The effects of allergen on airway narrowing dynamics as assessed by a lung slice technique

¹ Firestone Institute for Respiratory Health, St. Joseph's Healthcare, Dept of Medicine, McMaster University, Hamilton, Ontario, Canada

^* To whom correspondence should be addressed. E-mail: janssenl{at}mcmaster.ca.

	Abstract

Asthma is characterized by airway hyperresponsiveness (AHR): excessive airway narrowing in response to a variety of stimuli. Certain previous comparisons between mouse strains have shown that increased velocity of airway narrowing correlates with baseline airway responsiveness. These data prompted the investigation into our own models of induced AHR to see whether airway narrowing dynamics correlated with in vivo responsiveness.

In an attempt to reproduce some of the features of asthma, BALB/c mice were sensitized and subjected to either brief or chronic periods of allergen exposure. Brief exposure involved 2 challenges with intranasal chicken egg ovalbumin (IN OVA). Chronic exposure involved 6 H two-day periods of IN OVA challenges, each separated by 12 days. Control mice received intranasal saline challenges. Outcomes included videomicrometry of lung slices (magnitude and velocity of airway narrowing), in vivo respiratory physiology measurements and histological staining with morphometric analysis.

We found that neither brief nor chronic allergen exposure resulted in greater airway narrowing and increased velocity as compared to saline controls. Structural changes in the airway such as goblet cell hyperplasia, subepithelial fibrosis, and increased contractile tissue were detected in mice chronically challenged with allergen.

We conclude that increased responsiveness to methacholine following allergen-challenge may not be due to an intrinsic change to the smooth muscle per se, but rather to other changes in the lung, ultimately manifesting as an increase in respiratory resistance.