哮喘的发病机理：我们目前对哮喘的理解告诉我们哪些新的治疗方法？
2011/10/13
摘要
目前，哮喘的治疗主要采用肾上腺素能支气管扩张剂和抗炎药物，这些药物的特异性、有效性、药效时间和安全性已通过经典的药理学和医学化学进行了深入的研究。哮喘属于Th2型炎症性疾病，常常与特应性和过敏性共患病相关。基于此，我们可以采用针对该通路的治疗手段。目前，正在进行一项系统性综述，同时，Clinicaltrials.gov 网站也正在对进行中的临床试验进行回顾。治疗主要采用生物制剂，针对包括T细胞本身及其相关的细胞因子、趋化因子和受体在内的靶点。除了抗人IgE，动物模型和人体体外实验并未证实其他治疗能产生预期的效果。大部分的新治疗仅对非常小部分人产生效应。因此，需要对哮喘的分层具有更深入的理解、寻找哮喘相关通路、开发合适的诊断试验来靶向性选择针对特定哮喘表现型的治疗方式，这些都有利于新型药物的开发。目前，对哮喘的认识是，哮喘不仅仅是过敏性疾病，这使得需要改善预测性的动物模型。此外，一些环境因素以一种无序的方式作用于上皮细胞，参与了哮喘启动、巩固和恶化。哮喘整合模型中，将上皮细胞置于哮喘致病过程的前沿，这表明哮喘的治疗需要改善气道对吸入环境物质的抵抗，而不仅仅限于抑制炎症。
（刘国梁 审校）
J Allergy Clin Immunol. 2011 Jul 30. [Epub ahead of print]
Pathophysiology of asthma: What has our current understanding taught us about new therapeutic approaches?
Holgate ST.
Source
Division of Infection, Inflammation and Immunity, University of Southampton School of Medicine, Southampton General Hospital, Southampton, United Kingdom.
Abstract
Current asthma therapy is based on the use of adrenergic bronchodilator and anti-inflammatory drugs the specificity, efficacy, duration of action, and safety of which have been derived through classical pharmacology and medicinal chemistry. That asthma is a T(H)2-type inflammatory disorder frequently associated with atopy and allergic comorbidities has led to a concentrated effort to find treatments that act selectively on this pathway. A systematic literature review was undertaken, as well as a review of the Web site Clinicaltrials.gov for ongoing trials. Targets have included T cells themselves and their associated cytokines, chemokines, and receptors mostly targeted with biological agents. With the exception of anti-human IgE, none of these have met the expectations predicted from animal models and human in vitro tests. For most of these new therapies, only a very small subpopulation appears to respond. A case is made for a different approach to drug discovery based on acquiring a greater understanding of asthma stratification, the relevant pathways involved, and the development of appropriate diagnostic tests enabling the targeting of selective treatments to those asthmatic phenotypes most likely to respond. The recognition that asthma is more than allergy mandates improved predictive animal models and an appreciation that many of the environmental insults that initiate, consolidate, and exacerbate asthma operate through an epithelium functioning in a disorderly fashion. An integrated model that places the epithelium at the forefront of asthma pathogenesis suggests that greater emphasis should be placed on therapeutics that increase the airways’ resistance against the inhaled environment rather than focusing only on suppression of inflammation.
J Allergy Clin Immunol. 2011 Jul 30. [Epub ahead of print]
目前，哮喘的治疗主要采用肾上腺素能支气管扩张剂和抗炎药物，这些药物的特异性、有效性、药效时间和安全性已通过经典的药理学和医学化学进行了深入的研究。哮喘属于Th2型炎症性疾病，常常与特应性和过敏性共患病相关。基于此，我们可以采用针对该通路的治疗手段。目前，正在进行一项系统性综述，同时，Clinicaltrials.gov 网站也正在对进行中的临床试验进行回顾。治疗主要采用生物制剂，针对包括T细胞本身及其相关的细胞因子、趋化因子和受体在内的靶点。除了抗人IgE，动物模型和人体体外实验并未证实其他治疗能产生预期的效果。大部分的新治疗仅对非常小部分人产生效应。因此，需要对哮喘的分层具有更深入的理解、寻找哮喘相关通路、开发合适的诊断试验来靶向性选择针对特定哮喘表现型的治疗方式，这些都有利于新型药物的开发。目前，对哮喘的认识是，哮喘不仅仅是过敏性疾病，这使得需要改善预测性的动物模型。此外，一些环境因素以一种无序的方式作用于上皮细胞，参与了哮喘启动、巩固和恶化。哮喘整合模型中，将上皮细胞置于哮喘致病过程的前沿，这表明哮喘的治疗需要改善气道对吸入环境物质的抵抗，而不仅仅限于抑制炎症。
（刘国梁 审校）
J Allergy Clin Immunol. 2011 Jul 30. [Epub ahead of print]
Pathophysiology of asthma: What has our current understanding taught us about new therapeutic approaches?
Holgate ST.
Source
Division of Infection, Inflammation and Immunity, University of Southampton School of Medicine, Southampton General Hospital, Southampton, United Kingdom.
Abstract
Current asthma therapy is based on the use of adrenergic bronchodilator and anti-inflammatory drugs the specificity, efficacy, duration of action, and safety of which have been derived through classical pharmacology and medicinal chemistry. That asthma is a T(H)2-type inflammatory disorder frequently associated with atopy and allergic comorbidities has led to a concentrated effort to find treatments that act selectively on this pathway. A systematic literature review was undertaken, as well as a review of the Web site Clinicaltrials.gov for ongoing trials. Targets have included T cells themselves and their associated cytokines, chemokines, and receptors mostly targeted with biological agents. With the exception of anti-human IgE, none of these have met the expectations predicted from animal models and human in vitro tests. For most of these new therapies, only a very small subpopulation appears to respond. A case is made for a different approach to drug discovery based on acquiring a greater understanding of asthma stratification, the relevant pathways involved, and the development of appropriate diagnostic tests enabling the targeting of selective treatments to those asthmatic phenotypes most likely to respond. The recognition that asthma is more than allergy mandates improved predictive animal models and an appreciation that many of the environmental insults that initiate, consolidate, and exacerbate asthma operate through an epithelium functioning in a disorderly fashion. An integrated model that places the epithelium at the forefront of asthma pathogenesis suggests that greater emphasis should be placed on therapeutics that increase the airways’ resistance against the inhaled environment rather than focusing only on suppression of inflammation.
J Allergy Clin Immunol. 2011 Jul 30. [Epub ahead of print]
上一篇：
重度持续过敏性哮喘患者在奥玛珠单抗治疗期间的气道炎症和呼出气冷凝液嗜酸粒细胞趋化因子
下一篇：
学龄前哮喘高危儿童停用氟替卡松2年后的生长情况
