Department of Medicine, Section of Pulmonary and Critical Care, University of Chicago, Chicago, IL.
Department of Medicine, Section of Pulmonary and Critical Care, University of Chicago, Chicago, IL.
Chest. 2020 Mar;157(3):516-528. doi: 10.1016/j.chest.2019.10.009. Epub 2019 Oct 31.
This review focuses on recent clinical and translational discoveries in severe and uncontrolled asthma that now enable phenotyping and personalized therapies in these patients. Although asthma is common in both children and adults and typically responds to standard therapies, a subset of individuals with asthma experience severe and/or persistent symptoms despite appropriate therapies. Airflow obstruction leading to frequent symptoms requiring higher levels of controller therapy is the cardinal feature of severe asthma, but the underlying molecular mechanisms, or endotypes, are diverse and variable between individuals. Two major risk factors that contribute to severe asthma are genetics and environmental exposures that modulate immune responses, and although these often interact in complex manners that are not fully understood, certain endotypes converge in severe asthma. A number of studies have evaluated various features of patients with severe asthma and classified patients into phenotypes with clinical relevance. This phenotyping is now incorporated into clinical practice and can be used to guide advanced biological therapies that target specific molecules and inflammatory pathways that contribute to asthma pathogenesis.
这篇综述重点介绍了严重和无法控制的哮喘的最新临床和转化发现，这些发现现在可以对这些患者进行表型分析和个性化治疗。尽管哮喘在儿童和成人中都很常见，并且通常对标准治疗有反应，但仍有一部分哮喘患者尽管接受了适当的治疗，仍会出现严重和/或持续的症状。气流阻塞导致频繁出现需要更高水平的控制药物治疗的症状是严重哮喘的主要特征，但潜在的分子机制或表型在个体之间是多样的和可变的。导致严重哮喘的两个主要危险因素是遗传和环境暴露，这些因素会调节免疫反应，尽管这些因素通常以尚未完全理解的复杂方式相互作用，但某些表型在严重哮喘中趋于一致。许多研究已经评估了严重哮喘患者的各种特征，并将患者分为具有临床相关性的表型。这种表型分析现在已纳入临床实践，可以用于指导针对导致哮喘发病机制的特定分子和炎症途径的先进生物治疗。
