Division of Pulmonary, Critical Care and Environmental Medicine, School of Medicine, University of Missouri, Columbia, Missouri 65212, USA.
Curr Opin Allergy Clin Immunol. 2012 Feb;12(1):68-75. doi: 10.1097/ACI.0b013e32834ecb4f.
Severe asthma comprises heterogeneous phenotypes that share in common a poor response to traditional therapies. Recent and ongoing work with tyrosine kinase inhibitors suggests a potential beneficial role in treatment of severe asthma.
Various receptor and nonreceptor tyrosine kinase pathways contribute to aspects of airway inflammation, airway hyperresponsiveness, and remodeling of asthma. Selective and nonselective tyrosine kinase inhibitors may be useful to block pathways that are pathologically overactive or overexpressed in severe asthma. Recent in-vivo studies have demonstrated the utility of inhibitors against specific tyrosine kinases (epidermal growth factor receptor, c-kit/platelet derived growth factor receptor, vascular endothelial growth factor receptor, spleen tyrosine kinase, and janus kinase) in altering key aspects of severe asthma.
Asthma and even severe asthma does not consist of a single phenotype. Targeting key inflammatory and remodeling pathways engaged across subphenotypes with tyrosine kinase inhibitors appears to hold promise.
重度哮喘包含多种表型,这些表型的共同点是对传统疗法反应不佳。最近和正在进行的使用酪氨酸激酶抑制剂的研究表明,其在治疗重度哮喘方面可能具有潜在的益处。
各种受体和非受体酪氨酸激酶途径参与气道炎症、气道高反应性和哮喘重塑的各个方面。选择性和非选择性酪氨酸激酶抑制剂可能有助于阻断在重度哮喘中病理性过度活跃或过度表达的途径。最近的体内研究表明,针对特定酪氨酸激酶(表皮生长因子受体、c-kit/血小板衍生生长因子受体、血管内皮生长因子受体、脾酪氨酸激酶和 Janus 激酶)的抑制剂在改变重度哮喘的关键方面具有实用性。
哮喘甚至重度哮喘并不由单一表型组成。针对涉及多种表型的关键炎症和重塑途径的酪氨酸激酶抑制剂似乎具有很大的应用前景。