2型低度哮喘的治疗选择
2020/07/13
摘要
事实证明，靶向IgE或2型细胞因子IL-4、IL-5和IL-13的单克隆抗体分别在减轻严重过敏性哮喘和嗜酸性粒细胞性哮喘患者的急性发作和临床症状方面非常有效。然而，这些疗法并不适用于30-50%的表现为非过敏性、非嗜酸性、“2型低”的严重哮喘患者。这些患者构成了一种重要而常见的临床哮喘表型，由不同的、但知之甚少的病理生物学机制驱动。在这篇综述中，我们描述了低2型哮喘的异质性和临床特征，并总结了其潜在的病理生物学机制，包括与吸烟、肥胖、职业暴露相关的中性粒细胞气道炎症，可能是由持续的细菌感染和最近描述的IL-6途径的激活所驱动的。我们回顾了现有的可识别和解决的可治疗特征的治疗方案背后的证据基础。我们特别关注严重哮喘而不是难治性哮喘，关注气道细菌感染鉴定的新数据，长期使用低剂量大环内酯类药物的越来越多的证据基础（支气管热成形术的重要评估）以及在低2型疾病中使用生物制剂的证据。最后，我们综述了正在进行的其他途径的研究，包括TNF、IL-17、溶血素、载脂蛋白、I型干扰素、IL-6和肥大细胞。我们认为，低2型哮喘提供了识别和治疗可解决的临床问题的机会，目前是一个快速发展的领域，具有开发新的靶向治疗的潜力。
Treatment Options in type-2 Low Asthma.
Timothy Sc Hinks, Stewart J Levine, Guy G Brusselle.
Abstract
Monoclonal antibodies targeting IgE or the type-2 cytokines IL-4, IL-5 and IL-13 are proving highly effective in reducing exacerbations and symptoms in people with severe allergic and eosinophilic asthma respectively. However, these therapies are not appropriate for 30-50% of patients in severe asthma clinics who present with non-allergic, non-eosinophilic, "type-2 low" asthma. These patients constitute an important and common clinical asthma phenotype, driven by distinct, though poorly understood pathobiological mechanisms. In this review we describe the heterogeneity and clinical characteristics of type-2 low asthma and summarise current knowledge on the underlying pathobiological mechanisms, which includes neutrophilic airway inflammation often associated with smoking, obesity, occupational exposures and may be driven by persistent bacterial infections and by activation of a recently-described IL-6 pathway. We review the evidence base underlying existing treatment options for specific treatable traits which can be identified and addressed. We particularly focus on severe asthma as opposed to difficult-to-treat asthma, on emerging data on the identification of airway bacterial infection, on the increasing evidence base for the use of long-term low-dose macrolides, a critical appraisal of bronchial thermoplasty, and evidence for the use of biologics in type-2 low disease. Finally we review ongoing research into other pathways including TNF, IL-17, resolvins, apolipoproteins, type I interferons, IL-6 and mast cells. We suggest that type-2 low disease frequently presents opportunities for identification and treatment of tractable clinical problems and is currently a rapidly evolving field with potential for the development of novel targeted therapeutics.
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事实证明，靶向IgE或2型细胞因子IL-4、IL-5和IL-13的单克隆抗体分别在减轻严重过敏性哮喘和嗜酸性粒细胞性哮喘患者的急性发作和临床症状方面非常有效。然而，这些疗法并不适用于30-50%的表现为非过敏性、非嗜酸性、“2型低”的严重哮喘患者。这些患者构成了一种重要而常见的临床哮喘表型，由不同的、但知之甚少的病理生物学机制驱动。在这篇综述中，我们描述了低2型哮喘的异质性和临床特征，并总结了其潜在的病理生物学机制，包括与吸烟、肥胖、职业暴露相关的中性粒细胞气道炎症，可能是由持续的细菌感染和最近描述的IL-6途径的激活所驱动的。我们回顾了现有的可识别和解决的可治疗特征的治疗方案背后的证据基础。我们特别关注严重哮喘而不是难治性哮喘，关注气道细菌感染鉴定的新数据，长期使用低剂量大环内酯类药物的越来越多的证据基础（支气管热成形术的重要评估）以及在低2型疾病中使用生物制剂的证据。最后，我们综述了正在进行的其他途径的研究，包括TNF、IL-17、溶血素、载脂蛋白、I型干扰素、IL-6和肥大细胞。我们认为，低2型哮喘提供了识别和治疗可解决的临床问题的机会，目前是一个快速发展的领域，具有开发新的靶向治疗的潜力。
(中日友好医院呼吸与危重症医学科 王瑞茵 摘译 林江涛 审校)
(Eur Respir J (IF: 11.807). 2020 Jun 25;2000528.)
(Eur Respir J (IF: 11.807). 2020 Jun 25;2000528.)
Treatment Options in type-2 Low Asthma.
Timothy Sc Hinks, Stewart J Levine, Guy G Brusselle.
Abstract
Monoclonal antibodies targeting IgE or the type-2 cytokines IL-4, IL-5 and IL-13 are proving highly effective in reducing exacerbations and symptoms in people with severe allergic and eosinophilic asthma respectively. However, these therapies are not appropriate for 30-50% of patients in severe asthma clinics who present with non-allergic, non-eosinophilic, "type-2 low" asthma. These patients constitute an important and common clinical asthma phenotype, driven by distinct, though poorly understood pathobiological mechanisms. In this review we describe the heterogeneity and clinical characteristics of type-2 low asthma and summarise current knowledge on the underlying pathobiological mechanisms, which includes neutrophilic airway inflammation often associated with smoking, obesity, occupational exposures and may be driven by persistent bacterial infections and by activation of a recently-described IL-6 pathway. We review the evidence base underlying existing treatment options for specific treatable traits which can be identified and addressed. We particularly focus on severe asthma as opposed to difficult-to-treat asthma, on emerging data on the identification of airway bacterial infection, on the increasing evidence base for the use of long-term low-dose macrolides, a critical appraisal of bronchial thermoplasty, and evidence for the use of biologics in type-2 low disease. Finally we review ongoing research into other pathways including TNF, IL-17, resolvins, apolipoproteins, type I interferons, IL-6 and mast cells. We suggest that type-2 low disease frequently presents opportunities for identification and treatment of tractable clinical problems and is currently a rapidly evolving field with potential for the development of novel targeted therapeutics.
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上一篇：
一项来自法国早期计划数据的研究-美伯利单抗在重症嗜酸性粒细胞型及激素依赖型哮喘患者中的应用
下一篇：
支气管热成形术对重度哮喘患者气道结构及炎性介质的影响
