Purpose of the Study
To evaluate the effectiveness of a new precombined aerosol combination of salbutamol and nedocromil in preventing exercise-induced bronchoconstriction compared with salbutamol alone.
Twelve subjects (9 boys and 3 girls) 7 to 13 years of age were recruited from the Paediatric Asthma Clinic at Perugia General Hospital. All had asthma as defined by the American Thoracic Society.
The study was a double-blind, double dummy, randomized, crossover, placebo-controlled study. Before study entry, a screening exercise test was performed. Those with a drop of 15% or more in forced expiratory volume in 1 second (FEV1) after the screening test entered the blinded part of the study. In random, cross-over, blinded order, each patient was tested on 3 separate days with different treatments given by metered dose inhaler before exercise: salbutamol 200 μg, salbutamol (200 μg)/nedocromil (4 mg), or placebo. Pulmonary function tests and heart rate were measured preexercise and at 1, 5, 10, 15, and 30 minutes postexercise. Complete protection was considered if the percentage drop in FEV1 was <10% while clinical protection was considered if the percentage decrease after receiving the drug was half or less the percentage fall in the screening challenge.
No significant difference was noted in the maximum percentage decrease in FEV1 on screening versus placebo days. Both active drugs were significantly more protective than placebo for percentage decrease in FEV1 (salbutamol: P < .001; salbutamol/nedocromil: P < .005), but there was no difference between the two medication formulations. Complete protection was obtained in 12/12 (100%), 10/12 (83%), and 1/12 (8%) of subjects for the salbutamol/nedocromil combination, salbutamol alone, and placebo, respectively. Clinical protection was obtained in 12/12 (100%), 11/12 (92%), and 2/12 (16%) of children by salbutamol/nedocromil, salbutamol alone, and placebo, respectively.P values were <.01 for salbutamol versus placebo and salbutamol/nedocromil versus placebo in both complete and clinical protection. P values were not significant for salbutamol versus salbutamol/nedocromil in both protection parameters.
Although inhaled β-agonists alone are highly efficacious in preventing exercise-induced bronchoconstriction, in a minority of patients a combined treatment with salbutamol and nedocromil may be advantageous. This group may represent a subgroup of subjects who release more, or different, mediators in response to exercise.
In theory it seems reasonable that combined medications such as salbutamol/nedocrimil may be of more benefit to selected patients with exercise-induced asthma and may help with compliance by decreasing the number of inhalers. Overall, however, the vast majority of patients appear adequately protected with salbutamol alone.