β 2 -Adrenoceptor regulation and bronchodilator sensitivity after regular treatment with formoterol in subjects with stable asthma

57Citations
Citations of this article
21Readers
Mendeley users who have this article in their library.

Abstract

Objective: We have previously found that β 2 -adrenoceptor downregulation and bronchodilator desensitization to albuterol occurred at 36 hours after stopping regular treatment with twice daily salmeterol. In this study we have evaluated these same effects with formoterol given once or twice daily on a regular basis. Methods: In a randomized, placebo-controlled, double-blind, double-dummy crossover study, 16 subjects with mild-to- moderate stable asthma (mean [SD] age, 32.5 [15.3] years; mean [SD] FEV 1 , 73.2 [12.1] percent predicted) receiving regular inhaled corticosteroid therapy received 1 week of treatment with formoterol dry powder (24 μg twice daily [8 AM/8 PM]), formoterol (24 μg once daily [8 PM]), or identical placebo. Lymphocyte β 2 -adrenoceptor parameters and a dose-response curve to inhaled albuterol (200 to 1600 μg) were evaluated at 36 hours after the last dose of each treatment period. Results: There were no significant differences in the mean values for albuterol dose-response effects among the three treatment regimens. Comparison of maximal bronchodilator responses between treatments (mean and SEM as change from baseline) revealed no significant differences between treatments for FEV 1 (0.47 L [0.06 L] for placebo vs 0.48 L [0.07 L] for 24 μg once daily formoterol vs 0.51 L [0.08 L] for 24 μg twice daily formoterol) or for forced expiratory flow, mid-expiratory phase (FEF 25-75 ) (0.80 L/sec [0.12 L/sec] for placebo vs 0.80 L/sec [0.16 L/sec] for 24 μg once daily formoterol vs 0.89 L/sec [0.14 L/sec] for 24 μg twice daily formoterol). Formoterol also had no significant effect on mean lymphocyte β 2 -adrenoceptor density. However, in five of seven patients with the homozygous Gly-16 polymorphism, β 2 -adrenoceptor density was downregulated by twice daily formoterol, whereas only two such cases exhibited a reduction in maximal FEV 1 response to albuterol. Conclusions: The results of this study showed that for patients taking inhaled corticosteroids, overall β 2 -adrenoceptor regulation and associated bronchodilator sensitivity to inhaled albuterol were unaltered at 36 hours after stopping regular treatment with formoterol. However, in a subset of patients who were Gly-16 homozygous, there was a tendency towards downregulation but not desensitization. Further studies in subjects with more severe asthma are required to assess the clinical relevance of these findings.

Cite

CITATION STYLE

APA

Aziz, I., Hall, I. P., McFarlane, L. C., & Lipworth, B. J. (1998). β 2 -Adrenoceptor regulation and bronchodilator sensitivity after regular treatment with formoterol in subjects with stable asthma. Journal of Allergy and Clinical Immunology, 101(3), 337–341. https://doi.org/10.1016/S0091-6749(98)70245-3

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free