Center for Animal Biotechnology  CAB : Allergy/Asthma : Remodeling
 
CENTRE FOR ANIMAL BIOTECHNOLOGY  

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.(adapted from Snibson et a.,l 2005 CEA 35, 146).

Research outline

Airway remodeling in a sheep model for chronic allergic asthma

Ken Snibson (Lab Head), Joanne Van der Velden, Donna Barker, Garry Barcham & Emmanuel Koumoundouros

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

  • O’Reilly M, Hooper SB, Allison BJ, Flecknoe SJ, Snibson K, Harding R, Sozo F. Persistent bronchiolar remodeling following brief ventilation of the very immature ovine lung. Am J Physiol Lung Cell Mol Physiol 2009 (accepted August 11 2009)
  • Snibson K, De Matteo*, R, Koumoundouros E, Thompson B, Harding R. Lung function in developing lambs: is it affected by preterm birth? Journal of Applied Physiology 2009 (in press)
  • Bischof RJ, Bourke JE, Hirst SJ, Meeusen ENT, Snibson KJ, Van Der Velden. Measurement and Impact of Remodeling in the Lung: Airway Neovascularization in Asthma J. Proc Am Thorac Soc 2009
  • E. Koumoundouros, E., Snibson, K. J. and Mareels I M Y. Oesophageal techniques for deriving the lung dynamics of quietly breathing sheep 2008; IEEE Eng Med Biol Soc 1 2435-
  • Scheerlinck J., Snibson K., Bowles V. B., and Sutton P. Biomedical applications of sheep models: From asthma to vaccines. Trends Biotechnol 26(5): 259-66 2008
  • K Snibson and Richard Harding. Postnatal growth rate but not mild preterm birth influences airway structure in adult sheep challenged with House Dust Mite. Ex lung Research, 34 (2) 2008
  • Maritz, G., Probyn, M., De Matteo, R., Snibson, K., Harding R. Lung parenchyma at maturity is influenced by postnatal growth but not by moderately preterm birth in sheep. Neonatology 93 (1) 28-35 2008
  • Lofthouse, S., and Snibson, K., Claims of current corticosteroid patents for treating asthma, Recent Patents on Inflammation & Allergy Drug Discovery, 1 146-150 2007
  • Snibson, K. J., McMurtrie, L. S., Bischof, R. J., Koumoundouros, E., Cock, M., Harding, R.: Altered airway responsiveness in adult sheep born prematurely: Effects of allergen exposure. Ex lung Research 32 (6) 215-228 2006
  • Koumoundouros, E., Bischof, R. J., Meeusen, E. N., Mareels, I, M., Snibson, K., J.: Chronic airway disease: Deteriorating pulmonary function in sheep associated with repeated challenges of house dust mite. Ex lung Research 32 (7) 321-330 2006
  • Snibson, K. J., Bischof, R. J., Slocombe, R. F., and Meeusen, E. N.: Airway remodeling and inflammation in sheep lungs after chronic airway challenge with house dust mite. Clin Exp Allergy 35: (2) 146-152, 2005
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