Am. J. Respir. Crit. Care Med., Volume 156, Number 6, December 1997, 1731-1737

Comparison of Salmeterol and Albuterol-induced Bronchoprotection Against Adenosine Monophosphate and Histamine in Mild Asthma

DAVID A. TAYLOR, MARIANNE W. JENSEN, SARAH L. AIKMAN, JEANETTE G. HARRIS, PETER J. BARNES, and BRIAN J. O'CONNOR

Royal Brompton Clinical Studies Unit, Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College School of Medicine, London, United Kingdom

Short-acting ₂-agonists provide greater protection to bronchoconstriction induced by adenosine-5'-monophosphate (AMP) than does methacholine. Because AMP produces bronchoconstriction through release of mediators from mast cells, and methacholine directly constricts airway smooth muscle, this suggests that ₂-agonists stabilize mast cells in vivo. This in vivo property has not been demonstrated with long-acting ₂-agonists. We undertook two double-blind, randomized, crossover, placebo-controlled studies to investigate the effects of salmeterol and albuterol on airway responsiveness (AR) to AMP and histamine in patients with mild asthma. In the first study, 19 patients attended on four occasions to inhale salmeterol 50 µg or placebo 2 h before challenge with AMP or histamine. In the second study 16 patients (13 of whom had participated in the first study) were studied in a similar fashion but inhaled albuterol 400 µg or placebo 30 min prior to challenge. Salmeterol reduced AR to AMP and histamine by 3.4 ± 0.3 and 3.9 ± 0.3 doubling doses, respectively (NS). In contrast, albuterol demonstrated a greater protective effect on AMP than on histamine, reducing AR by 5.1 ± 0.3 and 3.8 ± 0.2 doubling doses, respectively (p < 0.005). Thus, in contrast to albuterol, salmeterol did not demonstrate mast-cell stabilizing properties in vivo at a time corresponding to maximal bronchodilatation. These findings might be explained by the unique pharmacologic profile of salmeterol in combination with the differential ₂-adrenoceptor pharmacology of bronchial mast cells and bronchial smooth muscle.

This article has been cited by other articles:

				L. Prieto, V. Gutierrez, V. Torres, S. Uixera, and J. Marin Effect of Salmeterol on Seasonal Changes in Airway Responsiveness and Exhaled Nitric Oxide in Pollen-Sensitive Asthmatic Subjects* Chest, September 1, 2002; 122(3): 798 - 805. [Abstract] [Full Text] [PDF]

				R.I. Ketchell, M.W. Jensen, D. Spina, and B.J. O'Connor Dose-related effects of formoterol on airway responsiveness to adenosine 5'-monophosphate and histamine Eur. Respir. J., April 1, 2002; 19(4): 611 - 616. [Abstract] [Full Text] [PDF]

				P.J. Barnes Scientific rationale for inhaled combination therapy with long-acting {beta}2-agonists and corticosteroids Eur. Respir. J., January 1, 2002; 19(1): 182 - 191. [Abstract] [Full Text] [PDF]

				J. C. KIPS and R. A. PAUWELS Long-acting Inhaled beta 2-Agonist Therapy in Asthma Am. J. Respir. Crit. Care Med., September 15, 2001; 164(6): 923 - 932. [Full Text] [PDF]

				H.J. van der Woude and R. Aalbers Unaltered perception of dyspnoea during treatment with long-acting {beta}2-agonists Eur. Respir. J., August 1, 2001; 18(2): 269 - 271. [Abstract] [Full Text] [PDF]

				S. G. M. Cloosterman, I. D. Bijl-Hofland, C. L. A. van Herwaarden, R. P. Akkermans, F. J. J. van den Elshout, H. T. M. Folgering, and C. P. van Schayck A Placebo-Controlled Clinical Trial of Regular Monotherapy With Short-Acting and Long-Acting {beta}2-Agonists in Allergic Asthmatic Patients Chest, May 1, 2001; 119(5): 1306 - 1315. [Abstract] [Full Text] [PDF]

				D.C. Grootendorst, P.J. Sterk, and H.G.M. Heijerman Effect of oral prednisolone on the bronchoprotective effect of formoterol in patients with persistent asthma Eur. Respir. J., March 1, 2001; 17(3): 374 - 379. [Abstract] [Full Text] [PDF]

				R. E. ALDRIDGE, R. J. HANCOX, D. ROBIN TAYLOR, J. O. COWAN, M. C. WINN, C. M. FRAMPTON, and G. IAN TOWN Effects of Terbutaline and Budesonide on Sputum Cells and Bronchial Hyperresponsiveness In Asthma Am. J. Respir. Crit. Care Med., May 1, 2000; 161(5): 1459 - 1464. [Abstract] [Full Text]

				O. J. Dempsey, A. M. Wilson, E. J. Sims, C. Mistry, and B. J. Lipworth Additive Bronchoprotective and Bronchodilator Effects With Single Doses of Salmeterol and Montelukast in Asthmatic Patients Receiving Inhaled Corticosteroids Chest, April 1, 2000; 117(4): 950 - 953. [Abstract] [Full Text] [PDF]

				G. P. ANDERSON Interactions between Corticosteroids and beta -Adrenergic Agonists in Asthma Disease Induction, Progression, and Exacerbation Am. J. Respir. Crit. Care Med., March 1, 2000; 161(3): S188 - 196. [Full Text] [PDF]

				J. A. NIGHTINGALE, D. F. ROGERS, and P. J. BARNES Differential Effect of Formoterol on Adenosine Monophosphate and Histamine Reactivity in Asthma Am. J. Respir. Crit. Care Med., June 1, 1999; 159(6): 1786 - 1790. [Abstract] [Full Text]