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病毒诱导的气道疾病概述。

Overview of virus-induced airway disease.

作者信息

Johnston Sebastian L

机构信息

Department of Respiratory Medicine, National Heart & Lung Institute and Wright Fleming Institute of Infection & Immunity, Imperial College London, Norfolk Place, London W2 1PG, UK.

出版信息

Proc Am Thorac Soc. 2005;2(2):150-6. doi: 10.1513/pats.200502-018AW.

Abstract

Acute exacerbations of asthma and chronic obstructive pulmonary disease (COPD) are the major cause of morbidity, mortality, and health costs of both diseases. Currently available treatments are poorly effective in both acute treatment of and prevention of acute exacerbations. New treatments for intervention and prophylaxis are therefore required; to facilitate their development, we must understand the causes and mechanisms of exacerbations. Respiratory viral infections (2/3 rhinoviruses) precipitate 80% or more of asthma exacerbations in children, and the majority of exacerbations of asthma and COPD in adults, but mechanisms of virus-induced lower airway inflammation and of host resistance against respiratory viruses are poorly understood. Development of in vitro experimental models of virus infection has identified interferon-beta and nitric oxide as possible therapeutic targets to augment antiviral immunity, and nuclear factor-kappaB as a target for development of anti-inflammatory therapies. In vivo models could also serve to identify and validate targets and as an experimental system to test candidate molecules as they emerge into clinical studies. Studies in asthma have paved the way for development of an asthma model; a similar experimental model in COPD would accelerate development of new therapies for these common diseases with enormous burdens of illness.

摘要

哮喘和慢性阻塞性肺疾病(COPD)的急性加重是这两种疾病发病、死亡及医疗费用的主要原因。目前可用的治疗方法在急性加重的治疗和预防方面效果不佳。因此,需要新的干预和预防治疗方法;为了促进这些方法的开发,我们必须了解急性加重的原因和机制。呼吸道病毒感染(2/3为鼻病毒)引发了80%或更多儿童哮喘急性加重,以及大多数成人哮喘和COPD的急性加重,但病毒诱导的下呼吸道炎症机制以及宿主对呼吸道病毒的抵抗力尚不清楚。病毒感染体外实验模型的开发已确定β-干扰素和一氧化氮可能是增强抗病毒免疫力的治疗靶点,而核因子-κB是抗炎治疗开发的靶点。体内模型也可用于识别和验证靶点,并作为一个实验系统来测试进入临床研究的候选分子。哮喘研究为哮喘模型的开发铺平了道路;COPD中类似的实验模型将加速针对这些负担巨大的常见疾病的新疗法的开发。

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