Department of Biomedical Engineering, University of Massachusetts, Lowell, MA, U.S.A.
Department of Aerospace, Industrial, and Mechanical Engineering, California Baptist University, Riverside, CA, U.S.A.
Comput Methods Programs Biomed. 2021 Jun;204:106079. doi: 10.1016/j.cmpb.2021.106079. Epub 2021 Apr 3.
Accurate knowledge of the delivered doses to the diseased site in the respiratory tract is crucial to elicit desired therapeutic outcomes. However, such information is still difficult to obtain due to inaccessibility for measurement or visualization, complex network structure, and challenges in reconstructing lung geometries with disease-invoked airway remodeling. This study presents a novel method to simulate the airway remodeling in a mouth-lung geometry extending to G9.
Statistical shape modeling was used to extract morphological features from a lung geometry database and four new models (i.e., M1-M4) were generated with parameter-controlled dilated/constricted bronchioles in the left-lower (LL) lung. The variations in airflow and particle deposition due to the airway remodeling were simulated using a well-tested k-ω turbulence model and a Lagrangian tracking approach.
Significant variations in flow partitions between the lower and upper lobes of the left lung, as well as between the left and right lungs. The flow partition into the LL lobe varied by 10-fold between the most dilated and constricted models in this study. Significantly lower doses were also predicted on the surface of the constricted LL bronchioles G4-G9, as well as into the peripheral airways beyond G9. However, the total dosimetry in the mouth-lung geometry (up to G9) exhibited low sensitivity to the LL lobar remodeling. Results in this study suggest that the optimal nanomedicine should be 2-10 nm in diameter if targeted at the constricted bronchioles G4-G9 as in topical inhalation therapy but should be larger than 20 nm if targeted at the alveolar region as in systemic therapy.
This study highlights the large dose variability from local airway remodeling and the need to consider these variations in the treatment planning for pneumonia and other obstructive respiratory diseases.
准确了解呼吸道病变部位的药物剂量对于获得预期的治疗效果至关重要。然而，由于病变气道的不可及性或可视化困难、气道网络结构复杂以及对伴有气道重塑的肺部几何结构进行重建的挑战，此类信息仍然难以获取。本研究提出了一种新方法，可模拟扩展到 G9 的口-肺气道重塑。
采用统计形状建模方法从肺几何形状数据库中提取形态特征，并在左肺中下叶（LL）生成四个具有参数控制的扩张/收缩细支气管的新模型（即 M1-M4）。采用经过充分验证的 k-ω 湍流模型和拉格朗日跟踪方法模拟气道重塑引起的气流和颗粒沉积变化。
左肺下叶和上叶以及左、右肺之间的气流分配发生显著变化。在本研究中，最扩张和最收缩模型之间的 LL 叶流量分配差异可达 10 倍。在收缩的 LL 细支气管 G4-G9 表面以及 G9 以外的外周气道中，预测的剂量也显著降低。然而，口-肺几何形状（直至 G9）的总剂量学对 LL 叶间重塑的敏感性较低。本研究结果表明，如果针对局部吸入治疗中收缩的细支气管 G4-G9（如局部吸入治疗），则最佳的纳米药物的直径应为 2-10nm；如果针对全身治疗中的肺泡区域（如全身治疗），则应大于 20nm。
本研究强调了局部气道重塑引起的剂量变化很大，在肺炎和其他阻塞性呼吸道疾病的治疗计划中需要考虑这些变化。
