Preclinical animal models of asthma and chronic obstructive pulmonary disease

Abstract

Animal models of disease serve a vital function in the search for novel therapeutic approaches. While these systems cannot replicate human disease, they can be used to mimic and investigate mechanisms believed to be central to disease pathogenesis. In this review, we discuss the most relevant and commonly used animal models for asthma and chronic obstructive pulmonary disease (COPD); specifically, models developed for the mouse, rat and guinea pig. Allergens, such as ovalbumin, can be used to induce an IgE-dependent response characterized by early- and late-phase bronchoconstriction, inflammation and airway hyper-responsiveness similar to what occurs in asthmatics. Similarly, elastase and cigarette smoke can be used to replicate steroid-insensitive and progressive inflammation, which leads to lung pathologies that are observed in COPD patients. We also discuss how these models are developing in new ways to more closely reflect the clinical disease. Unfortunately, these models have limitations due to differences in genetics, anatomy and physiology among the species, many of which we have highlighted; however, understanding these differences, careful characterization of these models and parallel in vitro or ex vivo studies using human and relevant animal tissues will overcome some of these issues. In spite of these limitations, as long as studies are designed and interpreted appropriately, in vivo models will continue to be vital for furthering our understanding of disease pathogenesis and for developing new therapies.

Keywords::

• allergen
• animal models
• asthma
• chronic obstructive pulmonary disease
• cigarette smoke
• COPD
• drug discovery
• inflammation
• lung

Acknowledgements

We would like to acknowledge Dr Mark Birrell and Mr David Hele for their helpful comments and Mrs Lucy Rollinson for her assistance in the preparation of this manuscript.

Financial & competing interests disclosure

C Stevenson is supported by a Capacity Building Award in Integrative Mammalian Biology funded by the BBSRC, BPS, HEFCE, KTN and MRC. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.