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Confirmed β₁₆ Arg/Arg Polymorphism in a Patient with Uncontrolled Asthma

Internal Medicine Specialty Resident, Virginia Commonwealth University Health System, Medical College of Virginia Hospitals, Richmond, VA

Denise R Kockler, PharmD BCPS

Director, Drug Information Services, Virginia Commonwealth University Health System, Medical College of Virginia Hospitals; Assistant Clinical Professor, School of Pharmacy, Virginia Commonwealth University

Leigh Anne Hylton Gravatt, PharmD BCPS

Clinical Specialist, Internal Medicine, Virginia Commonwealth University Health System, Medical College of Virginia Hospitals; Assistant Clinical Professor, School of Pharmacy, Virginia Commonwealth University

Reprints: Dr. Kockler, School of Pharmacy, Virginia Commonwealth University, 401 N. 12th St., PO Box 980042, Richmond, VA 23298, fax 804/628-3919, dkockler{at}mcvh-vcu.edu

OBJECTIVE: To report a case of confirmed β₁₆ Arg/Arg polymorphism (Arg/Arg) in a patient with uncontrolled asthma.

CASE SUMMARY: A 49-year-old black female presented to the emergency department with acute shortness of breath with subsequent intubation. After extubation, she reported multiple hospitalizations for asthma with one prior intubation, adherence to asthma medications, and very frequent use of her short-acting β₂-agonist (SABA). Because of her asthma history, self-reported adherence, and race, she was tested for β₂-adrenoreceptor genotype, which revealed Arg/Arg. Based on these findings, β₂-agonists were discontinued and tiotropium (maintenance) and ipratropium (primary rescue) were initiated as part of her asthma regimen. Application of the Naranjo probability scale revealed probable causality between uncontrolled asthma in our patient and SABA use. The patient is followed in our outpatient pulmonary clinic and, at time of writing, had not been admitted to our hospital for asthma-related events.

DISCUSSION: Approximately 15% of Americans with asthma are Arg/Arg, with an increased prevalence in black and Asian populations. It is hypothesized that changes in the degree of sensitivity or desensitization to the bronchodilator effect of β₂-agonists may occur in these individuals. Data exist, although they are conflicting, suggesting that inhaled β₂-agonists may worsen clinical outcomes. Trials have reported declines in peak expiratory flow rates plus increases in asthma symptoms and exacerbations when SABAs have been used regularly in patients with Arg/Arg. Studies evaluating long-acting β₂-agonists (LABAs) have inconsistent results. Preliminary data suggest that anticholinergics may serve as a beneficial primary rescue medication instead of β₂-agonists in patients with Arg/Arg.

CONCLUSIONS: Clinicians should be aware of factors (eg, race and polymorphisms) that may predict unfavorable outcomes with regular SABA and possibly LABA use. Patients with poor asthma control despite adherence to asthma therapy may benefit from β₂-adrenoreceptor genotyping and, possibly, from anticholinergics.

Key Words: anticholinergic, asthma, β-agonist, polymorphism

Published Online, April 22, 2008. www.theannals.com, DOI 10.1345/aph.1K682