Asthma

Selig, William M.; Chapman, Richard W.

doi:10.1007/978-3-0348-7775-6_5

Cited by 3 publications

(5 citation statements)

References 112 publications

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“…2) represents a significant advantage over mice as the link between the immunological events that drive acute physiological responses to allergen inhalation and the development of non‐specific AHR can be investigated. Rats are often used as a standard model for testing new drug therapies; in particular, the efficacy and toxicity of new drugs are often tested in rats before proceeding with clinical trials [81].…”

Section: Relative Merits Of Different Speciesmentioning

confidence: 99%

“…The guinea‐pig is the most widely used model and test system for contact hypersensitivity to chemical irritants and proteins. Guinea‐pigs are also often used as a ‘screening’ model for drugs that act through particular pathways that are seen to be relevant to human asthma and have been useful in the development of drugs such as corticosteroids and β 2 receptor‐agonists [81]. The response of isolated guinea‐pig airways to pharmacological agonists has been compared directly with humans to determine whether they are a good model for human airways [86].…”

Section: Relative Merits Of Different Speciesmentioning

confidence: 99%

“…From an immunological point of view, IgG1 seems to play a critical role in allergic responses in guinea‐pigs [81]. After repeated challenge guinea‐pigs also become tolerant to the allergen [90].…”

Section: Relative Merits Of Different Speciesmentioning

confidence: 99%

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Animal models of asthma

Zosky

Sly

2007

Clin Experimental Allergy

261

195

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SummaryAnimal models of asthma are a tool that allows studies to be conducted in the setting of an intact immune and respiratory system. These models have highlighted the importance of T-helper type 2 driven allergic responses in the progression of asthma and have been useful in the identification of potential drug targets for interventions involving allergic pathways. However, a number of drugs that have been shown to have some efficacy in animal models of asthma have shown little clinical benefit in human asthmatics. This may be due to a number of factors including the species of animal chosen and the methods used to induce an asthmatic phenotype in animals that do not normally develop a disease that could be characterized as asthma. The range of animal models available is vast, with the most popular models being rodents (inbred mice and rats) and guinea-pigs, which have the benefit of being easy to handle and being relatively cost effective compared with other models that are available. The recent advances in transgenic technology and the development of species-specific probes, particularly in mice, have allowed detailed mechanistic studies to be conducted. Despite these advances in technology, there are a number of issues with current animal models of asthma that must be recognized including the disparity in immunology and anatomy between these species and humans, the requirement for adjuvant during senitization in most models, the acute nature of the allergic response that is induced and the use of adult animals as the primary disease model. Some larger animal models using sheep and dogs have been developed that may address some of these issues but they also have different biology from humans in many ways and are extremely costly, with very few probes available for characterizing allergic responses in the airway in these species. As research in this area continues to expand, the relative merits and limitations of each model must be defined and understood in order to evaluate the information that is obtained from these models and to extrapolate these findings to humans so that effective drug therapies can be developed. Despite these issues, animal models have been, and will continue to be, vital in understanding the mechanisms that are involved in the development and progression of asthma.

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Section: Relative Merits Of Different Speciesmentioning

confidence: 99%

Section: Relative Merits Of Different Speciesmentioning

confidence: 99%

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Animal models of asthma

Zosky

Sly

2007

Clin Experimental Allergy

261

195

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“…(d) Sheep are currently the only animal model that have been shown to develop an EPR, LPR and AHR where there is a link between the acute allergic response and the development non-specific hyperresponsiveness. therapies; in particular, the efficacy and toxicity of new drugs are often tested in rats before proceeding with clinical trials [81].…”

Section: Ratsmentioning

confidence: 99%

“…The guinea-pig is the most widely used model and test system for contact hypersensitivity to chemical irritants and proteins. Guinea-pigs are also often used as a 'screening' model for drugs that act through particular pathways that are seen to be relevant to human asthma and have been useful in the development of drugs such as corticosteroids and b 2 receptor-agonists [81]. The response of isolated guinea-pig airways to pharmacological agonists has been compared directly with humans to determine whether they are a good model for human airways [86].…”

Section: Guinea-pigsmentioning

confidence: 99%

Animal models of asthma

Akkoç¹

2010

mpj

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Animal models of asthma are a tool that allows studies to be conducted in the setting of an intact immune and respiratory system. These models have highlighted the importance of T-helper type 2 driven allergic responses in the progression of asthma and have been useful in the identification of potential drug targets for interventions involving allergic pathways. However, a number of drugs that have been shown to have some efficacy in animal models of asthma have shown little clinical benefit in human asthmatics. This may be due to a number of factors including the species of animal chosen and the methods used to induce an asthmatic phenotype in animals that do not normally develop a disease that could be characterized as asthma. The range of animal models available is vast, with the most popular models being rodents (inbred mice and rats) and guinea-pigs, which have the benefit of being easy to handle and being relatively cost effective compared with other models that are available. The recent advances in transgenic technology and the development of species-specific probes, particularly in mice, have allowed detailed mechanistic studies to be conducted. Despite these advances in technology, there are a number of issues with current animal models of asthma that must be recognized including the disparity in immunology and anatomy between these species and humans, the requirement for adjuvant during senitization in most models, the acute nature of the allergic response that is induced and the use of adult animals as the primary disease model. Some larger animal models using sheep and dogs have been developed that may address some of these issues but they also have different biology from humans in many ways and are extremely costly, with very few probes available for characterizing allergic responses in the airway in these species. As research in this area continues to expand, the relative merits and limitations of each model must be defined and understood in order to evaluate the information that is obtained from these models and to extrapolate these findings to humans so that effective drug therapies can be developed. Despite these issues, animal models have been, and will continue to be, vital in understanding the mechanisms that are involved in the development and progression of asthma.

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Preclinical animal models of asthma and chronic obstructive pulmonary disease

Stevenson¹,

Belvisi²

2008

Expert Review of Respiratory Medicine

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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.

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Asthma

Cited by 3 publications

References 112 publications

Animal models of asthma

Animal models of asthma

Animal models of asthma

Preclinical animal models of asthma and chronic obstructive pulmonary disease

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