Use of Inhaled Medications in the Management of Chronic Airway Disease

Information produced by Julie Stegeman, DVM, DACVIM, Nashville Veterinary Specialists - Clarksville

In small animal practice, we treat patients with chronic airway disease on a daily basis. In the dog, this includes chronic bronchitis, chronic rhinitis, pulmonary infiltrates with eosinophils, collapsing trachea, and chronic obstructive pulmonary disease (often the end- stage of chronic bronchitis). In the cat, we most commonly treat asthma, bronchitis, and chronic rhinitis. Common features of all of these conditions are inflammatory cell infiltrates and increased airway secretions, with varying degrees of eosinophilia, bronchial constriction, structural alterations and secondary bacterial infections. These diseases require life-long management with the goal of controlling clinical signs and slowing disease progression.

A large handful of systemic medications are available to treat these diseases, but are associated with differing degrees of side effects. Systemic corticosteroids are typically quite effective in controlling inflammation, and thus the clinical signs in most of these conditions. Unfortunately, corticosteroids are also associated with polydipsia, polyuria, polyphagia, weight gain (which exacerbates respiratory conditions), ligamentous weakness, muscular weakness, muscle mass loss, and ironically, notable alterations in breathing patterns in many dogs. In cats, insulin resistance and drug-induced diabetes mellitus is a risk of systemic corticosteroids. Systemic bronchodilators are problematic for the side effects of tachycardia, hypertension, and excitability. When these same classes of drugs are used locally, (i.e. when they are inhaled), there are minimal to no systemic side effects, and therapy is delivered directly to the site where it is needed the most. This presentation will review the most common inhaled medications and how to use these tools for long term therapy.

Inhaled corticosteroids are indicated any time chronic corticosteroid therapy is needed for airway disease, from nose to alveolus. This is especially true if the pet is known to be sensitive to systemic steroids, has diabetes mellitus, Cushing’s disease, pancreatitis, or for use in patients on other systemic immune suppressive therapy such as chemotherapy. Inhaled bronchodilators are useful in patients that are hypertensive or that become excitable on oral bronchodilators.

Inhaled medications are NOT expected to be helpful in the early stages of disease, because airway obstruction with mucus is common initially, and an inhaled medication cannot penetrate past that mucus. Inhaled medications are also not accepted by all pets. For example, brachycephalic breeds may be difficult to fit to a face mask, and some animals panic when the mask is placed across their muzzle. Therefore, control is typically achieved with oral medications, and control is maintained with inhaled medications where possible. Typically, there is a 2-4 week period of weaning off of oral medications while the inhaled medication begun (typically corticosteroids).

Inhaled medications can be administered via nebulization, or via a metered-dose inhaler. Nebulization allows administration of tiny droplets of medication that penetrate as far as the alveoli. A wide range of medications can be nebulized, including antibiotics (most often aminoglycosides), corticosteroids, bronchodilators, mucolytics, and often just saline. The disadvantage of nebulization is primarily the time it takes to give the medication and the dispersal of excess medication into the surrounding air (which is then inhaled by the caretaker). Nebulization usually takes 5-10 minutes. One way to make nebulization easier is to place the patient in a small carrier that has approx. 80 % of the openings covered by plastic wrap, with the nebulizer placed in front of the patient’s face.

Metered-dose inhalers are a more precise way to administer inhaled medications. The design of these inhalers has changed in recent years, such that the propellant changed from chlorofluorocarbon to hydrofluorocoarbon, or more commonly breath-actuated inhalers. The newer “discus” and turbohaler styles are not suitable for use in animals, as they typically deliver a powder, not a solution. The inhalers that are usually used for our patients are those that are used for pediatric or debilitated human patients.

Since we cannot ask our patients to properly use a metered dose inhaler (“puffer”), we must use an adapter, consisting of a hollow tube spacing chamber which holds the actuated dose of medication, and a face mask to deliver the dose to the pet. The mask must fit over the nostrils and the mouth, and the pet must inhale several times to receive the dose of medication. There are several companies that sell these devices, or even a pediatric administration set may be used on a small pet. The chamber/ mask apparatus from Aerodawg/ Aerokat (Trudell medical supply) has a one-way valve between the chamber and mask, which allows the pet owner to actually watch to be sure that the pet is inhaling the medicine.

The majority of pets can be taught to tolerate the inconvenience of receiving the inhaled medication with the help of the owner remaining calm and direct, and giving a treat afterwards. Reluctant cats can be bundled in a towel, and owners of reluctant dogs have to be reminded that most dogs are trainable. It is best in some cases to simply get the pet used to having something against the front of its face, such as an empty toilet paper tube, and reward the pet for remaining still when that is applied, then move on to the mask alone, and then the full apparatus next. We have helped elderly clients and owners of fractious cats learn the best way to give the medication. The websites also offer videos and written instructions (www.aerokat.com, www.aerodawg.com). Another very helpful support website is www.FritztheBrave.com; it has extensive links to support groups, tips on administration of medications, and useful suggestions.

Fluticasone may be the ideal glucocorticoid for inhalation. It has about 20 times the affinity for glucocorticoid receptors compared to dexamethasone, has very poor oral bioavailability and high first-pass metabolism. Thus there is low risk for systemic side effects. It is available as a metered dose inhaler in three strengths- 40, 110 and 220 mcg per puff (125 and 250 mcg inhalers outside the US). For cats and small dogs, the 40 or 110 mcg inhalers are best, and given at a starting dose of 2 puffs BID. For dogs larger than 20 kg, the 220 mcg dose is best. Flunisolide is a similar inhaled glucocorticoid that is widely available as well.

The extent of systemic absorption and effects will of course vary with patient and dose. In two feline studies, Flunisolide 250mcg did suppress the hypothalamic-pituitary-adrenal axis, but fluticasone up to 220 mcg did not. However, the study designs were not parallel, and cross reaction with oral prednisolone may have flawed the flunisolide study. In a canine study, Fluticasone 220 mcg did mildly suppress the hypothalamic-pituitary-adrenal axis, but none were into an addisonian range. All studies have found much less effect on systemic immune parameters vs oral steroids.

Several studies have examined the efficacy of inhaled glucocorticoids. In 2006, Kirschvink et al examined the feline bronchial response to inhaled carbachol with or without fluticasone pre-treatment (250 mcg BID for 2 weeks). The treated cats had significantly less bronchial reactivity, lower BAL cell counts, and lower Prostaglandin F2α in the fluid compared to controls, supporting the assessment that inflammation was reduced in this experimental model of asthma. At the ACVIM Forum in 2008, Phil Padrid reported results in 300 consecutive clinical feline asthma patients that were started on inhaled fluticasone and oral prednisolone. Of the 246 cats with mild to moderate signs, 201 were tapered off of oral prednisolone in 4 week, whereas 45/246 needed every other day Prednisolone with their inhaled fluticasone to control their clinical signs. There were 54 cats with severe signs of asthma, 34 of which could be tapered off of prednisolone, and 20 cats that needed prednisolone every other day along with the inhaled fluticasone to control their clinical signs.

There are a few potential side effects of inhaled glucocorticoids. In cats and small dogs, there can be thinning and bending of the pinnae, facial dermatitis, focal (facial) demodecosis, facial hair thinning, and even activation of Herpetic keratoconjunctivitis. Ocular irritation or coughing with administration can also occur. All of these are very uncommon, and are easily addressed. Iatrogenic Cushing’s is possible, but rare. The author has seen one case of this in a geriatric Australian Shepherd that historically also had severe side effects on low dose oral prednisone.

Bronchodilators are the other type of widely used inhaled medication. These are fast-acting and can be used multiple times within a short period if a patient is in crisis. Albuterol is the most commonly used inhaled bronchodilator. It is also known as salbutamol in every other country besides the US. Albuterol should not be used without ongoing corticosteroid therapy, because it can be pro-inflammatory. It was discovered that human asthma patients on inhaled albuterol (a Beta-2 agonist), had an increased risk of death compared to those not receiving the drug, the so-called “Beta-paradox”. Albuterol is a racemic mixture, and the S-enantiomer is pro-inflammatory. Pure D-albuterol is available but is much more expensive. Inhaled albuterol can be used for chronic management up to QID, provided the pet is also managed with inhaled steroids, and can be used in an asthmatic crisis every 30 min for up to 4 hours.

In summary, inhalant therapy can be very useful in long term management of chronic airway disease. It is a relatively easily learned technique for most clients, given proper guidance and instruction. Inhaled medications have minimal systemic side effects, and a low risk of complications. Some patients require a combination of oral and inhaled medications to control their symptoms.