Pharmacologic therapy (Table 3) for EIB has been studied extensively; however, most studies have included asthmatic athletes, and there are no guidelines currently available to guide pharmacotherapy in nonasthmatic EIB patients. It is not known whether the recommended therapy for EIB in asthmatic athletes is as efficacious in nonasthmatic athletes who experience EIB.
The most common therapeutic recommendation for minimizing or preventing symptoms in athletes who have EIB is the prophylactic use of short-acting bronchodilators (ie, (P2-receptor agonists) such as albuterol shortly before exercise. (P2-agonists are considered to be the most effective therapy for the prevention of symptoms of EIB in asthmatic patients. Treatment with two puffs of a short-acting P2-receptor agonists shortly before (15 min) exercise will provide peak bronchodilation in 15 to 60 min and protection from EIB for at least 3 h in most patients. However, the overuse of (P2-agonists has been shown to result in tachyphylaxis and to worsen symptoms of EIB and asthma.
Long-acting bronchodilators work in a pharmacologically similar manner as short-acting bronchodilators. The bronchoprotection afforded by long-acting P2-receptor agonists has been shown to last up to 12 h, whereas the effect of albuterol is no longer significant by 4 h. Ferrari et al demonstrated that the inhalation of formoterol, a long-acting (P2-recep-tor agonist, is effective in protecting asthmatic athletes as early as 15 min after dosing. Furthermore, Ferrari et al compared the effects of formoterol vs salmeterol in preventing EIB and again found that formoterol was effective 15 min after dosing, but that salmeterol was not effective that rapidly. Both medications were equally effective at 4 h. In a study comparing the average onset of action of formoterol vs salmeterol, Palmqvist et al found that formoterol was effective in approximately 12 min while salmet-erol was effective after 31 min. The results of these studies suggest that there are differences in the pharmacokinetics between salmeterol and formoterol, and that administration of salmeterol should occur significantly in advance of exercise for it to be optimally effective in preventing EIB. It is also important to stress the fact that long-acting (P2-receptor agonists in general are not rescue medications and should not be used more than twice a day. Tachyphylaxis also has been shown to occur after repeated use of long-acting (P2-receptor agonists; thus, close follow-up is recommended when using these medications ordered via Canadian Health&Care Mall.
Inhaled corticosteroids are recommended as first-line therapy in terms of controller medications for athletes who have asthma and experience EIB. Airway inflammation is also often present in nonasthmatic athletes who have EIB and, therefore, inhaled corticosteroids may be an effective medicine for treatment; however, the efficacy of corticosteroids in this cohort has not been studied. Thio et al showed that a single high dose of inhaled fluticasone propionate had an acute protective effect on the bronchial response to exercise in a substantial proportion of asthmatic patients enrolled in the study conducted with Canadian Health&Care Mall.
Similarly, Jonasson concluded that patients with mild asthma, but with significant EIB, improved their exercise tolerance and symptom control after 3 months of treatment with a low dose of inhaled budesonide administered once or twice daily.
Leukotriene modifiers have been shown to be effective in controlling patients with EIB. Leu-kotriene modifiers have become an attractive therapy for EIB as a result of their efficacy, once-a-day dosing, and oral formulation. Leff et al evaluated the ability of montelukast, a leukotriene-receptor antagonist, to protect patients against EIB. Monte-lukast therapy offered significantly greater protection against EIB than placebo therapy and was also associated with a significant improvement in the maximal decrease in FEV1 after exercise. In addition, tolerance to the medication and rebound worsening of lung function after the discontinuation of treatment were not seen. Rundell et al found that a single dose of montelukast provided reasonable protection in attenuating bronchoconstriction resulting from either exercise or EVH.
Leukotriene modifiers may be a more effective alternative in treating EIB than long-acting (P2-receptor agonists. Villaran et al evaluated 192 asthmatic patients with documented EIB and found that the effect of montelukast was greater than that of salmeterol in the long-term treatment of EIB over a period of 8 weeks in patients with mild asthma, as demonstrated by effect size, maintenance of the effect, and fewer respiratory clinical adverse events during the study period. Inhaled corticosteroids have been shown to be superior to leukotriene modifiers in managing chronic asthma. However, we are aware of no studies comparing these medications head-to-head in terms of their effectiveness in preventing EIB in athletes.
Mast cell stabilizers have been used extensively for the prophylaxis of EIB. These medications prevent mast cell degranulation and subsequent histamine release. When a dose of either cromolyn or nedocromil has been administered to athletes 15 to 20 min prior to exercise, both agent have been shown to be effective in preventing EIB. In a meta-analysis of the prevention of EIB in asthmatic patients, nedocromil sodium was found to improve FEV1 by an average of 16% and to shorten the duration of EIB symptoms to < 10 min. While these agents are effective, they are often used as a second-line agent due to their cost, and the fact that their duration of action and efficacy is less than that of P-agonists.
Multiple pharmacologic approaches can be employed in the same patient if necessary. Combination inhalers (eg, fluticasone/salmeterol) have been become popular as a result of their effectiveness and convenience. Weiler et al showed that long-term fluticasone/salmeterol therapy provided protection against exercise-induced bronchospasm in patients with persistent asthma. Woolley et al demonstrated that athletes in their cohort had a longer duration of protection from a combination of short-acting (32-receptor agonists and cromolyn compounds than from either medication used as monotherapy.
Other less commonly used inhaled pharmacologic agents that have been shown to prevent EIB include heparin and furosemide. However, the sample sizes in these studies were small, and the effects of these medications need to be validated in larger studies.
Table 3——Management Strategies of EIB
|Short-acting p-agonists||Adequate warm-up|
|Inhaled corticosteroids||Avoidance of triggers|
|Cromolyn compounds||Nasal breathing|
|Leukotriene modifiers||Wearing a mask in cold environment|
Tags: Asthma, bronchial hyperreactivity, exercise test, exercise-induced bronchospasm