Abstract
Background: The development of tolerance following the use of long acting beta(2) agonists in asthmatic patients with either the homozygous arginine (Arg-16) or glycine (Gly-16) genotypes is poorly documented, especially in relation to the acute reliever response to salbutamol in constricted airways. A study was undertaken to evaluate the Arg-16 and Gly-16 genotypes for the acute salbutamol response following methacholine bronchial challenge between the first and last doses of formoterol ( FM) and salmeterol (SM) combination inhalers.
Methods: Parallel groups of 10 matched homozygous Arg-16 and 10 homozygous Gly-16 patients completed a randomised, double blind, double dummy, crossover study. Following a 1 week washout period, patients received treatment for 2 weeks with either inhaled budesonide (BUD) 200 mug + FM 6 mug ( two puffs twice daily) or inhaled fluticasone propionate ( FP) 250 mg + SM 50 mg ( one puff twice daily). After washouts and randomised treatments ( 1 hour after the first and last inhalation) a methacholine challenge was performed followed by salbutamol 200 mg, with recovery over 30 minutes ( the primary outcome).
Results: Washout values for forced expiratory volume in 1 second ( FEV1), methacholine hyperreactivity, and salbutamol recovery were similar for both treatments and genotypes. Pre-challenge FEV1 values for both genotypes did not differ significantly between the first and last doses of each treatment. Salbutamol recovery as mean ( SE) area under the 30 minute time-response curve was significantly delayed (p<0.05) equally in both genotype and treatment groups. There were no differences in salbutamol recovery in either genotype or treatment group.
Conclusion: Acute salbutamol recovery in methacholine constricted airways was significantly delayed to a similar degree in both genotypes due to cross tolerance induced by FM or SM.
Original language | English |
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Pages (from-to) | 662-667 |
Number of pages | 6 |
Journal | Thorax |
Volume | 59 |
Issue number | 8 |
DOIs | |
Publication status | Published - Aug 2004 |
Keywords
- BRONCHODILATOR SUBSENSITIVITY
- INHALED CORTICOSTEROIDS
- FUNCTIONAL ANTAGONISM
- GENETIC POLYMORPHISMS
- RECEPTOR
- ALBUTEROL
- EXACERBATIONS
- ASSOCIATION
- EFORMOTEROL
- MODERATE