磷酸二酯酶抑制剂在哮喘治疗中的潜在作用。

Neil Martin, Peter T Reid
{"title":"磷酸二酯酶抑制剂在哮喘治疗中的潜在作用。","authors":"Neil Martin,&nbsp;Peter T Reid","doi":"10.2165/00151829-200605030-00006","DOIUrl":null,"url":null,"abstract":"<p><p>Asthma is a chronic inflammatory condition characterised by reversible airflow obstruction and airway hyperreactivity. The course of the illness may be punctuated by exacerbations resulting in deterioration in quality of life and, in some cases, days lost from school or work. That asthma is common and increasingly prevalent magnifies the importance of any potential economic costs, and promoting asthma control represents an important public health agenda. While lifestyle changes represent a valuable contribution in some patients, the majority of asthmatic patients require therapeutic intervention. The recognition of the role of inflammation in the pathogenesis of asthma has led to an emphasis on regular anti-inflammatory therapy, of which inhaled corticosteroid treatment remains the most superior. In selected patients, further improvements in asthma control may be gained by the addition of regular inhaled long-acting beta(2)-adrenoceptor agonists or oral leukotriene receptor antagonists to inhaled corticosteroid therapy. However, a significant minority of patients with asthma remain poorly controlled despite appropriate treatment, suggesting that additional corticosteroid nonresponsive inflammatory pathways may be operative. Furthermore, some patients with asthma display an accelerated decline in lung function, suggesting that active airway re-modeling is occurring. Such observations have focused attention on the potential to develop new therapies which complement existing treatments by targeting additional inflammatory pathways. The central role of phosphodiesterase (PDE), and in particular the PDE4 enzyme, in the regulation of key inflammatory cells believed to be important in asthma - including eosinophils, lymphocytes, neutrophils and airway smooth muscle - suggests that drugs designed to target this enzyme will have the potential to deliver both bronchodilation and modulate the asthmatic inflammatory response. In vivo studies on individual inflammatory cells suggest that the effects are likely to be favorable in asthma, and animal study models have provided proof of concept; however, first-generation PDE inhibitors have been poorly tolerated due to adverse effects. The development of second-generation agents such as cilomilast and roflumilast heralds a further opportunity to test the potential of these agents, although to date only a limited amount of data from human studies has been published, making it difficult to draw firm conclusions.</p>","PeriodicalId":87162,"journal":{"name":"Treatments in respiratory medicine","volume":"5 3","pages":"207-17"},"PeriodicalIF":0.0000,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2165/00151829-200605030-00006","citationCount":"5","resultStr":"{\"title\":\"The potential role of phosphodiesterase inhibitors in the management of asthma.\",\"authors\":\"Neil Martin,&nbsp;Peter T Reid\",\"doi\":\"10.2165/00151829-200605030-00006\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Asthma is a chronic inflammatory condition characterised by reversible airflow obstruction and airway hyperreactivity. The course of the illness may be punctuated by exacerbations resulting in deterioration in quality of life and, in some cases, days lost from school or work. That asthma is common and increasingly prevalent magnifies the importance of any potential economic costs, and promoting asthma control represents an important public health agenda. While lifestyle changes represent a valuable contribution in some patients, the majority of asthmatic patients require therapeutic intervention. The recognition of the role of inflammation in the pathogenesis of asthma has led to an emphasis on regular anti-inflammatory therapy, of which inhaled corticosteroid treatment remains the most superior. In selected patients, further improvements in asthma control may be gained by the addition of regular inhaled long-acting beta(2)-adrenoceptor agonists or oral leukotriene receptor antagonists to inhaled corticosteroid therapy. However, a significant minority of patients with asthma remain poorly controlled despite appropriate treatment, suggesting that additional corticosteroid nonresponsive inflammatory pathways may be operative. Furthermore, some patients with asthma display an accelerated decline in lung function, suggesting that active airway re-modeling is occurring. Such observations have focused attention on the potential to develop new therapies which complement existing treatments by targeting additional inflammatory pathways. The central role of phosphodiesterase (PDE), and in particular the PDE4 enzyme, in the regulation of key inflammatory cells believed to be important in asthma - including eosinophils, lymphocytes, neutrophils and airway smooth muscle - suggests that drugs designed to target this enzyme will have the potential to deliver both bronchodilation and modulate the asthmatic inflammatory response. In vivo studies on individual inflammatory cells suggest that the effects are likely to be favorable in asthma, and animal study models have provided proof of concept; however, first-generation PDE inhibitors have been poorly tolerated due to adverse effects. The development of second-generation agents such as cilomilast and roflumilast heralds a further opportunity to test the potential of these agents, although to date only a limited amount of data from human studies has been published, making it difficult to draw firm conclusions.</p>\",\"PeriodicalId\":87162,\"journal\":{\"name\":\"Treatments in respiratory medicine\",\"volume\":\"5 3\",\"pages\":\"207-17\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2006-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.2165/00151829-200605030-00006\",\"citationCount\":\"5\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Treatments in respiratory medicine\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.2165/00151829-200605030-00006\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Treatments in respiratory medicine","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2165/00151829-200605030-00006","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 5

摘要

哮喘是一种以可逆性气流阻塞和气道高反应性为特征的慢性炎症。病程可能因病情恶化而中断,导致生活质量下降,在某些情况下,失去上学或工作的时间。哮喘是常见的,而且越来越普遍,这放大了任何潜在经济成本的重要性,促进哮喘控制是一项重要的公共卫生议程。虽然生活方式的改变对一些患者来说是一个有价值的贡献,但大多数哮喘患者需要治疗干预。认识到炎症在哮喘发病机制中的作用,导致强调常规抗炎治疗,其中吸入皮质类固醇治疗仍然是最优越的。在选定的患者中,通过在吸入皮质类固醇治疗中加入常规吸入长效β(2)-肾上腺素能受体激动剂或口服白三烯受体拮抗剂,可进一步改善哮喘控制。然而,尽管接受了适当的治疗,仍有少数哮喘患者控制不佳,这表明额外的皮质类固醇无反应性炎症途径可能是有效的。此外,一些哮喘患者表现出肺功能的加速下降,表明正在发生主动气道重塑。这些观察结果将注意力集中在开发新疗法的潜力上,这些疗法可以通过靶向其他炎症途径来补充现有的治疗方法。磷酸二酯酶(PDE),特别是PDE4酶,在哮喘中被认为是重要的关键炎症细胞(包括嗜酸性粒细胞、淋巴细胞、中性粒细胞和气道平滑肌)的调节中的核心作用表明,针对这种酶设计的药物将有可能提供支气管扩张和调节哮喘炎症反应。对单个炎症细胞的体内研究表明,该效应可能对哮喘有利,动物研究模型已经提供了概念证明;然而,由于不良反应,第一代PDE抑制剂的耐受性较差。第二代药物如cilomilast和roflumilast的开发预示着测试这些药物潜力的进一步机会,尽管迄今为止只有有限数量的人体研究数据已发表,因此很难得出确定的结论。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
The potential role of phosphodiesterase inhibitors in the management of asthma.

Asthma is a chronic inflammatory condition characterised by reversible airflow obstruction and airway hyperreactivity. The course of the illness may be punctuated by exacerbations resulting in deterioration in quality of life and, in some cases, days lost from school or work. That asthma is common and increasingly prevalent magnifies the importance of any potential economic costs, and promoting asthma control represents an important public health agenda. While lifestyle changes represent a valuable contribution in some patients, the majority of asthmatic patients require therapeutic intervention. The recognition of the role of inflammation in the pathogenesis of asthma has led to an emphasis on regular anti-inflammatory therapy, of which inhaled corticosteroid treatment remains the most superior. In selected patients, further improvements in asthma control may be gained by the addition of regular inhaled long-acting beta(2)-adrenoceptor agonists or oral leukotriene receptor antagonists to inhaled corticosteroid therapy. However, a significant minority of patients with asthma remain poorly controlled despite appropriate treatment, suggesting that additional corticosteroid nonresponsive inflammatory pathways may be operative. Furthermore, some patients with asthma display an accelerated decline in lung function, suggesting that active airway re-modeling is occurring. Such observations have focused attention on the potential to develop new therapies which complement existing treatments by targeting additional inflammatory pathways. The central role of phosphodiesterase (PDE), and in particular the PDE4 enzyme, in the regulation of key inflammatory cells believed to be important in asthma - including eosinophils, lymphocytes, neutrophils and airway smooth muscle - suggests that drugs designed to target this enzyme will have the potential to deliver both bronchodilation and modulate the asthmatic inflammatory response. In vivo studies on individual inflammatory cells suggest that the effects are likely to be favorable in asthma, and animal study models have provided proof of concept; however, first-generation PDE inhibitors have been poorly tolerated due to adverse effects. The development of second-generation agents such as cilomilast and roflumilast heralds a further opportunity to test the potential of these agents, although to date only a limited amount of data from human studies has been published, making it difficult to draw firm conclusions.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
自引率
0.00%
发文量
0
期刊最新文献
Idiopathic Pulmonary Fibrosis Nosocomial pneumonia : rationalizing the approach to empirical therapy. Managing asthma in expectant mothers. New strategies for the treatment of pulmonary hypertension in sickle cell disease : the rationale for arginine therapy. Antioxidant strategies in respiratory medicine.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1