Tools
Tools
Sims, Erika J. 
ORCID: https://orcid.org/0000-0002-7898-0331 and Lipworth, Brian J.
(2004)
Concomitant occasional use of salbutamol influences bronchoprotective responsiveness afforded by formoterol in patients with the glycine-16 genotype.
European Journal of Clinical Pharmacology, 59 (11).
pp. 791-795.
Abstract
Background: Predisposition to subsensitivity with long-acting β2-agonists (LABA) or regular short-acting β2-agonists (SABA) is related to polymorphisms at codon 16 of the β2-adrenoceptor. Objective: To determine whether the use of occasional SABA induces further baseline downregulation of the β2-adrenoceptor to that of endogenous catecholamines alone, in Gly-16 patients. Methods: A post-hoc analysis of two studies was performed. Twenty-three homozygous Gly-16 asthmatic patients received 12 μg inhaled formoterol either o.d. or b.i.d. for 2 weeks. Patients had been supplied with ipratropium bromide (IB) to use as reliever therapy preferentially over salbutamol. Spirometry and adenosine monophosphate (AMP) bronchial challenge was performed after 7–14 days of placebo and after active treatment. Results: A review of domiciliary diary card data indicated 13 patients (mean FEV1: 76.8% pred., AMP PC20: 23.4 mg/ml) did not require salbutamol, and 10 patients (mean FEV1: 77.9% pred., AMP PC20: 27.9 mg/ml) required occasional salbutamol (1.67 puffs/day) during run-in and/or formoterol periods. No significant difference in spirometry or AMP PC20 were found between the populations after placebo. After formoterol, compared with placebo, patients requiring occasional salbutamol had no improvement in AMP PC20 [geometric mean PC20 (and 95% CI): 28.0 mg/ml (20.5–38.4) versus 34.46 mg/ml (25.1–47.3)], while those patients not requiring salbutamol had a significant (p<0.05) improvement in AMP PC20 with formoterol compared with placebo [89.9 mg/ml (52.4–154.3) versus 30.6 mg/ml (17.8–52.5)]. This amounted to a 3.12-fold (95% CI: 0.16–6.07) geometric mean fold difference between groups. Conclusions: Our results indicate that homozygous Gly-16 patients using occasional salbutamol have reduced responsiveness to formoterol in terms of bronchoprotection to AMP than patients not using salbutamol. Patients expressing the homozygous gly-16 genotype of the β2-adrenoceptor genotype receiving a LABA may benefit from the substitution of their usual SABA for an alternative reliever.
| Item Type: | Article |
|---|---|
| Faculty \ School: | Faculty of Medicine and Health Sciences > Norwich Medical School |
| UEA Research Groups: | Faculty of Medicine and Health Sciences > Research Groups > Norwich Clinical Trials Unit Faculty of Medicine and Health Sciences > Research Centres > Population Health Faculty of Medicine and Health Sciences > Research Groups > Public Health and Health Services Research (former - to 2023) |
| Depositing User: | EPrints Services |
| Date Deposited: | 25 Nov 2010 11:11 |
| Last Modified: | 13 Jun 2024 14:30 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/13686 |
| DOI: | 10.1007/s00228-003-0703-2 |
Actions (login required)
 |
View Item |