Department of Chemical and Biomolecular Engineering, University of Delaware, 150 Academy St., Newark, Delaware, 19716, USA.
Department of Chemical Engineering, Oklahoma State University, Stillwater, Oklahoma, USA.
AAPS PharmSciTech. 2023 Jul 31;24(6):162. doi: 10.1208/s12249-023-02619-3.
The airway of pediatric patients' changes through development, presenting a challenge in developing pediatric-specific aerosol therapeutics. Our work aims to quantify geometric variations and aerosol deposition patterns during upper airway development in subjects between 3.5 months-6.9 years old using a library of 24 pediatric models and 4 adult models. Computational fluid-particle dynamics was performed with varying particle size (0.1-10 μm) and flow rate (10-120 Lpm), which was rigorously analyzed to compare anatomical metrics (epiglottis angle (θ), glottis to cricoid ring ratio (GC-ratio), and pediatric to adult trachea ratio (H-ratio)), inhaler metrics (particle diameter, [Formula: see text], and flow rate, Q), and clinical metrics (age, sex, height, and weight) against aerosol deposition. Multivariate non-linear regression indicated that all metrics were all significantly influential on resultant deposition, with varying influence of individual parameters. Additionally, principal component analysis was employed, indicating that [Formula: see text], Q, GC-ratio, θ, and sex accounted for 90% of variability between subject-specific deposition. Notably, age was not statistically significant among pediatric subjects but was influential in comparing adult subjects. Inhaler design metrics were hugely influential, thus supporting the critical need for pediatric-specific inhalable approaches. This work not only improves accuracy in prescribing inhalable therapeutics and informing pediatric aerosol optimization, but also provides a framework for future aerosol studies to continue to strive toward optimized and personalized pediatric medicine.
儿童患者的气道在发育过程中会发生变化，这给开发针对儿科的气溶胶治疗方法带来了挑战。我们的工作旨在使用 24 个儿科模型和 4 个成人模型库，量化 3.5 个月至 6.9 岁儿童上呼吸道发育过程中的几何变化和气溶胶沉积模式。使用不同的颗粒尺寸（0.1-10μm）和流速（10-120Lpm）进行计算流体-颗粒动力学，对其进行了严格的分析，以比较解剖学指标（会厌角（θ）、声门到环状软骨比（GC-比）和儿科到成人气管比（H-比））、吸入器指标（粒径、[公式：见文本]和流速，Q）和临床指标（年龄、性别、身高和体重）与气溶胶沉积的关系。多元非线性回归表明，所有指标对沉积结果都有显著影响，各参数的影响程度不同。此外，还进行了主成分分析，结果表明，[公式：见文本]、Q、GC-比、θ 和性别占个体沉积变异性的 90%。值得注意的是，年龄在儿科患者中没有统计学意义，但在比较成人患者时具有影响力。吸入器设计指标具有巨大的影响力，因此支持了针对儿科的可吸入方法的迫切需求。这项工作不仅提高了开具可吸入治疗药物的准确性，并为儿科气溶胶优化提供了信息，而且为未来的气溶胶研究提供了一个框架，以继续努力实现优化和个性化的儿科医学。
