Animal models of asthma: utility and limitations

Abstract

Clinical studies in asthma are not able to clear up all aspects of disease pathophysiology. Animal models have been developed to better understand these mechanisms and to evaluate both safety and efficacy of therapies before starting clinical trials. Several species of animals have been used in experimental models of asthma, such as Drosophila, rats, guinea pigs, cats, dogs, pigs, primates and equines. However, the most common species studied in the last two decades is mice, particularly BALB/c. Animal models of asthma try to mimic the pathophysiology of human disease. They classically include two phases: sensitization and challenge. Sensitization is traditionally performed by intraperitoneal and subcutaneous routes, but intranasal instillation of allergens has been increasingly used because human asthma is induced by inhalation of allergens. Challenges with allergens are performed through aerosol, intranasal or intratracheal instillation. However, few studies have compared different routes of sensitization and challenge. The causative allergen is another important issue in developing a good animal model. Despite being more traditional and leading to intense inflammation, ovalbumin has been replaced by aeroallergens, such as house dust mites, to use the allergens that cause human disease. Finally, researchers should define outcomes to be evaluated, such as serum-specific antibodies, airway hyperresponsiveness, inflammation and remodeling. The present review analyzes the animal models of asthma, assessing differences between species, allergens and routes of allergen administration.

G Protein–Coupled Receptors in Asthma Therapy: Pharmacology and Drug Action

“…Numerous animal models have been used to decipher various aspects of asthma pathophysiology, identify novel therapeutic targets, and test the efficacy of emerging therapies. Reports using models of Drosophila melanogaster (Roeder et al, 2009), canines (Padrid, 1992;Zosky and Sly, 2007), felines (Norris Reinero et al, 2004), rats (Kucharewicz et al, 2008), equines (Herszberg et al, 2006), sheep (Zosky and Sly, 2007;Scheerlinck et al, 2008), guinea pigs (Canning and Chou, 2008), nonhuman primates (Coffman and Hessel, 2005), and mice (Zosky and Sly, 2007;Nials and Uddin, 2008;Chapman et al, 2014;Aun et al, 2017) can be found in the literature. Although felines and equines spontaneously display asthma-like symptoms, 1% of cats develop eosinophilic bronchitis (Padrid, 2000;Aun et al, 2017), and horses develop heaves resulting from moldy hay (Barton and Gehlen, 2016); they are not financially viable models for asthma research.…”

Optimising experimental research in respiratory diseases: an ERS statement

“…In addition, the importance of obesity, age (neonatal and aged mice) and the microbiome in asthma onset and progression should be taken into account (table 9) [104,105]. The advantages and disadvantages of specific animal species in experimental models of asthma should be considered [106]; e.g. for investigating early and late asthmatic responses, neuronal aspects and cough, including activity of β2-bronchodilators and pharmacological studies, research in the guinea pig can provide important insights [107][108][109].…”

Perinatal nicotine with or without early life influenza infection leads to lung dysfunction with age.

“…Smoking cessation is the most effective means for reducing disease progression, although, many smokers with COPD are undiagnosed and thus unaware that their habit is harming them drastically (28). Once a patient is diagnosed with COPD, treatment is based on the progression of the disease state as determined by spirometry and whether the symptoms are intermittent or persistent ( (110). Asthma is not a murine disease and thus mice must become sensitized to increase allergen immunogenicity, which is followed by an allergen challenge (110).…”

“…Once a patient is diagnosed with COPD, treatment is based on the progression of the disease state as determined by spirometry and whether the symptoms are intermittent or persistent ( (110). Asthma is not a murine disease and thus mice must become sensitized to increase allergen immunogenicity, which is followed by an allergen challenge (110).…”

“…IgE, epithelial hypertrophy, airway remodeling, TH2 immune response upregulation, and most importantly, ARH (110).…”