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气道疾病对吸入药物沉积的影响。

The effects of airway disease on the deposition of inhaled drugs.

机构信息

Department of Medicine, University of California, San Diego, CA, USA.

Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.

出版信息

Expert Opin Drug Deliv. 2024 Aug;21(8):1175-1190. doi: 10.1080/17425247.2024.2392790. Epub 2024 Aug 19.

DOI:10.1080/17425247.2024.2392790
PMID:39136493
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11412782/
Abstract

INTRODUCTION

The deposition of inhaled medications is the first step in the pulmonary pharmacokinetic process to produce a therapeutic response. Not only lung dose but more importantly the distribution of deposited drug in the different regions of the lung determines local bioavailability, efficacy, and clinical safety. Assessing aerosol deposition patterns has been the focus of intense research that combines the fields of physics, radiology, physiology, and biology.

AREAS COVERED

The review covers the physics of aerosol transport in the lung, experimental, and in-silico modeling approaches to determine lung dose and aerosol deposition patterns, the effect of asthma, chronic obstructive pulmonary disease, and cystic fibrosis on aerosol deposition, and the clinical translation potential of determining aerosol deposition dose.

EXPERT OPINION

Recent advances in in-silico modeling and lung imaging have enabled the development of realistic subject-specific aerosol deposition models, albeit mainly in health. Accurate modeling of lung disease still requires additional refinements in existing imaging and modeling approaches to better characterize disease heterogeneity in peripheral airways. Nevertheless, recent patient-centric innovation in inhaler device engineering and the incorporation of digital technology have led to more consistent lung deposition and improved targeting of the distal airways, which better serve the clinical needs of patients.

摘要

简介

吸入药物的沉积是产生治疗反应的肺部药代动力学过程的第一步。不仅肺部剂量,更重要的是沉积药物在肺部不同区域的分布决定了局部生物利用度、疗效和临床安全性。评估气溶胶沉积模式一直是物理学、放射学、生理学和生物学等领域研究的重点。

涵盖范围

本文综述了肺部气溶胶传输的物理学、实验和计算模型方法,以确定肺部剂量和气溶胶沉积模式,哮喘、慢性阻塞性肺疾病和囊性纤维化对气溶胶沉积的影响,以及确定气溶胶沉积剂量的临床转化潜力。

专家意见

最近在计算模型和肺部成像方面的进展使得能够开发出逼真的、针对个体的气溶胶沉积模型,尽管主要是在健康人群中。对肺部疾病的准确建模仍需要对现有成像和建模方法进行额外的改进,以更好地描述外周气道的疾病异质性。尽管如此,最近在吸入器装置工程方面的以患者为中心的创新以及数字技术的融入导致了更一致的肺部沉积和对远端气道的更好靶向,更好地满足了患者的临床需求。

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本文引用的文献

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Development of an effective two-equation turbulence modeling approach for simulating aerosol deposition across a range of turbulence levels.开发一种有效的双方程湍流建模方法,用于模拟不同湍流水平下的气溶胶沉积。
J Aerosol Sci. 2024 Jan;175:106262. doi: 10.1016/j.jaerosci.2023.106262.
2
Small Airway Disease in Pre-Chronic Obstructive Pulmonary Disease with Emphysema: A Cross-Sectional Study.伴有肺气肿的慢性阻塞性肺疾病前期的小气道疾病:一项横断面研究。
Am J Respir Crit Care Med. 2024 Mar 15;209(6):683-692. doi: 10.1164/rccm.202301-0132OC.
3
Modeled small airways lung deposition of two fixed-dose triple therapy combinations assessed with in silico functional respiratory imaging.
通过计算机模拟功能呼吸成像评估两种固定剂量三联疗法组合对小气道肺部沉积的影响。
Respir Res. 2023 Sep 23;24(1):226. doi: 10.1186/s12931-023-02534-y.
4
Automated bidirectional coupling of multiscale models of aerosol dosimetry: validation with subject-specific deposition data.气溶胶剂量学多尺度模型的自动双向耦合:基于个体沉积数据的验证
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Treatment with inhaled antibiotics in bronchiectasis, side effects, and evaluation of the tolerance test; analysis from the BATTLE randomized controlled trial.支气管扩张症中吸入抗生素的治疗、副作用和耐受试验评估;来自 BATTLE 随机对照试验的分析。
Clin Respir J. 2023 Aug;17(8):748-753. doi: 10.1111/crj.13663. Epub 2023 Jul 17.
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Effect of Combined Hypertonic Saline and Salbutamol on Ciliary Beating Frequency and Mucociliary Transport in Human Nasal Epithelial Cells of Healthy Volunteers and Patients with Cystic Fibrosis.联合高渗盐水和沙丁胺醇对健康志愿者和囊性纤维化患者鼻腔上皮细胞纤毛摆动频率和黏液纤毛传输的影响。
J Aerosol Med Pulm Drug Deliv. 2023 Aug;36(4):171-180. doi: 10.1089/jamp.2022.0026. Epub 2023 May 17.
7
In Silico Quantification of Intersubject Variability on Aerosol Deposition in the Oral Airway.口腔气道气溶胶沉积个体间变异性的计算机模拟定量分析
Pharmaceutics. 2023 Jan 3;15(1):160. doi: 10.3390/pharmaceutics15010160.
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The Use of Single Photon Emission Computed Tomography in Aerosol Medicine.单光子发射计算机断层扫描在气溶胶医学中的应用。
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