The understanding of inhaled particle respiratory tract deposition is a key link to understand the health effects of particles or the efficiency for medical drug delivery via the lung. However, there are few experimental data on particle respiratory tract deposition, and the existing data deviates considerably when comparing results for particles > 1 μm. We designed an experimental set-up to measure deposition in the respiratory tract for particles > 1 μm, more specifically 2.3 μm, with careful consideration to minimise foreseen errors. We measured the deposition in seventeen healthy adults (21–68 years). The measurements were performed at tidal breathing, during three consecutive 5-minute periods while logging breathing patterns. Pulmonary function tests were performed, including the new airspace dimension assessment (AiDA) method measuring distal lung airspace radius (rAiDA). The lung characteristics and breathing variables were used in statistical models to investigate to what extent they can explain individual variations in measured deposited particle fraction. The measured particle deposition was compared to values predicted with whole lung models. Model calculations were made for each subject using measured variables as input (e.g., breathing pattern and functional residual capacity). The measured fractional deposition for 2.3 μm particles was 0.60 ± 0.14, which is significantly higher than predicted by any of the models tested, ranging from 0.37 ± 0.08 to 0.53 ± 0.09. The multiple-path particle dosimetry (MPPD) model most closely predicted the measured deposition when using the new PNNL lung model. The individual variability in measured particle deposition was best explained by breathing pattern and distal airspace radius (rAiDA) at half inflation from AiDA. All models underestimated inter-subject variability even though the individual breathing pattern and functional residual capacity for each participant was used in the model. Whole lung models need to be tuned and improved to predict the respiratory tract particle deposition of micron-sized particles, and to capture individual variations – a variation that is known to be higher for aged and diseased lungs. Further, the results support the hypothesis that the AiDA method measures dimensions in the peripheral lung and that rAiDA, as measured by the AiDA, can be used to better understand the individual variation in the dose to healthy and diseased lungs.

中文翻译：

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吸入2μm颗粒肺沉积与肺特征和沉积模型关系的实验研究

了解吸入颗粒呼吸道沉积是了解颗粒对健康的影响或通过肺部输送医疗药物的效率的关键环节。然而，颗粒物呼吸道沉积的实验数据很少，并且现有数据在比较> 1 μm颗粒物的结果时偏差较大。我们设计了一个实验装置来测量呼吸道中 > 1 μm（更具体地说是 2.3 μm）颗粒的沉积，并仔细考虑以尽量减少可预见的误差。我们测量了 17 名健康成年人（21-68 岁）的沉积情况。测量是在潮式呼吸时进行的，在三个连续的 5 分钟周期内进行，同时记录呼吸模式。进行了肺功能测试，包括测量远端肺空域半径（rAiDA）的新空域尺寸评估（AiDA）方法。肺部特征和呼吸变量用于统计模型，以研究它们可以在多大程度上解释测量的沉积颗粒分数的个体差异。将测量的颗粒沉积与全肺模型预测的值进行比较。使用测量变量作为输入（例如，呼吸模式和功能残气量）对每个受试者进行模型计算。测得的 2.3 μm 颗粒沉积分数为 0.60 ± 0.14，显着高于任何测试模型的预测值（范围为 0.37 ± 0.08 至 0.53 ± 0.09）。使用新的 PNNL 肺部模型时，多路粒子剂量测定 (MPPD) 模型最能准确地预测测量的沉积。测量的颗粒沉积的个体差异最好通过呼吸模式和 AiDA 半充气时的远端空域半径 (rAiDA) 来解释。尽管模型中使用了每个参与者的个体呼吸模式和功能残气量，但所有模型都低估了受试者间的变异性。全肺模型需要调整和改进，以预测微米级颗粒的呼吸道颗粒沉积，并捕捉个体差异——已知老年和患病肺部的差异更大。此外，结果支持以下假设：AiDA 方法测量周围肺的尺寸，并且由 AiDA 测量的 rAiDA 可用于更好地了解健康和患病肺部剂量的个体差异。