Adrenergic beta(2)-receptor genotype predisposes to exacerbations in steroid-treated asthmatic patients taking frequent albuterol or salmeterol

K. Basu, Colin N. A. Palmer, Roger Tavendale, Brian J. Lipworth, Somnath Mukhopadhyay

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    Abstract

    Background: On-demand inhaled albuterol is commonly prescribed worldwide. We have shown that the Arg16 allele of the adrenergic beta(2)-receptor agonist gene (ADRB2) predisposes to exacerbations in young asthmatic patients taking regular salmeterol.

    Objective: We have now extended our previous population by 636 patients and explored the role of the Arg16 allele on asthma exacerbations in the context of the use of on-demand albuterol and regular salmeterol.

    Methods: Arg/Gly status at position 16 of ADRB2 was assessed in 1182 young asthmatic patients (age, 3-22 years) from Scotland. Asthma exacerbations, use of beta-agonists and other medications over the previous 6 months, and lung function were also studied.

    Results: An increased risk of exacerbations per copy of he Arg16 allele was observed in asthmatic patients, regardless of treatment regimen (odds ratio [OR], 1.30; 95% CI, 1.09-1.55; P = .003). This appears to be largely due to exposure to beta(2)-agonists because the risk of exacerbations observed in patients with the Arg16 allele was only observed in those receiving daily inhaled long- or short-acting beta(2)-agonist treatment (OR, 1.64; 95% CI, 1.22-2.20; P =.001). In contrast, there was no genotypic risk for exacerbations in patients using inhaled beta(2)-agonists less than once a day (OR, 1.08; 95% CI, 0.85-1.36; P =.525). The Arg16 genotype-associated risk for exacerbations was significantly different in those exposed to beta(2)-agonists daily versus those that were not (test for interaction, P =.022).

    Conclusion: The Arg16 genotype of ADRB2 is associated with exacerbations in asthmatic children and young adults exposed daily to beta(2)-agonists, regardless of whether the exposure is to albuterol or long-acting agonists, such as salmeterol. (J Allergy Clin Immunol 2009;124:1188-94.)

    Original languageEnglish
    Pages (from-to)1188-1194.e3
    Number of pages7
    JournalJournal of Allergy and Clinical Immunology
    Volume124
    Issue number6
    DOIs
    Publication statusPublished - Dec 2009

    Keywords

    • Asthma
    • child
    • polymorphism
    • asthma exacerbations
    • albuterol
    • salmeterol
    • beta(2)-adrenoceptor
    • adrenergic beta(2)-receptor agonist gene
    • FILAGGRIN NULL MUTATIONS
    • EARLY-CHILDHOOD
    • LUNG-FUNCTION
    • FOLLOW-UP
    • BETA(2)-ADRENERGIC RECEPTOR
    • BETA(2)-AGONIST THERAPY
    • YOUNG-ADULTS
    • CHILDREN
    • POLYMORPHISMS
    • BRONCHIOLITIS

    Cite this

    @article{351f621e247645a4808893c13eeba057,
    title = "Adrenergic beta(2)-receptor genotype predisposes to exacerbations in steroid-treated asthmatic patients taking frequent albuterol or salmeterol",
    abstract = "Background: On-demand inhaled albuterol is commonly prescribed worldwide. We have shown that the Arg16 allele of the adrenergic beta(2)-receptor agonist gene (ADRB2) predisposes to exacerbations in young asthmatic patients taking regular salmeterol.Objective: We have now extended our previous population by 636 patients and explored the role of the Arg16 allele on asthma exacerbations in the context of the use of on-demand albuterol and regular salmeterol.Methods: Arg/Gly status at position 16 of ADRB2 was assessed in 1182 young asthmatic patients (age, 3-22 years) from Scotland. Asthma exacerbations, use of beta-agonists and other medications over the previous 6 months, and lung function were also studied.Results: An increased risk of exacerbations per copy of he Arg16 allele was observed in asthmatic patients, regardless of treatment regimen (odds ratio [OR], 1.30; 95{\%} CI, 1.09-1.55; P = .003). This appears to be largely due to exposure to beta(2)-agonists because the risk of exacerbations observed in patients with the Arg16 allele was only observed in those receiving daily inhaled long- or short-acting beta(2)-agonist treatment (OR, 1.64; 95{\%} CI, 1.22-2.20; P =.001). In contrast, there was no genotypic risk for exacerbations in patients using inhaled beta(2)-agonists less than once a day (OR, 1.08; 95{\%} CI, 0.85-1.36; P =.525). The Arg16 genotype-associated risk for exacerbations was significantly different in those exposed to beta(2)-agonists daily versus those that were not (test for interaction, P =.022).Conclusion: The Arg16 genotype of ADRB2 is associated with exacerbations in asthmatic children and young adults exposed daily to beta(2)-agonists, regardless of whether the exposure is to albuterol or long-acting agonists, such as salmeterol. (J Allergy Clin Immunol 2009;124:1188-94.)",
    keywords = "Asthma, child, polymorphism, asthma exacerbations, albuterol, salmeterol, beta(2)-adrenoceptor, adrenergic beta(2)-receptor agonist gene, FILAGGRIN NULL MUTATIONS, EARLY-CHILDHOOD, LUNG-FUNCTION, FOLLOW-UP, BETA(2)-ADRENERGIC RECEPTOR, BETA(2)-AGONIST THERAPY, YOUNG-ADULTS, CHILDREN, POLYMORPHISMS, BRONCHIOLITIS",
    author = "K. Basu and Palmer, {Colin N. A.} and Roger Tavendale and Lipworth, {Brian J.} and Somnath Mukhopadhyay",
    year = "2009",
    month = "12",
    doi = "10.1016/j.jaci.2009.07.043",
    language = "English",
    volume = "124",
    pages = "1188--1194.e3",
    journal = "Journal of Allergy and Clinical Immunology",
    issn = "0091-6749",
    publisher = "Elsevier",
    number = "6",

    }

    TY - JOUR

    T1 - Adrenergic beta(2)-receptor genotype predisposes to exacerbations in steroid-treated asthmatic patients taking frequent albuterol or salmeterol

    AU - Basu, K.

    AU - Palmer, Colin N. A.

    AU - Tavendale, Roger

    AU - Lipworth, Brian J.

    AU - Mukhopadhyay, Somnath

    PY - 2009/12

    Y1 - 2009/12

    N2 - Background: On-demand inhaled albuterol is commonly prescribed worldwide. We have shown that the Arg16 allele of the adrenergic beta(2)-receptor agonist gene (ADRB2) predisposes to exacerbations in young asthmatic patients taking regular salmeterol.Objective: We have now extended our previous population by 636 patients and explored the role of the Arg16 allele on asthma exacerbations in the context of the use of on-demand albuterol and regular salmeterol.Methods: Arg/Gly status at position 16 of ADRB2 was assessed in 1182 young asthmatic patients (age, 3-22 years) from Scotland. Asthma exacerbations, use of beta-agonists and other medications over the previous 6 months, and lung function were also studied.Results: An increased risk of exacerbations per copy of he Arg16 allele was observed in asthmatic patients, regardless of treatment regimen (odds ratio [OR], 1.30; 95% CI, 1.09-1.55; P = .003). This appears to be largely due to exposure to beta(2)-agonists because the risk of exacerbations observed in patients with the Arg16 allele was only observed in those receiving daily inhaled long- or short-acting beta(2)-agonist treatment (OR, 1.64; 95% CI, 1.22-2.20; P =.001). In contrast, there was no genotypic risk for exacerbations in patients using inhaled beta(2)-agonists less than once a day (OR, 1.08; 95% CI, 0.85-1.36; P =.525). The Arg16 genotype-associated risk for exacerbations was significantly different in those exposed to beta(2)-agonists daily versus those that were not (test for interaction, P =.022).Conclusion: The Arg16 genotype of ADRB2 is associated with exacerbations in asthmatic children and young adults exposed daily to beta(2)-agonists, regardless of whether the exposure is to albuterol or long-acting agonists, such as salmeterol. (J Allergy Clin Immunol 2009;124:1188-94.)

    AB - Background: On-demand inhaled albuterol is commonly prescribed worldwide. We have shown that the Arg16 allele of the adrenergic beta(2)-receptor agonist gene (ADRB2) predisposes to exacerbations in young asthmatic patients taking regular salmeterol.Objective: We have now extended our previous population by 636 patients and explored the role of the Arg16 allele on asthma exacerbations in the context of the use of on-demand albuterol and regular salmeterol.Methods: Arg/Gly status at position 16 of ADRB2 was assessed in 1182 young asthmatic patients (age, 3-22 years) from Scotland. Asthma exacerbations, use of beta-agonists and other medications over the previous 6 months, and lung function were also studied.Results: An increased risk of exacerbations per copy of he Arg16 allele was observed in asthmatic patients, regardless of treatment regimen (odds ratio [OR], 1.30; 95% CI, 1.09-1.55; P = .003). This appears to be largely due to exposure to beta(2)-agonists because the risk of exacerbations observed in patients with the Arg16 allele was only observed in those receiving daily inhaled long- or short-acting beta(2)-agonist treatment (OR, 1.64; 95% CI, 1.22-2.20; P =.001). In contrast, there was no genotypic risk for exacerbations in patients using inhaled beta(2)-agonists less than once a day (OR, 1.08; 95% CI, 0.85-1.36; P =.525). The Arg16 genotype-associated risk for exacerbations was significantly different in those exposed to beta(2)-agonists daily versus those that were not (test for interaction, P =.022).Conclusion: The Arg16 genotype of ADRB2 is associated with exacerbations in asthmatic children and young adults exposed daily to beta(2)-agonists, regardless of whether the exposure is to albuterol or long-acting agonists, such as salmeterol. (J Allergy Clin Immunol 2009;124:1188-94.)

    KW - Asthma

    KW - child

    KW - polymorphism

    KW - asthma exacerbations

    KW - albuterol

    KW - salmeterol

    KW - beta(2)-adrenoceptor

    KW - adrenergic beta(2)-receptor agonist gene

    KW - FILAGGRIN NULL MUTATIONS

    KW - EARLY-CHILDHOOD

    KW - LUNG-FUNCTION

    KW - FOLLOW-UP

    KW - BETA(2)-ADRENERGIC RECEPTOR

    KW - BETA(2)-AGONIST THERAPY

    KW - YOUNG-ADULTS

    KW - CHILDREN

    KW - POLYMORPHISMS

    KW - BRONCHIOLITIS

    U2 - 10.1016/j.jaci.2009.07.043

    DO - 10.1016/j.jaci.2009.07.043

    M3 - Article

    VL - 124

    SP - 1188-1194.e3

    JO - Journal of Allergy and Clinical Immunology

    JF - Journal of Allergy and Clinical Immunology

    SN - 0091-6749

    IS - 6

    ER -