Low Kathy, Bardin Philip G
Lung and Sleep Medicine, Monash University and Medical Centre, 246 Clayton Road, Clayton, Melbourne, VIC, 3168, Australia.
Hudson Institute, Melbourne, VIC, Australia.
Mol Diagn Ther. 2017 Jun;21(3):235-247. doi: 10.1007/s40291-016-0252-x.
Asthma affects over 300 million people worldwide. Most asthmatics are well controlled with inhaled corticosteroids and long-acting beta-agonists; however, a proportion of patients are unresponsive and attain limited disease control. This group represents a considerable healthcare and financial burden, particularly patients who experience frequent exacerbations and require hospital admission. Development of new biological agents and disease biomarkers has provided novel avenues for treatment. These treatments have been highly successful, reducing exacerbations and yielding modest improvements in quality of life and lung function. However, only a proportion of severe asthmatics respond to this targeted treatment, highlighting the heterogeneity of severe asthma. One of the first biological therapies targeted immunoglobulin E (IgE) and demonstrated modest benefit but could only be used in a subgroup of patients. Recent research has shown that treatment aimed at the T helper-2-(Th)-high pathways and cytokines such as interleukin (IL)-5, IL-4, and IL-13 may also be effective in another partially overlapping subgroup. A blood eosinophil count over a defined threshold (generally ≥300 cells/μl) was a reliable biomarker and identified the majority of responders in this group. Further discovery and validation of biological markers to define asthmatic phenotypes that may benefit from biological treatments remain an area of intense interest and research. We review the latest information pertaining to biological agents and demonstrate how patient responders may potentially be identified for treatment.
哮喘影响着全球超过3亿人。大多数哮喘患者通过吸入皮质类固醇和长效β受体激动剂得到良好控制;然而,一部分患者无反应,疾病控制有限。这一群体构成了相当大的医疗和经济负担,尤其是那些频繁发作并需要住院治疗的患者。新型生物制剂和疾病生物标志物的开发为治疗提供了新途径。这些治疗取得了巨大成功,减少了发作次数,并在生活质量和肺功能方面有适度改善。然而,只有一部分重度哮喘患者对这种靶向治疗有反应,这突出了重度哮喘的异质性。最早的一种生物疗法靶向免疫球蛋白E(IgE),显示出适度疗效,但只能用于一部分患者亚组。最近的研究表明,针对辅助性T细胞2(Th2)高途径以及白细胞介素(IL)-5、IL-4和IL-13等细胞因子的治疗在另一个部分重叠的亚组中可能也有效。超过特定阈值(一般≥300个细胞/μl)的血液嗜酸性粒细胞计数是一个可靠的生物标志物,可识别该组中的大多数有反应者。进一步发现和验证用于定义可能从生物治疗中获益的哮喘表型的生物标志物仍然是一个备受关注和研究的领域。我们综述了与生物制剂相关的最新信息,并展示了如何潜在地识别适合治疗的有反应患者。