Treatment of equine asthma should combine environmental changes and medical therapy. The goals of medical therapy are to control airway inflammation and relieve airflow obstruction using mainly corticosteroids and bronchodilators or antimicrobials when infection is suspected. There are few peer- reviewed clinical trials published regarding the therapy of mild equine asthma.
Most of the drugs and dosages recommended are based on studies performed on horses with severe asthma (RAO); however, a good clinical response has been observed using those guidelines. Both systemic and aerosolized drugs are effective, but the potential for adverse effects and prolonged elimination times is greater with systemic administration.
The advantages of aerosol therapy are ease of administration and safety. The disadvantages are the cost of delivery devices and drugs (metered-dose inhalers). Non-steroidal anti-inflammatory and antihistamine drugs are ineffective for the treatment of equine asthma.
Fig. 1A Aerosol therapy using Flexine
Images courtesy of Laurent L. Couëtil | DVM, PhD, DACVIM
ENVIRONMENTAL MANAGEMENT:
Inhaled dust particles play an important role in the pathophysiology of equine asthma, and treatment should always include recommendations to decrease exposure to environmental irritants to the airways. Two main approaches help reduce the exposure of the horse’s airways to respirable
particles. The first approach is to use feedstuffs and bedding that generate low dust levels.
The second approach is to increase the removal of airborne particles by improving ventilation in the barn or stall. The ideal environment for horses with severe asthma is pasture because exposure to dust is significantly less than in the stalls. If the horse cannot be kept on pasture, ventilation in the barn and stall, the type of bedding, feedstuffs, and general management should be scrutinized to minimize allergen exposure.
Most horses improve clinically one to two weeks after being turned outside on pasture. Horses that only improve partially after being placed on pasture would benefit from medical therapy. Once the horse becomes free of clinical disease (remission), medication can be discontinued. Because of the disease’s nature, susceptible horses may suffer another bout of it when exposed to allergens.
Horses with summer pasture-associated asthma are generally affected between June and September. The recommended environment for these horses during the summer is low-dust indoor housing. The management of affected horses may be complicated if they suffer from both classic and summer pasture-associated asthma.
Studies have demonstrated effective reduction in dust exposure when horses were fed haylage or soaked hay instead of dry hay. Supplementation of the diet with omega-3 polyunsaturated fatty acids in combination with low-dust feed is also effective in resolving clinical signs over a shorter period in horses with both moderate and severe asthma.
MEDICAL THERAPY: Antibiotics
A large proportion of racehorses suffering from respiratory disease because of poor performance, cough, or nasal discharge are treated with antimicrobials, usually without supportive evidence of bacterial infection. However, there is currently no controlled study reporting the efficacy of antimicrobials in the treatment of mild asthma. Available data shows no association between response to treatment and the type of antimicrobial used, duration of treatment, or time elapsed between repeated examinations.
Only 50% of racehorses diagnosed with mild asthma based on excess tracheal mucus respond favorably to a single course of antibiotic therapy. Therefore, there is currently no evidence-based data supporting the use of antimicrobials in horses with mild asthma.
Some horses with asthma that develop exacerbations of clinical signs secondary to bacterial infection documented based on tracheal wash cytology and culture would benefit from antimicrobial therapy. Complete resolution would require following up with appropriate therapy aimed at controlling airway inflammation once infection is resolved.
Systemic Corticosteroids
Corticosteroids are potent inflammation inhibitors proven to be effective in treating severe asthma. Recommended dosages are summarized in Table 1. Triamcinolone acetonide is a long-acting corticosteroid that may improve lung function for two to four weeks after administration of a single dose, but administration should not be repeated at intervals of less than three months because of the risk of complications such as laminitis.
Dexamethasone induces a marked improvement in clinical outcomes within hours of treatment, but maximal benefit may take a week. A reduction in BALF neutrophilia is evident within three days of therapy. Dexamethasone has good oral bioavailability; however, it may be impaired by feeding. Oral administration of the drug may require high dosages (0.16 mg/kg) and be given after fasting to achieve consistent results. Treatment of severely asthmatic horses with dexamethasone 21-isonicotinate reduces airway obstruction within three days after treatment initiation, with a maximum effect obtained after seven days. Isoflupredone acetate has similar efficacy to
dexamethasone.
Prednisone is poorly absorbed after oral administration of tablets or liquid forms. Conversely, both liquid and tablet forms of prednisolone are well absorbed in the horse with a bioavailability 50%. The recommended dose is 0.5-1 mg/kg, once a day. Deleterious side effects associated with corticosteroid therapy depend on drug potency, dose used, and treatment duration. Adrenal suppression may be minimized by giving medication in the morning, when using alternate-day therapy. Long-acting and potent corticosteroids (e.g., triamcinolone, dexamethasone) are more likely to cause adverse effects such as immune suppression, iatrogenic Cushing’s disease, adrenal cortex suppression, and laminitis.
Discontinuation of dexamethasone after an extended treatment period (>3 weeks) should be done carefully to avoid acute adrenocortical insufficiency. Dexamethasone results in adrenal suppression for up to three days as compared to less than 24 hours for prednisolone. Therefore, discontinuation
Fig. 1B Aeroltherapy with Aservo EquiHaler
of prolonged dexamethasone therapy should be performed by slowly decreasing the dose until the least suppressive amount (0.01 mg/kg) is given every fourth day for at least two weeks.
Alternatively, dexamethasone therapy may be replaced by an equipotent dose of prednisolone (1 mg dexamethasone ≈ 8 mg prednisolone) that will be tapered down to alternate day treatment. Before treatment is discontinued, an ACTH stimulation test should be performed to assess the adrenocortical
reserve necessary for the horse to cope with stress.
Inhaled Corticosteroids
Administration of therapeutic substances via inhalation has the advantage of delivering high concentrations of the drug directly into the lungs while minimizing the amount absorbed systemically, and therefore, reducing the risk of adverse effects. In addition, systemic side effects and drug residue are decreased. At least five different inhaled corticosteroids are available to treat inflammatory lung diseases in humans: beclomethasone dipropionate, budesonide, flunisolide, fluticasone propionate, and triamcinolone acetonide. A common test of potency for inhaled corticosteroids, called the McKenzie skin blanching test, allows relative ranking of the compounds from least to most potent (relative to dexamethasone potency = 1): flunisolide = triamcinolone acetonide (330) < beclomethasone dipropionate (600) < budesonide (980) < fluticasone propionate (1200).
Recommended dosages for these off-label inhaled corticosteroids are summarized in Table 2. The latest and only inhaled corticosteroid approved for the treatment of equine asthma is ciclesonide (Aservo Equihaler; Boehringer Ingelheim).
Clinical experience suggests that a combination of environmental measures aimed at decreasing dust exposure, coupled with inhalation therapy using the same drugs effective against severe asthma is also beneficial for mild disease. Currently available aerosol delivery devices used to administer drugs packaged in metered-dose inhalers (MDI) provide similar clinical efficacy (AeroHippus™ and Equine Haler™).4 The Aservo Equihaler includes both the canister with inhalable drug and the aerosol delivery device in one handheld device. Improved clinical signs, decreased airway hyperresponsiveness, and reduced pulmonary inflammation are usually detectable within two weeks of therapy. Therapy with inhaled corticosteroids results in faster improvement of clinical signs and lung function as compared to environmental management alone.
Fig. 1C Aerosol therapy using AeroHippus
Systemic bronchodilators
Bronchodilators are indicated to relax airway smooth muscle and relieve airflow obstruction, but they should not be used alone for extended periods of time because they have no anti-inflammatory properties and do not reduce
airway hyperresponsiveness.
In addition, prolonged use of certain types of bronchodilators (e.g., beta2-agonists) as solo medications induces airway receptor downregulation and renders the drug less effective. This phenomenon is prevented by the combined use of beta2-agonists with corticosteroids.
The three classes of substances available as systemic bronchodilators are anticholinergic, beta2-agonist, and methylxanthine drugs (Table 1). Atropine is an anticholinergic drug that provides rapid and marked improvement in lung
function. However, potentially serious side effects such as ileus and abdominal pain can develop when high doses are used (22–88 mg) or with repeated administration. Another anticholinergic drug, glycopyrrolate, has similar efficacy to atropine but without deleterious effects on gut motility. These drugs may be used as a single dose for the rapid relief of severe airway obstruction and for diagnostic purposes.
Clenbuterol hydrochloride syrup (Ventipulmin®) is approved for the treatment of severe equine asthma. Treatment should be initiated at the low end of the dose and increased progressively if no clinical response is noted. Some horses (25 %) may not respond to clenbuterol, even at the high end of the dose. Clenbuterol also has anti-inflammatory properties and may help airway mucociliary clearance. Mild side effects such as sweating, muscle tremors, and excitement occur in less than 10 % of horses treated with oral clenbuterol. Albuterol (a beta2-receptor agonist) is poorly absorbed orally; however, inhalation therapy results in rapid but short-lived improvement in lung function (~1 hour).
Methylxanthine and derivatives may be beneficial in horses with asthma. However, plasma levels necessary for bronchodilation vary widely between horses, and the range between effective and toxic concentration is narrow. Aminophylline and theophylline, administered every 12 hours improves lung function and clinical signs in up to 50% of affected horses. Common side effects are hyperesthesia, hyperexcitability, and muscle tremors.
Pentoxifylline administered to horses with severe asthma results in significant improvement in lung function and is not associated with adverse effects.
Inhaled Bronchodilators
Two main classes of inhaled bronchodilators have been used in the horse: beta2-agonists and anticholinergic drugs (Table 2). Beta2-agonists induce airway smooth muscle relaxation regardless of bronchoconstriction mechanism and inhibit mast cell degranulation. Albuterol, levalbuterol, pirbuterol, and fenoterol are short-acting bronchodilators (one to two hours) with rapid onset of action (five minutes). Some horses may benefit from the effects of albuterol for up to seven hours.
Salmeterol and formoterol are long-acting beta2-agonists (six to eight hours) suitable for twice-daily dosing but with slow onset of action (15 minutes). Salmeterol is currently only available as a dry powder “diskus” that cannot be administered to horses. Albuterol results in maximal bronchodilation with 540 μg from metered dose inhaler (~ 1 μg/kg) using an AeroHippus or Equine Haler delivery device but only 150 μg (~0.3 μg/kg) when administered with ultrasonic nebulizer (e.g., Sahoma or Flexineb).
Ipratropium bromide is an anticholinergic drug chemically derived from atropine but devoid of side effects when administered by inhalation. Nebulization of 2 μg/kg causes bronchodilation for approximately six hours with a maximum effect obtained one hour after administration. The effects of anticholinergic drugs on airway smooth muscle are additive to beta2-agonists.
Other Therapies
Supplementation of the diet with omega-3 polyunsaturated fatty acids (e.g., DHA and EPA; Aleira®) in combination with reducing exposure to dust, results in improved clinical signs and lung function, as well as reduced airway inflammation.
Sodium cromoglycate (cromolyn) improves clinical signs and decreases bronchial hyperresponsiveness when administered to horses with mild asthma characterized by a high mast cell count in BAL fluid. However, it is ineffective for the treatment of mild asthma with other inflammatory profiles.
Oral administration of low-dose (50–150 U q24 hours) interferon alpha (IFNα) for five days reduces neutrophil, macrophage, lymphocyte, and total nucleated cell counts in the BALF of racehorses with mild asthma, as well as cough for at least two weeks.10 Higher doses of IFNα (450 U) appear to be less effective. Endoscopic scores based on respiratory exudate, cough, and pharyngeal lymphoid hyperplasia were significantly reduced after one week of therapy but were similar to placebo at two weeks.
Recommended Reading
- Clements JM, Pirie RS. Respirable dust concentrations in equine stables. Part 2: the benefits of soaking hay and optimising the environment in a neighbouring stable. Res Vet Sci 2007;83:263–268.
- Nogradi N, Couetil LL, Messick J, et al. Omega-3 fatty acid supplementation provides an additional benefit to a low-dust diet in the management of horses with chronic lower airway inflammatory disease. J Vet Intern Med Am Coll Vet Intern Med 2015;29:299–306.
- Ramzan PHL, Parkin TDH, Shepherd MC. Lower respiratory tract disease in Thoroughbred racehorses: analysis of endoscopic data from a UK training yard. Equine Vet J 2008;40:7–13.
- Bertin FR, Ivester KM, Couëtil LL. Comparative efficacy of inhaled albuterol between two hand-held delivery devices in horses with recurrent airway obstruction. Equine Vet J 2011;43:393–398.
- Leclere M, Lavoie-Lamoureux A, Joubert P, et al. Corticosteroids and antigen avoidance decrease airway smooth muscle mass in an equine asthma model. Am J Respir Cell Mol Biol 2012;47:589–596.
- Couëtil LL, Chilcoat CD, DeNicola DB, et al. Randomized, controlled study of inhaled fluticasone propionate, oral administration of prednisone, and environmental management of horses with recurrent airway obstruction. Am J Vet Res 2005;66:1665–1674.
- Read JR, Boston RC, Abraham G, et al. Effect of prolonged administration of clenbuterol on airway reactivity and sweating in horses with inflammatory airway disease. Am J Vet Res 2012;73:140–145.
- Arroyo MG, Couëtil LL, Nogradi N, et al. Efficacy of Inhaled Levalbuterol Compared to Albuterol in Horses with Recurrent Airway Obstruction. J Vet Intern Med 2016;30:1333–1337.
- Hare JE, Viel L, O’Byrne PM, et al. Effect of sodium cromoglycate on light racehorses with elevated metachromatic cell numbers on bronchoalveolar lavage and reduced exercise tolerance. J Vet Pharmacol Ther 1994;17:237–244.
- Moore I, Horney B, Day K, et al. Treatment of inflammatory airway disease in young standardbreds with interferon alpha. Can Vet J Rev Vét Can 2004;45:594–601.
- Lavoie JP, Bullone M, Rodrigues N, Germim P, Albrecht B, von Salis-Soglio M. Effect of different doses of inhaled ciclesonide on lung function, clinical signs related to airflow limitation and serum cortisol levels in horses with experimentally induced mild to severe airway obstruction. Equine Vet J. 2019 Nov;51(6):779-786. doi: 10.1111/evj.13093.
- Pirie RS, Mueller HW, Engel O, Albrecht B, von Salis-Soglio M. Inhaled ciclesonide is efficacious and well tolerated in the treatment of severe equine asthma in a large prospective European clinical trial. Equine Vet J. 2021 Nov;53(6):1094-1104. doi: 10.1111/evj.13419.
About the Author
Laurent L. Couëtil, DVM, PhD, DACVIM
Hagyard Equine Medical Institute
Dr. Couëtil is a professor of large animal medicine at Purdue University College of Veterinary Medicine and Director of the Equine Research Program. He obtained his veterinary degree from the National Veterinary School of Alfort, France and then worked several years in equine practice in France. Dr. Couëtil completed a large animal medicine residency at Tufts University and a PhD in respiratory physiology at the University of Liège, Belgium. He is past President of the Large Animal Internal Medicine specialty of the ACVIM.
Dr. Couëtil’ s research interests are Equine Sports Medicine and, in
particular, asthma in horses.