Nebulization could be a valuable solution to administer drugs to neonates receiving noninvasive respiratory support. Small and irregular tidal volumes and air leaks at the patient interface, which are specific characteristics of this patient population and are primarily responsible for the low doses delivered to the lung (D_DL) found in this application, have not been thoroughly addressed in in vitro and in vivo studies for quantifying D_DL. Therefore, we propose a compartment-based mathematical model able to describe convective aerosol transport mechanisms to complement the existing deposition models. Our model encompasses a mechanical ventilator, a nebulizer, and the patient; the model considers the gas flowing between compartments, including air leaks at the patient–ventilator interface. Aerosol particles are suspended in the gas flow and homogeneously distributed. The impact of breathing pattern variability, volume of the nebulizer, and leaks level on D_DL is assessed in representative conditions. The main finding of this study is that convective mechanisms associated to air leaks and breathing patterns with tidal volumes smaller than the nebulizer dramatically reduce the D_DL (up to 70%). This study provides a possible explanation to the inconsistent results of drug aerosolization in clinical studies and may provide guidance to improve nebulizer design and clinical procedures.

中文翻译：

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基于隔室的数学模型用于研究无创呼吸支持期间接受雾化药物的新生儿中对流气溶胶的运输

对于接受无创呼吸支持的新生儿，雾化可能是有价值的解决方案。病人接口的小而不规则的潮气量和漏气是该病人人群的特殊特征，并且主要是造成本申请中发现的向肺部输送低剂量（D _DL）的原因，在体外尚未完全解决和体内研究以量化D _DL。因此，我们提出了一个基于隔室的数学模型，该模型能够描述对流气溶胶传输机制，以补充现有的沉积模型。我们的模型包括机械呼吸机，雾化器和患者。该模型考虑了隔室之间的气体流动，包括患者-呼吸机接口处的空气泄漏。气溶胶颗粒悬浮在气流中并均匀分布。在代表性条件下评估呼吸模式变化，雾化器体积和泄漏水平对D _DL的影响。这项研究的主要发现是，与漏气和呼吸模式相关的对流机制，潮气量小于雾化器，大大降低了D _DL（高达70％）。这项研究为临床研究中药物雾化的不一致结果提供了可能的解释，并可能为改进雾化器设计和临床程序提供指导。