A randomized, masked, crossover, clinical trial of the efficacy and safety of nebulized albuterol sulfate and dexamethasone sodium phosphate in asthmatic horses.
Abstract: Nebulization of injectable dexamethasone sodium phosphate (DSP; 0.01 mg/kg) to horses with severe equine asthma (SEA) was previously found to be ineffective. Horses with SEA have marked bronchoconstriction that decreases peripheral lung deposition of nebulized drugs. Administration of a bronchodilator immediately before nebulizing dexamethasone may improve efficacy. Objective: Evaluate the therapeutic effects and optimal dose of nebulized DSP after nebulized albuterol in horses with SEA. Methods: Seven horses with SEA from a research herd. Methods: In this masked randomized crossover trial, horses were assigned to one of 3 treatment groups: (1) 0.04 mg/kg DSP IV; (2) 0.01 mg/kg DSP by nebulization; and (3) 0.02 mg/kg DSP by nebulization, in a 3 × 3 Latin square design. All horses were treated q24h for 7 days and received albuterol (0.3 μg/kg) 10 min before DSP. Clinical score, pulmonary function testing, bronchoalveolar lavage fluid (BALF) cytology, adrenocorticotropic hormone stimulation test, plasma and BALF DSP concentrations and routine blood test results were compared between groups and over time. Results: Nebulized DSP resulted in similar lung deposition as IV DSP but did not suppress adrenocortical function. However, nebulized DSP did not improve clinical signs, lung function, or BALF cytology. Only IV DSP improved lung function. None of the treatments performed influenced BALF neutrophil proportions. Conclusions: Nebulization of albuterol before DSP minimizes systemic absorption of dexamethasone and preserves adrenal function of horses with SEA. Our results do not support the use of nebulized DSP at the doses used for the treatment of SEA.
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Overview
This clinical trial investigated whether administering a bronchodilator (albuterol) before nebulizing dexamethasone sodium phosphate (DSP) would improve the treatment of severe equine asthma (SEA) in horses.
The study compared different doses and routes of DSP administration to evaluate their effects on lung function, clinical signs, immune response, and safety.
Background
Severe equine asthma (SEA) is a chronic respiratory condition in horses marked by bronchoconstriction, inflammation, and difficulty breathing.
Previous research indicated that nebulized DSP at 0.01 mg/kg was ineffective, likely because bronchoconstriction limits the peripheral lung deposition of nebulized drugs.
Hypothesis: Administering a bronchodilator (albuterol) before nebulizing DSP could open airways and improve drug delivery to the lungs, enhancing treatment efficacy.
Study Design and Methods
Seven SEA-affected horses from a research herd participated in a randomized, masked crossover clinical trial with a 3×3 Latin square design.
The three treatment regimens were:
Intravenous (IV) DSP at 0.04 mg/kg
Nebulized DSP at 0.01 mg/kg
Nebulized DSP at 0.02 mg/kg
Before administering DSP, all horses were nebulized with albuterol at 0.3 μg/kg 10 minutes earlier to open airways.
Treatments were given once every 24 hours for 7 days per treatment period.
Several parameters were measured to assess treatment efficacy and safety:
Clinical scores reflecting respiratory signs
Pulmonary function tests measuring lung mechanics
Bronchoalveolar lavage fluid (BALF) cytology to evaluate airway inflammation
Adrenocorticotropic hormone (ACTH) stimulation test to check adrenal gland function
Measurements of DSP concentration in plasma and BALF to study drug deposition and absorption
Routine blood tests to detect systemic effects or adverse reactions
Key Findings
Nebulized DSP (both 0.01 and 0.02 mg/kg) achieved similar lung deposition levels compared to IV administration, indicating that albuterol improved drug delivery to some extent.
Nebulized DSP did not suppress adrenal function, as shown by the preserved response in the ACTH stimulation test, implying minimal systemic absorption.
Despite adequate lung deposition, nebulized DSP did not improve clinical respiratory signs, lung function measures, or reduce airway inflammation assessed by BALF cytology.
Only IV DSP at 0.04 mg/kg led to improvements in lung function, demonstrating it was the only effective treatment in this trial.
None of the treatment protocols had an effect on neutrophil proportions in the BALF, indicating persistent inflammation unaffected by DSP nebulization.
Conclusions and Clinical Implications
Using albuterol nebulization before DSP enhances lung deposition of nebulized DSP without causing systemic side effects or adrenal suppression.
However, nebulized DSP at the studied doses (0.01 and 0.02 mg/kg) does not improve lung function or clinical outcomes in SEA horses.
IV DSP remains the more effective approach for improving lung function in SEA, but with associated systemic corticosteroid effects.
The findings suggest that nebulized corticosteroid treatment may require different dosing strategies or formulations to be therapeutically effective.
Clinicians should be cautious about relying on nebulized DSP at these doses for SEA treatment, as efficacy was not demonstrated despite good lung delivery.
Cite This Article
APA
Tyson KN, Couetil LL, Ivester KM, Murray L, Mukhopadhyay A, Marmolejo JF, Jannasch A.
(2026).
A randomized, masked, crossover, clinical trial of the efficacy and safety of nebulized albuterol sulfate and dexamethasone sodium phosphate in asthmatic horses.
J Vet Intern Med, 40(2), aalag030.
https://doi.org/10.1093/jvimsj/aalag030
Department of Veterinary Clinical Sciences, Purdue University College of Veterinary Medicine, West Lafayette, IN 47907, United States.
Couetil, Laurent L
Department of Veterinary Clinical Sciences, Purdue University College of Veterinary Medicine, West Lafayette, IN 47907, United States.
Ivester, Kathleen M
Department of Veterinary Clinical Sciences, Purdue University College of Veterinary Medicine, West Lafayette, IN 47907, United States.
Murray, Laura
Department of Veterinary Clinical Sciences, Purdue University College of Veterinary Medicine, West Lafayette, IN 47907, United States.
Mukhopadhyay, Abhijit
Department of Veterinary Clinical Sciences, Purdue University College of Veterinary Medicine, West Lafayette, IN 47907, United States.
Marmolejo, Jackeline Franco
Metabolite Profiling Facility, Bindley Bioscience Center, Purdue University, West Lafayette, IN 47907, United States.
Jannasch, Amber
Metabolite Profiling Facility, Bindley Bioscience Center, Purdue University, West Lafayette, IN 47907, United States.
MeSH Terms
Animals
Horses
Albuterol / therapeutic use
Albuterol / administration & dosage
Albuterol / adverse effects
Dexamethasone / analogs & derivatives
Dexamethasone / administration & dosage
Dexamethasone / therapeutic use
Dexamethasone / adverse effects
Horse Diseases / drug therapy
Asthma / drug therapy
Asthma / veterinary
Cross-Over Studies
Bronchodilator Agents / therapeutic use
Bronchodilator Agents / administration & dosage
Bronchodilator Agents / adverse effects
Female
Male
Nebulizers and Vaporizers / veterinary
Administration, Inhalation
Bronchoalveolar Lavage Fluid / cytology
Grant Funding
Nortev Ltd. Galway, Ireland
Indiana and the Purdue University College of Veterinary Medicine
Conflict of Interest Statement
Nortev Ltd. provided some funding to help support 2 workshops on equine asthma organized by Dr. Laurent Couetil (2019 and 2023). The other authors declare no conflicts of interest.
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