Effect of prolonged administration of clenbuterol on airway reactivity and sweating in horses with inflammatory airway disease.

The research study investigates whether long-term use of clenbuterol, a medication used to treat respiratory conditions, can cause tolerance to its bronchoprotective effects and impact sweating in horses with inflammatory airway disease. Furthermore, it examines the time frame in which this tolerance may occur.

Research Methods

• The study involved 8 Thoroughbred horses diagnosed with inflammatory airway disease.
• Using a crossover design, the horses received either clenbuterol or a placebo for 21 days, separated by a washout period of 30 or more days. The researchers conducted this to ensure any lingering effects of clenbuterol were thoroughly diminished before beginning the next treatment.
• Airway reactivity was assessed at the beginning of the treatment and every week thereafter by using flowmetric plethysmography and histamine broncho-provocation. This assessment help to understand changes in the horse’s airway.
• Sweat function was evaluated by monitoring the response to administered epinephrine initially, and every ten days post the start of treatment.

Research Findings

• The study found that clenbuterol caused a significant reduction in airway sensitivity to inhaled histamine initially, specifically measured by the decreased concentration of histamine required to increase total airway obstruction by 35% (PC35). The effect was at its peak on the 14th day of treatment.
• By the 21st day of the treatment, tolerance was evident as airway reactivity increased. This was evident as seven out of eight horses ended up having a PC35 value below the baseline level. However, the airway sensitivity returned to the base levels during the washout period.
• The administration of clenbuterol did not influence the sweating response to epinephrine administration.

Conclusions

• The research concludes that prolonged administration of clenbuterol initially reduces the sensitivity of histamine-induced airway obstruction. Nonetheless, a tolerance to this effect develops over time, which reflected increased airway reactivity by the end of the 21-day treatment period.
• Although no changes in sweat response were detected during the treatment, the researchers pointed out that the method used might not have been sensitive enough to perceive subtle changes.
• The study suggests that the long-term administration of clenbuterol could potentially reduce its therapeutic effectiveness for bronchodilation in horses with inflammatory airway disease. Doctors have to consider the development of tolerance when deciding on the treatment duration.