A 12-year-old Thoroughbred gelding was examined for a cough whilst being stabled over the winter. There was limited available turnout so the horse remained stabled on shavings in a stable barn. The horse was fed dry hay. There was no previous history of coughing.
The clinical examination was unremarkable. The owner described an intermittent dry cough occurring at rest and exercise. At this time the owner was advised to introduce environmental changes to reduce dust exposure. The horse was moved to a stable away from the hay store and started on soaked hay. An inflammatory blood profile was taken which revealed no abnormalities.
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Despite implementation of environmental changes the cough persisted. The horse was re-examined two months later at the clinic. On this occasion the horse presented with a bilateral mucopurulent nasal discharge and persistent cough. The horse was tachypneic (25 breaths per minute) with increased abdominal effort; the remainder of the clinical examination was unremarkable. A re-breathing examination was performed to aid auscultation of abnormal lung sounds; there were no adventitious sounds and the trachea was normal on auscultation.
Problem list
Intermittent cough at exercise and at rest
Mucopurulent nasal discharge
Recurrent episodes
Tachypneic
Differential Diagnosis List
Recurrent airway obstruction (RAO)
Inflammatory airway disease
Viral infection
Bronchopneumonia
Pulmonary neoplasia
Lungworm
The signalment and history alongside the clinical signs of coughing, nasal discharge, laboured respiratory effort and exercise intolerance in the absence of pyrexia, suggested RAO. An endoscopic examination of the upper and lower airways to assess tracheal secretions and to obtain a fluid sample for a tracheal wash was performed. Endoscopy revealed inflammation of the pharyngeal recess, mild lymphoid hyperplasia, erythema of the trachea and a thickened carina. The tracheal wash (TW) sample was mucoid.
The cytology report from the TW indicated chronic irritation and inflammation however the cell populations were unable to indicate a specific underlying aetiology. Neutrophillic inflammation was not a strong feature; however low-moderate levels of macrophages and Curschman spirals were present, both of which can be associated with RAO. Bacterial culture yielded a scant growth of Enterobacter spp and Pasteurella spp sensitive to trimethoprim sulphonamides; treatment for a possible bacterial tracheitis was initiated alongside a mucolytic for the mucus present in the airway. Dembrexine hydrochloride (Sputolosin, Boerhinger Ingleheim) (0.3mg/kg q12h PO) and trimethoprim sulfadiazine (Trimediazine Plain, Vetquinol) (30mg/kg q12h PO) were administered for 10days followed by re-examination. A Broncho alveolar lavage (BAL) was advised in order to determine the presence of lower airway inflammation specifically; however the horse was improving and the client declined at this time.
Improvement was seen initially however after 5months following initial presentation the cough and nasal discharge resumed. The clinical examination was again unremarkable. A thick muco-purulent TW sample was obtained which revealed marked neutrophilic inflammation >95% of the nucleated cells and a negative bacterial culture. These results were consistent with RAO and as a result treatment for RAO was initiated. Inhaled salbutamol (400ug q12h) followed 5minutes later by beclomethasone (3000ug q12h) for 6weeks. This was administered using a MDI and an AeroHippus, Equine Aerosol Chamber (Trundell Medical). A decision was made to perform a BAL 6weeks later to assess response to treatment.
On re-examination the nasal discharge had ceased with a residual cough only at exercise. The BAL sample at this time revealed <3% neutrophils. A TW was also taken which showed 7% neutrophils confirming an improvement in disease severity.
A residual cough persisted despite being on continuous treatment. As a result a Flexineb nebuliser was trialled. Dexamethasone was used as the inhaled agent; 0.5ml sterile water with 0.5ml dexamethasone (Dexadresson, Intervet) once daily for two weeks and then every other day for two weeks.
Discussion
RAO is a common disease of older usually stabled horses. Hotchkiss et al, 2007 reported an estimated disease prevalence of 14% in the UK (Hotchkiss et al, 2007). The history, signalment and clinical signs presented in this case supported a diagnosis of RAO (Leclere et al, 2011).
The clinical signs most likely represent hypersensitivity/exaggerated response to inhaled pro-inflammatory agents such as hay dust, moulds, spores, forage mites, endotoxins and inorganic components which cause significant distal airway inflammation in susceptible horses (Robinson and Chairperson, 2001). The relative importance of these allergens in the aetiopathogenesis of RAO is difficult to determine; it’s likely all contribute through an additive and/or synergistic mechanism (Pirie et al, 2003).
Endoscopic examination revealed excess mucus as a result of neutrophilic inflammation and a blunted carina due to oedema and remodelling (Koblinger et al, 2011). Changes within the airway result from mucus metaplasia, smooth muscle hypertrophy and fibrosis. Bronchospasm of the airway alongside mucus and neutrophil accumulation leads to obstruction (Robinson et al, 2000). The initial treatment with a mucolytic, dembrexine hydrochloride (Sputolosin, Boerhinger Ingleheim) initially provided improvement in clinical signs by fragmenting the sputum fibre network so reducing mucus viscoelasticity (Matthews, Hackett and Lawton, 1988).
The owner was reluctant to perform a BAL initially due to the increased stress to the horse. The initial TW cytology couldn’t confirm a diagnosis despite the presence of Curschmann’s spirals which can indicate RAO (Reed and Bayly, 1998). Although it’s important to interpret culture results in light of cytology and clinical signs, paying less attention to scanty mixed growths of bacteria, the culture results were used to direct initial treatment for a possible bacterial tracheitis (McGorum, 2007). In this case where the clinical signs and signalment supported RAO a BAL alongside the TW would have provided a more reliable diagnosis. A BAL is more representative of the lower airways as it allows elucidation of the cellular response to lung injury (Derksen et al, 1989). Macrophages and lymphocytes are the predominant cell populations in BAL in normal horses whereas RAO is characterised by a non-septic inflammatory reaction, >25% neutrophils of the total nucleated cell count (Robinson, 2001).
Management of this disease involves three principles; environmental control to reduce allergens, corticosteroids to reduce inflammation and bronchodilators to relieve respiratory distress (Durham, 2001). It can be difficult to persuade owners that environmental changes are as important as medical treatment. In many cases clinical remission can be achieved by moving horses to either pasture or an indoor low-airborne dust environment (Vandenput et al, 1998). Green pasture is the best option to reduce clinical signs and horses should remain outdoors at all times with a supplementary pelleted diet; this was not practicable in this case (Jackson et al, 2000). The limited available turnout during winter made management problematic. Bedding on rubber matting in conjunction with cardboard and shredded paper provides the lowest dust levels for a stabled horse (Tanner et al, 1998). In most horses with RAO the main source of dust is from hay and bedding; in this case the horse had originally been stabled adjacent to the hay barn. Soaking hay reduces the dust challenge however not sufficiently to resolve symptoms of RAO (Clements and Pirie, 2007).
Treatment is based around a combination of bronchodilators and corticosteroids. Bronchodilators aim to alleviate respiratory distress associated with bronchospasm. Clenbuterol a B2 adrenergic agonist is most commonly administered orally to effect (Erichsen et al, 1994). In addition to its bronchodilator effect, clenbuterol has also been shown to have an anti-inflammatory effect (Lann et al, 2006). The efficacy of inhaled B2 adrenergic agonists has also been recognised, inducing a rapid, significant bronchodilation in horses demonstrating RAO (Bertin et al, 2011).
Due to the effectiveness found with inhaled agents in human patients, this route was investigated in horses. By using bronchodilators prior to administration of corticosteroids a deeper penetration of inhaled drug can be achieved (Rush et al, 1998). The horse’s demeanour in this case made him suitable for inhaled medications and he tolerated treatment well.
The advantage of inhaled corticosteroids is that a higher concentration of drug can be administered locally to the airways leading to a rapid onset of action, reducing the dose required and the subsequent side effects associated with corticosteroids (Duvvier et al, 1997). In severe cases systemic steroids are used initially to improve lung function as inhaled steroids require good pulmonary distribution to be effective (Ammann et al, 2008).
MDI are not licensed for horses and therefore they were used with due consideration of the cascade and the owners informed consent for the use of off-label medications according to Section 4.17 of the Supporting Guidance to the RCVS Code of Professional Conduct (RCVS, 2014). They are most efficient and effective when used with a ‘spacer’ which directs flow of the drug through a one way valve which opens on inspiration. The AeroHippus EAC, (Trundell Medical) is designed to be used with a MDI. The presence of the Flow-Vu® indicator enables owners to count the number of breaths the horse has taken through the chamber and ensures a satisfactory seal, both of which aid the correct and optimal delivery of the drug to the lungs (Trundell Medical International, 2015).
Nebulisers can also be used to distribute aerosol medication. Nebulisation has been shown to improve drug concentration in the lungs while minimising systemic concentrations and potential toxicity (Sustronck et al, 1995). Fultz et al (2014) demonstrated that delivery via nebulization can increase the concentration of a drug in the pulmonary epithelial lining fluid (PELF) (Fultz et al, 2014). A Flexineb nebuliser was tried with this case due to its chronic nature and the clinical signs subsequently resolved.
Although the mainstay of treatment is corticosteroids, recurrence of clinical signs will recur within 3days of treatment cessation if environment improvements are not made (Jackson et al, 2000). There is evidence of persistent chronic peripheral airway obstruction, in the absence of neutrophilic airway inflammation, even when RAO cases are maintained in a low dust environment. This supports the evidence for development of irreversible ultrastructural changes in the lung induced by prolonged repeated exacerbation, but also low grade airway inflammation (Miskovic et al, 2007). In these cases thoracic radiographs should be used to rule out irreversible lung pathology (Lavoie et al, 2004).
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