Asthma and lower airway diseaseAdrenergic β2-receptor genotype predisposes to exacerbations in steroid-treated asthmatic patients taking frequent albuterol or salmeterol
Section snippets
Methods
We have continued the recruitment of children with physician-diagnosed asthma for the BREATHE study beyond the publication of our initial results.7 The current dataset includes information about demographic, anthropometric, and clinical details from 1182 patients attending 29 primary care practices and 2 secondary care asthma clinics in Tayside, Scotland, from 2004-2008 (age, 3-22 years).
The study was approved by the Tayside Committee on Medical Research and Ethics. Informed consent was
Results
The population characteristics are typical of children and young adults with well-controlled asthma derived from both primary and secondary care (Table IV). We had collected data on 546 children previously7 and have now increased our study population to 1190 participants, of whom 1182 were white. Further analysis was performed on data from white participants. The data from other ethnic groups were not sufficient for further analysis. The prevalence of the Arg/Arg16 genotype was 15.3%, the
Discussion
The study shows for the first time that there is an increase in risk of exacerbations per copy of the Arg16 allele in children and young adults with asthma taking frequent (once daily or more) as-required doses of inhaled albuterol. This effect is not observed in participants with asthma who are not exposed to β2-agonist on a daily basis. The study also extends our previous findings of an increase in the risk of exacerbations per copy of the Arg16 allele in children and young adults with asthma
References (40)
- et al.
Use of regularly scheduled albuterol treatment in asthma: genotype-stratified, randomised, placebo-controlled cross-over trial
Lancet
(2004) - et al.
Filaggrin null mutations are associated with increased asthma severity in children and young adults
J Allergy Clin Immunol
(2007) - et al.
A polymorphism controlling ORMDL3 expression is associated with asthma that is poorly controlled by current medications
J Allergy Clin Immunol
(2008) - et al.
Beta2-adrenoceptor polymorphisms and asthma from childhood to middle age in the British 1958 birth cohort: a genetic association study
Lancet
(2006) - et al.
Effect of ADRB2 polymorphisms on response to long-acting β2-agonist therapy: a pharmacogenetic analysis of two randomised studies
Lancet
(2007) - et al.
Injuries and noncommunicable diseases: emerging health problems of children in developing countries
Bull World Health Org
(1999) - et al.
The burden of asthma in the United States: level and distribution are dependent on interpretation of the national asthma education and prevention program guidelines
Am J Respir Crit Care Med
(2002) British Thoracic Society Scottish Intercollegiate Guidelines Network
Thorax
(2008)- et al.
Guidelines for management of asthma at primary and secondary levels of health care in India (2005) [A Consensus Statement Developed under the World Health Organization and Government of India Collaborative Programme (2004-2005)]
Indian J Chest Dis Allied Sci
(2005) Global strategy for asthma management and prevention
(2002)
Pediatric asthma: promoting best practice. Guide for Managing Asthma in Children
Arginine-16 beta2 adrenoceptor genotype predisposes to exacerbations in young asthmatics taking regular salmeterol
Thorax
Global strategy for asthma management and prevention: GINA executive summary
Eur Respir J
Polymorphism of the beta2-adrenoceptor and the response to long-term beta2-agonist therapy in asthma
Eur Respir J
The effect of polymorphisms of the beta(2)-adrenergic receptor on the response to regular use of albuterol in asthma
Am J Respir Crit Care Med
Asthma exacerbations during long term beta agonist use: influence of beta(2) adrenoceptor polymorphism
Thorax
Exacerbations—the asthma paradox
Am J Respir Crit Care Med
The social and economic consequences of childhood asthma across the lifecourse: a systematic review
Child Care Health Dev
The prehospital management of children with acute asthma
J Paediatr Child Health
Keeping children with asthma out of hospitals: parents' and physicians' perspectives on how pediatric asthma hospitalizations can be prevented
Pediatrics
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Support for the study was approved by the Gannochy Trust (Perth, Scotland), Scottish Enterprises Tayside, and the Perth and Kinross Council. C. N. A. P. is supported by the Scottish Executive Genetic Health Initiative Award.
Disclosure of potential conflict of interest: B. J. Lipworth has provided consulting advice regarding the fluticasone/formoterol combination for Mundipharma, provided a speakers' bureau talk on budesonide formoterol for AstraZeneca and a speakers' bureau talk on heterogeneity in asthma and airway remodeling for Merck, has received research support from Merck Sharpe & Dohme and Neolab, and has provided legal consultation on formoterol equivalence for TEVA. S. Mukhopadhyay has served as an expert advisor for and received research support from Merck Sharpe & Dohme. The rest of the authors have declared that they have no conflict of interest.
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These authors contributed equally to this work.