Synergistic effect of disodium cromoglycate and reproterol in preventing exercise-induced asthma (EIA) in adults

Objective: To compare the protective effect of disodium cromoglycate (D), reproterol (R), their fixed drug combination (A) (Allergospasmin® N/Aarane® N), and placebo (P) in adults with EIA.

Methods: Double-blind, randomised, placebo-controlled, multi-centre, 4-fold crossover study. At each visit patients underwent a standardised treadmill test to provoke EIA. Patients with stable asthma, baseline FEV₁≥70% predicted and twice proven EIA (i.e. max. decrease in FEV₁ by ≥15% compared to baseline) were randomised to inhale either a dose of A, D, R, or P 20 minutes before exercise challenge. FEV₁ was measured before inhalation, prior to exercise, and at 5 to 60 minutes after exercise. A stepwise hierarchical statistical test was applied based on crossover ANOVA to prove superiority of A vs. R, A vs. D, A vs. P, R vs. P, and D vs. P.

Results: 61 patients (mean age 31±12 years, 32 males) completed the study. Statistical significance was obtained for all pairwise comparisons for both the maximal percentage decrease in FEV₁ after exercise and the baseline adjusted area under the FEV₁ curve.

Confirmatory test results (crossover ANOVA)
Comparison	Difference in % FEV1-fall	95%-confidence interval			p-value
A – R	-2.24	-4.10	to	-0.38	0.0193
A – D	-13.03	-16.15	to	-9.91	<0.0001
A – P	-19.13	-23.06	to	-15.20	<0.0001
R – P	-17.04	-21.39	to	-12.70	<0.0001
D – P	-6.10	-9.23	to	-2.97	0.0002

Conclusion: This study confirmed a synergistic effect of disodium cromoglycate and reproterol in their fixed drug combination in preventing exercise-induced asthma in adults.