Role of leukotrienes in exercise-induced bronchoconstriction

Exercise-induced bronchoconstriction (EIB) refers to acute airflow obstruction that is triggered by a period of physical exertion. EIB occurs mainly in individuals with other features of asthma but is especially prominent in a subset of asthmatics with pronounced indirect airway hyperresponsiveness. Leukotrienes (LTs) play a critical role in the pathophysiology of EIB. Asthmatics who are susceptible to EIB have increased levels of cysteinyl LTs (cysLTs [ie, LTs C4, D4, and E4]) in induced sputum and exhaled breath condensate. Exercise challenge in individuals susceptible to this disorder initiates the sustained increase in cysLTs in the airways and an increase in the ratio of cysLTs to prostaglandin E2. The effects of cysLTs leading to secreted mucin release and smooth muscle constriction may be mediated in part through activation of sensory nerves. Therapies that block cysLT production or the cysLT1 receptor effectively reduce the severity of EIB.