Wake Forest University Health Sciences, Center for Genomics and Personalized Medicine Research, Medical Center Boulevard, Winston-Salem, NC 27157, United States.
Curr Opin Pharmacol. 2010 Jun;10(3):226-35. doi: 10.1016/j.coph.2010.05.013.
Current asthma treatments are effective for most but not all patients. Asthma is classified as a complex genetic disease with its pathogenesis and expression (severity) determined by the interaction of many genes and environmental factors. Asthma is characterized by its heterogeneity in terms of its clinical and inflammatory phenotypes and their responses to therapy. This disease heterogeneity likely has played a role in variable results from clinical trials that evaluate specific inhibitors of inflammatory mediators ('biologics') in asthma. Moreover, although existing treatments are effective and safe in most asthma patients they may be less effective or potentially harmful in others. In addition, if an individual with asthma is less responsive to standard therapies such as corticosteroids because of specific pharmacogenetic interactions then that patient with asthma will be classified as having more severe or difficult-to-treat asthma. Pharmacogenetic approaches hold the promise of matching individualized treatments to specific genotypes in a way that minimizes side effects while improving therapeutic outcomes.
目前的哮喘治疗方法对大多数患者有效,但并非对所有患者都有效。哮喘被归类为一种复杂的遗传疾病,其发病机制和表达(严重程度)由许多基因和环境因素的相互作用决定。哮喘的特点是其临床和炎症表型及其对治疗的反应存在异质性。这种疾病异质性可能在评估哮喘中炎症介质特定抑制剂(“生物制剂”)的临床试验中产生了不同的结果。此外,尽管现有的治疗方法在大多数哮喘患者中有效且安全,但在其他患者中可能效果较差或潜在有害。此外,如果由于特定的药物遗传学相互作用,哮喘患者对皮质类固醇等标准治疗的反应较差,那么该哮喘患者将被归类为患有更严重或更难治疗的哮喘。药物遗传学方法有望通过将个体化治疗与特定基因型相匹配,在最小化副作用的同时改善治疗效果。