Kuprat A P, Feng Y, Corley R A, Darquenne C
Pacific Northwest National Laboratory, Richland, WA, USA.
School of Chemical Engineering, Oklahoma State University, Stillwater, OK, USA.
J Aerosol Sci. 2025 Jan;183. doi: 10.1016/j.jaerosci.2024.106471. Epub 2024 Sep 19.
Determining the fate of inhaled aerosols in the respiratory system is essential in assessing the potential toxicity of inhaled airborne materials, responses to airborne pathogens, or in improving inhaled drug delivery. The availability of high-resolution clinical lung imaging and advances in the reconstruction of lung airways from CT images have led to the development of subject-specific in-silico 3D models of aerosol dosimetry, often referred to as computational fluid-particle-dynamics (CFPD) models. As CFPD models require extensive computing resources, they are typically confined to the upper and large airways. These models can be combined with lower-dimensional models to form multiscale models that predict the transport and deposition of inhaled aerosols in the entire respiratory tract. Understanding where aerosols deposit is only the first of potentially several key events necessary to predict an outcome, being a detrimental health effect or a therapeutic response. To that end, multiscale approaches that combine CFPD with physiologically-based pharmacokinetics (PBPK) models have been developed to evaluate the absorption, distribution, metabolism, and excretion (ADME) of toxic or medicinal chemicals in one or more compartments of the human body. CFPD models can also be combined with host cell dynamics (HCD) models to assess regional immune system responses. This paper reviews the state of the art of these different multiscale approaches and discusses the potential role of personalized or subject-specific modeling in respiratory health.
确定吸入气雾剂在呼吸系统中的命运，对于评估吸入性空气传播物质的潜在毒性、对空气传播病原体的反应或改善吸入药物递送至关重要。高分辨率临床肺部成像的可用性以及从CT图像重建肺气道的进展，促使了特定受试者的气溶胶剂量学计算机模拟3D模型的发展，通常称为计算流体-颗粒动力学（CFPD）模型。由于CFPD模型需要大量计算资源，它们通常局限于上呼吸道和大气道。这些模型可以与低维模型相结合，形成多尺度模型，以预测吸入气雾剂在整个呼吸道中的传输和沉积。了解气雾剂的沉积位置只是预测结果（有害健康影响或治疗反应）所需的几个潜在关键事件中的第一个。为此，已经开发了将CFPD与基于生理学的药代动力学（PBPK）模型相结合的多尺度方法，以评估有毒或药用化学品在人体一个或多个隔室中的吸收、分布、代谢和排泄（ADME）。CFPD模型还可以与宿主细胞动力学（HCD）模型相结合，以评估区域免疫系统反应。本文综述了这些不同多尺度方法的现状，并讨论了个性化或特定受试者建模在呼吸健康中的潜在作用。
