JW de Jong, TW van der Mark, GH Koeter and DS Postma
Department of Pulmonology, University Hospital Groningen, The Netherlands.

Regular monotherapy with inhaled beta 2-agonists may lead to a temporary increase of airway obstruction and increase of airway responsiveness after cessation of treatment. We investigated whether anti-inflammatory therapy may affect these rebound phenomena. In a double-blind, placebo-controlled study, we assessed lung function (FEV1) and airway responsiveness (PC20 methacholine [PC20]) during and after cessation of 2 wk of regular treatment with placebo and low-dose (250 micrograms) and high-dose (1,000 micrograms) inhaled terbutaline three times daily. Patients with mild allergic asthma (means [+/- SD] age of 28.2 +/- 6.6 yr, mean FEV1% of 91.9 +/- 14.6%, and geometric mean PC20 of 0.25 mg/ml) were studied. One group (n = 16) was randomized to budesonide treatment, 400 micrograms three times daily; the other group (n = 14) to placebo. PC20 and FEV1 were measured 10, 14, 34, and 82 h after the last terbutaline or placebo inhalation. A different method of statistical analysis was used, in that measurements performed at 10, 14, and 34 h were expressed relative to 82 h values in each period as an area-under-the-curve (AUC) value. FEV1 did not significantly change during placebo and budesonide treatment. Mean PC20 and morning and evening peak expiratory flow were significantly higher during budesonide treatment (p < 0.01). PC20 did not significantly change after cessation of terbutaline treatment in both placebo and budesonide treatment groups. AUC-FEV1 values after cessation of treatment with both doses of terbutaline were significantly different from the 82 h values (p < 0.05). The decrease in FEV1 was significantly greater after the last terbutaline and placebo inhalation in the placebo group compared with the budesonide treatment group (p = 0.02). We conclude that cessation of regular treatment after 2 wk with both low-dose and high-dose inhaled terbutaline does not result in a significant rebound airway responsiveness in patients with mild asthma. However, the results suggest a small rebound bronchoconstriction that does not occur when asthmatic patients are also treated with budesonide.

This article has been cited by other articles:

				S. R. Salpeter, T. M. Ormiston, and E. E. Salpeter Meta-Analysis: Respiratory Tolerance to Regular {beta}2-Agonist Use in Patients with Asthma Ann Intern Med, May 18, 2004; 140(10): 802 - 813. [Abstract] [Full Text] [PDF]

				B Lipworth, G H Koppelman, A P Wheatley, I Le Jeune, W Coutie, H Meurs, H F Kauffman, D S Postma, and I P Hall {beta}2 adrenoceptor promoter polymorphisms: extended haplotypes and functional effects in peripheral blood mononuclear cells Thorax, January 1, 2002; 57(1): 61 - 66. [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]

				P. J. BARNES, S. PEDERSEN, and W. W. BUSSE Efficacy and Safety of Inhaled Corticosteroids . New Developments Am. J. Respir. Crit. Care Med., March 1, 1998; 157(3): S1 - 53. [Full Text] [PDF]