Greenblatt Elliot Eliyahu, Winkler Tilo, Harris Robert Scott, Kelly Vanessa Jane, Kone Mamary, Katz Ira, Martin Andrew R, Caillibotte George, Venegas Jose
1 Department of Mechanical Engineering, Massachusetts Institute of Technology , Boston, Massachusetts.
2 Massachusetts General Hospital and Harvard Medical School , Boston, Massachusetts.
J Aerosol Med Pulm Drug Deliv. 2016 Feb;29(1):57-75. doi: 10.1089/jamp.2014.1197. Epub 2015 May 15.
A previous PET-CT imaging study of 14 bronchoconstricted asthmatic subjects showed that peripheral aerosol deposition was highly variable among subjects and lobes. The aim of this work was to identify and quantify factors responsible for this variability.
A theoretical framework was formulated to integrate four factors affecting aerosol deposition: differences in ventilation, in how air vs. aerosol distribute at each bifurcation, in the fraction of aerosol escaping feeding airways, and in the fraction of aerosol reaching the periphery that is exhaled. These factors were quantified in 12 of the subjects using PET-CT measurements of relative specific deposition sD*, relative specific ventilation sV* (measured with dynamic PET or estimated as change in expansion between two static HRCTs), average lobar expansion F, and breathing frequency measured during aerosol inhalation f.
The fraction of the variance of sD* explained by sV* (0.38), by bifurcation effects (0.38), and by differences in deposition along feeding airways (0.31) were similar in magnitude. We could not directly estimate the contribution of aerosol that was exhaled. Differences in expansion did not explain any fraction of the variability in sD* among lobes. The dependence of sD* on sV* was high in subjects breathing with low f, but weakened among those breathing faster. Finally, sD*/sV* showed positive dependence on F among low f subjects, while the dependence was negative among high f subjects.
The theoretical framework allowed us to analyze experimentally measured aerosol deposition imaging data. When considering bronchoconstricted asthmatic subjects, a dynamic measurement of ventilation is required to evaluate its effect on aerosol transport. The mechanisms behind the identified effects of f and F on aerosol deposition need further study and may have important implications for aerosol therapy in subjects with heterogeneous ventilation.
先前一项针对14名支气管收缩型哮喘患者的PET-CT成像研究表明，受试者和肺叶之间的外周气溶胶沉积差异很大。这项工作的目的是识别并量化导致这种差异的因素。
构建了一个理论框架，以整合影响气溶胶沉积的四个因素：通气差异、空气与气溶胶在每个分支处的分布差异、气溶胶从供气气道逸出的比例以及到达外周并呼出的气溶胶比例。使用PET-CT测量相对比沉积sD*、相对比通气sV*（通过动态PET测量或估计为两个静态HRCT之间的扩张变化）、平均肺叶扩张F以及气溶胶吸入期间测量的呼吸频率f，对其中12名受试者的这些因素进行了量化。
由sV解释的sD方差比例（0.38）、由分支效应解释的比例（0.38）以及由沿供气气道的沉积差异解释的比例（0.31）在大小上相似。我们无法直接估计呼出的气溶胶的贡献。扩张差异并未解释肺叶之间sD变异性的任何比例。在呼吸频率低的受试者中，sD对sV的依赖性较高，但在呼吸较快的受试者中这种依赖性减弱。最后，在呼吸频率低的受试者中，sD/sV*对F呈正相关，而在呼吸频率高的受试者中这种相关性为负。
该理论框架使我们能够分析实验测量的气溶胶沉积成像数据。在考虑支气管收缩型哮喘患者时，需要对通气进行动态测量以评估其对气溶胶传输的影响。已确定的f和F对气溶胶沉积的影响背后的机制需要进一步研究，并且可能对通气不均一的受试者的气溶胶治疗具有重要意义。
