Kannan Ravishekar, Arey Ryan, Przekwas Andrzej, Berlinski Ariel, Singh Narender
CFD Research Corporation, 701 McMillian Way NW, Suite D, Huntsville, Alabama 35806, USA.
Pediatric Aerosol Research Laboratory, Arkansas Children's Research Institute. 13 Children's Way, Little Rock, AR 72202, USA.
J Pulm Med Respir Care. 2022;4(1).
The efficacy of pediatric oral drug delivery using dry powder inhalers, such as Turbuhaler®, is dependent on the age and health of the test subjects. The available clinical data for these studies is scant and rarely provide correlations between the health condition and the regional lung deposition. In particular, the data and the correlations for pre-school children are minimal. Deposition simulations were performed using the newly developed Quasi-3D whole lung model to analyze the effect of health conditions on the regional lung deposition from the Turbuhaler® in 3-year-old children. The healthy lung model was created from CT scan data. Cystic-fibrosis models were created by uniformly constricting the airways to various degrees. The simulated drug deposition outcomes were validated against the available experimental data. The results show that, while the dose deposited in the lungs exhibits minor variations, the Peripheral:Central (P/C) ratio is strongly affected by both the health condition and the inflow variations. The above ratio is reduced by ~30% for the severely diseased case, compared to its healthy counterpart, for the same inhalation profile. This indicates that lower doses reach the peripheral lung, in pediatric cystic-fibrosis subjects, thus requiring a larger therapeutic dose.
使用如都保（Turbuhaler®）等干粉吸入器进行儿科口服给药的疗效取决于受试对象的年龄和健康状况。这些研究的现有临床数据很少，很少能提供健康状况与肺部区域沉积之间的相关性。特别是，学龄前儿童的数据及相关性极少。使用新开发的准三维全肺模型进行沉积模拟，以分析健康状况对3岁儿童使用都保（Turbuhaler®）时肺部区域沉积的影响。通过CT扫描数据创建健康肺模型。通过将气道均匀地收缩到不同程度来创建囊性纤维化模型。针对可用的实验数据验证模拟的药物沉积结果。结果表明，虽然肺部沉积的剂量变化较小，但外周：中央（P/C）比率受到健康状况和流入变化的强烈影响。对于相同的吸入曲线，与健康对照相比，严重患病病例的上述比率降低了约30%。这表明在儿科囊性纤维化受试者中，较低剂量到达外周肺，因此需要更大的治疗剂量。
