Pathophysiology of Exercise-induced bronchoconstriction (EIB)

Pathophysiology of Exercise-induced bronchoconstriction (EIB) Exercise-induced bronchoconstriction (EIB) is defined as a transient narrowing of the airways after (vigorous) exercise and occurs in 10 to 15% of the general population with an even higher prevalence in athletes and patients with asthma. EIB is a form of airway hyperresponsiveness (AHR) whereby the airways have the tendency to constrict more easily and more forcefully in response to a bronchoconstrictor stimulus (1,2) and which may result in breathlessness, cough, wheezing, chest tightness, and mucus production (3). However, respiratory symptoms after vigorous exercise are neither sensitive nor specific for the presence of EIB and a formal diagnosis is often based on direct (histamine) or indirect (hyperventilation, exercise) bronchoprovocation tests that identify AHR consistent with EIB (3). There are currently no biomarkers that may predict the presence of EIB. The exact mechanisms underlying EIB have also insufficiently been elucidated. Dehydration and cooling (the osmotic and thermal hypothesis) are proposed to explain the pathogenesis of EIB. Current treatment of EIB is similar to the treatment of asthma. We hypothesize that intense physical activity in combination with environmental exposure such as air pollution and/or cold air exposure may induce epithelial dysfunction (with secretion of alarmins) and the activation of the innate immune system and leukocyte recruitment. In this project, (1) we want to further investigate the role of biomarkers (in serum and sputum) in the diagnosis of EIB in healthy subjects and athletes (w/wo asthma), (2) we want to unravel the pathophysiological mechanisms of EIB induced by exercising when exposed to cold air with/without air pollution, both in an animal model as well as in human subjects and (3) we want to evaluate the effect of targeted treatment (e.g. with azithromycin, anti-IL-13, anti-TSLP or other) in the prevention of EIB when exposed to cold air. References 1. Weiss JT, Dawson JC, Fraser C, Rybski W, Torres-Sánchez C, Bradley M, et al. Development and bioorthogonal activation of palladium-labile prodrugs of gemcitabine. J Med Chem. 2014 Jun 26;57(12):5395–404. 2. Boulet L-P, O’Byrne PM. Asthma and Exercise-Induced Bronchoconstriction in Athletes. N Engl J Med [Internet]. 2015 Feb 12 [cited 2021 May 31];372(7):641–8. Available from: https://www.nejm.org/doi/10.1056/NEJMra1407552 3. Pasnick SD, Carlos WG, Arunachalam A, Celestin FM, Parsons JP, Hallstrand TS, et al. Exercise-induced bronchoconstriction [Internet]. Vol. 11, Annals of the American Thoracic Society. American Thoracic Society; 2014 [cited 2021 May 31]. p. 1651–2. Available from: http://www.thoracic.org/