Hypersensitive Response in Asthmatic Guinea Pigs Following House Dust Mite Exposure

1. Experimental goal

The forced oscillation technique (FOT) using the flexiVent has been the gold standard for pulmonary function tests (PFTs) in small animal in vivo studies for many years^2,3. These FOT measurements provide detailed measurements of airway constriction using small amplitude oscillations. Common allergic models apply bronchoconstrictor challengers or bronchodilator challenges in isolation to investigate the severity of the disease. By adding an inhaled bronchodilator during a bronchoconstrictor challenge, the effectiveness of the recovery agent can be tested in a novel preclinical method. The study was validated by using a bronchodilator immediately prior to a bronchoconstrictor dose in mice using the flexiVent for aerosol delivery of both compounds and assessing allergic airway hyperresponsiveness.

2. Method

Balb/C mice were challenged with three 100µg house-dust mite extract instillations in the two weeks prior to measurements. Two days following the HDM instillations, mice were tracheostomized and connected to the flexiVent. The study ran four concentrations of methacholine (0, 10, 30, and 100mg/ml), and each was immediately preceded by either a saline or albuterol aerosol administration (0.083% in saline). The aerosol generation ran for ten seconds for both the albuterol/saline and the methacholine exposure at a duty cycle of 50%.

Airway mechanics were measured during the dose response, including the maximum using the flexiVent FX. The parameters measured were the total respiratory system resistance (Rrs), total respiratory system elastance (Ers), Newtonian resistance (Rn), tissue dampening (G), elastance (H) and airway hyperresponsiveness.

3. Select results

With the albuterol treated groups, their subjects saw significant attenuation of overall resistance, conducting airway resistance and tissue dampening, all indices of airway inflammation. The albuterol treatment also significantly blunted the overall lung stiffness. The tissue stiffness was reduced with the albuterol treatment, although not significantly.

4. Conclusion

Addison et al.’s study was able to demonstrate a method of testing the protective effects of bronchodilators in a traditional bronchoconstrictor study with the flexiVent system, a common measurement in allergic airway hyperresponsive models. As bronchoconstriction leads to wheezing and shortness of breath in asthmatic patients, testing bronchodilators protective effects on airway constriction is an important tool for the development of novel therapeutics.