Review of equine asthma syndrome

Equine asthma syndrome (EAS) is a heterogeneous group of different disease phenotypes associated with lower airway inflammation. The pathogenesis of EAS has not been completely defined; however, it is almost certainly multifactorial – as it is in humans – where allergens, genetics, pathogens and microbiome all play a role.

Phenotypes

Although a heritable basis for severe EAS has been reported in several breeds, no genetic risk factors or useful genetic markers have been identified in horses¹. Exposure to airborne organic dust plays a key role in induction of severe equine asthma, and many allergenic and immune modulatory agents are present in stable dust, including endotoxins, moulds, peptidoglycan, proteases, microbial toxins, mites, plant debris, ammonia and inorganic dusts².

A role for bacteria in lower airway disease in thoroughbred racehorses is suspected. Certain viruses may play a role in triggering or exacerbating equine asthma in some individuals; however, their ubiquitous nature makes it hard to draw firm conclusions³.

Neutrophils play a key role in the pathology of EAS, and inflammatory neutrophilic bronchiolitis is the primary lesion⁴. Other pathological changes – including airway constriction, mucus production and airway remodelling – also occur, to varying degrees.

Various different nomenclatures have been used to describe the phenotypes of EAS over the years. The 2007 and 2016 American College of Veterinary Internal Medicine consensus statements on inflammatory airway disease of horses brought some clarity to the situation by defining two principal phenotypes of EAS based on clinical findings, endoscopic findings and broncho-alveolar lavage fluid (BALF) cytology. These were mild/moderate EAS (mEAS) and severe EAS (sEAS)^5,6. These phenotypes should not be thought of as an inevitable continuum of disease, and many cases of mEAS resolve without progressing to sEAS. An additional phenotype – tracheal inflammatory airway disease (IAD) in racehorses – is also best considered in isolation, and key features of each phenotype are discussed now.

sEAS and summer pasture-associated sEAS

Previously known as recurrent airway obstruction (RAO) and chronic obstructive pulmonary disease, sEAS-affected horses are usually older than seven years of age, with a history of disease severity fluctuating across several months. Symptoms usually occur when horses are exposed to dust from hay and bedding, with clinical signs during housing. A form of sEAS known as summer pasture-associated sEAS is thought to be triggered by grass pollens and usually improves during the winter or when horses are kept indoors. Horses can suffer from both forms.

Clinical findings include increased respiratory effort (dyspnoea), often with obvious diaphragmatic flattening during expiration (and subsequent development of a heave line). This is not seen with mEAS and is a hallmark finding of sEAS. Coughing and nasal discharge are common. Thoracic auscultation can reveal increased breath sounds (including crackles and wheezes); however, this is a very insensitive measure, and many horses with sEAS have no audible abnormalities. Clinical signs can be controlled in most cases, but sEAS cannot be cured.

mEAS (now separated into mild EAS and moderate EAS)

Usually affecting younger horses, mEAS is associated with milder clinical signs, including poor performance and occasional coughing. The horse that “coughs a couple of times when starting work” almost certainly has clinically relevant mEAS that may well be affecting performance.

It has been suggested that mild and moderate EAS should be categorised separately, with mild EAS representing horses with poor performance and no clinical signs of respiratory disease³. It has been found mEAS often resolves spontaneously or with treatment, and the risk of recurrence is low.

Tracheal IAD (tIAD)

In racehorses, a syndrome of increased tracheal mucus, coughing and poor performance has been reported, which is associated with high tracheal wash fluid (TWF) bacterial counts and anecdotally responds to antimicrobials⁷.

Essentially it represents a form of infectious tracheobronchitis without signs of systemic disease. Within the veterinary profession serving the needs of the racing industry, a feeling exists that the consensus statement is not applicable to this form of the disease (although it is mentioned in the statement) and a requirement exists for further research on the syndrome⁸.

Diagnosis of EAS

Debate regarding the necessity and practicalities of further diagnostics for EAS exists. The author finds it easiest to remember that the diagnostic methods required, and exactly what we hope to gain from them, varies depending on the phenotype. Practically speaking, the tools available include the clinical exam (including rebreathing) and history, endoscopy, BALF cytology, and TWF cytology and culture. Occasionally, haematology and biochemistry can be useful to look for evidence of infection. Ultrasonography and radiography are rarely required. The following key points can aid decision-making in practice:

• A diagnosis of sEAS can often be made on clinical examination and history only, whereas ones for mEAS and tIAD cannot.
• Endoscopic assessment of the upper and lower respiratory tract is almost always useful. It allows assessment of mucosal inflammation and carina sharpness, scoring of tracheal mucus accumulation (using a 1-5 scale), assessment of the nature of tracheal fluid (for example, mucoid, mucopurulent or haemorrhagic) and identification of any foreign material included in aspirated feed⁹.
• Cytologic analysis (and possibly microbial culture) of airway secretions are invaluable for proper diagnosis and to help guide therapy of horses with respiratory disease. TWF or BALF can be used.
• Analysis of TWF is indicated for the diagnosis of infectious localised disease of the lower respiratory tract, whereas BALF analysis is more useful for diffuse lung diseases, including EAS10. BALF cytology correlates with histopathological lung disease and poor performance, whereas TWF cytology does not. BALF analysis is, therefore, recommended for the cytological confirmation of EAS¹⁰.
• Unfortunately, concerns with the use of BALF (including increased technical expertise, owner reluctance, time out of training and lack of belief in the value of the procedure) mean its use is not always straightforward⁸.
• For sEAS with marked clinical signs, analysis of BALF is rarely indicated and collection is potentially detrimental to the patient. However, TWF cytology can be used to help investigate any associated infection before starting appropriate treatment.
• For mild and moderate EAS, cytological examination of BALF is recommended as the gold standard for diagnosis; however, the analysis of TWF at the same time is still recommended and useful in many cases. BALF neutrophil, mast cell and eosinophil counts above 5%, 2% and 1% respectively are considered indicative of some degree of EAS¹⁰.
• For tIAD, analysis of TWF and endoscopic findings is the industry-recognised standard. Cut-offs for cytological analysis are poorly defined, although TWF neutrophil percentages greater than 20% have been suggested as indicative of equine asthma¹¹.

EAS treatment

Management and prevention strategies

A set of general recommendations is included in Panel 1. Improving air quality can improve performance in horses with mEAS, and a study has highlighted the importance of compliance with an environmental management protocol for resolution of disease in horses with sEAS, with poor compliance in nearly all cases¹².

The study also demonstrated that for many of the horses, adequate control of symptoms could not be achieved with any amount of stabling (that is, little benefit was seen in increasing turnout time if horses returned to the stable at all). Medical treatment is, therefore, almost always required.

Medication: corticosteroids

Anti-inflammatory medication with corticosteroids is essential to control inflammation associated with EAS, and robust new evidence has demonstrated they improve the clinical condition of affected horses¹³. Changes must be made to reduce dust alongside them. Corticosteroids can either be administered systemically or by inhalation. The following key points help with decision-making:

• Systemic corticosteroids are more efficacious than inhaled steroids and should always be used for rescue therapy of sEAS¹⁴. Licensed products are available for both IV and oral (tablet or powder) routes of administration.
• Concerns over inducing laminitis in individuals prone to endocrinological laminitis mean many horses with sEAS go without proper treatment. Studies have shown no association between administration of oral corticosteroids and laminitis¹⁵; however, the reluctance to use corticosteroids in patients at high risk or with a history of laminitis is understandable. Assessment of any insulin dysfunction (ideally using dynamic methods, but also with basal testing) can be helpful in these cases, but necessitates a delay in starting treatment. Additionally, if the results show evidence of hyperinsulineamia then it is unclear if this should preclude required corticosteroid treatment.
• More recently, a novel inhaled corticosteroid product has been licensed for treatment of sEAS in horses, and has been shown to improve lung function and clinical signs in horses, without suppressing serum cortisol¹⁶. This product may well have potential for immediate rescue therapy in horses with sEAS, where systemic corticosteroids are considered problematic.
• Horses with sEAS usually require lifelong anti-inflammatory therapy. The off-label use of inhaled corticosteroids (either nebulised or via metered-dose inhalers) is recommended to avoid the adverse effects of long-term steroid use (laminitis, altered bone metabolism, immunosuppression and hypothalamic-pituitary-adrenal axis suppression) as lower doses can be administered^5,14.

No corticosteroid appears to have a significant advantage in terms of efficacy. Studies have demonstrated that inhaled beclomethasone and fluticasone suppress endogenous cortisol to some degree – and, therefore, their effects should not be thought of as completely limited to the lungs^17,18. The exact implications of this on safety are unknown, though, and complications are extremely rare. Ciclesonide and nebulised low-dose dexamethasone sodium phosphate (5mg once a day) have been shown to not suppress endogenous cortisol^16,19.

• Many horses with mEAS only require a three to four-week course of oral or nebulised corticosteroid, alongside management changes.

Bronchodilators

Use of bronchodilators improves the respiratory mechanics and clinical signs in horses with severe clinical disease by relieving bronchospasm²⁰. They should, therefore, be used as a part of rescue therapy only. Note the following key points:

• The use of bronchodilators as the sole therapy to treat RAO exacerbation without environmental modification and/or corticosteroid administration is not recommended, as they do not effectively reduce inflammation.
• Symptoms of sEAS usually improve immediately following off-label administration of anticholinergics including atropine or hyoscine-N-butylbromide. This can also be a useful diagnostic test to prove reversibility of airway obstruction (a key feature of EAS).
• Clenbuterol is licensed for systemic use in the UK via the oral and IV routes. Prolonged administration of clenbuterol likely results in a clinically important reduction in its bronchodilatory effects, with tachyphylaxis occurring within three weeks²¹. So use should be restricted to two to three-week courses.
• Off-label aerosolised delivery of bronchodilators is also possible. This rapidly alleviates bronchospasm and may improve delivery of subsequently administered aerosolised corticosteroids²².

Others

Treatments including nebulised saline, mast cell stabilisers, mucolytics and antimicrobials may have a role in individual cases.