Department of Mechanical Engineering, California Baptist University, Riverside, CA, USA.
Department of Biomedical Engineering, University of Massachusetts, Lowell, MA, USA.
Inhal Toxicol. 2021 Mar;33(4):143-159. doi: 10.1080/08958378.2021.1912860. Epub 2021 Apr 18.
Respiratory diseases are often accompanied by alterations to airway morphology. However, inhalation dosimetry data in remodeled airways are scarce due to the challenges in reconstructing diseased respiratory morphologies. This study aims to study the airway remodeling effects on the inhalation dosimetry of nasally inhaled nanoparticles in a nose-lung geometry that extends to G9 (ninth generation). Statistical shape modeling was used to develop four diseased lung models with varying levels of bronchiolar dilation/constriction in the left-lower (LL) lobe (i.e. M1-M4). Respiratory airflow and particle deposition were simulated using a low Reynolds number - turbulence model and a Lagrangian tracking approach. Significant discrepancies were observed in the flow partitions between the left and right lungs, as well as between the lower and upper lobes of the left lung, which changed by 10-fold between the most dilated and constricted models.Much lower doses were predicted on the surface of the constricted LL bronchioles G4-G9, as well as into the peripheral airways beyond G9 of the LL lung. However, the LL lobar remodeling had little effect on the dosimetry in the nasopharynx, as well as on the total dosimetry in the nose-lung geometry (up to G9). It is suggested that airway remodeling may pose a higher viral infection risk to the host by redistributing the inhaled viruses to healthy lung lobes. Airway remodeling effects should also be considered in the treatment planning of inhalation therapies, not only because of the dosimetry variation from altered lung morphology but also its evolution as the disease progresses.
呼吸道疾病常伴有气道形态的改变。然而，由于重建病变呼吸道形态的挑战，重塑气道对鼻吸入纳米颗粒吸入剂量的影响的数据仍然缺乏。本研究旨在研究气道重塑对延伸到 G9 代（第九代）的鼻-肺几何模型中经鼻吸入纳米颗粒吸入剂量的影响。采用统计形状建模的方法，针对左肺下叶（LL）支气管扩张/收缩程度不同的情况，建立了四个病变肺模型（M1-M4）。采用低雷诺数-湍流模型和拉格朗日跟踪方法模拟呼吸气流和颗粒沉积。结果显示，左、右肺之间以及左肺下叶和上叶之间的气流分配存在显著差异，在最扩张和最收缩的模型之间，这种差异变化了 10 倍。在收缩的 LL 支气管 G4-G9 表面以及 LL 肺的 G9 以外的外周气道中，预测的剂量要低得多。然而，LL 叶状重塑对鼻咽部的剂量以及鼻-肺几何模型（直到 G9）中的总剂量几乎没有影响。气道重塑可能通过将吸入的病毒重新分布到健康的肺叶，从而对宿主造成更高的病毒感染风险。在吸入治疗的治疗计划中，还应考虑气道重塑的影响，不仅因为改变的肺形态导致剂量变化，还因为疾病进展时其会发生演变。
