Equine Asthma: Updates on Evidence Based Therapy

Equine Asthma: Updates on Evidence Based Therapy

Erin M Beasley DVM, PhD, DACVIM-LAIM
University of Georgia
Large Animal Medicine

Objectives

This session will briefly review the case-definition and typical work-up required to make a diagnosis of Equine Asthma. Interpretation of cytology and culture of lower airway samples will be discussed. The majority of the session will focus on treatment and management strategies that are evidence-based with provision of case examples to illustrate these strategies.

2016 ACVIM Consensus Statement- A brief summary
Asthma, a human medical term to describe the constellation of symptoms including; shortness of breath, a tight feeling in the chest and cough associated with restriction of expiratory airflow occurs within a wide range of clinical severity. The authors of the equine consensus statement suggest that equine asthma also occurs on a scale of severity with inflammatory airway disease representing a mild to moderate form of asthma and recurrent airway obstruction (RAO) representing severe asthma. The impetus for the change in terminology was based on the realization that 1) IAD and RAO likely represent a spectrum of chronic inflammatory airway diseases that is similar to human asthma and perhaps most importantly, that 2) Research funding opportunities are enhanced when investigators can introduce their work as an “animal-model” of a human disease.
The pathogenesis of equine asthma remains incompletely defined. It is accepted to be a multifactorial condition with environmental, hereditary, genetic, individual (age, breed) and infectious causes as important factors in disease development. At this time, there is no conclusive evidence to demonstrate a link between an infectious (e.g.viral or bacterial) pathogen with equine asthma. Researchers continue to investigate the question of whether some forms of equine asthma are an allergy-mediated process. Thus far, there are no studies to support Ig-E mediated pathogenesis, but T cell, particularly regulatory Tcell, mediated immunomodulation may be an important mechanism.

Case Definition and Clinical Work-Up

 Equine asthma is a chronic, non-infectious lower respiratory disease that occurs most commonly in middle aged to older horses. Mild asthma can occur in any age horse. Clinical signs, independent of severity, are typically present for at least 4 weeks. The disease is defined by demonstration of lower respiratory tract inflammation that results in a varying degree of bronchoconstriction and mucus production. The severity of the disease is likely related both to chronicity and to the myriad factors listed above. 

The goal of the clinical work-up is to demonstrate evidence of lower airway inflammation whilst ruling out the presence of infection. Clinical history, physical examination, complete blood count and measurement of inflammatory protein concentrations in combination with lower airway imaging and cytology and/or culture results constitute a comprehensive approach to confirming a diagnosis. The question of what is a comprehensive minimum data base for making the diagnosis in the field is currently being examined. Confirmation of disease in mild cases, where the primary complaint is poor performance with absence of clinical signs at rest, typically requires more sensitive diagnostics such as bronchoalveolar lavage and/or histamine bronchoprovication (pulmonary function testing). 

History and clinical signs 

Poor performance is difficult to define objectively and can include prolonged recovery from exercise (increased rate) or exaggerated respiratory rate and effort during exercise. Many conditions cause poor performance; therefore, it is critical to rule out other disease processes [e.g. cardiovascular, musculoskeletal, neurologic, gastrointestinal] that might be contributing to the complaint of poor performance. 

Cough, when documented, is helpful as it supports the diagnosis. In fact, bronchoalveolar lavage fluid (BALF) neutrophilia is associated with chronic cough. However, an absence of cough does not rule out mild asthma. Horses that cough may be more likely to develop severe asthma over time. Owners most often notice cough during exercise and often think that coughing once or twice at the onset of exercise (usually as they first start trotting or cantering) is normal! Cough often occurs early during exercise and may or may not be noticed at rest. Cough that occurs at rest, usually while eating, is a typical clinical sign of horses with asthma. 

Rebreathing examination may be normal in horses with mild asthma. Abnormal ausculatory findings range from increased breath sounds to mild end expiratory wheezes to crackles, severe diffuse wheezes, and an expanded (hyperinflated) lung field. Horses with large airway sounds or areas of absent breath sounds should be thoroughly evaluated for other diseases. 

Decreased appetite is common in horses that have severe asthma as the work of breathing makes it difficult or impossible to spend time eating. A poor appetite is also one of the most common nonspecific signs of generalized illness and other causes of a decline in appetite should be ruled out. 

Comorbidities such as insect bite hypersensitivity and anhidrosis can occur along with equine asthma. It is unclear if there is a direct link between diseases or if it is merely that both diseases occur in the same season. From a distance, anhidrosis can mimic a flare of severe of equine asthma, with increased respiratory rate, effort and nostril flaring. However, upon careful evaluation and anamnesis it will become evident that the horse is not sweating appropriately and the respiratory tract is working overtime to cool the horse. In some cases, both conditions occur together and these horses are some of the most severely affected. Referral of such cases to a temperature controlled hospital or clinic setting can alleviate clinical signs quickly while management and treatment strategies are initiated. 

The consensus statement dedicated a portion of the manuscript to describing the phenotypes consistent with IAD (mild asthma) vs. RAO (moderate to severe asthma) and they are summarized in the table below. The exclusion criteria that follow are equally as helpful and important as the typical clinical signs (which can be vague) and diagnostic criteria are for making a diagnosis of mild asthma. Exclusion criteria recommended for mild asthma in the recent consensus include: 1-evidence of systemic infection [fever, lethargy, anorexia or hematologic abnormalities consistent with infection] or 2-increased respiratory rate or effort at rest [severe asthma]. The presence of either of the above criteria precludes making a diagnosis of mild equine asthma (IAD) alone. Transtracheal aspirate (TTA) remains unhelpful for the diagnosis of mild asthma, as there is no correlation between TTA and excess tracheal mucus. Endoscopy is a superior diagnostic test to confirm excessive tracheal mucus. Tracheal mucus alone (score of ≥ 2/5 for race horses and ≥ 3/5 for sport or pleasure horses) is suggested as an alternative method for diagnosing mild equine asthma. [NOTE: It is important to remember that a TTA in combination with minimum database and diagnostic imaging are critical for ruling out bacterial bronchopneumonia and are indicated in many cases.] 

Diagnostic imaging (to rule out other diseases). In general, transthoracic ultrasound examination of asthmatic horses is normal. Horses with asthma may have mild to moderate, focal to multifocal narrow based comet tail artifacts upon transthoracic ultrasonography. Abnormal findings (diffuse or broad based comet tails, regions of consolidated lung, pleural space disease) should increase the suspicion for a separate or concomitant disease process. Thoracic radiography is indicated in all cases of suspected equine asthma, findings may range from normal (in mild cases) to a bronchointerstitial or bronchial pattern. Rarely, in severe, chronic disease a vascular pattern is recognized in horses with lower airway induced right-sided heart disease.
Endoscopy for evaluation of tracheal mucus in mild asthma cases only.
Score of ≥ 2/5 for racehorses and ≥ 3/5 for sport or pleasure horses. However, there is no data to suggest that mucus scores improve in response to treatment. Older horses and pleasure horses can have mucus accumulation without clinical signs. This diagnostic criteria should be reserved for young racehorses.

Transtracheal Aspirate
Neutrophilia with or without Curschmann’s spirals
TTA cytology: Recently, Jocelyn et al evaluated neutrophil morphology from TTA samples of 1100 horses to determine a relationship with positive culture of lower airway pathogens. Culture of pathogenic bacteria had 4.5 times increased odds of degenerative neutrophils on cytology compared to negative culture. Degenerate neutrophil morphology correlated to septic lower airway inflammation.
TTA culture: The trachea is not a sterile environment. The microbiome of the equine trachea has become a research interest. Microorganisms are frequently isolated from asymptomatic horses and are often isolated from horses with impaired pulmonary clearance. It is vitally important to interpret culture results in the context of the entire clinical picture. Light growth of non-pathogenic bacteria in a horse free of clinical and clinicopathologic signs of infection do not require antimicrobial therapy. Horses with an abnormal immune system (untreated pituitary pars intermedia dysfunction or common variable immunodeficiency) are likely exceptions to this paradigm. Judicious antimicrobial use should be a priority. Veterinarians have an important role in reducing bacterial resistance pressure. Colitis is a serious complication that can occur with antimicrobial therapy.

Bronchoalveolar lavage
Mild to moderate asthma: Mild increases in neutrophils, eosinophils or metachromatic cells (mast cells)
Severe asthma: Moderate to severe increases in neutrophils
BALF should not be routinely used for culture as it is not collected with aseptic technique and passes through the nasopharynx. BALF fluid can be submitted for EHV-5 PCR and other viral etiologies when indicated.
Pulmonary Function Testing (Histamine Bronchoprovication)
Airway hyperresponsiveness can be detected in response to increasing concentrations of histamine with specialized equipment (computer program, elastic resistance bands, and a pneumotachometer). Respiratory effort is measured with elastic bands placed around the thorax and abdomen. The bands are connected to a computer program that can sense and measure the change in stretch from breathing excursions while airflow resistance is simultaneously measured with a pneumotachometer. This modality is available at the University of Georgia as well as other universities and referral centers.

“Rescue therapy”
As an aside, for horses with severe equine asthma that are in respiratory distress upon evaluation, a single dose of N-butylscopalammonium bromide (Buscopan) will temporarily, yet effectively result in bronchodilation and thus a rapid improvement in breathing effort and respiratory rate will be noted. This medication will only improve signs temporarily and will not make a significant difference in horses that are in respiratory distress from other disease processes. NOTE: Buscopan will also cause a transient increase in heart rate and should not be administered to horses with suspected cardiovascular disease or arrhythmia.

A presumptive diagnosis of severe asthma can be made on the basis of the presence of a chronic cough (weeks), increased respiratory rate at rest, and wheezes on rebreathing examination in the
absence of evidence of a septic process (e.g. fever or an inflammatory leukogram). Improvement in respiratory rate and effort following buscopan administration would also support this presumptive diagnosis. Mild to copious mucoid nasal discharge may be present intermittently.

Management and Treatment

The aims of therapy are to reduce airway inflammation and reduce the magnitude of aeroallergens in the environment. 

There is little use in prescribing treatment for equine asthma if the management and environment are not going to be addressed. Equine asthma is a condition that most horses will live with for life. Clinical episodes can be reduced in frequency and severity with many horses going into remission. However, the key factor in maintaining remission is making management changes and training horse owners to recognize subtle signs of recurrence. 

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