The latest approach to the management of inflammatory airway disease is through inhalation therapy with nebulizers or metered-dose inhalers (MDI). With inhalation therapy, high drug concentrations are delivered directly to the lungs via nebulizers or metered-dose inhalers (MDI), and systemic side effects are avoided or minimized. The onset of action for inhaled bronchodilators and anti-inflammatory drugs is substantially shorter than that of oral or parenteral formulations. Nebulizers have long been used in animals, but the overall efficiency of dug delivery is low and the equipment is cumbersome and inconvenient for owners. Administration of medications via MDI is now commonplace in the treatment of human asthma and appears to be beneficial in the management of animals as well. Human MDI are designed to provide optimal lung delivery following actuation during a slow, deep inhalation. However, this is impossible to control in animals. The addition of spacers enables MDI to be used in animals. Spacers decrease the amount of drug deposited in the oropharynx (up to 80% of the actuated dose with the MDI alone), thereby reducing systemic drug absorption. Even in human medicine, the relative potencies, risks of adverse effects, and the optimal dose of the different inhaled asthma medications are still unclear. Drugs available in MDI formulations include β2 agonists, glucocorticoids, ipratropium bromide, cromolyn sodium, and nedocromil. Each product delivers a set amount of drug per actuation (puff). In the USA, MDI are labeled according to the amount of drug delivered at the mouthpiece, while in Canada and the EU, they are labeled according to the amount of drug delivered from the valve. For client convenience, MDI are color-coded to aid identification.
Short-acting β2 agonists such as albuterol (salbutamol) in MDI are the medications of choice for treating acute exacerbations of bronchoconstriction, as they relax smooth muscle and promptly increase airflow. While effective for symptomatic relief, β2 agonists do not control inflammation. Monotherapy may exacerbate airway disease and has been proved to increase morbidity and mortality in human asthmatics. Tolerance may develop with chronic therapy.
Salmeterol is a long-acting β2 agonist; its onset of action is slow (15–30 min), but its duration of action is >12 hr. It is not recommended for use in acute bronchoconstriction, but daily use with glucocorticoids provides better control of symptoms than simply increasing the glucocorticoid dose. It is not available in an MDI in all countries.
Inhaled glucocorticoids are the most potent inhaled anti-inflammatory drugs available. In humans, early intervention with inhaled glucocorticoids improves asthma control, normalizes lung function, and may prevent irreversible airway damage. The potential risk of adverse effects is well balanced by their efficacy in management of chronic inflammation. Oral candidiasis (thrush), dysphonia, and reflex cough and bronchospasm are the most common adverse effects in humans; all of these effects are reduced by the use of a spacer. The risk of systemic adverse effects, such as suppression of the hypothalamic-pituitary axis, is less than with oral prednisone therapy. Inhaled glucocorticoid formulations include fluticasone, beclomethasone, flunisolide, and triamcinolone. Currently, fluticasone is considered the most potent formulation with the longest duration of action.
Ipratropium bromide is a quaternary derivative of atropine that lacks its adverse effects and is available in an MDI (500 μg/actuation). In asthmatic humans, ipratropium bromide is used as an additional reliever medication to reverse bronchoconstriction when inhaled short-acting β2 agonists do not provide enough relief. Its anticholinergic action also decreases mucous secretions. In an experimental model of feline asthma, longterm antigen sensitization caused an augmented muscarinic receptor response to acetylcholine. Modulation of muscarinic receptors with anticholinergic drugs may be useful for treatment of asthmatic cats. Currently, there are no published reports of the use of ipratropium in cats; however, it has shown efficacy for recurrent airway obstruction in horses. It is not well absorbed after inhalation, so it does not cause systemic anticholinergic effects.
Cromolyn Sodium and Nedocromil
Cromolyn sodium and nedocromil sodium are chloride-channel blockers that modulate mast cell mediator release and eosinophil recruitment. They are both available in MDI. Cromolyn sodium and nedocromil sodium have strong human safety profiles, but nedocromil sodium has been reported to have a broader spectrum of efficacy. In humans, the clinical response to these drugs is less predictable than the response to glucocorticoids. There are no published reports of the use of cromolyn or nedocromil in asthmatic cats or dogs with bronchitis; however, pretreatment with nedocromil sodium aerosols attenuated viral-induced airway inflammation in Beagle puppies. Further investigation of these drugs in asthmatic cats seems warranted given the sensitivity of cats to serotonin released from degranulating mast cells.
Suggested Treatment Regimens
For emergency management of dyspnea in cats and dogs, 2–4 puffs of albuterol (salbutamol) should be given every 5 min until clinical signs resolve. Additional therapy may include oxygen and an IV dose of a rapid-acting glucocorticoid.
Current recommendations for therapy of feline asthma and chronic canine bronchitis are to use albuterol (salbutamol) as needed for bronchodilation and 220 μg of fluticasone bid. For initial therapy of moderately affected animals, a 5-day course of oral prednisone/prednisolone at 1 mg/kg may be helpful. Several affected animals may require 1 mg/kg of prednisone/prednisolone every other day. Adjunctive therapy with ipratropium, nedocromil, or cromolyn may be useful in some patients. Therapy must be individualized for each patient.
For horses with recurrent airway obstruction, environmental management and a combination of bronochodilator and anti-flammatory therapy is recommended. Current recommendations are to use 500 μg of albuterol (salbutamol) every 2 hr as needed and fluticasone at 2–4 μg/kg bid. Beclomethasone has also been used 1–3 μg/kg, bid, but it causes more adrenal suppression in horses than fluticasone at these doses.
Last full review/revision March 2012 by Patricia M. Dowling, DVM,MSc, DACVIM, DACVCP