PT  - JOURNAL ARTICLE
AU  - Steve Turner
AU  - Kaninika Basu
AU  - Lauren Bignell
AU  - Jon Ayres
AU  - Roger Tavendale
AU  - Brian Lipworth
AU  - Anil Mehta
AU  - Somnath Mukhopadhyay
AU  - Colin Palmer
TI  - Interaction between the Arg16 homozygous genotype, inhaled corticosteroids and long acting beta agonists for asthma exacerbations in children? Leukotriene receptor antagonists to the rescue?
DP  - 2013 Sep 01
TA  - European Respiratory Journal
PG  - 3497
VI  - 42
IP  - Suppl 57
4099  - http://erj.ersjournals.com/content/42/Suppl_57/3497.short
4100  - http://erj.ersjournals.com/content/42/Suppl_57/3497.full
SO  - Eur Respir J2013 Sep 01; 42
AB  - Introduction. Here we test the hypothesis that when compared to children with at least one Gly16 allele, children homozygous for the Arg16 SNP of the B2AR gene are at increased risk for asthma exacerbation if treated with long acting beta agonists (LABA) and that this risk is countered by leukotriene receptor antagonist (LTRA) treatment.Methods. Children with asthma were recruited in two cohorts using a common methodology. Details of exacerbations and asthma treatment were determined from questionnaire. DNA was extracted, Arg16Gly genotype was determined and analyses adjusted for confounders.Results. Questionnaire and DNA were available in 2036 children, mean age 9.5 years (SD 3.8), 59% male. There were 1098 children treated with inhaled corticosteroid (ICS) monotherapy, 364 with ICS+ LABA, 164 with ICS+LTRA and 325 with ICS+LABA+LTRA. Compared to children with at least one Gly16 allele, children homozygous for Arg16 were at increased risk for exacerbations in the group with ICS monotherapy (OR 1.53 [95% CI 1.06, 2.23] p=0.025) and ICS+LABA (OR 1.96 [95% CI 1.02, 3.77] p=0.045). Arg16 homozygous genotype was not associated with increased risk for exacerbation in children treated with ICS+ LTRA± LABA. There was no evidence of an Arg16 gene dose effect.Conclusions. There is a modest increase in asthma exacerbations among those homozygous for Arg16, compared to others, if treated with ICS±LABA. This increased risk seems to be countered by treatment with LTRA. On a whole population basis, these observations could explain many potentially avoidable exacerbations in children with asthma.