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Beta2-adrenoceptor regulation and bronchodilator sensitivity after regular treatment with formoterol in subjects with stable asthma.
J Allergy Clin Immunol. 1998 Mar; 101(3):337-41.JA

Abstract

OBJECTIVE

We have previously found that beta2-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] FEV1, 73.2 [12.1] percent predicted) receiving regular inhaled corticosteroid therapy received 1 week of treatment with formoterol dry powder (24 microg twice daily [8 AM/8 PM]), formoterol (24 microg once daily [8 PM]), or identical placebo. Lymphocyte beta2-adrenoceptor parameters and a dose-response curve to inhaled albuterol (200 to 1600 microg) 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 FEV1 (0.47 L [0.06 L] for placebo vs 0.48 L [0.07 L] for 24 microg once daily formoterol vs 0.51 L [0.08 L] for 24 microg twice daily formoterol) or for forced expiratory flow, mid-expiratory phase (FEF25-75) (0.80 L/sec [0.12 L/sec] for placebo vs 0.80 L/sec [0.16 L/sec] for 24 microg once daily formoterol vs 0.89 L/sec [0.14 L/sec] for 24 microg twice daily formoterol). Formoterol also had no significant effect on mean lymphocyte beta2-adrenoceptor density. However, in five of seven patients with the homozygous Gly-16 polymorphism, beta2-adrenoceptor density was downregulated by twice daily formoterol, whereas only two such cases exhibited a reduction in maximal FEV1 response to albuterol.

CONCLUSIONS

The results of this study showed that for patients taking inhaled corticosteroids, overall beta2-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.

Authors+Show Affiliations

Department of Clinical Pharmacology and Therapeutics and Respiratory Medicine, Ninewells Hospital and Medical School, University of Dundee, Scotland, United Kingdom.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9525449

Citation

Aziz, I, et al. "Beta2-adrenoceptor Regulation and Bronchodilator Sensitivity After Regular Treatment With Formoterol in Subjects With Stable Asthma." The Journal of Allergy and Clinical Immunology, vol. 101, no. 3, 1998, pp. 337-41.
Aziz I, Hall IP, McFarlane LC, et al. Beta2-adrenoceptor regulation and bronchodilator sensitivity after regular treatment with formoterol in subjects with stable asthma. J Allergy Clin Immunol. 1998;101(3):337-41.
Aziz, I., Hall, I. P., McFarlane, L. C., & Lipworth, B. J. (1998). Beta2-adrenoceptor regulation and bronchodilator sensitivity after regular treatment with formoterol in subjects with stable asthma. The Journal of Allergy and Clinical Immunology, 101(3), 337-41.
Aziz I, et al. Beta2-adrenoceptor Regulation and Bronchodilator Sensitivity After Regular Treatment With Formoterol in Subjects With Stable Asthma. J Allergy Clin Immunol. 1998;101(3):337-41. PubMed PMID: 9525449.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Beta2-adrenoceptor regulation and bronchodilator sensitivity after regular treatment with formoterol in subjects with stable asthma. AU - Aziz,I, AU - Hall,I P, AU - McFarlane,L C, AU - Lipworth,B J, PY - 1998/4/3/pubmed PY - 1998/4/3/medline PY - 1998/4/3/entrez SP - 337 EP - 41 JF - The Journal of allergy and clinical immunology JO - J. Allergy Clin. Immunol. VL - 101 IS - 3 N2 - OBJECTIVE: We have previously found that beta2-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] FEV1, 73.2 [12.1] percent predicted) receiving regular inhaled corticosteroid therapy received 1 week of treatment with formoterol dry powder (24 microg twice daily [8 AM/8 PM]), formoterol (24 microg once daily [8 PM]), or identical placebo. Lymphocyte beta2-adrenoceptor parameters and a dose-response curve to inhaled albuterol (200 to 1600 microg) 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 FEV1 (0.47 L [0.06 L] for placebo vs 0.48 L [0.07 L] for 24 microg once daily formoterol vs 0.51 L [0.08 L] for 24 microg twice daily formoterol) or for forced expiratory flow, mid-expiratory phase (FEF25-75) (0.80 L/sec [0.12 L/sec] for placebo vs 0.80 L/sec [0.16 L/sec] for 24 microg once daily formoterol vs 0.89 L/sec [0.14 L/sec] for 24 microg twice daily formoterol). Formoterol also had no significant effect on mean lymphocyte beta2-adrenoceptor density. However, in five of seven patients with the homozygous Gly-16 polymorphism, beta2-adrenoceptor density was downregulated by twice daily formoterol, whereas only two such cases exhibited a reduction in maximal FEV1 response to albuterol. CONCLUSIONS: The results of this study showed that for patients taking inhaled corticosteroids, overall beta2-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. SN - 0091-6749 UR - https://www.unboundmedicine.com/medline/citation/9525449/Beta2_adrenoceptor_regulation_and_bronchodilator_sensitivity_after_regular_treatment_with_formoterol_in_subjects_with_stable_asthma_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0091-6749(98)70245-3 DB - PRIME DP - Unbound Medicine ER -