Investigating phenotypes of asthma in elite performance athletes
thesisposted on 02.12.2013, 12:36 by Neil Martin
There is a high prevalence of exercise induced bronchoconstriction (EIB) in elite athletes. It has been suggested that damage to the airway epithelium is the key effector process and that EIB in athletes is due to different mechanisms than exercise induced asthma. Whether testing strategies are as valid in athletes is controversial, but regulatory bodies continue to advocate the use of objective tests for diagnosis. How responses to these relate to sport, airways inflammation and to symptoms is unclear. We investigated responses to direct and indirect challenge tests and patterns of airways inflammation in symptomatic, international, endurance athletes. We focused on differences between pool-based and non-pool based endurance athletes to see if environmental factors played a significant role. We also investigated the interaction between airways epithelial and human lung mast cells in vitro and compared these between healthy and asthmatic donors. Of the challenges assessed, EVH related most closely to eosinophilic airways inflammation. The other tests examined did not relate particularly closely to each other, to eosinophilic airways inflammation or to markers of mast cell activation. There were no differences between pool and non-pool based athletes in terms of patterns of airways inflammation or airway mediator release in response to challenge testing. Pool-based athletes had significantly more airways hypereactivity when compared to non-pool based athletes. Those who test positive to EVH have more eosinophilic airways inflammation and more epithelial cells in their sputum than those who have a negative test. All indirect challenge tests increased the level of PGE2 in the airways compared to direct testing, even when corrected for degree of bronchoconstriction, suggesting epithelial stress. In vitro, an intact, healthy epithelium significantly suppresses constituitive and IgE mediated human lung mast cell histamine secretion. This suppression is attenuated in asthmatic or injured epithelium and is mediated by a small, labile, lipid soluble mediator. There is a significant heterogeneity in airways inflammation and airways hyperreactivity in elite performance athletes. The role of the epithelial cell in the development of EIB requires further exploration. The interaction between the epithelium and human lung mast cells needs to be fully elucidated and its potential for therapeutic manipulation further explored.