The allergic mouse model of asthma: normal smooth muscle in an abnormal lung?

TLDR

Mice with allergically inflamed airways are widely used as animal models of asthma, yet their relevance to human asthma remains unclear. The study aimed to examine the time course of respiratory input impedance changes during induced bronchoconstriction in BALB/c mice sensitized and challenged with ovalbumin. This was achieved by measuring respiratory input impedance over time during induced bronchoconstriction in these sensitized mice. Bronchoconstriction in mice causes complete closure of large lung regions, especially when allergically inflamed, and the resulting hyperresponsiveness can be fully explained by airway mucosa thickening and increased airway closure propensity without additional smooth muscle shortening, suggesting that therapies targeting surface tension at the air‑liquid interface may benefit certain asthma phenotypes.

Abstract

Mice with allergically inflamed airways are widely used as animal models of asthma, but their relevance for human asthma is not understood. We, therefore, examined the time course of changes in respiratory input impedance during induced bronchoconstriction in BALB/c mice sensitized and challenged with ovalbumin. Our results indicate that bronchoconstriction in mice is accompanied by complete closure of substantial regions of the lung and that closure increases markedly when the lungs are allergically inflamed. With the aid of an anatomically accurate computational model of the mouse lung, we show that the hyperresponsiveness of mice with allergically inflamed airways can be explained entirely by a thickening of the airway mucosa and an increased propensity of the airways to close, without the involvement of any increase in the degree of airway smooth muscle shortening. This has implications for the pathophysiology of asthma and suggests that at least some types of asthma may benefit from therapies aimed at manipulating surface tension at the air-liquid interface in the lungs.