EFFICACY OF AEROSOL DRUG DELIVERY IN SMALL ANIMALS

Few scientific studies report on the safety or efficacy of these aerosol therapies in companion animals. Although there are plentiful descriptions of aerosol therapy in textbooks and at continuing education meetings, there are few controlled published studies of animals with naturally occurring disease. The information that has been published about aerosol drug delivery in dogs or cats includes the following:

• Bordetella bronchiseptica was shown to be susceptible to aminoglycosides delivered directly onto the respiratory epithelium,⁶ and such administration of aminoglycosides resulted in little if any systemic drug absorption.⁷
• A preliminary study suggested better recovery in dogs with kennel cough treated with nebulized aminoglycosides, but this study lacked a control population, and bacterial infection was not confirmed.⁸
• One study demonstrated the ability to deliver particles by nebulization to the lower airways in conscious, unsedated cats by aerosol.⁹
• An inhaled corticosteroid (flunisolide 250 μg b.i.d.) reduced eosinophil percentage in bronchoalveolar lavage fluid in cats with experimentally induced asthma but did not affect allergen-specific IgE, airway hyperresponsiveness, or blood lymphocyte phenotype.¹⁰
• A dose of 250 μg fluticasone propionate given once a day for two weeks diminished airway inflammation and reactivity in a group of cats with mild chronic bronchitis.¹¹
• A recent study found that much lower doses of a corticosteroid (44 μg fluticasone b.i.d.) were as effective as higher doses (either 110 or 220 μg fluticasone b.i.d.) in reducing experimentally induced allergic eosinophilic airway inflammation without measurable suppression of the hypothalamic-adrenal axis.¹² Airway reactivity was not assessed.
• A positive response to corticosteroids delivered by MDI was reported in a small retrospective study of dogs with bronchitis.¹³
• Other studies demonstrate reduced suppression of the hypothalamic-pituitary-adrenal axis in dogs and cats treated with inhaled vs. oral corticosteroids, but these studies did not evaluate the therapeutic efficacy of the corticosteroids for the treatment of any disease.^14,15
• A combination of ipratropium (an anticholinergic bronchodilator) with salbutamol reduced airflow limitation in cats with experimentally induced asthma.¹⁶

Because of the questions still surrounding the efficacy of drug delivery by aerosol, these drugs should generally be used as adjuncts in treating animals with moderate to severe signs of disease. Once signs have improved, inhalant therapy may replace medications traditionally administered by other routes.

Other uses for inhalation therapy include treating lung cancer or systemic disease. Several reports describe the use of aerosolized drug delivery with chemotherapeutic or immunomodulating drugs in treating spontaneous primary and metastatic cancers in dogs.^17-19 Dogs have also been used as a model in the development of insulins to be delivered via needle-free aerosol.²⁰ Such an insulin product was FDA-approved for use in people (Exubera—Nektar) but was withdrawn from the U.S. market because of a lack of consumer demand. Recently, nebulized regular insulin was demonstrated to effectively lower blood glucose concentrations in five healthy domestic cats.²¹

Small animals have been used as models for other aerosol therapies, including treatment aimed at cardiovascular and hemodynamic perturbations (e.g. inhaled nitric oxide for pulmonary hypertension), vaccination, and even gene therapy.²² As delivery systems are developed specifically for animals and as our knowledge of the efficacy of this system of drug delivery grows, we are likely to use more inhalational therapy in small-animal patients.

Leah A. Cohn, DVM, PhD, DACVIM
Department of Veterinary Medicine and Surgery
College of Veterinary Medicine
University of Missouri
Columbia, MO 65211