Brown James S, Bennett William D
Center for Environmental Medicine, Asthma, and Lung Biology, University of North Carolina at Chapel Hill, USA.
J Aerosol Med. 2004 Fall;17(3):239-48. doi: 10.1089/jam.2004.17.239.
In patients with cystic fibrosis (CF), the lung regions most affected by infection are presumed to be poorly ventilated and, hence, difficult to treat with inhaled therapeutic aerosols. Current dosimetric models do not adequately describe regional particle deposition in CF. We have developed a multiple-path particle deposition model and compared model predictions with the observed pattern of coarse particle (5 microm, mass median aerodynamic diameter) deposition in ten CF patients and eight healthy volunteers. Our model divides the lung into quadrants, separated at lobar bronchi, representing apical and basal lung regions. The volume and ventilation of quadrants were experimentally determined from a xenon equilibrium and multi-breath washout, respectively. Regional ventilation in the healthy lung was assumed to be determined largely by regional compliance. In CF patients, the deviations in regional ventilation from that observed in the healthy subjects were assumed to be due to regional resistance. A "custom" lung morphology was calculated for each subject based on their lung volume (functional residual capacity plus one-half tidal volume) and ventilation to each quadrant. Input parameters for particle deposition calculations were "custom" lung morphology, breathing pattern, and inhaled particle size. Relative to healthy subjects, the CF patients had reduced ventilation to the apices and increased ventilation to the bases of the lung. In healthy subjects, the general pattern of particle deposition followed ventilation. However, in the CF patients, the model predicted increased particle deposition in the large airways of the apices (an obstructed and poorly ventilated region) and to a lesser extent in the basal lung (relatively healthier and better-ventilated region), whereas particle deposition in the parenchyma was only increased in the basal lung and was decreased or absent in the apical lung. Our modeling strategy improves estimates of regional aerosol deposition and may be useful for predicting breathing conditions and particle size for optimal drug delivery in a given CF patient.
在囊性纤维化（CF）患者中，肺部受感染影响最严重的区域被认为通气不良，因此难以通过吸入治疗性气雾剂进行治疗。目前的剂量学模型无法充分描述CF患者肺部区域的颗粒沉积情况。我们开发了一种多路径颗粒沉积模型，并将模型预测结果与10名CF患者和8名健康志愿者中粗颗粒（质量中位空气动力学直径为5微米）沉积的观察模式进行了比较。我们的模型将肺部分为几个象限，在叶支气管处分开，代表肺尖和肺基底部区域。象限的体积和通气分别通过氙气平衡和多次呼吸冲洗实验测定。健康肺的区域通气被认为主要由区域顺应性决定。在CF患者中，区域通气与健康受试者的差异被认为是由于区域阻力所致。根据每个受试者的肺容积（功能残气量加一半潮气量）和每个象限的通气量，为其计算了一种“定制”的肺形态。颗粒沉积计算的输入参数为“定制”肺形态、呼吸模式和吸入颗粒大小。与健康受试者相比，CF患者肺尖的通气减少，肺底部的通气增加。在健康受试者中，颗粒沉积的总体模式与通气情况一致。然而，在CF患者中，模型预测肺尖大气道（阻塞且通气不良区域）的颗粒沉积增加，肺底部（相对更健康且通气较好区域）的颗粒沉积增加程度较小，而实质内的颗粒沉积仅在肺底部增加，在肺尖则减少或不存在。我们的建模策略改进了区域气溶胶沉积的估计，可能有助于预测特定CF患者的呼吸状况和颗粒大小，以实现最佳药物递送。
