对2型炎症型未控制持续性哮喘治疗中的关键问题的认识
2021/02/09
摘要
哮喘是一种复杂的呼吸系统疾病，其严重程度和治疗反应之间并不一致。目前已确定了一些具有独特临床和炎症特征的哮喘表型。基于不同分子信息的内型有助于进一步了解哮喘的异质性。2型炎症包括固有免疫系统（2型固有淋巴细胞）和适应性免疫系统（辅助性T细胞2型）免疫系统，其支持哮喘慢性炎症的复杂病理生理学的基础，以及共患病（如慢性鼻-鼻窦炎伴鼻息肉、过敏性鼻炎和特应性皮炎）的存在。2型炎症的特点是2型细胞因子白细胞介素（IL）-4、IL-5和IL-13上调，免疫球蛋白E（IgE）介导的免疫介质释放，以及上皮或表皮屏障功能受损。最近一些使用靶向生物制剂进行个体化治疗的研究显示，靶向这些关键的2型细胞因子是有效的。2型细胞因子下游的生物标志物水平升高，包括呼出气一氧化氮、血清IgE、血液和痰中嗜酸性粒细胞，与2型炎症的发生机制有关，其有可能对诊断、预测和监测治疗的反应性有帮助。本综述的目的是总结目前对哮喘中2型炎症生物学的认识，探讨其对2型炎症共患病的影响，并讨论在生物医药时代如何利用2型炎症生物标志物进行个体化治疗。
Understanding the key issues in the treatment of uncontrolled persistent asthma with type 2 inflammation.
William W Busse, Monica Kraft, Klaus F Rabe, Yamo Deniz, Paul Rowe, Marcella Ruddy, Mario Castro.
Abstract
Asthma is a complex respiratory disease that varies in severity and response to treatment. Several asthma phenotypes with unique clinical and inflammatory characteristics have been identified. Endotypes, based on distinct molecular profiles, help to further understand the heterogeneity within asthma. Type 2 inflammation, involving both the innate (type 2 innate lymphoid cell) and adaptive (T helper type 2 cells) immune systems, underpins the complex pathophysiology of chronic inflammation in asthma, as well as the presence of comorbid disease (such as chronic rhinosinusitis with nasal polyps, allergic rhinitis, and atopic dermatitis). Type 2 inflammation is characterised by upregulation of type 2 cytokines interleukin (IL)-4, IL-5, and IL-13, immunoglobulin E (IgE)-mediated release of immune mediators, and dysfunction of epithelial or epidermal barriers. Targeting these key proximal type 2 cytokines has shown efficacy in recent studies adopting a personalised approach to treatment using targeted biologics. Elevated levels of biomarkers downstream of type 2 cytokines, including fractional exhaled nitric oxide, serum IgE, and blood and sputum eosinophils, have been linked to mechanisms involved in type 2 inflammation, and have the potential to aid diagnosis, and predict and monitor response to treatment. The objective of this review is to summarise the current understanding of the biology of type 2 inflammation in asthma, examine its influence on type 2 inflammatory comorbidities, and discuss how type 2 inflammatory biomarkers can be harnessed to further personalise treatments in the age of biologic medicines.
哮喘是一种复杂的呼吸系统疾病，其严重程度和治疗反应之间并不一致。目前已确定了一些具有独特临床和炎症特征的哮喘表型。基于不同分子信息的内型有助于进一步了解哮喘的异质性。2型炎症包括固有免疫系统（2型固有淋巴细胞）和适应性免疫系统（辅助性T细胞2型）免疫系统，其支持哮喘慢性炎症的复杂病理生理学的基础，以及共患病（如慢性鼻-鼻窦炎伴鼻息肉、过敏性鼻炎和特应性皮炎）的存在。2型炎症的特点是2型细胞因子白细胞介素（IL）-4、IL-5和IL-13上调，免疫球蛋白E（IgE）介导的免疫介质释放，以及上皮或表皮屏障功能受损。最近一些使用靶向生物制剂进行个体化治疗的研究显示，靶向这些关键的2型细胞因子是有效的。2型细胞因子下游的生物标志物水平升高，包括呼出气一氧化氮、血清IgE、血液和痰中嗜酸性粒细胞，与2型炎症的发生机制有关，其有可能对诊断、预测和监测治疗的反应性有帮助。本综述的目的是总结目前对哮喘中2型炎症生物学的认识，探讨其对2型炎症共患病的影响，并讨论在生物医药时代如何利用2型炎症生物标志物进行个体化治疗。
(中日友好医院呼吸与危重症医学科 顾宪民 摘译 林江涛 审校)
(Eur Respir J. 2021 Feb 4;2003393. doi: 10.1183/13993003.03393-2020.)
(Eur Respir J. 2021 Feb 4;2003393. doi: 10.1183/13993003.03393-2020.)
Understanding the key issues in the treatment of uncontrolled persistent asthma with type 2 inflammation.
William W Busse, Monica Kraft, Klaus F Rabe, Yamo Deniz, Paul Rowe, Marcella Ruddy, Mario Castro.
Abstract
Asthma is a complex respiratory disease that varies in severity and response to treatment. Several asthma phenotypes with unique clinical and inflammatory characteristics have been identified. Endotypes, based on distinct molecular profiles, help to further understand the heterogeneity within asthma. Type 2 inflammation, involving both the innate (type 2 innate lymphoid cell) and adaptive (T helper type 2 cells) immune systems, underpins the complex pathophysiology of chronic inflammation in asthma, as well as the presence of comorbid disease (such as chronic rhinosinusitis with nasal polyps, allergic rhinitis, and atopic dermatitis). Type 2 inflammation is characterised by upregulation of type 2 cytokines interleukin (IL)-4, IL-5, and IL-13, immunoglobulin E (IgE)-mediated release of immune mediators, and dysfunction of epithelial or epidermal barriers. Targeting these key proximal type 2 cytokines has shown efficacy in recent studies adopting a personalised approach to treatment using targeted biologics. Elevated levels of biomarkers downstream of type 2 cytokines, including fractional exhaled nitric oxide, serum IgE, and blood and sputum eosinophils, have been linked to mechanisms involved in type 2 inflammation, and have the potential to aid diagnosis, and predict and monitor response to treatment. The objective of this review is to summarise the current understanding of the biology of type 2 inflammation in asthma, examine its influence on type 2 inflammatory comorbidities, and discuss how type 2 inflammatory biomarkers can be harnessed to further personalise treatments in the age of biologic medicines.
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