Evidence for the roles of histamine and prostaglandins as mediators in exercise-induced asthma: the inhibitory effect of terfenadine and flurbiprofen alone and in combination

We investigated the effects of terfenadine, a histamine H1-receptor antagonist, and flurbiprofen, a cyclooxygenase inhibitor, on exercise-induced bronchoconstriction to assess the contribution of the mast cell products histamine and prostaglandins. Eight asthmatics were studied on 4 occasions with treadmill exercise tests. Terfenadine or placebo was administered 3 h prior to exercise, and flurbiprofen or placebo was administered 2 h prior to exercise, in a double-blind randomized trial. Airway calibre was determined by measurement of the forced expiratory volume in one second (FEV1) immediately prior to exercise challenge, and over 30 min post-exercise. Following placebo, the mean maximum percentage fall in FEV1 was 39%. This fell to 25% after terfenadine (p less than 0.05), 27% after flurbiprofen (p less than 0.05), and 30% after the active combination (NS). Analysis of the areas under curves of percentage falls in FEV1 over 30 min showed significant inhibition on all 3 active drug days (p less than 0.05). We conclude that histamine release and prostaglandin generation contribute to exercise-induced bronchoconstriction, although the interaction between these mediators appears complex.

This article has been cited by other articles:

				M. S. Davis, J. R. Malayer, L. Vandeventer, C. M. Royer, E. C. McKenzie, and K. K. Williamson Cold weather exercise and airway cytokine expression J Appl Physiol, June 1, 2005; 98(6): 2132 - 2136. [Abstract] [Full Text] [PDF]

				Z. Csoma, E. Huszar, E. Vizi, G. Vass, Z. Szabo, I. Herjavecz, M. Kollai, and I. Horvath Adenosine level in exhaled breath increases during exercise-induced bronchoconstriction Eur. Respir. J., May 1, 2005; 25(5): 873 - 878. [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]

				J. D. BRANNAN, S. D. ANDERSON, K. GOMES, G. G. KING, H. KIM CHAN, and J. PAUL SEALE Fexofenadine Decreases Sensitivity to and Montelukast Improves Recovery from Inhaled Mannitol Am. J. Respir. Crit. Care Med., May 1, 2001; 163(6): 1420 - 1425. [Abstract] [Full Text]

				H. W. F. M. De Gouw, S. J. Marshall-Partridge, H. Van der Veen, J. G. Van den Aardweg, P. S. Hiemstra, and P. J. Sterk Role of nitric oxide in the airway response to exercise in healthy and asthmatic subjects J Appl Physiol, February 1, 2001; 90(2): 586 - 592. [Abstract] [Full Text] [PDF]

				R. SUZUKI and A. N. FREED Heparin Inhibits Eicosanoid Metabolism and Hyperventilation-induced Bronchoconstriction in Dogs Am. J. Respir. Crit. Care Med., June 1, 2000; 161(6): 1850 - 1854. [Abstract] [Full Text]

				R. Crapo Guidelines for Methacholine and Exercise Challenge Testing---1999 . THIS OFFICIAL STATEMENT OF THE AMERICAN THORACIC SOCIETY WAS ADOPTED BY THE ATS BOARD OF DIRECTORS, JULY 1999 Am. J. Respir. Crit. Care Med., January 1, 2000; 161(1): 309 - 329. [Full Text]

				A. N. Freed, Y. Wang, S. McCulloch, T. Myers, and R. Suzuki Mucosal injury and eicosanoid kinetics during hyperventilation-induced bronchoconstriction J Appl Physiol, November 1, 1999; 87(5): 1724 - 1733. [Abstract] [Full Text] [PDF]

				H. Milgrom and L. M. Taussig Keeping Children With Exercise-induced Asthma Active Pediatrics, September 1, 1999; 104 (3): e38 - e38. [Abstract] [Full Text] [PDF]

				J. D. BRANNAN, H. KOSKELA, S. D. ANDERSON, and N. CHEW Responsiveness to Mannitol in Asthmatic Subjects with Exercise- and Hyperventilation-induced Asthma Am. J. Respir. Crit. Care Med., October 1, 1998; 158(4): 1120 - 1126. [Abstract] [Full Text] [PDF]

				A. N. Freed, V. Taskar, B. Schofield, and C. Omori Hyperventilation-induced airway injury and vascular leakage in dogs: effects of alpha 1-adrenergic agonists J Appl Physiol, December 1, 1997; 83(6): 1884 - 1889. [Abstract] [Full Text] [PDF]