In Applications, flexiVent

Due to the wide variety of strains available and ease of procurement and care, the mouse dominates in vivo pre-clinical research. Although a robust model, important divergences from human physiology makes translation from murine to clinical success challenging. Animal models such as rats, ferrets, non-human primates, and guinea pigs (GP), offer established alternatives which can more closely model human disease development or physiological responses.

In asthma disease modeling, the GP in particular displays a response that is better aligned with human asthma in comparison to mouse models1. For instance, mouse airway smooth muscles are unresponsive to important agonists such as histamine, and the majority of mast cells are present in the trachea and larger airways. GPs are histamine sensitive and show a more even distribution of mast cells throughout the lung parenchyma and alveoli as seen in humans2, 3.

In their recent publication, Ramos-Ramirez et al. seek to build upon previous studies that establish asthma development in GPs via OVA methodology4. In their work, they instead show that it is possible to use the more clinically relevant house-dust mite (HDM) installation method to develop an asthmatic phenotype in GPs. Animals are exposed once per week to HDM for 5 weeks to develop asthma. Confirmation of disease development is done via collecting respiratory parameters via whole-body plethysmography as well as highly detailed parameters via flexiVent methods. Characterization shows changes in general breathing metrics such as penH when animals encounter HDM; breathing patterns change by over 200% of baseline values within a half-hour of the challenge. This change is not found in non-allergic animals. Elevated respiratory resistance (Rn), tissue damping (G) and tissue elastance (H) are expected allergic responses to bronchoconstrictive agents and is found in the allergic but not control animals as well (see Figure 1 below).

asthma disease modeling guinea pig

Histological evaluation of inflammatory responses in BAL and mast cell responses are also outcomes of the study. The increase of IgE, IgG1, IgG2, and IL-13, greater numbers of mast cells, and other morphological changes in allergic and not control animals are consistent with the previous respiratory data results.

Overall, Dr. Ramos-Ramirez provides a guideline for the creation of clinically relevant asthma disease in an animal model that more closely mirrors the expression of asthma in humans. It also shows the additive power of using multiple methods to properly characterize an emerging model. Plethysmography, lung function outcomes and histological information all strengthen the basis of important studies and tackle disease research challenges in the future.

 

asthma disease modeling

 


 

References

1Adner et al. 2020. Back to the future: re-establishing guinea pig in vivo asthma models. Clinical Science; 134: 1219–1242. DOI:10.1042/CS20200394

2Bachelet et al. 1988. Distribution and histochemical characterization of pulmonary mast cells in the rat and guinea pig. Int Arch Allergy Appl Immunol; 87:225e9. DOI: 10.1159/000234677

3Lei et al. 2013. Insights into mast cell functions in asthma using mouse models. Pulmonary Pharmacology & Therapeutics; 26: 532e539.

4Ramos-Ramírez et al. 2020. A new house dust mite-driven and mast cell-activated model of asthma in the guinea pig. Clin Exp Allergy; 00:1–12. DOI: 10.1111/cea.13713. DOI: 10.1016/j.pupt.2013.03.019

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