Sangwan Sanjay, Condos Rany, Smaldone Gerald C
Division of Pulmonary and Critical Care Medicine, Department of Medicine, State University of New York, Stony Brook, New York 11794-8172, USA.
J Aerosol Med. 2003 Winter;16(4):379-86. doi: 10.1089/089426803772455631.
For metered dose inhalers (MDIs), high-flow cascade impaction with a United States Pharmacopia (USP) throat provides a useful prediction of in vivo lung and oropharyngeal aerosol deposition. Particles expected to deposit in the lung are included in the "fine particle fraction" measured on the bench. Comparable in vitro standards are not available for nebulizers. The present study compared aerosol deposition in an in vitro model using low-flow cascade impaction with deposition in vivo in human subjects. A low-flow (1 Lmin), 10-stage cascade impactor measured aerodynamic distributions of aerosolized interferon-gamma (IFN-gamma) from two nebulizers (Misty-Neb and AeroEclipse). (99m)Technetium diethylene triaminepenta-acetic acid ((99m)Tc-DTPA) was used as the radiolabel. Two bench conditions were specified: no breathing (standing cloud) and simulated ventilation with a piston pump (tidal volume 750 mL frequency 25 per minute and duty cycle 0.5). Mass median aerodynamic diameter (MMAD) for both nebulizers was affected by ventilation (Misty-Neb vs. AeroEclipse: 5.2 vs. 4.6 microm for standing cloud and 3.1 vs. 2.2 microm during ventilation). In three subjects, measured values of oropharyngeal deposition averaged 68.1 +/- 0.08% for Misty-Neb and 30.9 +/- 0.03% for AeroEclipse. In vivo deposition patterns compared to aerosol distributions from both nebulizers indicated that, for wet nebulization, penetration of aerosol beyond the upper airways (fine particle fraction) will occur only for aerosol particles below 2.5 microm. This assessment requires that the bench aerosol distribution be measured under conditions of clinical use (i.e., during tidal breathing).
对于定量吸入器（MDIs），使用美国药典（USP）喉罩的高流量级联冲击法可有效预测体内肺部和口咽气溶胶沉积情况。预计沉积在肺部的颗粒包含在实验台上测量的“细颗粒部分”中。对于雾化器，尚无类似的体外标准。本研究比较了使用低流量级联冲击法的体外模型中的气溶胶沉积与人体受试者体内的沉积情况。一台低流量（1升/分钟）的十级级联冲击器测量了来自两种雾化器（Misty-Neb和AeroEclipse）的雾化干扰素-γ（IFN-γ）的空气动力学分布。锝-二乙三胺五乙酸（（99m）Tc-DTPA）用作放射性标记物。指定了两种实验台条件：无呼吸（静止云雾）和用活塞泵模拟通气（潮气量750毫升，频率每分钟25次，占空比0.5）。两种雾化器的质量中值空气动力学直径（MMAD）受通气影响（Misty-Neb与AeroEclipse相比：静止云雾时为5.2对4.6微米，通气时为3.1对2.2微米）。在三名受试者中，Misty-Neb的口咽沉积测量值平均为68.1±0.08%，AeroEclipse为30.9±0.03%。与两种雾化器的气溶胶分布相比，体内沉积模式表明，对于湿雾化，仅2.5微米以下的气溶胶颗粒才会穿透上呼吸道（细颗粒部分）。这种评估要求在临床使用条件下（即潮式呼吸期间）测量实验台气溶胶分布。
