Are mice good physiological models of asthma

Background:Asthma is a chronic inflammatory disease of the lungs that is characterised by airway hyperresponsiveness (AHR) to bronchoconstricting stimuli. The physiological response of the asthmatic lung to inhaled allergen is often characterised by two distinct phases; an early phase response (EPR) within the first hour following exposure which subsides and a late phase response (LPR) that is more prolonged and may occur several hours later. Ideally, a model of asthma should be able to mimic all phases of the lung dysfunction associated with asthma. This study aimed to characterise the AHR, EPR and LPR in a commonly used mouse model of asthma.

Methods: Balb/c mice were systemically sensitised with ovalbumin (OVA) adsorbed onto Alum and challenged with 1, 3 or 6 OVA aerosols. Anaesthetised, tracheostomised and ventilated mice were assessed for AHR to inhaled methacholine (MCh) and EPR (to 5% OVA) using a modification of the low frequency forced oscillation technique (LFOT) in order to measure changes in airway resistance (Raw), tissue damping (G) and tissue elastance (H). The LPR was measured using a combination of plethysmography, to calculate lung volume, and LFOT. Bronchoalveolar lavage and serum were used to assess inflammation and antibodies respectively.

Results: AHR was induced by 1 or 6 OVA aerosols (Raw, G and H) with a limited response seen after 3 OVA aerosols (H only). EPRs required a minimum of 3 OVA aerosols. There was no evidence of a physiological late phase response in any of the groups.

Conclusion: The absence of a physiological late phase response and the lack of association between the EPR, LPR and AHR suggest that mice may not be appropriate models of an asthmatic phenotype.