Inflammation Discovery Translational Area, Hoffmann-La Roche, Nutley, NJ 07110, USA.
Pharmacol Ther. 2011 May;130(2):93-105. doi: 10.1016/j.pharmthera.2010.10.008. Epub 2010 Nov 11.
Asthma and chronic obstructive pulmonary disease (COPD) are complex inflammatory airway diseases characterised by airflow obstruction that remain leading causes of hospitalization and death worldwide. Animal modelling systems that accurately reflect disease pathophysiology continue to be essential to the development of new therapies for both conditions. In this review, we describe preclinical in vivo models that recapitulate many of the features of asthma and COPD. Specifically, we discuss the pro's and con's of the standard models and highlight recently developed systems designed to more accurately reflect the complexity of both diseases. For instance, clinically relevant allergens (i.e. house dust mite) are now being used to mimic the inflammatory changes and airway remodelling that result after chronic allergen exposures. Additionally, systems are being developed to mimic steroid-resistant and viral exacerbations of allergic inflammation - aspects of asthma where there is an acute need for new therapies. Similarly, COPD models have evolved to align with the improved clinical understanding of the factors contributing to disease progression. This includes using cigarette smoke to model not only airway inflammation and remodelling, but some systemic changes (e.g. hypertension and skeletal muscle alterations) that are thought to influence disease. Further, mouse genetics are being exploited to gain insights into the genetics of COPD susceptibility. The new models of asthma and COPD described herein demonstrate that improved clinical understanding of the diseases and better preclinical models is an iterative process that will hopefully lead to therapies that can effectively manage severe asthma and COPD.
哮喘和慢性阻塞性肺疾病（COPD）是复杂的气道炎症性疾病，其特征是气流阻塞，它们仍然是全球导致住院和死亡的主要原因。能够准确反映疾病病理生理学的动物模型系统对于这两种疾病的新疗法的开发仍然至关重要。在这篇综述中，我们描述了可重现哮喘和 COPD 许多特征的临床前体内模型。具体来说，我们讨论了标准模型的优缺点，并强调了最近开发的旨在更准确地反映这两种疾病复杂性的系统。例如，现在使用临床相关过敏原（例如屋尘螨）来模拟慢性过敏原暴露后导致的炎症变化和气道重塑。此外，正在开发模拟类固醇耐药和病毒加重过敏炎症的系统——这是哮喘中急需新疗法的方面。同样，COPD 模型也在发展，以适应对导致疾病进展的因素的临床理解的提高。这包括使用香烟烟雾来模拟不仅是气道炎症和重塑，还有一些被认为会影响疾病的全身变化（例如高血压和骨骼肌改变）。此外，正在利用小鼠遗传学来深入了解 COPD 易感性的遗传学。本文描述的哮喘和 COPD 的新模型表明，对疾病的临床理解的提高和更好的临床前模型是一个迭代过程，希望这将导致能够有效治疗严重哮喘和 COPD 的疗法。
