Am. J. Respir. Crit. Care Med., Volume 163, Number 6, May 2001, 1420-1425

Fexofenadine Decreases Sensitivity to and Montelukast Improves Recovery from Inhaled Mannitol

JOHN D. BRANNAN, SANDRA D. ANDERSON, KERRY GOMES, GREGORY G. KING, H. KIM CHAN, and J. PAUL SEALE

Department of Respiratory Medicine, Royal Prince Alfred Hospital, Camperdown, NSW, Australia; and Institute of Respiratory Medicine, and Departments of Pharmacy and Pharmacology, University of Sydney, Sydney, NSW, Austraila

We studied, separately, the effects of the histamine antagonist, fexofenadine hydrochloride, and the leukotriene antagonist, montelukast sodium, and their placebos on airway sensitivity to and recovery from inhaled mannitol in 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 fexofenadine 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 mannitol 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). However, recovery of FEV₁ to baseline was faster with montelukast, with the area under the percent reduction FEV₁-versus-time curve reduced (220 ± 121% change·min) compared with placebo (513 ± 182% change·min) (p < 0.001). We conclude that whereas histamine is important for the initial airway response, leukotrienes are important in sustaining the airway response to inhaled mannitol.

This article has been cited by other articles:

				P. A. Munoz, F. P. Gomez, H. A. Manrique, J. Roca, J. A. Barbera, I. H. Young, S. D. Anderson, and R. Rodriguez-Roisin Pulmonary gas exchange response to exercise- and mannitol-induced bronchoconstriction in mild asthma J Appl Physiol, November 1, 2008; 105(5): 1477 - 1485. [Abstract] [Full Text] [PDF]

				J. D. Brannan, M. Gulliksson, S. D. Anderson, N. Chew, J. P. Seale, and M. Kumlin Inhibition of mast cell PGD2 release protects against mannitol-induced airway narrowing. Eur. Respir. J., May 1, 2006; 27(5): 944 - 950. [Abstract] [Full Text] [PDF]

				T. S. Hallstrand, M. W. Moody, M. M. Wurfel, L. B. Schwartz, W. R. Henderson Jr., and M. L. Aitken Inflammatory Basis of Exercise-induced Bronchoconstriction Am. J. Respir. Crit. Care Med., September 15, 2005; 172(6): 679 - 686. [Abstract] [Full Text] [PDF]

				G. P. Currie and D. K.C. Lee Beneficial Antiinflammatory Effects of Leukotriene Receptor Antagonists in Asthma Chest, April 1, 2005; 127(4): 1458 - 1458. [Full Text] [PDF]

				I.E. Zuhlke, F. Kanniess, K. Richter, D. Nielsen-Gode, S. Bohme, R.A. Jorres, and H. Magnussen Montelukast attenuates the airway response to hypertonic saline in moderate-to-severe COPD Eur. Respir. J., December 1, 2003; 22(6): 926 - 930. [Abstract] [Full Text] [PDF]

				J.D. Brannan, M. Gulliksson, S.D. Anderson, N. Chew, and M. Kumlin Evidence of mast cell activation and leukotriene release after mannitol inhalation Eur. Respir. J., September 1, 2003; 22(3): 491 - 496. [Abstract] [Full Text] [PDF]

				G.F. Joos and B. O'Connor Indirect airway challenges Eur. Respir. J., June 1, 2003; 21(6): 1050 - 1068. [Abstract] [Full Text] [PDF]

				M. J. TOBIN Asthma, Airway Biology, and Nasal Disorders in AJRCCM 2001 Am. J. Respir. Crit. Care Med., March 1, 2002; 165(5): 598 - 618. [Full Text] [PDF]