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Original Research |

ADRB2 Polymorphisms and Budesonide/Formoterol Responses in COPDADRB2 Polymorphisms and Treatment Response in COPD

Eugene R. Bleecker, MD, FCCP; Deborah A. Meyers, PhD; William C. Bailey, MD, FCCP; Anne-Marie Sims, PhD; Sarah R. Bujac, MSc; Mitch Goldman, MD, PhD; Ubaldo J. Martin, MD
Author and Funding Information

From the Center for Genomics and Personalized Medicine (Drs Bleecker and Meyers), Wake Forest School of Medicine, Winston-Salem, NC; University of Alabama Lung Health Center (Dr Bailey), University of Alabama at Birmingham, Birmingham, AL; AstraZeneca (Dr Sims and Ms Bujac), Alderley Park, England; and AstraZeneca LP (Drs Goldman and Martin), Wilmington, DE

Correspondence to: Eugene R. Bleecker, MD, Center for Genomics and Personalized Medicine, Wake Forest School of Medicine, Medical Center Blvd, Winston-Salem, NC 27157; e-mail: ebleeck@wakehealth.edu


Funding/Support: This work was supported by AstraZeneca LP. Drs Bleecker and Meyers were partially supported by the National Institutes of Health [Grant HL 056899].

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2012;142(2):320-328. doi:10.1378/chest.11-1655
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Background:  Effects of β2-adrenergic receptor gene (ADRB2) polymorphism on therapeutic responses to long-acting β2-adrenergic agonists have not been evaluated in long-term COPD trials. We aimed to investigate the effects of the ADRB2 Gly16Arg polymorphism on response to formoterol alone or in combination with the inhaled corticosteroid budesonide in patients with COPD.

Methods:  Patients ≥ 40 years of age with moderate to very severe COPD from the 12-month trial I (NCT00206167) or the 6-month trial II (NCT00206154) were randomly assigned to bid budesonide/formoterol pressurized metered-dose inhaler (pMDI) 320/9 μg or 160/9 μg, budesonide pMDI 320 μg + formoterol dry powder inhaler 9 μg (trial II), budesonide pMDI 320 μg (trial II), formoterol dry powder inhaler 9 μg, or placebo. The effect of Gly16Arg on predose FEV1 and 1-h postdose FEV1, exacerbations, diary variables, and adverse events were analyzed.

Results:  No significant interaction between genotype and treatment response was observed for predose (P ≥ .197) or postdose FEV1 (P ≥ .125) in either pharmacogenetic study (n = 2,866). The number of COPD exacerbations per patient-treatment year was low and similar across genotypes for the active treatment groups (both studies). Percentages of patients with adverse events were similar across Gly16Arg genotype groups for each treatment.

Conclusion:  Therapeutic response and tolerability to long-term treatment with formoterol alone or in combination with budesonide was not modified by ADRB2 Gly16Arg genotype in two large independent pharmacogenetic studies in patients with moderate to very severe COPD.

Trial registry:  ClinicalTrials.gov; Nos.: NCT00206167, NCT00206154; URL: clinicaltrials.gov.

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