Holgate Stephen T
IIR Division, School of Medicine, Southampton General Hospital, Southampton, UK.
Curr Opin Pulm Med. 2009 Jan;15(1):63-71. doi: 10.1097/MCP.0b013e32831da867.
The use of inhaled corticosteroids, short and long acting beta2-adrenoceptor agonists and inhibitors of leukotrienes provide most asthmatic patients with good disease control. However, none of these therapies are specifically directed to the underlying causal pathways of asthma. In this review the role of selective inhibitors of the inflammatory cascade are presented with a particular emphasis on biologics.
Apart from antihuman immunoglobulin E, biologics have had little impact on this disease. However, with the definition of critical pathways in driving ongoing inflammation and airway remodelling, the situation is about to change with several exciting new approaches being on the horizon. Specific cytokines that are considered central to the Th2 inflammatory response as therapeutic targets are discussed along with some entirely new approaches such as restoration of mucosal innate immunity and epithelial barrier function and the application of radiofrequency ablation of airway smooth muscle or thermal bronchoplasty.
What is becoming clear in filling the pipeline with new asthma therapies that treat the underlying disease causes is the need for closer working between clinical academics and industry to ensure that there is a rapid and sustained transfer of knowledge on novel targets through to their validation, proof of concept studies and clinical trials.
吸入性糖皮质激素、短效和长效β2肾上腺素能受体激动剂以及白三烯抑制剂的使用为大多数哮喘患者提供了良好的疾病控制。然而，这些疗法均未针对哮喘的潜在病因途径。在本综述中，将介绍炎症级联反应选择性抑制剂的作用，尤其着重于生物制剂。
除抗人免疫球蛋白E外，生物制剂对该疾病影响甚微。然而，随着驱动持续性炎症和气道重塑的关键途径得以明确，随着几种令人振奋的新方法即将出现，情况将会改变。文中讨论了被视为Th2炎症反应核心治疗靶点的特定细胞因子，以及一些全新的方法，如恢复黏膜固有免疫和上皮屏障功能，以及应用气道平滑肌射频消融术或热支气管成形术。
在开发治疗潜在疾病病因的新哮喘疗法方面，日益明确的是，临床学者与产业界需要更紧密合作，以确保关于新靶点的知识能迅速且持续地从验证、概念验证研究转化至临床试验。
