.

Objective of the Study

• The main goal of the study was to examine the effectiveness and possible side effects of the PDE-4 inhibitor, known as L-826,141, on horses that have been diagnosed with ‘heaves’, a chronic airway disease akin to asthma in humans.

Methodology

• In two separate studies, horses were given daily exposure to moldy hay to trigger heave-like symptoms. Later, these horses were given either L-826,141 or dexamethasone, a common anti-inflammatory drug.
• In the first study, the horses were initially given a placebo for 14 days before being treated with L-826,141 or dexamethasone from days 15 to 29. The researchers assessed pulmonary function and bronchoalveolar (BAL) cytology weekly.
• In the second study, horses were treated with L-826,141 for 8 days.

Findings

• The studies found that while the administration of L-826,141 could cause some changes in cells, it did not lead to significant improvement in lung function.
• In contrast, dexamethasone did lead to significant improvement in lung mechanics and overall airway function in all the horses.
• Interestingly, neither drug had a substantial impact on BAL total cell counts and differential cytology, indicating that neither drug directly affected lung inflammation cells.

Conclusion

• Given the evidence provided by this study, the researchers assert that following 14 days of L-826,141 administration, there is no considerable improvement in airway function or inflammation in horses diagnosed with “heaves”.
• This leads them to suggest that the PDE-4 enzyme may not play a significant role in the inflammatory response witnessed in equine lung diseases such as “heaves”.