Inflammatory Basis of Exercise-Induced Bronchoconstriction

Abstract

Purpose of the Study. To establish whether epithelial cell and mast cell activation with release of inflammatory mediators occurs during exercise-induced bronchoconstriction (EIB) and how histamine and cysteinyl leukotriene antagonists alter the airway events occurring during EIB. Study Population. There were 25 patients aged 14 to 55 whose asthma was being treated only with a short-acting β2 agonist as needed and who experienced a fall in FEV1 of ≥15% after an exercise challenge. Methods. Induced sputum was obtained at baseline and 30 minutes after exercise challenge. In a randomized, double-blind crossover study, the cysteinyl leukotriene antagonist montelukast and antihistamine loratadine, or 2 matched placebos, were administered for 2 doses before exercise challenge. Results. The percentage of columnar epithelial cells in induced sputum at baseline was associated with the severity of EIB. After exercise challenge, histamine, tryptase, and cysteinyl leukotrienes significantly increased in the airways, and there was an increase in columnar epithelial cells in the sputum. The concentration of columnar epithelial cells was associated with the levels of histamine and cysteinyl leukotrienes. Treatment with montelukast and loratadine inhibited the release of cysteinyl leukotrienes and histamine but did not inhibit the release of columnar epithelial cells. Conclusion. Epithelial cells, mast cell mediators, and eicosanoids are released into the airways during EIB, supporting an inflammatory basis for EIB. Reviewer Comments. “Exercise-induced asthma” (EIA) is not a disease unto itself. As the authors point out, “[EIB] is a highly prevalent condition present in approximately half of patients with asthma.” Most such patients, if questioned carefully, will admit to symptoms under circumstances other than exercise, such as with upper respiratory infections or irritant or allergen exposures. It is better to consider EIB a very common phenomenon among patients with asthma. There are 2 competing hypotheses of the mechanism of EIB: (1) loss of heat leads to vascular engorgement as the airways rewarm after exercise, initiating bronchoconstriction; and (2) loss of water leads to a change in airway osmolarity that initiates epithelial cell and mast cell activation, leading to the release of inflammatory mediators in the airways that cause bronchoconstriction. These 2 theories are not necessarily mutually exclusive, and the former theory may apply more to the minority of patients who complain of symptoms only after they finish exercising (ie, when they stop breathing through an open mouth). If the number of desquamated epithelial cells before exercise is taken as an indication of the level of ongoing airway inflammation, this study would suggest that patients with worse baseline inflammation would have worse EIB. Also of note is that the combination of the cysteinyl leukotriene antagonist and antihistamine did not inhibit the desquamation. For patients in whom a short-acting β2 agonist does not prevent EIB or who have any abnormality on baseline spirometry, a truly and broadly antiinflammatory medication (ie, inhaled corticosteroids) would seem to be the most appropriate treatment for EIB.