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2624968 
Journal Article 
Abstract 
Increased baseline airway resistance and smooth muscle content in sheep exposed to repeated challenges of house dust mite 
Koumoundouros, E; Van Der Velden, JL; Bischof, RJ; Mareels, IMY; Snibson, KJ 
2010 
Yes 
American Journal of Respiratory and Critical Care Medicine
ISSN: 1073-449X
EISSN: 1535-4970 
181 
A3963 
English 
WOS:000208771003309 
is part of a larger document 3452678 Proceedings of the American Thoracic Society 2010 International Conference, May 14-19, 2010, New Orleans
Over a lifetime, it is well established that asthmatics have accelerated declines in FEV1, when compared to non-asthmatics. The lung function decline in asthmatics has been associated with long-term structural changes to airway tissue architecture (airway remodeling). These changes include increased airway smooth muscle (ASM) content, neovascularisation, and increased sub-epithelial collagen deposition.

Aim: Here, we assess the relationship between ASM content and baseline lung function in a sheep model of asthma.

Methods: A group of sheep were sensitized to allergen via three fortnightly sc injections of house dust mite (HDM). Sheep with high levels of serum HDM-IgE were exposed to weekly pulmonary challenges of HDM over an 18 month period. The sheep were monitored for baseline resistance throughout the challenge regime. At autopsy, the lungs from all sheep were inflation-fixed with paraformaldehyde at 20 cmH2O pressure. Airway tissues were sectioned and stained with Masson’s trichrome for morphometric analyses of smooth muscle and collagen content.

Results: There was a significant increase in baseline resistance in HDM-challenged sheep over the lengthy period of repeated HDM challenges. The HDM-challenged sheep (n = 9) had significantly higher increases in baseline resistances compared to the control sheep (n = 6, 435 ± 275 % and 110 ± 120 % respectively, p<0.01). Accompanying these changes were significant increases in the percentage area of smooth muscle in generation 8 bronchioles of HDM challenged sheep (3.5 ± 3.0 % and 1.5 ± 1.0 % respectively, p<0.05) and in generation 6 bronchioles (3.5 ± 1.5 % and 2.0 ± 1.0 % respectively, p<0.05) when compared to equivalent airways in control sheep. There were no significant differences in airway collagen content between HDM-challenged and control sheep.

Conclusion: In this large animal model of chronic asthma, the long-term decline in baseline lung function is associated with increased content of airway smooth muscle. 
American Thoracic Society 2010 International Conference 
New Orleans, LA 
May 14-19, 2010