An Experimental Model of Allergic Asthma in Cats Sensitized to House Dust Mite or Bermuda Grass Allergen

Abstract

Background: Animal models are used to mimic human asthma, however, not all models replicate the major characteristics of the human disease. Spontaneous development of asthma with hallmark features similar to humans has been documented to occur with relative frequency in only one animal species, the cat. We hypothesized that we could develop an experimental model of feline asthma using clinically relevant aeroallergens identified from cases of naturally developing feline asthma, and characterize immunologic, physiologic, and pathologic changes over 1 year. Methods: House dust mite (HDMA) and Bermuda grass (BGA) allergen were selected by screening 10 privately owned pet cats with spontaneous asthma using a serum allergen-specific IgE ELISA. Parenteral sensitization and aerosol challenges were used to replicate the naturally developing disease in research cats. The asthmatic phenotype was characterized using intradermal skin testing, serum allergen-specific IgE ELISA, serum and bronchoalveolar lavage fluid (BALF) IgG and IgA ELISAs, airway hyperresponsiveness testing, BALF cytology, cytokine profiles using TaqMan PCR, and histopathologic evaluation. Results: Sensitization with HDMA or BGA in cats led to allergen-specific IgE production, allergen-specific serum and BALF IgG and IgA production, airway hyperreactivity, airway eosinophilia, an acute T helper 2 cytokine profile in peripheral blood mononuclear cells and BALF cells, and histologic evidence of airway remodeling. Conclusions: Using clinically relevant aeroallergens to sensitize and challenge the cat provides an additional animal model to study the immunopathophysiologic mechanisms of allergic asthma. Chronic exposure to allergen in the cat leads to a variety of immunologic, physiologic, and pathologic changes that mimic the features seen in human asthma.

Functional response to inhaled salbutamol and/or ipratropium bromide in Ascaris suum-sensitised cats with allergen-induced bronchospasms

“…Neither incremental doses of inhaled allergen nor 12 consecutive challenges with fixed doses of aeroallergen (Norris Reinero et al, 2004) proved to be sufficient to elicit an EAR in research cats with experimental asthma. Thus, factors other than the intensity of allergen exposure during challenge appear to impact the occurrence and magnitude of allergen-induced EAR.…”

“…On the basis of sensitisation to experimental (Ascaris suum) or clinically relevant allergens (Bermuda grass, house-dust mite), these models successfully mimicked many hallmark features of both feline and human diseases: eosinophilic airway inflammation, reversible airflow limitation subsequent to inhalation of specific allergens, non-specific bronchial hyperresponsiveness and airway remodelling (permanent structural changes within airways) at advanced stages (Padrid et al, 1995;Norris Reinero et al, 2004;Kirschvink et al, 2007).…”

Animal Models of Allergic Diseases

“…In the past 10 years, such similarities have led to the development of two feline asthma models for preclinical studies [139][140][141]. Like in people, in cats asthma is extremely common and triggered by aeroallergens and the clinical manifestations include cough, wheeze and episodic expiratory respiratory distress [138].…”

Enantiomer-Specific Effects of Albuterol on Airway Inflammation in Healthy and Asthmatic Cats

“…These features include clinical signs of cough, wheeze, and episodic respiratory distress; bronchoconstriction reversible with β-agonists, eosinophilic inflammation of the airways, and remodeling changes of the airways. Repeated airway challenge using a clinically relevant allergen (Bermuda grass allergen, BGA) led to development of a model of allergic asthma in the cat with many features of human asthma, including elevated BGA-specific IgE, airway hyperreactivity, airway eosinophilia, an acute T helper 2 cytokine profile, and histologic evidence of smooth muscle hyperplasia, epithelial erosion, and goblet cell/submucosal mucous gland hyperplasia [19]. This feline model is therefore an excellent preclinical model for the study of allergen-induced human asthma.…”