A multi-scale modelling framework for airway hyper-responsiveness and remodelling in asthma

哮喘气道高反应性和重塑的多尺度建模框架

• 批准号: G0901174/1
• 负责人: Bindi Brook
• 金额: $ 58.42万
• 依托单位: University of Nottingham
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0901174%2F1
• 关键词: multi; scale; modelling; framework; airway

Asthma is a disease that affects the airways that carry air in and out of the lungs. During an asthmatic attack, triggered by irritants such as dust or smoke, the muscle cells that line the walls of the airways, contract and tighten so that the airway becomes narrower. The lining of the airways becomes inflamed and sticky mucus or phlegm is produced. All these reactions cause the airways to become narrower and irritated - leading to the symptoms of asthma such as coughing and wheezing. Over time, repeated episodes of asthma can cause the number of muscle cells to increase resulting in the airway wall getting thicker. There is currently no cure for asthma, and although it can be managed with regular medication, complications can still arise. Considerable research is currently being undertaken to identify the factors that cause asthma - from genetic to environmental factors. Other research is aimed at understanding why asthmatic airways narrow so much and so fast, and at identifying the factors that cause the airway walls to thicken. Much of the research has been carried out on very specific aspects of the disease. For instance, one research group will look very closely at the chemicals that are released inside the muscle cell as a result of inhaling the irritant. Another group may focus on the components in the muscle cell that cause it to contract. Yet another group might look at how the muscle cells together (the tissue) responds to manipulations such as stretching. All these different things, however, interact during an asthmatic attack, but it is not easy to work out what the effect of these interactions are, just by looking at the individual measurements.The intention of this work is to create a new mathematical framework that combines physics, mathematics and biological information from on-going experiments. The research will bridge the gaps between the different levels (cells to tissues) as well as develop new models at each level. This framework will thus help us to understand how the processes involved in asthma interact with each other, and so to understand what might happen if we could disrupt one of the processes. For instance, does the mathematical model predict a lessening of symptoms? Or does it predict a shuffle-around of the interactions, thus compensating for the disruption? Answers to these important questions will help scientists move closer towards finding new, more effective, therapies.

哮喘是一种疾病，它会影响将空气输送进肺和排出肺的呼吸道。在由灰尘或烟雾等刺激物引发的哮喘发作期间，排列在气道壁上的肌肉细胞收缩并收紧，从而使呼吸道变得狭窄。呼吸道内壁发炎，产生粘稠的粘液或痰。所有这些反应都会导致呼吸道变窄和刺激--导致哮喘的症状，如咳嗽和喘息。随着时间的推移，反复发作的哮喘会导致肌肉细胞数量增加，导致气道壁变厚。目前还没有治愈哮喘的方法，尽管可以通过常规药物治疗，但仍可能出现并发症。目前正在进行大量研究，以确定引起哮喘的因素--从遗传因素到环境因素。其他研究的目的是了解为什么哮喘的呼吸道变得如此之窄、如此之快，并确定导致气道壁增厚的因素。许多研究都是针对这种疾病的非常具体的方面进行的。例如，一个研究小组将非常仔细地研究由于吸入刺激物而在肌肉细胞内释放的化学物质。另一组可能专注于肌肉细胞中导致其收缩的成分。还有一组人可能会观察肌肉细胞(组织)一起对伸展等操作的反应。然而，在哮喘发作期间，所有这些不同的东西都会相互作用，但仅通过单独的测量来计算这些相互作用的影响并不容易。这项工作的目的是创建一个新的数学框架，将正在进行的实验中的物理、数学和生物信息结合在一起。这项研究将弥合不同层次(细胞到组织)之间的差距，并在每个层次上开发新的模型。因此，这个框架将帮助我们理解哮喘涉及的各个过程是如何相互作用的，从而理解如果我们可以扰乱其中一个过程可能会发生什么。例如，数学模型预测了症状的减轻吗？或者，它预测了互动的洗牌，从而补偿了干扰？这些重要问题的答案将帮助科学家朝着寻找新的、更有效的疗法更近一步。