Katan Janna Tenenbaum, Hofemeier Philipp, Sznitman Josué
Department of Biomedical Engineering, Technion-Israel Institute of Technology , Haifa, Israel .
J Aerosol Med Pulm Drug Deliv. 2016 Jun;29(3):288-98. doi: 10.1089/jamp.2015.1271. Epub 2016 Feb 23.
Inhalation therapy targeted to the deep alveolated regions holds great promise, specifically in pediatric populations. Yet, inhalation devices and medical protocols are overwhelmingly derived from adult guidelines, with very low therapeutic efficiency in young children. During the first years of life, airway remodeling and changing ventilation patterns are anticipated to alter aerosol deposition with underachieving outcomes in infants. As past research is still overwhelmingly focused on adults or limited to models of upper airways, a fundamental understanding of inhaled therapeutic transport and deposition in the acinar regions is needed to shed light on delivering medication to the developing alveoli.
Using computational fluid dynamics (CFD), we simulated inhalation maneuvers in anatomically-inspired models of developing acinar airways, covering the distinct phases of lung development, from underdeveloped, saccular pulmonary architectures in infants, to structural changes in toddlers, ultimately mimicking space-filling morphologies of a young child, representing scaled-down adult lungs. We model aerosols whose diameters span the range of sizes acknowledged to reach the alveolar regions and examine the coupling between morphological changes, varying ventilation patterns and particle characteristics on deposition outcomes.
Spatial distributions of deposited particles point to noticeable changes in the patterns of aerosol deposition with age, in particular in the youngest age group examined (3 month). Total deposition efficiency, as well as deposition dispersion, vary not only with the phases of lung development but also and critically with aerosol diameter.
Given the various challenges when prescribing inhalation therapy to a young infant, our findings underline some mechanistic aspects to consider when targeting medication to the developing alveoli. Not only does the intricate coupling between acinar morphology and ventilation patterns need to be considered, but the physical properties (i.e., aerodynamic size) of therapeutic aerosols also closely affect the anticipated success rates of the inhaled medication.
针对深肺泡区域的吸入疗法前景广阔，尤其在儿科人群中。然而，吸入装置和医疗方案绝大多数源自成人指南，在幼儿中的治疗效率极低。在生命的最初几年，气道重塑和通气模式的变化预计会改变气溶胶沉积，导致婴儿治疗效果不佳。由于过去的研究仍主要集中在成人或局限于上呼吸道模型，因此需要对腺泡区域吸入治疗的传输和沉积有基本的了解，以阐明如何将药物输送到发育中的肺泡。
我们使用计算流体动力学（CFD），在受解剖学启发的发育中腺泡气道模型中模拟吸入动作，涵盖肺发育的不同阶段，从婴儿期未发育的囊状肺结构，到幼儿期的结构变化，最终模拟幼儿的空间填充形态，即缩小版的成人肺。我们对直径跨越公认可到达肺泡区域范围的气溶胶进行建模，并研究形态变化、不同通气模式和颗粒特性对沉积结果的耦合作用。
沉积颗粒的空间分布表明，气溶胶沉积模式随年龄有显著变化，特别是在研究的最年幼年龄组（3个月）。总沉积效率以及沉积分散度不仅随肺发育阶段而变化，而且关键地随气溶胶直径而变化。
鉴于给幼儿开吸入疗法处方时存在各种挑战，我们的研究结果强调了在将药物靶向发育中的肺泡时需要考虑的一些机制方面。不仅需要考虑腺泡形态与通气模式之间的复杂耦合，治疗性气溶胶的物理性质（即空气动力学尺寸）也密切影响吸入药物的预期成功率。
