Table 2.

Animal Models of Asthma.

Animal	Stimuli	Predominant Cell Type, Immunopathology	Characteristics Shared with Human Asthma	Strengths	Limitations
Inducible Models
Mouse [17,18,19,37,275]	OVA +/− LPS, HDM, Cockroach, Alternaria alternata antigen, pollen	Eosinophils, Neutrophils Th2-high and Th2-low asthma models are available, depending on sensitization/challenge conditions	Bronchoconstriction Airway hyperresponsiveness Goblet cell hyperplasia/↑ Mucus production Airway smooth muscle hypertrophy Subepithelial fibrosis	Low cost Transgenic or gene-knockout strains Short gestation length Wide availability of mouse-specific reagents and assays	Lack of ability to model chronicity due to tolerance Limited/indirect measures of pulmonary function, generally requires anesthesia
Guinea Pig [85,276]	OVA, HDM	Eosinophils, Neutrophils Th2-high asthma, IgE-mediated	Bronchoconstriction, Airway hyperresponsiveness, Goblet cell hyperplasia/↑ Mucus production Subepithelial fibrosis	Low cost	Neutrophils are the primary phagocytes within alveoli (vs. alveolar macrophages) Lack of ability to model chronicity due to tolerance
Rabbit [122,123,277,278,279]	OVA, Alternaria tenuis antigen	Eosinophils Th2-high asthma, IgE-mediated	Bronchoconstriction, Airway hyperresponsiveness	Low cost	Sensitization can occur within 24 h of birth to optimize early and late airway responses Rabbits have heterophils instead of neutrophils
Sheep [140,143,146,147,280,281,282,283,284]	HDM, Ascaris suum antigen	Eosinophils Th2-high asthma, IgE-mediated	Bronchoconstriction Airway hyperresponsiveness ↑ airway collagen deposition ↑ bronchial smooth muscle thickness Goblet cell hyperplasia/↑ Mucus production	Similar placental physiology to humans Body size and anatomy allow pulmonary function assessment in conscious animals and large BAL fluid volume/cell number Lifespan is amenable to modeling chronic asthma	Cost Limited species-specific assays and antibodies
Rat [152,153,154]	OVA, HDM	Eosinophils Th2-high asthma, IgE-mediated	Bronchoconstriction, Airway hyperresponsiveness, Goblet cell hyperplasia/↑ Mucus production	Low cost Transgenic or gene-knockout strains Short gestation length Availability of rat-specific reagents and assays	Weak bronchoconstriction Require high levels of antigen exposure Limited/indirect measures of pulmonary function, generally requires anesthesia
Dog [285]	Ascaris suum antigen, Ragweed antigen, Ozone	Neutrophils, Eosinophils IgE-mediated	Airway hyperresponsiveness	Relative low cost among other large animal models	Limited species-specific assays and antibodies Public concerns with laboratory testing on companion animals
Nonhuman Primates [286,287,288]	Ozone, Ascaris suum antigen, HDM, Pollen, Tobacco smoke	Eosinophil Th2-high asthma, IgE-mediated	Bronchoconstriction Airway hyperresponsiveness ↑ Mucus production Subepithelial fibrosis	Upright, bipedal stance mirrors human posture to a greater extent than other quadruped species Greater overlap in airway transcriptome between rhesus macaques and humans Similarities in immune system compared to humans, many anti-human antibodies and reagents are cross-reactive with monkey antigens	Cost, Ethics of research involving nonhuman primates
Naturally Occurring Models
Cat [205]	Dust/dust mites, Smoke (tobacco or fireplace), Pollen, Household chemicals	Eosinophils Th2-high asthma, IgE-mediated	Bronchoconstriction Airway remodeling	Indoor client-owned cats have similar environmental exposures to their owners Feline patients (no per diem fee) represent a recruitable population for testing novel therapeutics	Limited species-specific assays and antibodies
Horse [289,290]	Organic dust, Lipopolysaccharide, Fungal spores (e.g., Aspergillus sp.), Pollen	Neutrophils, Mast cells, Eosinophils, Mixed Th2-low and Th2-high asthma	Bronchoconstriction Airway hyperresponsiveness Airway remodeling Mucus production Bronchial angiogenesis	Spontaneous disease with similar triggers Pulmonary function testing can be performed at rest and during exercise Repeated collection of airway samples (large volume/cell recovery) and flexible bronchoscopy and long lifespan enable extended longitudinal studies (years ) Equine patients (no per diem fee) represent a recruitable population for testing novel therapeutics	Cost Limited species-specific assays and antibodies