Randomised study of the immunomodulatory effects of azithromycin in severely asthmatic horses.

The study used a randomised trial to investigate the effects of azithromycin, an antibiotic with immune-modulating properties, on severely asthmatic horses with hopes of improving lung function and decreasing elements of inflammation and remodelling.

Research Background and Hypothesis

• This research is based on the understanding that neutrophilic inflammation is a significant factor in airway obstruction and remodelling related to equine asthma.
• Azithromycin, an antibiotic, has shown immunomodulatory properties, such as reducing pulmonary neutrophilia, hyper-responsiveness in human asthma patients, and airway remodelling in rodent models with asthma. As a result, the study hypothesized that azithromycin could have similar effect on improving lung function, reducing mucus accumulation, and decreasing neutrophilia (a type of inflammation) in severe equine asthma.

Study Design and Methods

• The researchers used a blind, randomised, and crossover design for this study, and the effects of azithromycin were compared with ceftiofur, an antimicrobial that lacks immunomodulating capacity.
• They used six severe asthmatic horses during their clinical exacerbation and administered a 10-day treatment with either azithromycin or ceftiofur.
• They evaluated several variables including lung function, tracheal mucus accumulation, tracheal wash bacteriology, bronchial remodelling, airway neutrophilia, and the mRNA expression of proinflammatory cytokines in bronchoalveolar lavage fluid.

Study Findings

• While the treatment with azithromycin resulted in the decreased expression of IL-8 and IL-1β (proinflammatory cytokines), it didn’t improve other evaluated parameters.
• Ceftiofur, the comparison drug, had no effect on any parameter, suggesting that its use as a first-line treatment for severe equine asthma may not be effective.

Conclusion and Further Directions

• The observed reduction of neutrophilic chemoattractants with azithromycin justifies further investigations into the effects of prolonged treatment with macrolides on airway neutrophilia and remodelling.
• The researchers concluded that severe equine asthma should perhaps not be initially treated with antibiotics given their failure to affect any of the evaluated parameters.