The effect of amiloride on the airway response to metabisulphite in asthma: a negative report

Abstract

Frusemide, a loop diuretic, has been shown to potently inhibit several indirect bronchoconstrictor challenges in asthma. The mechanism by which nebulized frusemide protects against indirect bronchoconstrictor stimuli in asthma is not known. One mechanism could be related to inhibition of sodium transport. If this is the case, then amiloride, another inhibitor of sodium transport, should also protect against indirect bronchoconstrictor challenges. Ten subjects with mild asthma were administered either 10(-2) M amiloride or placebo, by nebulizer, in a double-blind crossover fashion. After each inhalation, forced expiratory volume in one second (FEV1) was recorded at 10 min intervals for 30 min, after which a metabisulphite challenge was performed. No significant difference in the response to metabisulphite was seen between placebo and amiloride treatment. The mean difference in provocative dose of metabisulphite producing a 20% fall in FEV1 (PD20) between placebo and amiloride was 1.015 doubling doses, 95% confidence interval (95% CI) -0.201 to 2.231, (p = 0.09). This result does not support the hypothesis that frusemide is acting to protect against bronchoconstrictor challenges in asthma by an effect on sodium transport.