Airway Remodeling in Asthma

Scope

The aim of this program is to develop and characterise a large animal model for airway remodeling during chronic asthma.

Remodeling changes in the airways of sheep after chronic challenge with HDM (right), compared with unchallenged (left) lung lobe of the same sheep.

Research outline

Airway remodeling in a sheep model for chronic allergic asthma

Ken Snibson, Rob Bischof* & Els Meeusen*
* Department of Physiology, Monash University
In collaboration with Dr R. Slocombe, School of Veterinary Science, Werribee, University of Melbourne.

Remodeling of structural and functional tissues in the lungs is a significant morbidity factor for chronic asthmatics. Sheep are well suited for studying the mechanisms that underlie airway remodeling as their lungs have similar morphological and physiological characteristics to human lungs. We have developed a chronic asthma model using sheep to examine remodeling of lung tissues during persistent allergic inflammation. Repeated challenges with house dust mite to sheep lungs induces many of the distinguishing features of remodeling in asthmatics. These include increased collagen deposition and airway smooth muscle bulk, mast cell and goblet cell hyperplasia and epithelial cell hypertrophy.

The sheep model we have developed for the study of airway remodeling is well placed to measure and correlate the physiological changes associated with the long-term decline in lung function in chronic asthmatics with the structural changes observed in the remodeling of lung tissues.

Key publications

• Snibson KJ, Bischof RJ, Slocombe RF & Meeusen ENT (2005). Airway remodeling and inflammation in sheep lungs after chronic airway challenge with house dust mite. Clin Exp Allergy 35:146-152.
• Bischof RJ, Snibson K, Shaw RJ and Meeusen ENT (2003). Induction of allergic inflammation in the lungs of sensitized sheep after local challenge with house dust mite. Clinical and Experimental Allergy 33:367-375.
• Snibson KJ, Bischof RJ, Slocombe RF, Meeusen EN (2002) A novel model for studying chronic inflammation and airway remodeling mechanisms. Proceedings of The Australasian Society of Immunology, Brisbane