27 Aug 2024
Victoria Colgate and Catriona Mackenzie assess the long-term options for managing this condition.
Image © mckornik / Adobe Stock
Equine asthma (EA) is a chronic respiratory condition that affects horses globally (Holley, 2024) and has a spectrum of impact from mild poor performance, to severe respiratory embarrassment and compromised welfare.
Although associated with a low direct mortality rate, its incurable nature means owner-elected euthanasia can be prevalent due to management costs (Couetil et al, 2020).
EA – now commonly adopted as an all-inclusive term for the previously described recurrent airway obstruction (RAO), inflammatory airway disease (IAD), chronic obstructive pulmonary disease and heaves – has a well-defined clinical presentation, but a complex of genetic, environmental and immunological aetiological triggers, all of which need further understanding to improve therapeutic options.
EA is characterised by chronic non-infectious inflammation of the lower airways, occurring as a result of susceptible horses being exposed to environmental allergens. The induced airway hyper-reactivity leads to bronchoalveolar neutrophilic inflammation, bronchospasm and mucus accumulation, culminating in airway narrowing and reduced airflow. This is demonstrated clinically as varying degrees of coughing, wheezing, expiratory dyspnoea, exercise intolerance and poor performance.
Two distinct phenotypes – severe equine asthma (sEA; previously known as RAO), and mild to moderate equine asthma (mEA; previously referred to as IAD) – exist, differentiated by sEA cases displaying increased respiratory effort at rest, while mEA cases suffer from milder airflow limitations often characterised by chronic coughing of more than three weeks and/or chronic poor performance (Kinnison et al, 2022). However, these distinct phenotypes are the visible endpoint of a variety of immunological pathways, triggered by a plethora of aetiological agents (Pirie, 2017a). Commonly cited aetiological triggers include numerous pro-inflammatory airborne allergens found in stable dust, such as moulds, fungi, mite debris, endotoxins, and β-glucans, with ammonia and other noxious gases also contributing to poor hygienic air quality (Pirie, 2017a).
As such, winter stabling is a significant risk factor for EA, but it is not a simple causative relationship, with different combinations of allergens potentially having additive and synergistic roles toward the resulting inflammatory response.
“[Consider] preventive measures and prophylactic treatments as colder weather approaches.”
Furthermore, some cases, previously termed summer pasture-associated RAO, are triggered by turnout and require permanent stabling to control clinical signs (Pirie, 2017b).
Equally, why only some horses exposed to these agents develop EA is not completely understood, but a strong, although complex, genetic element is thought to be involved (Houtsma et al, 2015).
When presented with an acute exacerbation and a horse in severe respiratory distress, treatment has to focus on a rescue protocol that necessitates administration of pharmacological agents to relieve symptoms through stimulating bronchodilation and reducing airway inflammation.
However, due to costs, potential adverse effects and reducing efficacy, long-term drug therapy is not suitable, and only environmental management to reduce exposure to the inciting airborne allergens will solve the underlying inflammation.
The foundation of symptomatic control for EA-susceptible horses lies in alteration of the animal’s environment to minimise exposure to inciting aero-allergens. This has proven efficacy, with respiratory inflammation reducing in horses kept in a low-dust environment, reducing the need to instigate medical treatment (Diez de Castro and Fernandez-Molina, 2024). The required management changes focus on three areas: feeding, bedding and ventilation.
Given the substantial proportion of daily time spent eating, forage has the most significant impact on respirable dust concentrations in the horse’s breathing zone (Neal, 2022). In most cases, permanent pasture turnout without provision of supplementary forage is the gold standard management option for which no substitute really exists (Jackson et al, 2000). But for horses on livery yards and under winter conditions of mud and poor grass availability, this can prove an impossibility, and stabling is necessitated.
Where provision of a preserved forage is required, consideration of the production and storage conditions, and treatments applied to it, must be given as they all affect its hygienic quality. A dust-free, complete, pelleted diet is ideal, and commercial hay steamers reduce respirable particle and mould content by up to 90% (Neal, 2022), although both can be prohibitively expensive.
Haylage is a feasible low-effort alternative, but its greater nutritional value and ability to induce a higher postprandial insulinaemic response (Diez de Castro and Fernandez-Molina, 2024) means it should be fed with care to obese horses or those with suspected endocrine disease.
Hay is commonly fed to stabled horses and contains large numbers of respirable particles, and potentially moulds, depending on the conditions under which it was baled and stored.
Soaking hay (full immersion) for at least 30 minutes has been shown to reduce respirable particle content by 60%, and feeding from the floor, rather than a haynet, reduces particle levels four-fold (Neal, 2022). However, the ability of prolonged soaking to reduce hay nutrient quality and palatability, and potential for bacteria to multiply in wet hay, should be taken into account.
Image © chelle129 / Adobe Stock
Regarding bedding, an alternative to straw is vital, but no other option has been shown to be consistently superior (Diez de Castro and Fernandez-Molina, 2024), although the combination of a wood shavings bed and feeding hay pellets reduced respirable particles by 50% (Westerfeld et al, 2024). What is important is that the bed is kept clean and dry to minimise growth of moulds and build-up of ammonia. Rubber mats can assist with this and reduce the amount of bedding needed (Neal, 2022).
Additionally, it is vital that horses are removed from the stable prior to mucking out, as the associated human activity can increase concentration of respirable particles by up to 20% (Neal, 2022). Ventilation affects the number and size of particles in the air, in turn affecting air quality (Diez de Castro and Fernandez-Molina, 2024), and is another factor to consider in the stabled horse – especially during winter, when it may be tempting to close barn doors and windows for warmth.
These are just a selection of management options, and it is clear that a holistic approach (Diez de Castro and Fernandez-Molina, 2024) considering the complete barn environment, rather than just an asthmatic horse’s stable, is required for effective antigen avoidance. However, owner compliance can be a significant limiting factor, with often only some recommendations implemented and on a short-term basis.
A combination of education on the benefits of antigen avoidance, and alternatives for when environmental alteration is truly impossible, are needed to achieve long-term reduction of airway inflammation in EA-susceptible horses.
Although the importance of environmental control cannot be overemphasised, inability to remove exposure to all aero-allergens means medical treatment is often required.
Corticosteroids, administered systemically or via the inhalation route, underpin the mainstay of therapy to reduce clinical signs and improve lung function. Their potent anti-inflammatory effect ensures their continued use, but the possibility of serious systemic sequelae – including immunosuppression, reduction in cortisol levels and induction of laminitis due to suppression of the hypothalamic-pituitary-adrenal axis – limit their long-term application.
Concern over systemic side effects has led to increasing interest in corticosteroid administration via the inhalation route, which allows direct drug delivery to the site of inflammation with minimal systemic absorption and at a lower dose to improve safety.
Ciclesonide and budesonide are specifically formulated for this purpose. However, in an acute exacerbation, inhalant delivery to the lower airways can be compromised by the mucus accumulation, bronchospasm and coughing found in horses suffering from severe respiratory distress (Mainguy-Seers and Lavoie, 2021), necessitating use of faster-acting systemic formulations such as IV dexamethasone.
The combination of delivery device and inhalant drug formulation can be prohibitively expensive for owners, and with limited residual effect following treatment cessation (Mainguy-Seers and Lavoie, 2021) and concerns over adverse effects of long-term therapy, novel treatment development is desperately needed.
As a result of the inflammation, bronchospasm and mucus accumulation, as well as potential for airway smooth muscle remodelling in the long term, EA horses suffer from significant airway narrowing.
Consequently, drugs that can achieve bronchodilation have a place in treatment, either as a rescue therapy to improve compliance and gas exchange in an acute exacerbation, or to improve delivery of aerosolised drugs, such as glucocorticoids, to their targets of action in the lower airways. Both sympathomimetic and parasympathomimetic drugs are able to achieve bronchodilation, but as airway smooth muscle tone is generally under parasympathetic control, the latter are more effective (Pirie, 2017b).
Atropine was traditionally the parasympatholytic drug of choice, and IV administration is proven to lead to reversal of bronchospasm and visible respiratory relief in EA affected horses (Pirie, 2014), but the potential exists for systemic side effects to include tachycardia, mydriasis and reduced gastrointestinal motility (Thomson and McPherson, 1983).
“As an incurable and chronic condition that requires specialist equine management even in periods of clinical remission, it is vital that [equine asthma] is always on our minds…”
Recently, IV N-butylscopolammonium bromide was found to be a safer alternative with similar potency, but reduced chance of significant side effects (Pirie, 2017b). The muscarinic antagonists glycopyrrolate and ipratropium are also options that can be administered through the inhalation route with rapid and more prolonged bronchodilatory effects (Pirie, 2017b).
The β-2 sympathomimetic bronchodilators (β-2 adrenergic agonists) achieve their effect through selective stimulation of β-2 receptors within the respiratory system, achieving relaxation of airway smooth muscle, but with fewer unwanted systemic effects (Thomson and McPherson, 1983). The archetypal example of this drug class is clenbuterol, often administered through the enteral route, but potential for tachyphylaxis with prolonged use has led to a preference for inhaled albuterol, having a more short-term local effect (Holley, 2024; Robins et al, 2023).
While bronchodilators have a rapid effect and can help to relieve clinical signs in an acute EA exacerbation, they do not alleviate the underlying inflammation. Consequently, they are not recommended as a sole treatment, but should be used in combination with corticosteroids as the first line of action to relieve respiratory distress.
While glucocorticoids and bronchodilators provide the mainstay of medical EA therapy, some other agents can be considered as adjunctive treatments.
With increased secretion and reduced clearance both leading to mucus accumulation in EA-affected horses, use of mucolytics has some rationale, and the inhaled mast cell stabiliser sodium cromoglycate has shown to improve respiratory scores in mEA-affected horses (Boivin et al, 2018). Supplementation with polyunsaturated omega-3 fatty acids also led to improved clinical signs and lung function in both mEA-affected (Pirie, 2017a) and sEA-affected horses (Diez de Castro and Fernandez-Molina, 2024).
With EA largely considered non-infectious, antimicrobial treatment has no sound rationale, although use has been shown to improve clinical scores, and it can be politically challenging to avoid in the presence of positive culture on a tracheal wash sample (Husulak et al, 2018).
Considering the potential deleterious effects of the glucocorticoids used as the mainstay of EA treatment, the need exists for research into novel methods, which currently revolve around genetics and immunomodulatory therapy. The realisation that multiple endotypes and inflammatory pathways, lead to the common phenotype of EA suggest that with advent of greater understanding, more targeted and personalised immunotherapy may be possible.
Such precision medicine is already implemented in humans (Couetil et al, 2020), and for equine asthma, development of antigen screening tests (Simões et al, 2022) are likely to be a key step.
Additionally, discovery that the intestinal microbiota of EA-affected horses does not adapt to changes in diet and management in the same way as unaffected horses (Leclere and Costa, 2020), and identification of the gut-lung axis suggest that early-life antigen exposure to generate tolerance, and probiotics, prebiotics and faecal microbiota transplants, may have a therapeutic place (Leduc et al, 2024).
With sEA exacerbations more commonly encountered during increased periods of stabling in winter (Bullone et al, 2016), the need exists to consider preventive measures and prophylactic treatments as colder weather approaches. However, clinical exacerbations have been encountered in heatwaves (Bullone et al, 2016) and the converse summer pasture-associated form of EA is also prevalent, where turnout is a risk factor and stabling the management solution (Thomas et al, 2021).
As an incurable and chronic condition that requires specialist equine management even in periods of clinical remission, it is vital that EA is always on our minds, and we work closely with owners to ensure optimal welfare of EA-affected horses.
● Use of some of the drugs mentioned in this article is under the veterinary medicine cascade.
