Background The Gly-to-Arg substitution at the 16 position (rs1042713) in the beta 2 adrenoceptor (ADRB2) gene is associated with enhanced down-regulation and uncoupling of beta-2 receptors. Objectives To undertake a meta-analysis to test the hypothesis that there is an interaction between the A allele of rs1042713 (Arg16 amino acid) and long acting beta agonist (LABA) exposure for asthma exacerbations in children. Methods Children with diagnosed asthma were recruited in five populations (BREATHE, GALA II, PACMAN, PAGES and PASS). A history of recent exacerbation and asthma treatment were determined from questionnaire data. DNA was extracted and the Gly16Arg genotype determined. Results Data from 4226 children of white Northern European and Latino origin were analysed and the odds ratio for exacerbation increased by 1.52 [1.17, 1.99] p=0.0021 for each copy of the A allele among the 637 children treated with inhaled corticosteroids (ICS) plus LABA but not for treatment with ICS alone (n=1758), nor ICS plus leukotriene receptor antagonist (LTRA, n=354) or ICS plus LABA plus LTRA (n=569). Conclusions The use of LABA as “add-on controller”, but not LTRA, is associated with increased risk of asthma exacerbations in children carrying one or two A alleles at rs1042713. Prospective genotype stratified clinical trials are now required to explore the potential role of rs1042713 genotyping for personalised asthma therapy in children.

The integration of personalized medicine (PM) into mainstream healthcare will only be successful if the public understands and supports this change. The aim was to understand the public perception of the barriers and facilitators towards the use of PM. A systematic review of the literature was conducted within six databases from 2006 to 2018. Twenty-one studies with 9507 participants were included. The key themes were familiarity and willingness to use PM, perceived benefits and perceived risks of PM. The review shows that the public is generally enthusiastic about the introduction of PM, although this should be interpreted with cautious optimism due to participants having a limited familiarity of the underlying principles of PM. The study defines areas where progress can be made to enhance this understanding and addresses legitimate concerns.

A systematic review of pharmacogenomic studies capturing adverse drug reactions (ADRs) related to asthma medications was undertaken, and a survey of Pharmacogenomics in Childhood Asthma (PiCA) consortia members was conducted. Studies were eligible if genetic polymorphisms were compared with suspected ADR(s) in a patient with asthma, as either a primary or secondary outcome. Five studies met the inclusion criteria. The ADRs and polymorphisms identified were change in lung function tests (rs1042713), adrenal suppression (rs591118), and decreased bone mineral density (rs6461639) and accretion (rs9896933, rs2074439). Two of these polymorphisms were replicated within the paper, but none had external replication. Priorities from PiCA consortia members (representing 15 institution in eight countries) for future studies were tachycardia (SABA/LABA), adrenal suppression/crisis and growth suppression (corticosteroids), sleep/behaviour disturbances (leukotriene receptor antagonists), and nausea and vomiting (theophylline). Future pharmacogenomic studies in asthma should collect relevant ADR data as well as markers of efficacy.

G547(P) Figure 1 Wheeze pathway checklist