Confirmed ₁₆ Arg/Arg Polymorphism in a Patient with Uncontrolled Asthma ^(June)

¹ Internal Medicine Specialty Resident, Virginia Commonwealth University Health System, Medical College of Virginia Hospitals, Richmond, VA
² Director, Drug Information Services, Virginia Commonwealth University Health System, Medical College of Virginia Hospitals; Assistant Clinical Professor, School of Pharmacy, Virginia Commonwealth University
³ Clinical Specialist, Internal Medicine, Virginia Commonwealth University Health System, Medical College of Virginia Hospitals; Assistant Clinical Professor, School of Pharmacy, Virginia Commonwealth University

	Abstract

OBJECTIVE: To report a case of confirmed ₁₆ 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 ₂-agonist (SABA). Because of her asthma history, self-reported adherence, and race, she was tested for ₂-adrenoreceptor genotype, which revealed Arg/Arg. Based on these findings, ₂-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 ₂-agonists may occur in these individuals. Data exist, although they are conflicting, suggesting that inhaled ₂-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 ₂-agonists (LABAs) have inconsistent results. Preliminary data suggest that anticholinergics may serve as a beneficial primary rescue medication instead of ₂-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 ₂-adrenoreceptor genotyping and, possibly, from anticholinergics.

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

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