Exercise induced bronchoconstriction in athletes : influence of airway dehydration on bronchial hyper-responsiveness, epithelial injury and mast cell activation

• Main Author: Simpson, Andrew John
• Other Authors: Kippelen, P.
• Published: Brunel University 2015
• Subjects: 616.2; Asthma
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.675875

Exercise-induced bronchoconstriction (EIB) is the most common chronic medical condition affecting elite athletes; our understanding of the condition remains however incomplete. The over-arching aim of this thesis was therefore to investigate the underlying mechanisms of EIB in athletes. More specifically, via induced and inhibited bronchoconstriction, the influence of airway dehydration on bronchial hyper-responsiveness, epithelial injury and inflammatory mediator release was investigated. The results of our first experiment suggest that mild, whole-body dehydration does not affect the severity of EIB in athletes; however, signs of small airway dysfunction were noticed post-dehydration. The clinical and functional relevance of these findings are yet to be evaluated. Our next two experiments showed that administration of a single, therapeutic dose of the inhaled 32-agonist terbutaline before bronchial provocation challenge with dry air I) reduced the severity of bronchoconstriction by 54% in athletes, ii) attenuated the rise in urinary CC16 (a marker of airway epithelial injury), and iii) inhibited the release of the mast-cell derived broncho-constrictive mediator prostaglandin (PG)Dz. These results suggest that local airway dehydration and mast cell activation have a key role in hyperpnoea-induced epithelial injury and bronchoconstriction in athletes. In our final study, using a newly developed mass spectrometry platform, we identified for the first time that exercise provocation is not solely associated with the release of potent broncho-constrictive mediators, such as PGD2 and thromboxane, but also with the release of the broncho-protective mediators PGE2 and PGI2. These results of naturally occurring broncho-protective agents in response to exercise open exciting new opportunities for drug development for ElB.