Effect of the 5-lipoxygenase inhibitor, fenleuton, on antigen-induced neutrophil accumulation and lung function changes in horses with chronic obstructive pulmonary disease.

This research investigates the impact of a 5-lipoxygenase inhibitor, fenleuton, in controlling bronchoconstriction and neutrophil accumulation situation in horses suffering from chronic obstructive pulmonary disease (COPD). The results highlight a significant reduction in the response to antigen challenge in cases with a pronounced increment in pleural pressure, suggesting the potential of 5-lipoxygenase inhibitors as bronchodilators in managing equine COPD.

Research Context

• The study emphasizes the role and impact of leukotrienes (LTD4 and LTB4) in causing bronchoconstriction and neutrophil accumulation in horse lungs, features typical of chronic obstructive pulmonary disease (COPD) in horses.
• To investigate the function and potential therapeutic benefits of these mediator agents in equine COPD’s development, the researchers examine the application and impact of a 5-lipoxygenase inhibitor, fenleuton.

Research Methodology

• Six horses diagnosed with COPD were subjected to a series of four antigen challenges, each a month apart. In this process, the horses received placebo treatment three times and fenleuton treatment once.
• Three horses were administered fenleuton before the second challenge, while the remaining three horses received the drug before the fourth antigen challenge.
• The research aimed to monitor and document changes in variables like radiolabelled neutrophil distribution, lung function, and peripheral leucocyte counts over a period of 7 hours following the antigen challenge initiation.

Main Findings

• Antigen challenge led to an increase in radioactive counts over the lungs and a decrease in peripheral leucocyte count. However, these responses were not significantly affected by pre-treatment with fenleuton.
• The team also observed that fenleuton pre-treatment did not significantly impact the changes in pleural pressure (delta Pplmax) and respiratory rate.
• In contrast, horses demonstrating a noticeably large increase in delta Pplmax showed a significant reduction (of 64% and 63%) in response to antigen challenge, suggesting that 5-lipoxygenase inhibitors could serve as effective bronchodilators in treating equine COPD.