Chronic non-infectious lower airway diseases are important causes of clinical and subclinical disease in the horse. Recently the term ‘equine asthma’ has been adopted as a syndrome encompassing inflammatory airway disease (IAD), recurrent airway obstruction (RAO) and summer pasture-associated obstructive airway disease (SPAOD) (Couëtil et al, 2016). This new classification means that most horses classically diagnosed with IAD are now described as having mild/moderate asthma, while those with RAO/SPAOD are usually classified as having severe equine asthma. Irrespective of terminology, the therapeutic principles for horses with equine asthma are environmental management, a reduction in airway inflammation and a reduction in airway obstruction. Therapeutically this involves the use of anti-inflammatory drugs, especially the corticosteroids. Bronchodilator therapies may be of value in the management of horses with severe equine asthma. Other immunotherapies and mucolytic agents may also have a role in the management of affected horses.
The systematic review of the therapeutic options in equine asthma by Ivester and Couëtil (2014) highlights the wide variety of potential therapeutic agents that can be used in such cases. This may include agents that are authorised for the management of allergic airway diseases, as well as medicines that are not authorised for its treatment but can be justified under the prescribing cascade (Figure 1). As described in the previous two articles in the series (Redpath and Bowen 2019a,b), when using medicines under the Cascade, their use should be justified on a case-by-case basis. This article will illustrate the decision-making processes that are applied by the authors when unauthorised medicines are considered in the management of equine asthma. Case examples are presented to demonstrate the decision-making process, and should not be considered as an endorsement of any specific unauthorised product. Readers may interpret the presented evidence differently and may select different treatment regimens based on their clinical judgement. This should not be considered as a ‘violation of the Cascade’ as long as the justifications are based on the clinical need of the individual horse.
Environmental management
Environmental management is a fundamental requirement for all horses with equine asthma, irrespective of severity. Failure to address the underlying airway insult by reducing specific and non-specific respirable airborne particles will oft en result in subsequent treatment failure or relapse of clinical signs. Details of environmental management have been thoroughly discussed in a recent review in this journal (Hotchkiss, 2019).
Medical management of equine asthma
Although clinical remission can occur in horses with adequate environmental management alone (Jackson et al, 2000), medical management is oft en required, either for the control of acute exacerbations (rescue therapy) or to expedite remission. In horses with SPAOD, environmental management alone is rarely effective and there is oft en greater reliance on drug-based therapies, reflecting our poor understanding of the allergens involved.
Airway inflammation is common to all cases of equine asthma and is generally managed with corticosteroid therapy (Calzetta et al, 2017, 2018); however, in severe asthma significant bronchoconstriction contributes to the severity of respiratory signs. In severely affected horses, the muscarinic (ipratropium, hyoscine, revatropate) and beta-adrenoceptor (salmeterol, pirbuterol) bronchodilators have been shown to improve respiratory mechanics and clinical signs (Calzetta et al, 2019). Although most widely used in clinical practice, there is a paucity of good-quality evidence that clenbuterol improves clinical severity of disease (Williamson and Davis, 2007), although experimental evidence of short-term efficacy is available (Read et al, 2012). Prolonged use of clenbuterol has been associated with receptor tachyphylaxis. This means that treatment in excess of 21 days is associated with a decrease in its bronchodilatory effects (Read et al, 2012). Concurrent use of dexamethasone and clenbuterol reduces the occurrence of beta-adrenoceptor tachyphylaxis (Abraham et al, 2002), although to date there is no proven evidence for the clinical benefit of this.
The change in terminology regarding equine asthma should refocus practitioners' treatment strategies to place greater reliance anti-inflammatory medication, irrespective of severity, and to reserve bronchodilator treatment for horses with severe asthma. Where expected responses to therapy are not realised, alternative therapeutics, including the use of inhaled bronchodilators, may facilitate remission of clinical signs. When considering these, medicines need to be selected based on the Cascade as discussed below.
Cascade implications in the management of equine asthma.
1. Authorised veterinary medicines for use in the horse for this condition
a. Corticosteroids
Prednisolone: two formulations of oral prednisolone are authorised for the management of RAO in horses in the UK (Table 1). Given the constant changing terminology relating to equine asthma, the authors consider that it is reasonable to use these in all forms of equine asthma without seeking consent for ‘off -label’ use when treating mild/moderate disease (IAD). Although authorised for the management of severe asthma (RAO), the evidence suggests that oral prednisolone has limited efficacy when compared to oral dexamethasone, which has been shown to provide more rapid and more effective improvement in clinical signs than prednisolone (Leclere et al, 2010). In that study, the dose of prednisolone (2.0 mg/kg) and dexamethasone (0.05 mg/kg) were not equipotent or consistent with authorised doses (prednisolone 1mg/kg, dexamethasone 0.08 mg/kg), suggesting that prednisolone may not provide the expected results when used in clinical cases at authorised doses. This conclusion is reinforced by a statement in the summary of product characteristics (SPC) of one product, that states: ‘Treatment with prednisolone may not sufficiently restore respiratory function in all cases, and in each individual case the use of medicinal products with more rapid onset of action may need to be considered’ (EMA, ND). Prednisolone can be used in food-producing animals (Table 2). The prednisolone formulations in the UK are only authorised for use for 10 days, and in the authors' experience limited clinical response can be expected over this time period.
Table 1. Authorised forms of medications for the management of equine asthma or for inflammatory*, inflammatory/allergic§ conditions in the horse
| Trade name and manufacturer | Authorised dose and route of administration |
|---|---|
| Corticosteroids | |
| Dexamethasone | |
| Colvasone 0.2%*+Norbrook Laboratories (GB) Ltd | 0.08 mg/kg IV/IM |
| Dexa-ject 2 mg/ml§Bimeda UK | 0.06 mg/kg IV/IM/IA |
| Dexadreson 2 mg/ml§Intervet UK Ltd | 0.06 mg/kg IV/IM/IA |
| Dexafast 2 mg/ml§Forte Healthcare Ltd | 0.06 mg/kg IV/IM/IA |
| Dexafort Suspension for Injection+§Intervet UK Ltd | 0.08 mg/kg IM only |
| Dexamecine 2 mg/ml§#vet-Agro Trading Sp. Zo.o | 0.06 mg/kg IV/IM/IA |
| Duphacort Q 0.2%*Zoetis UK Limited | 0.08 mg/kg IV/IM |
| Rapidexon 2 mg/ml§Dechra Veterinary Products Ltd | 0.06 mg/kg IV/IM/IA |
| Voren Suspension for Injection§Boehringer Ingelheim Animal Health UK Ltd | Long acting formulation. IM only 0.02 mg/kg dexamethasone-21-isonicotinate |
| Prednisolone | |
| Equipred 50mg tablets#Virbac Ltd | 1mg/kg PO for 10 days |
| Equisolon 33 mg/gBoehringer Ingelheim Animal Health UK Ltd | 1mg/kg PO for 10 days |
| Bronchodilators – clenbuterol | |
| Dilaterol 25 µg/ml syrupNimrod Veterinary Products Limited | 0.8 µg/kg BID PO |
| Equipulmin 25 µg/ml syrup#CP Pharma Handelsgesellschaft GmbH | 0.8 µg/kg BID PO |
| Ventipulmin granules 16 µg/gBoehringer Ingelheim Animal Health UK Ltd | 0.8 µg/kg BID PO |
| Ventipulmin syrup 25 µg/mlBoehringer Ingelheim Animal Health UK Ltd | 0.8 µg/kg BID PO |
| Ventipulmin solution for injection 30 µg/mlBoehringer Ingelheim Animal Health UK Ltd | 0.8 µg/kg BID SLOW IV |
| Mucolytics – Dembrexine | |
| Sputolosin oral powder 5 mg/gBoehringer Ingelheim Animal Health UK Ltd | 0.3mg/kg BID PO |
This table lists authorised systemic dose and authorised routes of administration.
+indicates products where SPC indicates drug can only be used in horses permanently excluded from human food chain even where products may be allowed based on EU legislation (37/2010).
IA: intra-articular; IM: intramuscular; IV: intravenous. All doses are once daily except were indicated otherwise (BID: twice daily).
#Not currently marketed in the UK.
Table 2. Use of medications in food-producing anima
| Medication | Use in food-producing horses | Comment | BHA detection time | FEI detection time |
|---|---|---|---|---|
| Corticosteroids | ||||
| Beclomethasone | Permitted | ND | ND | |
| No MRL required | ||||
| Ciclesonide | Data not yet available | |||
| Dexamethasone | Permitted | 5 days | 2 days | |
| 8d meat withdrawal | ||||
| Fluticasone | Allowed | ND | ND | |
| 6 month meat withdrawal | ||||
| Methylprednisolone | Permitted | MRL in cattle only | ND | 28 days |
| No MRL determined for horses | ||||
| Prednisolone | Permitted | 2 days | ND | |
| 10 days meat withdrawal | ||||
| Bronchodilators | ||||
| Atropine | Permitted | ND | ND | |
| No MRL required | ||||
| Clenbuterol | Permitted | 13 days (oral) | 7 days | |
| 28 day meat withdrawal | 6 days (IV) | |||
| Hyoscine | Permitted | 2 days | 1 day# | |
| 1 day meat withdrawal | ||||
| Ipratropium | Allowed | 5 days | ND | |
| 6 month meat withdrawal | ||||
| Salbutamol | NOT PERMITTED | 3 days | 4 days | |
| Salmeterol | NOT PERMITTED | 2 days | ||
| Mucolytics | ||||
| Dembrexine | Permitted | 4 days | 5 days | |
| 1 day meat withdrawal | ||||
| Acetylcysteine | Permitted | Not a controlled substance | ||
| No MRL required | ||||
| Mast cell stablisers | ||||
| Sodium cromoglycate | Permitted | ND | ND | |
| No MRL required | ||||
| Nedocromil | NOT PERMITTED | ND | ND | |
Medicines permitted are those listed in table 1 of EU regulation 37/2010 and those allowed in EU regulation 122/2013. MRL maximum residue limits. Where no MRL is established in the target species, veterinary surgeons should determine a safe withdrawal period. Stated withdrawal periods are from product datasheets. Detection times for sports are taken from FEI and British Horseracing Authority (BHA). Data accurate 1st December 2019.
#Detection time for hyoscine for product containing hyoscine alone. Metimazole (if using product where this is included with hyoscine) has 3-day detection time (FEI & BHA). ND: no data from this authority.
Dexamethasone: a range of injectable short-acting dexamethasone products are authorised for use in horses (Table 1) for the management of inflammatory and/or allergic conditions in the horse, and as such would be appropriate first-line treatments for the management of all forms of equine asthma. Given its superior efficacy, it is usually considered as a first-line medicine in horses with severe asthma by the authors. Dexamethasone can be used in food-producing horses (Table 2), although the SPC of some formulations incorrectly indicate that horses treated with dexamethasone must be permanently excluded from the human food chain. Long-acting formulations of dexamethasone-21-isonicotinate are also authorised for the management of allergic and inflammatory conditions. To the authors' knowledge, these are not currently marketed in the UK. They are not used by the authors, because the long duration of action does not allow for immediate adjustment of dosing in the event of adverse events.
Injectable formulations of dexamethasone have been shown to have the same efficacy when given orally to fasted horses compared to intravenous (IV) administration (Cornelisse et al, 2004). In the authors' experience, direct syringing of injectable solutions into the mouth leads to significant wastage and underdosing, due to the liquid nature of the product, although this may be preferable to mixing the solution in feed, which reduces oral bioavailability (Cornelisse et al, 2004; Grady et al, 2010). Both oral methods for administration of injectable dexamethasone can, therefore, result in sub-therapeutic dosing, while the magnitude of dose adjustment required to compensate for these effects is almost impossible to predict. As such, transitioning from injectable to oral dexamethasone using authorised products may result in clinical relapse when no appropriate dose adjustment is made. Furthermore, there are potential health risks to owners from the handling of all corticosteroids, although these risks may be greater when using solutions of dexamethasone in non-compliant horses. Formulation of in-house extemporaneous products based on injectable dexamethasone with thickening agents is discussed below.
Injectable dexamethasone solutions are frequently nebulised for the management of equine asthma (Figure 3). When used via this route, there is minimal systemic absorption or irritation of the airway (Haspel et al, 2018), despite the presence of benzyl alcohol in injectable formulations that has been associated with airway inflammation when combined with nebulised saline in people (Reynolds and Smith, 1995). The safety of suspension formulations of dexamethasone has not been evaluated in horses, and products that are not authorised for IV administration are not recommended. There was limited clinical efficacy of nebulised dexamethasone in one experimental study with hay-challenged horses (Mainguy-Seers et al, 2019). These findings contradict the authors' clinical impression, where twice-daily administration of nebulised dexamethasone (5 mg) in chronic equine asthma can be beneficial in reducing clinical signs of moderately affected horses (Case 1). Based on this research, the authors usually recommend systemic corticosteroids in the initial management of severe asthma, usually alongside other ‘rescue therapies’, followed by inhalation as part of ongoing management. Human health risks should be considered in all situations of nebulised medication, since human exposure can be difficult to predict. The effects of aerosolised corticosteroids could include local effects on the skin and cornea as well as the oral and respiratory cavities, predisposing to bacterial or fungal overgrowth. Ocular corticosteroid administration has also been known to increase intraocular pressure and cause glaucoma in people (Phulke et al, 2017). Although these risks may be theoretical, protective equipment, including gloves, masks and eye protection, should be considered, especially in owners at higher risks of complications.
Adverse effects: although systemic corticosteroids have been associated with the development of laminitis, the risks are thought to be low, except perhaps in animals already suffering from insulin dysregulation (McGowan et al, 2016; Jordan et al, 2017; Potter et al, 2019). They should be used with care in pregnant mares (and should not be handled by pregnant owners). Many of the authorised formulations mention the risk of exacerbation of gastrointestinal (GI) ulceration, and some formulations of injectable dexamethasone and both forms of oral prednisolone are specifically contraindicated with concurrent GI ulceration. Where this co-morbidity exists, the risks should be discussed with owners and, where appropriate, other medication, such as inhaled therapies, might be justified under the prescribing cascade.
Ciclesonide: ciclesonide (Aservo EquiHaler, Boehringer Ingelheim Vetmedica) is likely to be the first inhaled cortisteroid to be authorised for use in horses. At the time of writing, the European Medicines Agency (EMA) has adopted a positive opinion for this product, although a marketing authorisation had not been granted (EMA, 2019). Ciclesonide is a pro-drug that is activated in the lungs, therefore ingestion following nebulisation into the pharynx is unlikely to cause any biological effects. In the first experimental study of this product delivered through a bespoke non-pressurised metered-dose inhaler, ciclesonide (2.7 mg BID) provided similar responses in airway function to dexamethasone (0.06 mg/kg SID) (Lavoie et al, 2019). The study describes drug administration using a bespoke nozzle device (EquiHaler) that required a period of training for horses to accept. A previous study evaluated a nasal spacer with many similar characteristics and demonstrated good horse compliance (Derksen et al, 1996), although whether the behaviour of experimental horses will translate into clinical cases remains to be seen. Although the product does not appear to offer superior effects to dexamethasone, its main advantage appears to be an absence of any systemic effects. This may translate to reduced detection times for competition horses. Its use in food-producing animals will be dependent on the establishment of maximum residue limits, which have not been determined at the time of writing.
b. Bronchodilators
Clenbuterol: this is a sympathomimetic agent that is authorised for the treatment of bronchoconstriction associated with equine asthma. In addition to its bronchodilatory effect, clenbuterol reduces the inflammatory response in horses with severe equine asthma in experimental studies (Laan, 2006), most likely through changes in interleukin production, although the clinical impact of this effect in clinical cases in unproven. Oral and IV formulations are available (Table 1). The authors would only consider injectable formulation for ‘rescue therapy’ of severe acute exacerbations of disease. However, in the emergency presentation, parasympatholytic agents may provide a more effective therapy. In the severely hypoxic horse, the authors would balance the clinical benefit of bronchodilation against the risk of increasing myocardial oxygen demand following administration of beta-adrenoceptor agonists (Linder et al, 1990) and may use this to justify the use of hyoscine in severe cases (Case 2). Clenbuterol can be used in food-producing horses. Excessive (or rapid IV) dosing can result in tachycardia, due to its action on myocardial beta-adrenoceptors. Sweating is sometimes seen with oral administration, and in the authors' experience is a common but short-lived effect following IV injection.
c. Drugs affecting mucus clearance
Excessive mucus accumulation is a feature of severe equine asthma and is a result of both increased mucus viscosity (Gerber et al, 2000) and reduced mucociliary clearance in disease. Clenbuterol induces a short-lived enhancement of mucus clearance in horses with asthma (Turgut and Sasse, 1989) as well as having a mild protective effect from the deleterious effects of long-distance transport on mucus clearance (Norton et al, 2013). Dembrexine is authorised for the management of respiratory disease associated with abnormal amounts of mucus with increased viscosity. Given the limited evidence to justify its use, the poor response observed with therapy and the resolution of mucus accumulation with appropriate anti-inflammatory medication, it remains of questionable use in the management of clinical cases. Dembrexine can be used in food-producing horses.
2. Other authorised veterinary medicines
a. Corticosteroids
While oral forms of prednisolone are available for use in small animals, there is no obvious justification for their use in the management of equine asthma, although there may be indications in other inflammatory conditions where both small animal tablets and equine products exist at the same level of the Cascade. This can result in awkward conversations when clients realise the cost differential of a horse being treated with skin disease (where small animal prednisolone may be used) compared with equine asthma, with the same active ingredient. Oral dexamethasone tablets are available for use in dogs. However, the current authorised forms are chicken-flavoured, and the authors consider these inappropriate in herbivores.
Methylprednisolone is authorised for the treatment of musculoskeletal disorders in the horse and inflammatory conditions in small animals. The authors usually avoid long-acting formulations of corticosteroids in the management of equine asthma, as their use prevents acute dose adjustment. Recently it has been shown that intra-articular triamcinolone (which has no veterinary authorisation) improves lung function beyond the time that detectable concentrations are absent in plasma (Bessonnat et al, 2019). Whether similar outcomes will be achieved with methylprednisolone is not known. When using long-acting intra-articular medicines in horses with concurrent asthma, it should be recognised that these may impact on clinical signs during the period of treatment and that recurrence or exacerbation of clinical signs may occur after the therapeutic window has lapsed. Methylprednisolone can be used in food-producing horses, although no MRL has been established for horses.
b. Bronchodilators
While there are no medicines directly authorised as bronchodilators in this step of the Cascade, the parasympatholytic agents all have a direct bronchodilator effect and are the authors' preferred treatment for acute management of lower airway bronchospasm. Bronchoconstriction in equine asthma is a result of parasympathetic activation. Although beta-adrenoceptor agonists bring about physiological antagonism of that effect, parasympatholytic agents act directly to inhibit nerve conduction. Thus, parasympatholytic agents cause a more rapid clinical effect. Hyoscine (butyl scopolamine bromide) is authorised for the treatment of colic in the horse, but is also widely used to facilitate abdominal palpation per rectum (outside its marketing authorisation). As such, it is readily available in emergency situations (Case 2). Atropine is authorised for use in horses, although not specifically for the management of equine asthma. Hyoscine has been shown to cause similar improvement in lung function to atropine, but with fewer side effects (Couëtil et al, 2012; de Lagarde et al, 2014). Both atropine and hyoscine can be used in food-producing animals. Although the SPC for atropine incorrectly states that horses need to be excluded from the human food chain, it is listed in EU 37/2010 as not requiring an MRL in any species.
c. Mucolytic agents
Although there are no other authorised mucolytic agents in the UK, nebulisation with saline (0.9%) is used frequently to facilitate mucus clearance (Cha and Costa, 2017), although as with all mucolytic agents there is no robust evidence to support its use.
3. Human medicines or European veterinary medicines
a. Corticosteroids
Oral dexamethasone and prednisolone tablets are authorised for use in people. While tablets may not be appropriate in all cases, veterinary tablets authorised for use in small animals can result in clients counting out vast numbers on a daily basis (approximately 100). Human formulations are available in larger tablet strengths (40 mg and 30 mg tablets) that may improve the accuracy of dosing and client compliance. However, the expected release of 50 mg veterinary prednisolone tablets will remove this reason for selecting human formulations where tablets are the desired formulation.
Inhaled corticosteroids authorised for use in people are widely used in the long-term management of equine asthma, using metered-dose inhalers (MDI) or using nebulised solutions through a variety of spacer or mask devices. The primary advantage of inhaled corticosteroids is greater targeting of therapy to the lungs, potentially increasing their safety profile. Inhaled therapy often results in a lower drug detection time and can be particularly beneficial in the management of mild/moderate asthma (IAD) in competition horses. In severe asthma, drug delivery to the distal airways may be impaired by bronchoconstriction, and prior administration of bronchodilators may facilitate drug delivery, at least in the early stages of management of chronic disease. The most commonly used inhaled corticosteroids are fluticasone and beclomethasone. Both have good evidence of effect in improving lung function (Ammann et al 1998; Rush et al, 2000; Couëtil et al, 2005). Fluticasone is more potent than beclomethasone, has less systemic absorption (Rush et al, 2000; Laan et al, 2004) and may be considered superior, although it can be cost-prohibitive for long-term use.
The ongoing use of human inhaled corticosteroids may be altered if ciclesonide receives a marketing authorisation for use in equine asthma. They will still have a place in the management of horses that will not tolerate the bespoke nostril adapter, and for horses where there is an inadequate response to therapy. The VMD have specific guidance covering new medications and indicate that when new products come to market, veterinary surgeons should consider changing to the new product. However, where there are genuine concerns about affecting the stability of treatment protocol, they indicate this it may be justified to continue using the unauthorised medication (VMD, 2019). The terms of the marketing authorisation are unknown, but if its marketing authorisation only covers short duration of treatment, human medication may also be useful for chronic therapy. Beclomethasone can be used in food-producing horses, with no MRL being required. Fluticasone can be used in food-producing animals with a six-month meat withdrawal period. Detection times are not published for either of these medicines.
b. Bronchodilators
Inhaled and parenteral forms of bronchodilators are authorised for use in people either for the management of human asthma or for other conditions. Of the parasympatholytic agents, glycopyrrolate can be used by injection for acute bronchodilation as ‘rescue therapy’. It has fewer adverse effects than atropine but given the widespread availability of hyoscine in such cases, the authors do not use this product any longer. Although glycopyrrolate is permitted in food-producing animals with a 6-month withdrawal period, it is only indicated as essential for the management of life-threatening bradycardias and therefore should not be used in food-producing animals for the management of severe asthma. Injectable hyoscine is authorised for use in people. The authors would only justify its use in equine asthma in the presence of supply chain problems with the veterinary formulation.
Inhaled parasympatholytic agents have rapid, but short-lived effects on bronchiolar tone. Ipratropium is currently the recommended inhaled parasympatholytic and has limited systemic absorption. It can be administered through MDI or via nebulisation. The short duration of effect (Robinson et al, 1993) can be useful either before other inhaled medications to enhance delivery, or in horses with chronic severe asthma to remove residual bronchoconstriction before exercise (Case 3). The authors recommend its administration 1 hour before exercise. Ipratropium can be used in food-producing animals with a 6-month meat withdrawal period.
A range of beta-adrenoceptor agonists can be administered using MDIs. Of these, salbutamol (albuterol) and salmeterol are the most commonly used by the authors and often justified based on the evidence of published effectiveness or following relative treatment failure of oral clenbuterol. They are less likely to induce adverse effects, due to limited systemic absorption, and therefore might be of value in horses with hypoxia, or that develop sweating and/or tachycardia with systemic therapy. Salbutamol has a short duration of effect and therefore is most valuable before exercise, to remove residual bronchoconstriction. Salmeterol is longer lasting (12 hours) and can be useful for ongoing therapy. Neither drug can be used in food-producing animals.
c. Mucolytics
Acetylcysteine is a mucolytic substance that has potential value in the control of excessive tracheobronchial mucus when administered by nebulisation (2 g/animal; Stopyra et al, 2012) and has been shown to reduce proteolytic enzymes in tracheal mucus (Koivunen et al, 1996). There is no evidence to suggest a superior effect to dembrexine and therefore it is usually only recommended by the authors where excessive tracheal mucus persists despite appropriate anti-inflammatory therapy combined with dembrexine. Its popularity arises since it is not a controlled medicine in sports disciplines and can be used in food-producing animals with no MRL. Sterile solutions of acetylcysteine are available for use in people; these can be administered through commercial nebulisers.
d. Immunomodulators
Inhaled mast cell stabilisers are predominantly used as preventative agents, given for 1–2 weeks prior to challenge (Thompson and McPherson, 1981). They may also have value in the management of horses with mild to moderate asthma (Hare et al, 1994). These are usually reserved for chronic relapsing cases of mild asthma cases by the authors, following remission of clinical signs. The authors also use them in horses with mild asthma that are characterised by large numbers of mast cells on bronchoalveolar wash cytology. Sodium cromoglycate and nedocromil sodium are both available as MDIs for administration through spacer devices. Sodium cromoglycate can be used in food-producing animals.
4. Specials (medicines produced extemporaneously)
a. Corticosteroids
‘Special’ formulations of prednisolone and dexamethasone are available from licensed specials manufacturers. Dexamethasone paste can be very useful in providing a potent oral anti-inflammatory therapy for horses with severe asthma (Case 2). As previously stated, dexamethasone provides more rapid and effective improvements in airway function than prednisolone (Leclere et al, 2010). Therefore, the authors will use oral dexamethasone formulations in horses that have required initial stabilisation using parenterally administered dexamethasone, to prevent the risk of relapse by transitioning to less potent corticosteroids. Special formulations have advantages over human tablets and the use of injectable formulations orally, since they ensure medications are administered at the chosen dose, without wastage. They facilitate dosing before feeding, which has been shown to improve bioavailability in horses given dexamethasone (Cornelisse et al, 2004; Grady et al, 2010). The alternative, of using injectable formulations of dexamethasone orally, often results in significant underdosing, and although these preparations can be mixed with oral thickening agents to formulate an in-house ‘special’, the effect of this on subsequent bioavailability has not been established. Current advice from the Royal College of Veterinary Surgeons is that when using specials these should, where possible, be obtained from licensed specials manufacturers. Prednisolone pastes can also be considered under the Cascade, but since prednisolone is less efficacious in equine asthma (Leclere et al, 2010), the authors would rarely find a justification for its use. Paste formulations may reduce risks to human health when handling these products, since they will be neither inhaled (unlike powders) nor likely to come into contact with skin or mucus membranes. However, gloves should still be recommended when handling these medicines.
Conclusions
The prescribing cascade provides access to a wide range of therapeutic strategies and extends the route of administration of medication to provide access to inhaled human medications, medications for the acute management of disease and oral medications for long term management of equine asthma. While corticosteroids remain the main therapeutic group of agents in equine asthma, bronchodilators are useful in horses with severe asthma.
KEY POINTS
- The prescribing cascade (Cascade) is a risk-based algorithm that allows the selection of unauthorised medicines as appropriate to maintain animal welfare.
- Compliance with the Cascade involves the evidence-based justification of medicines used under the Cascade.
- Equine asthma can be described either by severity or based on previously accepted terminology where inflammatory airway disease is now described as mild/moderate asthma, while recurrent airway obstruction is now described as severe asthma.
- Corticosteroids have a role in the management of all forms of equine asthma. Dexamethasone and prednisolone are the only current authorised corticosteroids for use in horses, but inhaled therapy with other corticosteroids may be justified in specific cases.
- Oral clenbuterol therapy is the authorised bronchodilator used in the management of severe equine asthma but other, inhaled, bronchodilators may be useful in specific cases and many have a greater evidence base for efficacy.