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

Lung physiology during asthma

Scope

The aim of this program is to measure lung function in large animal models of respiratory diseases such as asthma.

Example of a bronchodilator treatment which opens airways after their closure by the allergen House Dust Mite (HDM).In this example, allergic sheep were given aerosols of HDM which resulted a steady increase in airway closure over 10 minute period. The sheep were then given a 2 minute aerosol of bronchodilator which completely reversed the allergen-induced airway closure for a period of up to 35 minutes.

Photographic example airway closure in allergic sheep after HDM allergen challenge. The photographs were taken through a fibre-optic bronchoscope immediately before (top), and 30 minutes after exposure to HDM (bottom)

Research outline

Physiology of asthmatic responses in sheep

Emmanuel Koumoundouros & Ken Snibson
We have developed Labview software to measure whole lung function in sheep models of respiratory disease. The lung function software allows us to measure disease symptoms such as airway twitchiness, and allergen–linked airway closure in allergic sheep. Our lung function protocols can be used on awake adult sheep as well as 6-8 week old lambs. The protocols are easily adaptable to other species of similar size (e.g. pigs and dogs).

We have also developed procedures to measure small airway function in lung segments of sheep. This involves using a wedged- bronchoscope procedure to measure the relative opening/closure of airways in specific lung regions. We also have the facility to make video clips of the opening and closing of these airways.

Sheep are well placed to test therapeutic procedures for a number of respiratory diseases due to the physiological and anatomical similarities between the sheep and human lung. The procedures we use to measure lung physiology can be repeatedly performed in conscious animals so that there are no confounding effects of anaesthetic agents. We anticipate that use of the sheep model will allow for the development of better-targeted drug designs and therapeutic intervention strategies for the control of a number of respiratory diseases, including asthma.

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)
  • Yen HH, Wee JL, Snibson KJ, Scheerlinck JP. Thoracic duct cannulation without thoracotomy in sheep: a method for accessing efferent lymph from the lung. Vet Immunol Immunopathol 2009;129(1-2):76-81.
  • 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 2435-8
  • 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
  • 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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