title: Mouse models of severe asthma: Understanding the mechanisms of steroid resistance, tissue remodelling and disease exacerbation.
abstract: Severe asthma has significant disease burden and results in high healthcare costs. While existing therapies are effective for the majority of asthma patients, treatments for individuals with severe asthma are often ineffective. Mouse models are useful to identify mechanisms underlying disease pathogenesis and for the preclinical assessment of new therapies. In fact, existing mouse models have contributed significantly to our understanding of allergic/eosinophilic phenotypes of asthma and facilitated the development of novel targeted therapies (e.g. anti-IL-5 and anti-IgE). These therapies are effective in relevant subsets of severe asthma patients. Unfortunately, non-allergic/non-eosinophilic asthma, steroid resistance and disease exacerbation remain areas of unmet clinical need. No mouse model encompasses all features of severe asthma. However, mouse models can provide insight into pathogenic pathways that are relevant to severe asthma. In this review, as examples, we highlight models relevant to understanding steroid resistance, chronic tissue remodelling and disease exacerbation. Although these models highlight the complexity of the immune pathways that may underlie severe asthma, they also provide insight into new potential therapeutic approaches.
authors.affiliation: Hunter Medical Research Institute, Priority Research Centre for Healthy Lungs, Newcastle, New South Wales, Australia.|Department of Microbiology and Immunology, School of Biomedical Sciences and Pharmacy, Faculty of Health, The University of Newcastle, Newcastle, New South Wales, Australia.
authors.forename: Steven
authors.identifier: 0000-0003-1240-5964
authors.initials: S
authors.lastname: Maltby
authors.affiliation: Hunter Medical Research Institute, Priority Research Centre for Healthy Lungs, Newcastle, New South Wales, Australia.|Department of Microbiology and Immunology, School of Biomedical Sciences and Pharmacy, Faculty of Health, The University of Newcastle, Newcastle, New South Wales, Australia.
authors.forename: Hock L
authors.initials: HL
authors.lastname: Tay
authors.affiliation: Hunter Medical Research Institute, Priority Research Centre for Healthy Lungs, Newcastle, New South Wales, Australia.|Department of Microbiology and Immunology, School of Biomedical Sciences and Pharmacy, Faculty of Health, The University of Newcastle, Newcastle, New South Wales, Australia.
authors.forename: Ming
authors.initials: M
authors.lastname: Yang
authors.affiliation: Hunter Medical Research Institute, Priority Research Centre for Healthy Lungs, Newcastle, New South Wales, Australia.|Department of Microbiology and Immunology, School of Biomedical Sciences and Pharmacy, Faculty of Health, The University of Newcastle, Newcastle, New South Wales, Australia.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Foster
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy / Q000276:immunology*; D004195:Disease Models, Animal; D018450:Disease Progression; D004802:Eosinophilia / Q000276:immunology*; D015848:Interleukin-5 / Q000037:antagonists & inhibitors; D051379:Mice; D010641:Phenotype; D012720:Severity of Illness Index
chemical_list: D000305:Adrenal Cortex Hormones; D000888:Antibodies, Anti-Idiotypic; D015848:Interleukin-5; C026408:anti-IgE antibodies
keywords: animal models; asthma; cell biology; cytokine; infection and inflammation