Centre for Inflammation, Centenary Institute and University of Technology Sydney , Sydney, Australia.
Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and the University of Newcastle , Newcastle, Australia.
Expert Opin Ther Targets. 2020 Sep;24(9):845-857. doi: 10.1080/14728222.2020.1786535. Epub 2020 Jul 7.
Asthma is a heterogeneous disease with complex multifactorial causes. It is possible to subclassify asthma into different phenotypes that have distinct immunological features. Eosinophilic asthma is a well-known phenotype of severe asthma; however, a large body of clinical and experimental evidence strongly associates persistent airway inflammation, including the accumulation of neutrophils in the bronchial mucosa, and resistance to corticosteroid therapy and non-Type-2 immune responses with severe asthma. Importantly, mainstay therapies are often ineffective in severe asthma and effective alternatives are urgently needed.
Here, we discussed recently developed mouse models of severe asthma that recapitulates key features of the disease in humans. We also provide findings from clinically relevant experimental models that have identified potential therapeutic targets for severe asthma. The most relevant publications on the topic of interest were selected from PubMed.
Increasing the understanding of disease-causing mechanisms in severe asthma may lead to the identification of novel therapeutic targets and the development of more effective therapies. Intense research interest into investigating the pathophysiological mechanisms of severe asthma has driven the development and interrogation of a myriad of mouse models that aim to replicate hallmark features of severe asthma in humans.
哮喘是一种具有复杂多因素病因的异质性疾病。可以将哮喘分为具有不同免疫学特征的不同表型。嗜酸性粒细胞性哮喘是一种众所周知的严重哮喘表型;然而,大量的临床和实验证据强烈表明持续性气道炎症与严重哮喘相关,包括中性粒细胞在支气管黏膜中的积聚,以及对皮质类固醇治疗和非 2 型免疫反应的抵抗。重要的是,严重哮喘的主要治疗方法往往无效,迫切需要有效的替代方法。
在这里,我们讨论了最近开发的模拟人类严重哮喘关键特征的小鼠模型。我们还提供了来自临床相关实验模型的发现,这些模型确定了严重哮喘的潜在治疗靶点。从 PubMed 中选择了与感兴趣主题最相关的出版物。
深入了解严重哮喘的致病机制可能会导致发现新的治疗靶点和开发更有效的治疗方法。对严重哮喘病理生理机制的研究兴趣日益浓厚,推动了众多旨在模拟人类严重哮喘标志性特征的小鼠模型的开发和研究。