The term “equine asthma” encompasses the syndromes of non-infectious inflammatory lower airway disease, with subcategories of mild-moderate and severe equine asthma being used to denote disease severity based on the presence or absence of clinical signs (at rest or at exercise), as well as cytological analysis of lower airway samples^1,2.

Although the term is all encompassing, no evidence suggests that a continuum of disease exists, with horses suffering from mild-moderate disease progressing inevitably to becoming a horse with severe equine asthma (SEA).

Poor performance (in particular, in horses exercising at speed) may be the only sign in horses with the mildest form of the disease. In these horses, evidence exists of airway inflammation on cytology of bronchoalveolar lavage fluid (BALF; typically an increase in the percentage of neutrophils, but in some cases mast cells and eosinophils)¹.

Horses affected by moderate equine asthma will also have an inflammatory response in BALF, but will additionally have clinical signs attributable to lower airway disease (cough, increased respiratory rate and effort, abnormal lung auscultation), but these signs are only evident at exercise¹.

Horses with SEA suffer from repeated cycles of disease and remission. In periods of disease, exacerbation horses with SEA will show varying degrees of laboured breathing (nostril flare, increased thoracic excursion, anal “pumping”), increased respiratory rate and abnormal thoracic auscultation at rest (classically, end expiratory wheezes). BALF neutrophil count will be increased, typically to a greater degree than the mild or moderate forms of the condition².

Despite a significant amount of research into the conditions, many ongoing questions persist relating to treatment, management and prevention. This article will discuss some of these questions, as well as highlight areas for future research.

How can we best manage cases where environmental conditions cannot be ‘optimised’?

Good evidence exists to show that in horses with SEA, the condition can be effectively treated and the animal will remain in remission with normalisation of BALF neutrophilia, reversal of bronchoconstriction and reduction in airway remodelling when housed at pasture, and fed a pelleted diet^3,4 (Figure 1).

In horses with mild-moderate EA, the evidence is less clear, but similar recommendations exist1. However, for many clients, this type of management is not possible or desirable, and therefore, strategies to optimise the environment of affected horses while working within the constraints of the housing available for the horse must be implemented.

Bedding type, forage type, location of the horse’s stable within the barn, cleaning and mucking out schedules, and location of storage of bedding and forage are all areas that should be evaluated to limit exposure of asthma-affected horses to airborne allergens in dust^3,4.

It is important to thoroughly inspect the horse’s environment, as owners are not always aware of how these factors might impact the amount of dust inhaled (Figure 2). For example, an owner may be bedding their horse on dust-free shavings, feeding steamed hay and allowing for turnout during times when the yard is being swept, but the horse’s stable is located next to and shares an air space with, a dusty arena. Simply moving the horse’s stable location may make a significant difference to the air quality and, therefore, the clinical signs in this horse.

Which forage?

The triggers for SEA are known to exist in hay and associated organic dust⁴. Regardless of the type of forage fed, every effort should be made to ensure that it is also of good quality, with no visible mould. Dry, mouldy hay is used in experimental studies to induce disease in asthmatic horses, with even good quality hay having high levels of respirable dust.

Respirable dust and mould levels can be decreased by steaming or soaking hay, or by feeding haylage. However, it is just as important that these processes are properly performed.

Steamed hay can reduce respirable dust release in vitro by 95 per cent and bacterial and mould content by 99%^5-8.

Commercially available steamers have spiked manifolds that push the steam into the hay and allow for appropriate temperatures to be maintained (temperatures of more than 90°C for longer than 10 minutes being required to kill mould, for example).

“Homemade” steamers are unlikely to reach sufficient temperatures and penetration of the hay, and may in some cases even exacerbate mould growth. Soaking of hay can also significantly reduce respirable dust, but prolonged soaking (longer than 60 minutes) can result in leaching of nutrients, and at even ambient temperatures (16°C) can also result in increased microbial contamination of the hay⁷.

Reducing the water-soluble carbohydrate content of the hay is advantageous when feeding to overweight horses or those at risk of laminitis, and in one study, soaking for nine hours and then steaming the hay was the most effective method for both reducing water-soluble carbohydrates and microbial contamination in hay⁸.

For asthmatic horses which do not require weight control, hay should only be soaked for 10 to 60 minutes and fed straight away, which should allow for maximal reduction of dust while conserving the nutrient quality of the hay and minimising microbial growth. Haylage is a conserved forage that is harvested at a higher moisture content than hay and can reduce exposure of respirable dust by 60% to 70% compared to dry hay⁶.

Which steroid should I use?

Systemic steroids

In horses when environmental management is not sufficient to result in clinical improvement or in horses during acute exacerbations of SEA, corticosteroids (systemic or inhaled) are effective in improving airway function and relieving clinical signs. In human medicine, inhaled bronchodilators combined with systemic steroids are typically given to patients presented to emergency departments with severe asthma exacerbations⁹.

A recent meta-analysis comparing the effectiveness of systemic versus inhaled CS in horses with SEA showed similar efficacy in improving clinical signs and lung function between the two routes of administration10. In practice, it is often more effective in the author’s experience to use systemic medications in an acute exacerbation – especially if a horse has not been “trained” to accept the delivery device for the inhaled medications.

Intramuscular or intravenous dexamethasone results in rapid (within three days) improvement in lung function, even when horses are kept indoors without measures to reduce dust¹¹. A starting dose of 0.05mg/kg IM or IV is often used, and when this dose was used for seven days, lung function returned to normal (pasture) levels, even when no management changes to minimise dust exposure were implemented¹².

Oral prednisolone, which is licensed for use in asthmatic horses at a dose of 1mg/kg by mouth once daily, does not appear to be as effective as dexamethasone. In one study, oral prednisolone (at a higher than label dose of 2mg/kg) was shown to have some efficacy at improving lung function of horses with severe asthma, even when kept indoors, but was not found to be as effective as oral dexamethasone (0.05mg/kg)¹².

Oral dexamethasone (used in an off-label manner) has been shown in several studies to be effective at doses as low as 0.01mg/kg^13,14. When using steroids orally, it is important to remember that the bioavailability is significantly reduced by feeding. In experimental studies, oral steroids are given on an empty stomach and the horse then not fed for up to 60 minutes¹⁵.

Inhaled steroids

Ciclesonide is the only licensed inhaled steroid available in the UK for horses. Ciclesonide is a prodrug that is metabolised in the lung epithelium following inhalation, resulting in a 100-fold increase in potency¹⁶. In a recent large (n=244) randomised controlled and blinded field study using a clinical score to test the efficacy of inhaled ciclesonide, a significantly higher response rate and improvement in clinical score was seen in treated horses versus controls¹⁶.

The drug does not cause adrenal suppression, suggesting minimal systemic activity, which may make it an appropriate choice in asthmatic horses that may be considered at increased risk for steroid associated laminitis. Other inhaled corticosteroids that have been used with success in horses with asthma include fluticasone, beclomethasone and budesonide^17,18.

The inhaled medications must be administered using commercially available devices incorporating a spacer and are placed either over one nostril, or fitted as a face mask over both nostrils. Nebulisation of medications is an alternative method of delivering drugs in asthmatic horses. In two recent studies, nebulised dexamethasone (5mg once daily for seven days; using two different types of nebulisers), however, did not result in a significant improvement in clinical score or pulmonary function tests in horses with SEA, despite improvements when the same (low) dose was given orally^13,14.

In both studies, systemic absorption (based on cortisol suppression) was identified. As such, treatment at this dose cannot be recommended for the treatment of horses with exacerbations of SEA, despite anecdotal reports that some horses respond to treatment.

Increasing the dose nebulised may improve efficacy, but would also presumably increase systemic absorption, negating a key perceived benefit of inhaled medications. Other nebulised medications, including lidocaine and budesonide (another steroid), have been investigated and may prove beneficial in the future. A recent study comparing the efficacy of nebulised lidocaine (1mg/kg twice daily) versus nebulised budesonide (1ug/kg twice daily) for 14 days in asthmatic horses showed an improvement in clinical score for both drugs, with lidocaine additionally resulting in a lower BALF neutrophil percentage and tracheal mucus score¹⁹.

Are any supplements beneficial?

Considering the challenges owners often face in improving their horse’s environment and the limitations in using medications, especially in competing horses, a “drug-free” supplement that could aid in prevention or treatment of asthma would be beneficial.

Omega-3 fatty acids have an anti-inflammatory effect via a number of different mechanisms, including reduction of substrates for pro-inflammatory mediators and reduction in the generation of inflammatory cytokines²⁰.

In one study, asthmatic horses were fed either with a supplement containing high concentrations of omega-3 fatty acids for eight weeks or placebo²⁰. Both groups had similar changes to their environment (no hay, fed pelleted feed). As expected with the environmental changes, both groups showed an improvement in the clinical signs, but the magnitude of the response was greater in the supplemented horses.

Additionally, supplemented horses showed significant improvements in their lung function and BALF neutrophilia, which was not seen in the placebo group²⁰. A second study investigated the impact of supplementing either fish oil (high in omega-3 fatty acids) or corn oil for four weeks in 55 racehorses fed a conventional diet (which included hay). BALF neutrophil percentage was significantly lower at the end of the four weeks in horses supplemented with fish oil, but not corn oil, suggesting that increasing omega-3 fatty acids in the diet may help mitigate neutrophilic asthma in horses²¹.

Future directions

Treatments

While currently available medications and environmental management can be very effective in treating horses with SEA, they are labour intensive, may be associated with side effects and in some cases client compliance is sub-optimal. As such, newer treatments and strategies are being developed in an attempt to overcome some of these impediments to effective treatment. One of these is the use of cytosine-phosphate-guanosine-oligodeoxynucleotides (CpG-ODN), which are molecules that direct the immune system towards a cell-mediated Th1 pathway and away from the pro-allergic humoral Th2 response, which is thought to dominate in horses with SEA.

The CpG-ODN is delivered by inhalation, and although several preliminary studies have shown some benefit in a small number of asthma affected horses, evidence is limited to support its use either as a standalone treatment or in combination with environmental modification²².

An improved understanding of the complex pathophysiology of asthma in people has led to the development of new treatment options for patients, in particular those with severe or refractory asthma. Biologic therapies target specific inflammatory pathways involved in the pathogenesis of asthma²³. In people, two specific endotypes, namely type 2 (T2) high and low have been identified based on the predominant cell type (eosinophil versus neutrophil) and the associated cytokines that are produced as part of the inflammatory response. Biologic therapies target inflammatory modulators that have been identified to play a key role in the pathogenesis of asthma, predominantly in the T2-high subset of patients and have demonstrated encouraging results specifically in this group²³. As these products predominately target an eosinophilic asthma rather than a neutrophilic asthma that is seen in horses, their use is likely not currently applicable to horses with SEA. If the immune response in horses with asthma is further clarified, it is possible that biologics may also be identified that could be beneficial.

Diagnostics

While the diagnosis of SEA during periods of disease exacerbation is relatively straightforward, diagnosis of disease in remission, and also for horses with mild-moderate equine asthma – especially when poor performance is the only “clinical sign” – can be challenging.

In humans, the gold standard for diagnosis of asthma is detection of variability in pulmonary function testing using spirometry or other methods of lung function testing. While lung function testing can be performed in horses, its use is typically restricted to a research setting.

Development of an easy to use, portable device to measure lung function in horses would significantly advance not only the diagnosis of asthma, but also be beneficial in monitoring response to treatment. Investigation of potential biomarkers for asthma has gained increasing interest in people with asthma^24,25. An ideal biomarker should be suitable to identify the disease as well as the specific endotype/phenotype, be useful in monitoring the disease and determining the prognosis, and easy to obtain with minimal discomfort or risk to the patient.

Currently, no “ideal” biomarker exists that has been identified for people with various types of asthma, but some of the biomarkers currently in use include analysis of exhaled breath, blood cells and serum biomarkers, as well as sputum cells and mediators. It is likely that panels of biomarkers – perhaps combining samples from exhaled breath, serum and sputum – may allow for better characterisation of asthma endotypes, with subsequent improvement in therapy^24,25.

Like in people, analysis of biomarkers in BALF, in peripheral blood and also in exhaled breath condensate have been investigated in horses²⁶. BALF neutrophilia is the major biomarker used for diagnosis of EA, with well-established cut off values.

Other biomarkers have yet to be sufficiently validated for clinical use in the horse, with overlap in results between normal and affected horses or lack of specificity for the disease being commonly reported.

The development of a biomarker or a panel of biomarkers that would allow for diagnosis, prognosis and monitoring of response to treatment would be hugely beneficial in horses with asthma²⁷.

Conclusion

Management of horses with asthma can be a challenging endeavour; despite well-characterised treatments that work well in experimental settings, not all horses will respond as well as we would like.

In many instances, this is because environmental changes to minimise dust cannot be optimised, or medications cannot be administered due to other health issues or due to competition schedules.

Ongoing research to explore competition legal therapies, to investigate other methods of diagnosing the condition and to identify possible biomarkers which could be used to “individualise” therapy is needed, and will hopefully benefit asthmatic horses in the future.

• Use of some of the drugs mentioned in this article is under the veterinary medicine cascade.