Bhardwaj Saurabh, Koullapis Pantelis, Kassinos Stavros C, Sznitman Josué
Department of Biomedical Engineering, Technion - Israel Institute of Technology, Haifa 3200003, Israel.
Computational Sciences Laboratory (UCY-CompSci), Department of Mechanical and Manufacturing Engineering,University of Cyprus, Nicosia 1678, Cyprus.
Eur J Pharm Sci. 2022 Jun 1;173:106172. doi: 10.1016/j.ejps.2022.106172. Epub 2022 Mar 26.
Despite the prevalence of inhalation therapy in the treatment of various respiratory diseases, predicting and optimizing lung deposition fractions of inhaled drugs for maximal efficacy remains challenging due to the complex anatomical structures of the extra-thoracic airways, notably the glottal region. One of the widespread speculations in current insilico simulations lies in assuming a static glottis during inhalation, while in reality inhalation leads to significant glottis cross-sectional area expansion. The present work attempts to explore, insilico, the influence of transient movement of the glottal structures on inhalation therapy outcomes. To this end, we adopted a CT-based realistic human tracheobronchial tree (TB) model and explored transient airflows and deposition outcomes for a broad range of inhaled aerosols (i.e., d=1-12 μm) under a dry powder inhaler (DPI) maneuver. Three different glottal expansion ratios, spanning static to 40 percent cross-sectional area expansion have been considered for the analysis. Our findings point to the tangible impact of glottal motion on airflow and particle deposition along the respiratory tract for a DPI maneuver, where a static glottis underpredicts the total particle deposition in the TB model for lower sized particles (d≤ 3 μm) compared to predictions for all dynamic glottal motions. In contrast, for larger size particles (i.e., 5 ≤d≤ 10 μm), a static glottis yields lower total deposition in the TB model compared with dynamic glottal motions. Our study also underlines that regional deposition of smaller micron-sized particles is most affected by glottal deformation in the conducting airways.
尽管吸入疗法在各种呼吸道疾病的治疗中普遍应用，但由于胸外气道，尤其是声门区域的复杂解剖结构，预测并优化吸入药物的肺沉积分数以实现最大疗效仍然具有挑战性。当前计算机模拟中一个普遍的推测是在吸入过程中假设声门是静态的，而实际上吸入会导致声门横截面积显著扩大。本研究试图在计算机模拟中探索声门结构的瞬态运动对吸入治疗效果的影响。为此，我们采用了基于CT的真实人类气管支气管树（TB）模型，并在干粉吸入器（DPI）操作下，针对广泛的吸入气溶胶（即直径d = 1 - 12μm）探索瞬态气流和沉积结果。分析中考虑了三种不同的声门扩张率，范围从静态到横截面积扩张40%。我们的研究结果表明，对于DPI操作，声门运动对呼吸道内的气流和颗粒沉积有显著影响，与所有动态声门运动的预测相比，静态声门会低估TB模型中较小尺寸颗粒（d≤3μm）的总颗粒沉积。相反，对于较大尺寸颗粒（即5≤d≤10μm），与动态声门运动相比，静态声门在TB模型中产生的总沉积较低。我们的研究还强调，较小微米尺寸颗粒的区域沉积受传导气道中声门变形的影响最大。
