EVIDENCE-BASED ANSWER
Inhaled short-acting beta-agonists (SABAs) are most effective in preventing exercise-induced bronchoconstriction, followed by inhaled mast cell stabilizers and anticholinergic agents (strength of recommendation [SOR]: A, multiple randomized control trials [RCTs]). Less evidence supports the use of leukotriene antagonists and inhaled corticosteroids, either individually or in combination (SOR: B). Underlying asthma, which commonly contributes to exercise-induced bronchoconstriction, should be diagnosed and controlled first (SOR: C).
CLINICAL COMMENTARY
Control the asthma and the need for pre-treatment often becomes unnecessary
Because truly isolated exercise-induced bronchoconstriction is uncommon in a nonasthmatic child, and because bronchospasm in a child during exercise more commonly indicates undiagnosed asthma, search for treatable asthma when a child wheezes with exercise. These children have sputum eosinophilia reflecting inflammation, and they are best served by addressing the underlying asthma with inhaled corticosteroids. Once the asthma is under control, their need for “the best pre-treatment” (a SABA) often becomes irrelevant. Ask the child whether he or she is having more shortness of breath and difficulty breathing after exercise than during exercise; this reveals those most likely to benefit from treatment.
Evidence summary
It is difficult to interpret studies on exercise-induced bronchoconstriction (the rather uncommon presence of exercise-induced bronchospasm in a nonasthmatic) and exercise-induced asthma (the more common situation of asthma worsened by exercise). Many studies include both types of patients.
A systematic review of 24 RCTs (of which 13 evaluated children) showed that SABAs, mast cell stabilizers, and anticholinergics provide a significant protective effect against exercise-induced bronchoconstriction with few adverse effects (the child subgroup analyses did not differ significantly from pooled results). Mast cell stabilizers were found less effective at attenuating bronchoconstriction than SABAs, with an average maximum decrease in the forced expiratory volume in 1 second (FEV1) of 11.9% compared with 4.6% for beta-agonists (child subgroup: weighted mean difference=7.3%; 95% confidence interval [CI], 3.9–10.7). Complete protection (defined in this study as maximum % decrease in FEV1 <15% post-exercise) and clinical protection (50% improvement over placebo) measures were included. Fewer children had complete protection (pooled: 66% vs 85%, odds ratio [OR]=0.3; 95% CI, 0.2–0.5) or clinical protection (pooled: 55% vs 77%, OR=0.4; 95% CI, 0.2–0.8).
Mast cell stabilizers were more effective than anticholinergic agents, with average maximum FEV1 decrease of 9.4% compared with 16.0% on anticholinergics (child subgroup: weighted mean difference=6.6%; 95% CI, 1.0–12.2). They also provided more individuals with complete protection (pooled: 73% vs 56%, OR=2.2; 95% CI, 1.3–3.7) and clinical protection (pooled: 73% vs 52%, OR=2.7; 95% CI, 1.1–6.4). Combining mast cell stabilizers with SABAs did not produce significant advantages in pulmonary function over SABAs alone. No significant subgroup differences were seen based on age, severity, or study quality.1
Another systematic review of 20 RCTs (15 studying children and 5 studying adults) with patients aged >6 years showed that 4 mg of nedocromil (Tilade) inhaled 15 to 60 minutes before exercise significantly reduced the severity and duration of exercise-induced bronchoconstriction compared with placebo. It had a greater effect on patients with severe exercise-induced bronchoconstriction (defined as an exercise-induced fall in lung function >30% from baseline).2
Eight RCTs (5 studying children) were included in a systematic review of patients aged >6 years that found no significant difference between nedocromil and cromoglycate with regards to decrease in FEV1, complete protection, clinical protection, or side effects.3