Equine asthma describes a chronic inflammatory airway condition of varying severity that causes clinical signs through three main pathogenic mechanisms: broncho-constriction, increased mucus production and airway inflammation. The condition is categorised as ‘severe’ if clinical signs, such as laboured breathing, are observed at rest and can be provoked by, for example, exposure to mouldy hay (Couetil et al, 2020). Airway inflammation is most commonly characterised by a neutrophilic cell influx, but mast cell or eosinophilic airway inflammation is also possible (Couetil et al, 2020). Equine asthma is usually triggered by environmental antigens, often present in the stable environment. Occasionally, equine asthma can also be triggered by factors present in both the stable and field environment (Mair, 1996). Therapy aims to achieve improvement or, ideally, resolution of the clinical signs caused by airway inflammation, bronchoconstriction and increased mucus production. The most important aspect of treatment is optimising the horse's environment. With the exception of pasture-associated asthma, turning horses out in a field continuously, without any time in a stable, often resolves the clinical signs completely (Jackson et al, 2000). In acute asthma exacerbation or in cases where the environment cannot be modified sufficiently, additional pharmacological treatment in the form of bronchodilators and anti-inflammatories (usually corticosteroids) might be necessary. This review will focus on the evidence behind the most commonly treatments used for severe equine asthma.
Modification of the environment
Hay consumption, particularly from round bales, is associated with neutrophilic airway inflammation and mucus accumulation in healthy horses, and it can trigger asthma attacks in horses with severe equine asthma (Robinson et al, 2006). Compared to pasture, feeding dry hay is associated with up to a 10-fold increase in exposure to airborne dust in the breathing zone (McGorum et al, 1998). Immersing hay in water decreases the respirable dust concentration by 60% and leaving hay soaking for 10–30 minutes or steaming for 80 minutes leads to a reduction of 93%, 96% and 95%, respectively (Blackman and Moore-Colyer, 1998; Clements and Pirie, 2007a). Feeding haylage results in a 60–70% reduction in dust exposure in the breathing zone compared to dry hay; feeding haylage to healthy Standardbreds reduced airway neutrophilia and inflammatory cytokine concentrations when compared to feeing dry hay (Clements and Pirie, 2007b; Olave et al, 2021). In addition, feeding haylage, but not steamed hay, increased the ratio of anti-inflammatory to pro-inflammatory lipids while reducing neutrophil proportions found in bronchoalveolar lavage fluid in healthy Thoroughbreds, which might be beneficial in horses with asthma (Orard et al, 2018; Diez de Castro and Fernandez-Molina, 2024).
Therefore, feeding steamed hay, soaked hay or haylage to horses with asthma is frequently recommended, because they all reduce dust exposure, mould counts and microbial counts (steamed and soaked hay only) (Diez de Castro and Fernandez-Molina, 2024). When feeding horses with severe equine asthma steamed or dry hay, no differences were detected in clinical scores and percentages of neutrophils and mRNA expression of inflammatory cytokines were increased in broncho-alveolar lavage fluid in both groups (Orard et al, 2018). Groups were small, with only five horses with severe equine asthma and six controls, and responses between horses varied widely. This resulted in the study being under-powered to detect differences in clinical scores, which could explain the lack of significant differences (Orard et al, 2018). However, the study highlighted that steaming does not eliminate all inflammatory stimuli from hay. If feeding steamed hay does not result in the anticipated improvement, changing to (ideally) pasture, soaked hay or haylage should be considered. Feeding soaked hay or hay pellets to horses with severe equine asthma during an asthma attack equally reduced clinical scores and improved airway function (Westerfeld et al, 2024). The study used a strict regimen of removing any leftover dried hay; this might be difficult to maintain for owners, particularly overnight (Westerfeld et al, 2024). To the author's knowledge, no study has investigated the effect of feeding haylage compared to dry hay to horses with severe asthma; feeding silage to horses with severe asthma stabled on wood shavings showed similar clinical and functional parameters compared to healthy horses on pasture. Despite clinical improvement, bronchial reactivity remained higher than normal, suggesting an increased susceptibility to bronchoconstriction (Vandenput et al, 1998). Supplementation with 30–60 g of omega-3 fatty acid in addition to a low dust diet led to a greater improved in some aspects of lung function compared to a low dust diet alone and could be considered as an adjunctive measure (Orard et al, 2018).
Bronchodilation
Clinical signs in horses with severe asthma are predominantely caused by bronchoconstriction. In contrast to corticosteroids, bronchodilators only relieve clinical signs associated with bronchoconstriction, not the underlying airway inflammation. Therefore, many clinicians consider anti-inflammatory treatment essential, with bronchodilators only being used in addition to corticosteroids and for short periods of time (Léguillette, 2021). Nevertheless, bronchodilators are indispensable as emergency treatment during an acute asthma attack and in the management of horses where veterinarians or owners are reluctant to use corticosteroids because of the risk of laminitis, and inhaled therapy is not suitable. Bronchodilators can be administered orally, by inhalation or, less commonly, injection.
Systemically-used bronchodilators
Most studies investigating the effects of bronchodilators focus on improvement of pulmonary function rather than improvement in clinical signs, expressed as clinical scores, as would be done in practice. Clinically noticeable improvement can be slower, and a return to normal values should not be expected imminently (Henrikson and Rush, 2001; Calzetta et al, 2020). The improvement might be difficult to detect when relying on clinical parameters, such as respiratory rate, effort and nostril flare, alone to judge the response (Couetil et al, 2012; de Lagarde et al, 2014). This is important to remember when using injectable bronchodilators for diagnostic purposes or as rescue medication. While a positive response to trial treatment with a bronchodilator confirms the presence of bronchoconstriction, a negative or equivocal immediate response does not rule out asthma. Atropine (0.02 mg/kg intravenously) is one of the most potent bronchodilators in horses and has been used for diagnosis and emergency relief. N-butylscopolammonium bromide (buscopan, 0.3 mg/kg intravenously) causes a similar but more short-lived (approximately 30–60 minute) improvement within 2 minutes of administration, and it is now preferred as it has fewer systemic side effects (de Lagarde et al, 2014; Mozo Vives et al, 2024). An underwhelming immediate response is likely as a result of persistent mucus accumulation, inflammation and airway smooth muscle remodelling, highlighting the need for concurrent anti-inflammatory treatment (de Lagarde et al, 2014).
Clenbuterol, a beta-2-adrenergic agonist, is the most commonly used oral bronchodilator in horses. It has a dose-dependent effect, but not all horses respond to treatment. Incremental doses (0.8–3.2 μg/kg twice daily) of clenbuterol achieved clinical improvement in 75% of the horses with severe asthma, while 25% did not respond (Erichsen et al, 1994). Only 24% of horses responded to the lowest dose. More severely affected horses required higher doses more frequently or did not respond compared to less severely affected animals (Erichsen et al, 1994). Oral clenbuterol also increases tracheal mucociliary clearance rate, has anti-inflammatory effects and decreases mucus production by goblet cells in horses (Kiely and Jenkins, 1985; Laan et al, 2006; van den Hoven et al, 2006; Norton et al, 2013). Tachyphylaxis can occur within 21 days, an effect that might be prevented or reversed by concurrent use of corticosteroids (Read et al, 2012). In vitro, clenbuterol has an anti-proliferative and antifibrotic effect on equine bronchial fibroblasts, which is synergistically enhanced by dexamethasone (Franke and Abraham, 2014). The antiproliferative effect was more pronounced with clenbuterol than salbutamol (Franke and Abraham, 2014).
Inhaled bronchodilators
Following inhalation of albuterol or salbutamol, an effect can be seen within 5 minutes and lasts for 30–60 minutes; one study reported that the effect lasted up to 180 minutes (Mozo Vives et al, 2024). A dose of 1–2 μg/kg (540–1000 μg for a 500 kg horse) is commonly suggested. When comparing intravenous N-butylscopolammonium bromide and inhaled salbutamol, both drugs have a similar bronchodilator potency. Salbutamol had a longer duration of action of approximately 180 minutes and, in contrast to N-butylscopolammonium bromide, no gastrointestinal and cardiovascular side effects. This suggests that salbutamol might be preferable for treatment of routine equine asthma exacerbation (Mozo Vives et al, 2024). The onset of action is slower with salmeterol (up to 60 minutes) but is maintained longer (approximately 6 hours).
Ipratropium is the only inhaled muscarinic cholinergic antagonist available that is commonly used in horses. The onset of action is approximately 60 minutes, and the duration of action is between 4 and 6 hours, with large variation between horses (McGorum et al, 2013). Whether systemic treatment with bronchodilators is more effective than inhaled bronchodilators when treating horses in acute respiratory distress, as it is the case for corticosteroids, has not been investigated to the author's knowledge.
Anti-inflammatory drugs
Systemic corticosteroids
Systemic corticosteroids (particularly dexamethasone at 0.04–0.1 mg/kg every 24 hours intravenously, intramuscularly or orally) are still the most effective drug in improving lung function in equine asthma, even if environmental management remains suboptimal (Lavoie et al, 2019a). Immediate improvement should not be expected as it takes 3–7 days until the treatment can take full effect (Robinson et al, 2002; Leclere et al, 2010). Systemic dexamethasone is more effective in the treatment of acute severe equine asthma attacks than inhaled corticosteroids (Robinson et al, 2009; Lavoie et al, 2019a), and is the preferred option as an initial therapeutic when clinical signs are severe. Because of its high efficacy in treating severe equine asthma, dexamethasone is often used as a ‘gold standard’ treatment, against which newer treatments are compared. Clinical benefits are seen for approximately 1 week, while adrenal suppression lasts for approximately 3 days. Adrenal suppression is taken as evidence for lasting systemic effects of corticosteroids and assumed to expose the horse to the risk of unwanted side effects. An additional benefit of corticosteroids is the prevention of clenbuterol-induced beta-2-adrenergic receptor downregulation on equine lymphocytes, but concurrent use does not prevent agonist-induced downregulation in equine bronchial fibroblast (Read et al, 2012).
Prednisolone (1.0–2.0 mg/kg orally every 24 hours) has a very similar, if less consistent and sometimes less profound, clinical effect compared to dexamethasone (Leclere et al, 2010). Prednisolone is not absorbed orally and is therefore not effective in the treatment of equine asthma (Peroni et al, 2002).
Inhaled corticosteroids
Inhaled corticosteroids are useful in clinically stable horses with severe asthma to decrease airway inflammation, improve lung function and prevent exacerbation of their asthma. Inhaled corticosteroids are considered advantageous as they predominately act locally with fewer systemic effects. Apart from rare anecdotal reports by horse owners, laminitis has not been associated with the use of inhaled corticosteroids to the author's knowledge. However, with the exception of ciclesonide, adrenal suppression is still present with all commonly used inhaled corticosteroids, including beclomethasone, fluticasone and budesonide (Léguillette, 2021). In an acute asthma crisis, inhaled corticosteroids are also less effective than systemic dexamethasone and are therefore not recommended (Robinson et al, 2009; Lavoie et al, 2019a).
Beclomethasone diproprionate is used in most equine studies and has a dose-dependent effect on lung function. At the highest dose tested (3750 μg every 2 hours), it improved lung function even in a stable environment (Ammann et al, 1998). Beclomethasone has a lower affinity to glucocorticoid receptors than fluticasone and may be less potent (Léguillette, 2021).
Inhaled fluticasone (6000 ug every 12 hours for 7 days) was as effective as dexamethasone (0.1 mg/kg intravenously every 24 hours for 7 days) in the prevention of an asthma attack. However, when treating an acute exacerbation, dexamethasone was more effective (Robinson et al, 2009). In mildly asthmatic horses, inhaled fluticasone (3000 μg every 12 hours for 15 days) decreased airway hyper-responsiveness similarly to dexamethasone (0.05 mg/kg intramuscularly every 24 hours) (Léguillette et al, 2017). It also improves lung function in antigenic environment (2000 μg every 12 hours), with further improvement when the horse was moved to a low antigenic environment (Leclere et al, 2012).
Inhaled budesonide administered at 450 μg, 900 μg and 1800 μg every 12 hours had a dose-dependent effect on lung function, with the highest dose being as potent as systemic dexamethasone. Serum cortisol and blood adrenocorticotropic hormone concentrations decreased with both treatments (Lavoie et al, 2019b).
Ciclesonide is a pro-drug that only becomes fully active once de-esterified in the lung to its metabolite desisobutyryl-ciclesonide. Desisobutyryl-ciclesonide has a 100–120-fold higher gluco-corticoid receptor binding affinity than ciclesonide, and a 12 times higher affinity than dexamethasone. As the effective drug elicits its glucocorticoid effects at the site of activation in the airways, the risk of systemic adverse reactions is reduced and there is no suppression of serum cortisol in most horses (but this can occur in individual animals). The drug is aerosolised using Soft Mist technology, which favours deep lung deposition by having a greater fine particle fraction than a metred dose inhaler with low velocity of particles. In an experimental setting, 2700 μg every 12 hours improved lung function during asthma exacerbation comparable to dexamethasone without suppression of serum cortisol (Lavoie et al, 2019a). An experimental study suggested that certain immunosuppressive effects seen with dexamethasone where absent in the ciclesonide group (Page et al, 2023). Tested under field conditions, the application was well tolerated with few adverse events. An improvement in quality of life was reported in 69% treated horses, but also in 43% receiving a placebo (Pirie et al, 2021). Unfortunately, access to the drug and device is limited in some countries.
Nebulised dexamethasone (5 mg=0.01 mg/kg; NEBU-TEC; Flexineb mask) did not improve lung function in two studies while causing hypothalamus–pituitary–adrenal axis suppression (Mainguy-Seers et al, 2019; de Wasseige et al, 2021). One study described a subjective impression of cough induction and discomfort in some horses (de Wasseige et al, 2021). There is currently no evidence to support the use of nebulised dexamethasone for the treatment of severe equine asthma.
Comparison systemic versus inhaled corticosteroids
One meta-analysis showed no differences between systemic and inhaled corticosteroids regarding the magnitude of clinical score improvement and lung function (Mainguy-Seers and Lavoie, 2021). Across all studies, systemic steroids were never inferior, and often superior, to inhaled steroids. Systemic steroids had a faster onset of action and greater improvement in severe asthma exacerbation, where mucus accumulation, bronchospasm and coughing might impair lower airways deposition of inhaled medication (Mainguy-Seers and Lavoie, 2021).
Conclusions
Environmental modifications remain the most important management strategy for horses with severe equine asthma. In an acute asthma attack, systemic corticosteroids in combination with systemic or inhaled bronchodilators are most effective, while inhaled corticosteroid treatment in horses with controlled severe asthma offers the lowest risk of side effects.