41. Targeting bronchodilators - can one identify responders vs non-responders?:

As we enter the era of pharmacogenetics we will become more aware of the need to tailor treatments according to the genetic make-up of the patients. Ultimately response, resistance, adverse reactions and hypersensitivity may all be related to amino acid sequencing on one or more chromosomes. This issue has recently been studied in asthmatics in a multicentre initiative in the USA involving an impressive array of scientists. The objective was to determine the relationship between beta2-adrenoceptor response and amino acid type at codon 16, specifically whether it was coded with arginine vs glycine. The prospective, randomized, double-blinded project was undertaken after previous research had suggested that arginine at codon 16 was associated with beta-stimulant resistance while glycine was associated with responsiveness (other work has also suggested that codon 27 substitution of glutamic acid for glutamine results in resistance).
Homozygous arg/arg and gly/gly subjects were studied with run-in and wash-out phases testing salbutamol vs placebo. The study not only confirmed the response to salbutamol treatment in the glycine group and suggested that patients could deteriorate with short-acting beta-agonists, but also introduced the question of whether even intermittent use of beta2-stimulants in arginine-coded subjects might have a sustained adverse effect on airway patency. This question was raised because of significant improvements in lung function in arg/arg subjects on placebo after exposure to short-acting beta stimulants. The study involved patients with mild asthma using salbutamol, and results cannot simply be applied to longer acting drugs and/or more severe forms of asthma.


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