Use of regularly scheduled albuterol treatment in asthma: genotype-stratified, randomised, placebo-controlled cross-over trial

Israel, Elliot; Chinchilli, Vernon M.; Ford, Jean G.; Boushey, Homer A.; Cherniack, Reuben M.; Craig, Timothy J.; Deykin, Aaron; Fagan, Joanne K.; Fahy, John V.; Fish, James E.; Kraft, Monica; Kunselman, Susan J.; Lazarus, Stephen C.; Lemanske, Robert F.; Liggett, Stephen B.; Martin, Richard J.; Mitra, Nandita; Peters, Stephen P.; Silverman, Eric S.; Sorkness, Christine A.; Szefler, Stanley J.; Wechsler, Michael E.; Weiss, Scott T.; Drazen, Jeffrey M.

doi:10.1016/s0140-6736(04)17273-5

Cited by 562 publications

(405 citation statements)

References 20 publications

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“…For ADRB1, the Gly49 and Arg389 variants seem, on balance, to be the variants that perform more favorably in heart failure patients given beta-blockade. In the case of ADRB2, the data reported by Israel et al 73 suggest an intriguing negative effect of Arg16 alleles on short-term beta agonist therapy. Whether this finding holds true for long-term exposure to beta-agonist therapy remains to be clarified.…”

Section: Implications For Pharmacogenomicsmentioning

confidence: 97%

“…30 Gly16 has also been linked to differential response to beta-agonist therapy (albuterol) in asthmatics. 73,74 In hypertensive populations, ADRB2 genetic association studies have yielded mixed results. Hypertension has been associated with the Arg16 and Gly16 alleles in different studies.…”

Section: Adrb2 Association Studiesmentioning

confidence: 99%

“…The unfavorable response to albuterol therapy in the Arg16 homozygotes prompted the authors to suggest that caution may need to be exercised in this group of subjects. 73 …”

Section: Haplotype Approaches To Adrb1 and Adrb2mentioning

confidence: 99%

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Pharmacogenetics of the human beta-adrenergic receptors

Taylor

2006

Pharmacogenomics J

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The beta-adrenergic receptors (ADRBs) are cell surface receptors that play central roles in the sympathetic nervous system. Pharmacological targeting of two of these receptors, ADRB1 and ADRB2, represents a widely used therapeutic approach for common and important diseases including asthma, hypertension and heart failure. Genetic variation in both ADRB1 and ADRB2 has been linked to both in vitro and clinical disease phenotypes. More recently, interest has shifted to studies that explore potential interaction between variation in ADRBs and medications directed at these important receptors. This paper reviews the current state of knowledge and understanding of ADRB genetic variation and explores the likely direction of future studies in this area.

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Section: Implications For Pharmacogenomicsmentioning

confidence: 97%

Section: Adrb2 Association Studiesmentioning

confidence: 99%

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Pharmacogenetics of the human beta-adrenergic receptors

Taylor

2006

Pharmacogenomics J

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“…65 This finding was found in two different Asthma Clinical Research Network (ACRN) trials. [66][67] The Beta-agonists study (BAGS) retrospective analysis of the ACRN BAGS trial evaluated the effects of Gly 16 Arg genotypes on daily peakflow during regular SABA therapy. In the BAGS trial, Isreal and co-workers retrospectively examined the effects of Gly 16 Arg genotypes in 190 patients with mild asthma treated with regular or as-needed receptor albuterol therapy over a 16-week period.…”

Section: Adrβ2 Pharmacogenetics and The Response To Chronic Regular mentioning

confidence: 99%

“…66 One of the first The BARGE trial was prospective pharmacogenetic studies (The BARGE Trial) was designed to examine the effects of Gly 16 Arg genotypes on asthma control during regular SABA therapy in asthma subjects selected and randomized based on individual genotypes. 67 Thus, the BARGE trial was a genotype-stratified, placebo-controlled, cross-over trial in which 37 Arg 16 homozygotes and 41 Gly 16 homozygotes with mild asthma were treated with regular or as-needed albuterol therapy over a 16-week period then crossed over to the alternative therapy. Additionally, rescue therapy with beta agonists was minimized by using ipratropium bromide as the primary reliever medication and albuterol being used only if ipratropium was found to be ineffective.…”

Section: Adrβ2 Pharmacogenetics and The Response To Chronic Regular mentioning

confidence: 99%

Pharmacogenetics of the β2-Adrenergic Receptor Gene

Ortega

Hawkins

Peters

et al. 2007

Immunology and Allergy Clinics of North America

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Asthma is a complex genetic disease with multiple genetic and environmental determinants contributing to the observed variability in response to common anti-asthma therapies. Asthma pharmacogenetic research has focused on multiple candidate genes including the β2-adrenergic receptor gene (ADRβ2) and its effect on individual responses to beta agonist therapy. At present, knowledge about the effects of ADRβ2 variation on therapeutic responses is evolving and should not alter current Asthma Guideline approaches consisting of the use of short acting beta agonists for as-needed symptom based therapy and the use of a regular long-acting beta agonist in combination with inhaled corticosteroid therapy for optimal control of asthma symptoms in those asthmatics who are not controlled on inhaled corticosteroid alone. This approach is based upon studies showing a consistent pharmacogenetic response to regular use of short acting beta agonists (SABA) and less consistent findings in studies evaluating long acting beta agonist (LABA). While emerging pharmacogenetic studies are provocative and should lead to functional approaches, conflicting data with responses to LABA therapy may be caused by factors that include small sample sizes of study populations and differences in experimental design that may limit the conclusions that may be drawn from these clinical trials at the present time.

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