Fexofenadine decreases sensitivity to and montelukast improves recovery from inhaled mannitol

We studied, separately, the effects of the histamine antagonist, fexofenadi ne hydrochloride, and the leukotriene antagonist, montelukast sodium, and t heir placebos on airway sensitivity to and recovery from inhaled mannitol i n subjects with asthma. Two 180-mg doses of fexofenadine were taken over 14 h, and three 10-mg doses of montelukast over 36 h, with the last dose 5 h before challenge. Fexofenadine reduced sensitivity to mannitol and the PD15 was (mean [95% confidence interval] 138 [95, 201]) mg versus placebo (51 [ 25, 106] mg) (p < 0.001). The final percent reduction in FEV1 with fexofena dine was 20.8 +/- 5.4% and not different from placebo (20.1 +/- 5.3%) (p = 0.7); however, recovery was slower with fexofenadine compared with placebo (p < 0.001). By contrast, montelukast had no effect on sensitivity to manni tol and the PD15 was 71 [36, 144] mg versus placebo (87 [51, 148] mg (p = 0 .35). The total dose of mannitol delivered and the final percent reduction in FEV1 with montelukast were 171 +/- 142 mg and 21 +/- 4% and for placebo were 182 +/- 144 mg and 20 +/- 5% (p = 0.35, p = 0.59, respectively). Howev er, recovery of FEV1 to baseline was faster with montelukast, with the area under the percent reduction FEV1-versus-time curve reduced (220 +/- 121% c hange.min) compared with placebo (513 +/- 182% change.min) (p < 0.001). We conclude that whereas histamine is important for the initial airway respons e, leukotrienes are important in sustaining the airway response to inhaled mannitol.