Concomitant occasional use of salbutamol influences bronchoprotective responsiveness afforded by formoterol in patients with the glycine-16 genotype

Erika J. Sims, Brian J. Lipworth

Research output: Contribution to journalArticle

6 Citations (Scopus)


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.
Original languageEnglish
Pages (from-to)791-795
Number of pages5
JournalEuropean Journal of Clinical Pharmacology
Issue number11
Early online date11 Dec 2003
Publication statusPublished - Jan 2004

Cite this