Python file of the computational framework.

In this paper, we present a new computational framework for the simulation of airway resistance, the fraction of exhaled nitric oxide, and the diffusion capacity for nitric oxide in healthy and unhealthy lungs. Our approach is firstly based on a realistic representation of the geometry of healthy lungs as a function of body mass, which compares well with data from the literature, particularly in terms of lung volume and alveolar surface area. The original way in which this geometry is created, including an individual definition of the airways in the first seven generations of the lungs, makes it possible to consider the heterogeneous nature of the lungs in terms of perfusion and ventilation. In addition, a geometry can be easily modified to simulate various abnormalities, local or global (constriction, inflammation, perfusion defect). The natural variability of the lungs at constant body mass is also considered. The computational framework includes the possibility to simulate, on a given (possibly modified) geometry, a test to measure the flow resistance of the lungs (including its component due to the not fully developed flow in the first generations of lungs), a test to measure the concentration of nitric oxide in the exhaled air, and a test to measure the diffusion capacity for nitric oxide. This is implemented in the framework by solving different transport equations (momentum and convection/diffusion) describing these tests. Through numerous simulations, we demonstrate the ability of our model to reproduce results from the literature, both for healthy lungs and lungs of patients with asthma or chronic obstructive pulmonary disease. Such a computational framework, through the possibilities of numerous and rapid tests that it allows, sheds new light on experimental data by providing information on the phenomena that take place in the distal generations of the lungs, which are difficult to access with imaging.

本研究提出一种全新的计算框架，用于模拟健康与病变肺部的气道阻力、呼出气一氧化氮分数（fraction of exhaled nitric oxide）以及一氧化氮弥散能力（diffusion capacity for nitric oxide）。本方法首先基于以体质量为自变量的健康肺部几何结构真实化建模，该模型与已有文献数据吻合度优异，尤其在肺容积与肺泡表面积两项指标上契合度突出。该几何模型的构建方式独具创新性：对肺部前7级气道进行个体化定义，由此可充分考量肺部灌注与通气的异质性特征。此外，该几何模型可便捷修改，以模拟各类局部或全身性肺部异常，包括气道狭窄、炎症反应、灌注缺损等。本框架同时纳入了体质量固定条件下肺部的自然生理变异特性。该计算框架支持在指定（可经修改的）几何模型上开展三类功能测试：其一为肺部气流阻力测试（涵盖肺部前几级气道内未充分发展流动所贡献的阻力组分），其二为呼出气一氧化氮浓度测试，其三为一氧化氮弥散能力测试。本框架通过求解对应三类测试的不同输运方程（动量方程与对流/扩散方程）实现上述模拟功能。通过大量模拟实验，本研究验证了所提模型可复现已有文献中健康肺部，以及哮喘、慢性阻塞性肺疾病（chronic obstructive pulmonary disease）患者肺部的相关实验结果。该计算框架可支持大量快速测试，能够通过获取肺部远端气道分支（现有成像技术难以观测的区域）内的生理现象信息，为实验数据的解析提供全新视角。