Metzger Nicole L, Kockler Denise R, Gravatt Leigh Anne Hylton
Virginia Commonwealth University Health System, Medical College of Virginia Hospitals, Richmond, VA 23298, USA.
Ann Pharmacother. 2008 Jun;42(6):874-81. doi: 10.1345/aph.1K682. Epub 2008 Apr 22.
To report a case of confirmed beta(16) Arg/Arg polymorphism (Arg/Arg) in a patient with uncontrolled asthma.
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 beta(2)-agonist (SABA). Because of her asthma history, self-reported adherence, and race, she was tested for beta(2)-adrenoreceptor genotype, which revealed Arg/Arg. Based on these findings, beta(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.
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 beta(2)-agonists may occur in these individuals. Data exist, although they are conflicting, suggesting that inhaled beta(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 beta(2)-agonists (LABAs) have inconsistent results. Preliminary data suggest that anticholinergics may serve as a beneficial primary rescue medication instead of beta(2)-agonists in patients with Arg/Arg.
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 beta(2)-adrenoreceptor genotyping and, possibly, from anticholinergics.
报告一例确诊为β(16)精氨酸/精氨酸多态性(Arg/Arg)的哮喘控制不佳患者。
一名49岁的黑人女性因急性呼吸急促到急诊科就诊,随后接受了插管治疗。拔管后,她报告曾多次因哮喘住院,之前有过一次插管经历,一直坚持使用哮喘药物,且频繁使用短效β(2)激动剂(SABA)。鉴于她的哮喘病史、自述的依从性以及种族,对她进行了β(2)肾上腺素能受体基因型检测,结果显示为Arg/Arg。基于这些发现,停用了β(2)激动剂,并开始使用噻托溴铵(维持治疗)和异丙托溴铵(主要急救药物)作为她哮喘治疗方案的一部分。应用纳兰霍概率量表显示,我们的患者哮喘控制不佳与使用SABA之间可能存在因果关系。该患者在我们的门诊肺科诊所接受随访,在撰写本文时,尚未因哮喘相关事件入住我院。
大约15%的美国哮喘患者为Arg/Arg,在黑人和亚洲人群中的患病率更高。据推测,这些个体对β(2)激动剂支气管扩张作用的敏感性或脱敏程度可能会发生变化。虽然现有数据相互矛盾,但有证据表明吸入β(2)激动剂可能会使临床结局恶化。试验报告称,在Arg/Arg患者中定期使用SABA时,呼气峰值流速会下降,哮喘症状和病情加重会增加。评估长效β(2)激动剂(LABA)的研究结果不一致。初步数据表明,在Arg/Arg患者中,抗胆碱能药物可能作为有益的主要急救药物替代β(2)激动剂。
临床医生应了解可能预示定期使用SABA甚至LABA会产生不良结局的因素(如种族和多态性)。尽管坚持哮喘治疗但哮喘控制不佳的患者可能会从β(2)肾上腺素能受体基因分型中获益,也可能从抗胆碱能药物中获益。