Single-Dose Agents in the Prevention of Exercise-Induced Asthma

Abstract

Exercise-induced asthma (EIA) refers to the transient narrowing of the airways that occurs after vigorous exercise in 50-60% of patients with asthma. The need to condition the air inspired during exercise causes water to be lost from the airway surface, and this is thought to cause the release of inflammatory mediators (histamine, leukotrienes, and prostaglandins) from mast cells. EIA is associated with airway inflammation and its severity is markedly reduced following treatment with inhaled corticosteroids. Drugs that inhibit the release of mediators and drugs that inhibit their contractile effects are the most successful in inhibiting EIA. Single doses of short-acting beta(2)-adrenoceptor agonists, given as aerosols immediately before exercise, are very effective in the majority of patients with asthma, providing about 80% protection for up to 2 hours. Long-acting beta(2)-adrenoceptor agonists (LABAs) given in single doses can be effective for up to 12 hours when used intermittently, but tolerance to the protective effect occurs if they are taken daily. Drugs such as cromolyn sodium (sodium cromoglicate) and nedocromil given as aerosols are less effective than beta(2)-adrenoceptor agonists (beta(2)-agonists), providing 50-60% protection for only 1-2 hours, but they have some advantages. They do not induce tolerance, the aerosol dosage can be easily titrated for the individual, and the protective effect is immediate. Because they cause no significant adverse effects, multiple doses can be used in a day. Leukotriene receptor antagonists, such as montelukast and zafirlukast, are also used for the prevention of EIA and provide 50-60% protection for up to 24 hours when given as tablets. Tolerance to the protective effect does not develop with regular use. If breakthrough EIA occurs, a beta(2)-agonist can be used effectively for rescue medication. For those patients with more persistent symptoms, the use of a LABA in combination with an inhaled corticosteroid has raised a number of issues with respect to the choice of prophylactic treatment for EIA. The most important issue is the development of tolerance to the protective effect of a LABA such that extra treatment may be needed in the middle of a treatment period. Recommending extra doses of a beta(2)-agonist to control EIA is not advisable on the basis that multiple doses can enhance the severity of EIA, delay spontaneous recovery from bronchoconstriction, and enhance responses to other contractile stimuli. It is time to take into account the advantages and disadvantages of the different drugs available to prevent EIA and to recognize that there are some myths related to their use in EIA.