Sá Rui Carlos, Zeman Kirby L, Bennett William D, Prisk G Kim, Darquenne Chantal
1 Department of Medicine, University of California , San Diego, La Jolla, California.
2 Department of Medicine, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina.
J Aerosol Med Pulm Drug Deliv. 2015 Dec;28(6):423-31. doi: 10.1089/jamp.2014.1189. Epub 2015 Mar 31.
Understanding the regional partition of deposition of inhaled particles within the lung is important for improving targeted delivery of inhaled aerosolized drugs. One factor affecting regional deposition is gravity. As the lung deforms under its own weight, changes in lung volume, in airway geometries, and in spatial patterns of ventilation distribution between postures have the potential to alter the regional distribution of deposited particles.
Using gamma-scintigraphy, we measured regional deposition and clearance of (99m)Tc labeled particles (5 μm) in 6 healthy subjects, with aerosol inhalation occurring both in the supine and seated postures at constant flow (0.5 L/sec) and breathing rate (15 breaths/min). After aerosol deposition, mucociliary clearance data were collected in the seated posture, immediately post-particle administration, 1 h 30 min, 4 h, and 22 h post-inhalation. Relative regional deposition was computed using retention (R) at the different time points, with (1-R(1h30min)), (R(1h30min)- R(4h)), and (R(4h)- R(22h)) corresponding to deposition in the large, intermediate, and small airways, respectively. Alveolar deposition was estimated as the relative retention at 22 h (R(22h)).
Relative deposition of coarse particles in the alveolar region decreased from 60±8% seated to 34±16% supine (p=0.04). This change was accompanied by an increase in relative deposition in the intermediate (7±3% seated to 16±17% supine, P=0.09) and small airways (19±6% seated to 34±13% supine, p=0.06) when inhalation occurred in the supine posture. No change was observed in central to peripheral deposition (C/P ratio), the skew of the deposition distribution, or the apex-to-base ratio of deposition between seated and supine postures.
Inhalation of coarse particles in the supine posture shifts relative deposition from the alveolar to the bronchial airways, when compared to the seated posture, likely driven by changes in functional residual capacity, and airway size, as well as changes in the regional distribution of ventilation between postures.
了解吸入颗粒在肺内的沉积区域划分对于改善吸入雾化药物的靶向递送至关重要。影响区域沉积的一个因素是重力。随着肺在自身重量作用下变形，肺容积、气道几何形状以及不同体位间通气分布空间模式的变化有可能改变沉积颗粒的区域分布。
我们使用γ闪烁扫描法，对6名健康受试者吸入（99m）Tc标记颗粒（5μm）后的区域沉积和清除情况进行了测量，吸入气雾剂时受试者分别处于仰卧位和坐位，气流恒定（0.5L/秒），呼吸频率恒定（15次/分钟）。气雾剂沉积后，在坐位收集黏液纤毛清除数据，分别在颗粒给药后即刻、吸入后1小时30分钟、4小时和22小时收集。使用不同时间点的滞留率（R）计算相对区域沉积，（1 - R（1小时30分钟））、（R（1小时30分钟） - R（4小时））和（R（4小时） - R（22小时））分别对应于大、中、小气道的沉积。肺泡沉积通过22小时时的相对滞留率（R（22小时））估算。
粗颗粒在肺泡区域的相对沉积从坐位时的60±8%降至仰卧位时的34±16%（p = 0.04）。当在仰卧位吸入时，这种变化伴随着中气道（从坐位时的7±3%增至仰卧位时的16±17%，P = 0.09）和小气道（从坐位时的19±6%增至仰卧位时的34±13%，p = 0.06）相对沉积的增加。仰卧位和坐位之间，中央到外周的沉积（C/P比）、沉积分布的偏度或沉积的尖底比均未观察到变化。
与坐位相比，仰卧位吸入粗颗粒会使相对沉积从肺泡转移至支气管气道，这可能是由功能残气量、气道大小的变化以及不同体位间通气区域分布的变化所驱动。
