A multi-scale model of gas transport in the lung to study heterogeneous lung ventilation during the multiple-breath washout test

The multiple-breath washout (MBW) is a lung function test that measures the degree of ventilation inhomogeneity (VI). The test is used to identify small airway impairment in patients with lung diseases like cystic fibrosis. However, the physical and physiological factors that influence the test outcomes and differentiate health from disease are not well understood. Computational models have been used to better understand the interaction between anatomical structure and physiological properties of the lung, but none of them has dealt in depth with the tracer gas washout test in a whole. Thus, our aim was to create a lung model that simulates the entire MBW and investigate the role of lung morphology and tissue mechanics on the tracer gas washout procedure. To this end, we developed a multi-scale lung model to simulate the inert gas transport in airways of all size. We then applied systematically different modifications to geometrical and mechanical properties of the lung model (compliance, residual airway volume and flow resistance) which have been associated with VI. The modifications were applied to distinct parts of the model, and their effects on the gas distribution within the lung and on the gas concentration profile were assessed. We found that variability in compliance and residual volume of the airways, as well as the spatial distribution of this variability in the lung had a direct influence on gas distribution among airways and on the MBW pattern (washout duration, characteristic concentration profile during each expiration), while the effects of variable flow resistance were negligible. Based on these findings, it is possible to classify different types of inhomogeneities in the lung and relate them to specific features of the MBW pattern, which builds the basis for a more detailed association of lung function and structure.

多次呼吸洗出试验（multiple-breath washout, MBW）是一项用于量化通气不均一性（ventilation inhomogeneity, VI）程度的肺功能检测技术，可用于识别囊性纤维化等肺部疾病患者的小气道功能障碍。然而，目前学界对影响该试验结果、区分健康与疾病状态的物理及生理因素尚未完全阐明。既往研究虽已借助计算模型更好地解析肺解剖结构与生理特性间的相互作用，但尚无模型能够全面深入地针对示踪气体洗出试验开展整体研究。为此，本研究旨在构建可完整模拟多次呼吸洗出试验过程的肺模型，以探究肺形态学特征与组织力学特性在示踪气体洗出过程中的作用机制。我们首先开发了一款多尺度肺模型，用于模拟不同尺寸气道内的惰性气体转运过程；随后，对该模型的几何与力学特性（顺应性、气道残余容积及流阻）进行系统性差异化修改——上述特性均与通气不均一性相关——并将修改作用于模型的不同部位，进而评估其对肺内气体分布及气体浓度分布曲线的影响。研究结果表明，气道顺应性与残余容积的变异性，以及该变异性在肺内的空间分布，会直接影响气道间的气体分布及多次呼吸洗出试验模式（包括洗出时长、每次呼气过程中的特征性浓度分布曲线），而可变流阻的影响则可忽略不计。基于上述发现，我们可对肺内不同类型的不均一性进行分类，并将其与多次呼吸洗出试验模式的特定特征建立关联，这为肺功能与肺结构间更精细的关联研究奠定了基础。