Modelling lung deposition of inhaled particles in cystic fibrosis

模拟囊性纤维化中吸入颗粒的肺部沉积

• 批准号: 2487407
• 金额: --
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2487407
• 关键词: Modelling; lung; deposition; inhaled; particles

This project will use mathematical and computational modelling to investigate fundamental physical mechanisms of flow and transport in lung airways, considering in particular features relevant to cystic fibrosis and related aspects of drug delivery. The presence of large quantities of highly viscous mucus in airways is a primary symptom of cystic fibrosis, making it challenging to effectively administer inhaled therapies deep into the lungs. Using the machinery of theoretical continuum mechanics, this project will seek to improve our understanding of how mucus is distributed and transported throughout the lungs, and how this could affect the efficacy of different methods of drug delivery. There will be an initial focus on the impact of the complex rheological properties of diseased mucus (such as its yield stress) on transport within small airways in the lung periphery, regions of the lungs that are difficult to study experimentally and difficult to resolve using medical imaging. In the later stages of the project, multi-scale modelling approaches exploiting tools from discrete calculus will be used to assess how small-airway transport processes impact on drug-delivery at the organ scale, allowing incorporation of the effects of ventilation in the whole airway tree. This will require solution of transport equations on massive discrete networks, which will require relatively intensive computation due to the large number of airways involved. This approach, combined with dimensionality reduction techniques, will allow investigation into the effects of airway geometry on transport in the lungs and on development of disease. Throughout the project, model development will be motivated by the physiological and clinical applications, in particular the effective delivery of inhaled aerosolised pharmaceuticals to damaged or blocked lung regions in cystic fibrosis. To achieve this, the student will be guided by a multidisciplinary team of supervisors, drawn from the Department of Mathematics and the Division of Infection, Immunity & Respiratory Medicine at the University of Manchester. The models emerging from the project are likely to have broader potential application beyond cystic fibrosis (for example, to fundamental fluid mechanics), but this disease-specific approach means that the project will give new capabilities to realistically test and optimise drug-delivery protocols in silico that can make a real difference to patient treatment.

该项目将使用数学和计算模型来研究肺气道中流动和运输的基本物理机制，特别考虑与囊性纤维化和药物输送相关方面相关的特征。气道中大量高粘性粘液的存在是囊性纤维化的主要症状，这使得有效地将吸入疗法深入肺部具有挑战性。使用理论连续介质力学的机械，该项目将寻求提高我们对粘液如何在整个肺部分布和运输的理解，以及这如何影响不同药物输送方法的功效。将有一个初步的重点是复杂的流变学性质的病变粘液（如其屈服应力）的影响，在肺外周，肺的区域，难以研究实验和难以解决使用医学成像的小气道内的运输。在该项目的后期阶段，将使用利用离散微积分工具的多尺度建模方法来评估小气道运输过程如何影响器官规模的药物递送，从而将通气的影响纳入整个气道树。这将需要在大规模离散网络上求解运输方程，由于涉及大量的气道，这将需要相对密集的计算。这种方法，结合降维技术，将允许调查的影响，气道几何形状的运输在肺和疾病的发展。在整个项目中，模型开发将受到生理和临床应用的推动，特别是将吸入雾化药物有效递送到囊性纤维化中受损或阻塞的肺部区域。为了实现这一目标，学生将由来自曼彻斯特大学数学系和感染，免疫和呼吸医学系的多学科主管团队指导。该项目产生的模型可能具有超越囊性纤维化的更广泛的潜在应用（例如，基础流体力学），但这种疾病特异性方法意味着该项目将提供新的能力，以现实地测试和优化药物输送方案，可以对患者治疗产生真实的影响。