Dataset Information

Childhood asthma exacerbations and the Arg16 ?2-receptor polymorphism: A meta-analysis stratified by treatment.

ABSTRACT: BACKGROUND:The Gly-to-Arg substitution at the 16 position (rs1042713) in the ?2-adrenoceptor gene (ADRB2) is associated with enhanced downregulation and uncoupling of ?2-receptors. OBJECTIVES:We sought 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 ?-agonist (LABA) exposure for asthma exacerbations in children. METHODS:Children with diagnosed asthma were recruited in 5 populations (BREATHE, Genes-Environments and Admixture in Latino Americans II, PACMAN, the Paediatric Asthma Gene Environment Study, and the Pharmacogenetics of Adrenal Suppression with Inhaled Steroid Study). A history of recent exacerbation and asthma treatment was determined from questionnaire data. DNA was extracted, and the Gly16Arg genotype was determined. RESULTS:Data from 4226 children of white Northern European and Latino origin were analyzed, and the odds ratio for exacerbation increased by 1.52 (95% CI, 1.17-1.99; P = .0021) for each copy of the A allele among the 637 children treated with inhaled corticosteroids (ICSs) plus LABAs but not for treatment with ICSs alone (n = 1758) or ICSs plus leukotriene receptor antagonist (LTRAs; n = 354) or ICSs plus LABAs plus LTRAs (n = 569). CONCLUSIONS:The use of a LABA but not an LTRA as an "add-on controller" is associated with increased risk of asthma exacerbation in children carrying 1 or 2 A alleles at rs1042713. Prospective genotype-stratified clinical trials are now required to explore the potential role of rs1042713 genotyping for personalized asthma therapy in children.

SUBMITTER: Turner S

PROVIDER: S-EPMC4931969 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Childhood asthma exacerbations and the Arg16 β2-receptor polymorphism: A meta-analysis stratified by treatment.

Turner Steve S Francis Ben B Vijverberg Susanne S Pino-Yanes Maria M Maitland-van der Zee Anke H AH Basu Kaninika K Bignell Lauren L Mukhopadhyay Somnath S Tavendale Roger R Palmer Colin C Hawcutt Daniel D Pirmohamed Munir M Burchard Esteban G EG Lipworth Brian B

The Journal of allergy and clinical immunology 20160107 1

<h4>Background</h4>The Gly-to-Arg substitution at the 16 position (rs1042713) in the β2-adrenoceptor gene (ADRB2) is associated with enhanced downregulation and uncoupling of β2-receptors.<h4>Objectives</h4>We sought 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 β-agonist (LABA) exposure for asthma exacerbations in children.<h4>Methods</h4>Children with diagnosed asthma were recruited in 5 pop ...[more]

PMID: 26774659

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Project description:BACKGROUND:Asthma exacerbations occur frequently despite the regular use of asthma-controller therapies, such as inhaled glucocorticoids. Clinicians commonly increase the doses of inhaled glucocorticoids at early signs of loss of asthma control. However, data on the safety and efficacy of this strategy in children are limited. METHODS:We studied 254 children, 5 to 11 years of age, who had mild-to-moderate persistent asthma and had had at least one asthma exacerbation treated with systemic glucocorticoids in the previous year. Children were treated for 48 weeks with maintenance low-dose inhaled glucocorticoids (fluticasone propionate at a dose of 44 μg per inhalation, two inhalations twice daily) and were randomly assigned to either continue the same dose (low-dose group) or use a quintupled dose (high-dose group; fluticasone at a dose of 220 μg per inhalation, two inhalations twice daily) for 7 days at the early signs of loss of asthma control ("yellow zone"). Treatment was provided in a double-blind fashion. The primary outcome was the rate of severe asthma exacerbations treated with systemic glucocorticoids. RESULTS:The rate of severe asthma exacerbations treated with systemic glucocorticoids did not differ significantly between groups (0.48 exacerbations per year in the high-dose group and 0.37 exacerbations per year in the low-dose group; relative rate, 1.3; 95% confidence interval, 0.8 to 2.1; P=0.30). The time to the first exacerbation, the rate of treatment failure, symptom scores, and albuterol use during yellow-zone episodes did not differ significantly between groups. The total glucocorticoid exposure was 16% higher in the high-dose group than in the low-dose group. The difference in linear growth between the high-dose group and the low-dose group was -0.23 cm per year (P=0.06). CONCLUSIONS:In children with mild-to-moderate persistent asthma treated with daily inhaled glucocorticoids, quintupling the dose at the early signs of loss of asthma control did not reduce the rate of severe asthma exacerbations or improve other asthma outcomes and may be associated with diminished linear growth. (Funded by the National Heart, Lung, and Blood Institute; STICS ClinicalTrials.gov number, NCT02066129 .).

Dataset Information

Childhood asthma exacerbations and the Arg16 ?2-receptor polymorphism: A meta-analysis stratified by treatment.

Publications

Childhood asthma exacerbations and the Arg16 β2-receptor polymorphism: A meta-analysis stratified by treatment.

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