Some asthma genotypes may not respond to ?2 agonists
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Specialist Registrar, Castle Hill Hospital, Hull, Yorkshire, UK; N.Batsford@doctors.org
Israel E, Chinchilli VM, Ford JG, et al. Use of regularly scheduled albuterol treatment in asthma: genotype-stratified, randomised, placebo-controlled cross-over trial. Lancet 2004;364:1505–12
This was a prospective crossover trial comparing the use of salbutamol with placebo in 78 mild asthmatics (diagnosed by chest physician, only using inhaled ? agonist <56 puffs/week, FEV1 >70%) aged 18–55 years. 50% had a genetic polymorphism resulting in homozygosity for arginine (Arg/Arg) at amino acid residue number 16 of the ?2 agonist receptor instead of glycine (Gly/Gly), as in the other half. Each patient was matched with a patient from the other group by FEV1.
Following a 6 week run in period using a placebo metered dose inhaler (two puffs qds; rescue medication ipratropium inhaler), each pair was randomised to receive either active salbutamol (90 μg) or placebo (two puffs qds) for 16 weeks followed by an 8 week run out period using placebo and then crossed over. In the Gly/Gly group there was no change in pre-inhaler morning peak expiratory flow rate (PEFR) with placebo but an increase in PEFR with salbutamol producing a difference of 14 l/min (p<0.05). In the Arg/Arg group the reverse occurred with a difference of –10 l/min (p<0.05). This group also needed to use their ipratropium inhaler more, which did produce an increase in PEFR. Similar results were seen in FEV1, symptom scores, and rescue inhaler use.
It appears that Gly/Gly patients respond to salbutamol while those with Arg/Arg seem to get better when salbutamol is withdrawn. It may be that the latter group actually responds to ipratropium. A longer treatment trial is needed with more patients with more severe asthma and with other genetic polymorphisms, using other ?2 agonists, to determine if reliever strategies excluding salbutamol are more suitable for Arg/Arg patients.(N Batsford)
Israel E, Chinchilli VM, Ford JG, et al. Use of regularly scheduled albuterol treatment in asthma: genotype-stratified, randomised, placebo-controlled cross-over trial. Lancet 2004;364:1505–12
This was a prospective crossover trial comparing the use of salbutamol with placebo in 78 mild asthmatics (diagnosed by chest physician, only using inhaled ? agonist <56 puffs/week, FEV1 >70%) aged 18–55 years. 50% had a genetic polymorphism resulting in homozygosity for arginine (Arg/Arg) at amino acid residue number 16 of the ?2 agonist receptor instead of glycine (Gly/Gly), as in the other half. Each patient was matched with a patient from the other group by FEV1.
Following a 6 week run in period using a placebo metered dose inhaler (two puffs qds; rescue medication ipratropium inhaler), each pair was randomised to receive either active salbutamol (90 μg) or placebo (two puffs qds) for 16 weeks followed by an 8 week run out period using placebo and then crossed over. In the Gly/Gly group there was no change in pre-inhaler morning peak expiratory flow rate (PEFR) with placebo but an increase in PEFR with salbutamol producing a difference of 14 l/min (p<0.05). In the Arg/Arg group the reverse occurred with a difference of –10 l/min (p<0.05). This group also needed to use their ipratropium inhaler more, which did produce an increase in PEFR. Similar results were seen in FEV1, symptom scores, and rescue inhaler use.
It appears that Gly/Gly patients respond to salbutamol while those with Arg/Arg seem to get better when salbutamol is withdrawn. It may be that the latter group actually responds to ipratropium. A longer treatment trial is needed with more patients with more severe asthma and with other genetic polymorphisms, using other ?2 agonists, to determine if reliever strategies excluding salbutamol are more suitable for Arg/Arg patients.(N Batsford)