Sodium Cromoglycate Alone and in Combination With Montelukast on the Airway Response to Mannitol in Asthmatic Subjects

Abstract

Background. Mannitol, inhaled as a dry powder, is used for bronchial provocation to identify bronchial hyperresponsiveness. Bronchoconstriction is associated with an increase in urinary excretion of the metabolites of prostaglandin D₂ and leukotriene E₄. Sodium cromoglycate provides about 60% protection against the fall in forced expiratory volume in one second (FEV₁) provoked by inhaled mannitol and appears to do so by inhibiting the release of prostaglandin D₂ but not leukotriene E₄.The leukotriene receptor antagonist montelukast does not alter sensitivity to mannitol, as measured by the provoking dose to cause a 15% fall in FEV₁ to mannitol, but it significantly enhances recovery from the bronchoconstriction provoked by mannitol. Objective. The authors proposed that the combination of these two drugs would be superior to sodium cromoglycate alone and result in greater protection from the bronchoconstriction provoked by mannitol. Methods. The % fall in FEV₁ from baseline and the area under the 30-min FEV₁ time curve and time to recover to 95% baseline FEV₁ were used to express protection from 40 mg sodium cromoglycate alone, and in combination with 10 mg montelukast, in subjects with asthma. Mannitol was inhaled in the dose that caused a 20% fall in FEV₁ on the screening day. The prechallenge medications were randomised on the 3 treatment days and were (1) placebo sodium cromoglycate and placebo montelukast; (2) sodium cromoglycate and placebo montelukast; and (3) sodium cromoglycate and montelukast. Results. The protection by sodium cromoglycate alone on the % fall in FEV₁ was 64.4% ± 21.0% versus 65.8% ± 62.8% (p = NS) on the combination. The protection on the area under the 30-min FEV₁ time curve for sodium cromoglycate was 81.8% ± 14.0% (p <.04) and 89.3% ± 9.8% for the combination (p <.001) compared with placebo. Recovery to 95% baseline FEV₁ by 5/10 min occurred in 58%/66% of subjects on sodium cromoglycate and 66%/83% on the combination compared with 0%/0% on placebo. Conclusion. The addition of montelukast to sodium cromoglycate provided only a small additional benefit against the airway response to mannitol.