Lung Deposition and Respirable Mass During Wet Nebulization

Abstract

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).

In Vitro Comparison of Aerosol Delivery Using Different Face Masks and Flow Rates With a High-Flow Humidity System

“…6,7,9,10 Harris and Smaldone 10 demonstrated that, as an accessory for a jet nebulizer, the front-loaded mask configuration was more efficient than the bottom-loaded mask configuration, which is in contrast to our study. Our data showed that the designs of the face masks we tested do not influence aerosol delivery with a VMN at the flows tested.…”

“…Studies have shown that the design of the face mask affects the amount of aerosolized drug delivery. [6][7][8] The deposition of aerosolized drug delivered with a face mask through a high-flow heated humidified oxygen system has not been examined.…”

Physicochemical Aspects and Efficiency of Albuterol Nebulization: Comparison of Three Aerosol Types in an In Vitro Pediatric Model

“…34 Hence, even if the ultrasonic nebulizer gave the largest particle size, all 3 types of nebulizers proved satisfactory according to this criterion. Sangwan et al 35 compared 2 jet nebulizers and found respirable fractions of 6% and 14%. Skaria et al 36 compared the respirable fraction of a vibrating mesh nebulizer (Omron NE U22) with the Sidestream.…”

Randomized Controlled Trial of a Breath-Activated Nebulizer in Patients with Exacerbation of COPD

“…Hess et al 8 showed that the AeroEclipse nebulizer produced more fine particle mass (percent of particles Ͻ 4.7 m multiplied by total aerosol output) than commercially available SVNs. Sangwan and colleagues 22 conducted in vivo and in vitro comparisons of a standard SVN and the AeroEclipse nebulizer. The in vitro experiment showed that the AeroEclipse generated smaller particles than the SVN in both a standing cloud and during ventilation.…”