Controlled, parametric, individualized, 2D and 3D imaging measurements of aerosol deposition in the respiratory tract of healthy human volunteers: in vivo data analysis

J Aerosol Med Pulm Drug Deliv. 2014 Oct;27(5):349-62. doi: 10.1089/jamp.2013.1065. Epub 2014 Jan 8.

Abstract

Background: To provide a validation dataset for aerosol deposition modeling, a clinical trial was performed in which the inhalation parameters and the inhaled aerosol were controlled or characterized.

Methods: Eleven, healthy, never-smokers, male participants completed the study. Each participant performed two inhalations of (99m)Tc-labeled aerosol from a vibrating mesh nebulizer, which differed by a single controlled parameter (aerosol particle size: "small" or "large"; inhalation: "deep" or "shallow"; carrier gas: air or a helium-oxygen mix). The deposition measurements were made by planar imaging, and single photon emission computed tomography-computed tomography (SPECT-CT).

Results: The difference between the mean activity measured by two-dimensional imaging and that delivered from the nebulizer was 2.7%, which was not statistically significant. The total activity deposited was significantly lower in the left lung than in the right lung (p<0.0001) with a mean ratio (left/right) of 0.87±0.1 standard deviation (SD). However, when normalized to lung air volume, the left lung deposition was significantly higher (p=0.0085) with a mean ratio of 1.08±0.12 SD. A comparison of the three-dimensional central-to-peripheral (nC/P3D) ratio showed that it was significantly higher for the left lung (p<0.0001) with a mean ratio (left/right) of 1.36±0.20 SD. The effect of particle size was statistically significant on the nC/P3D ratio (p=0.0014), extrathoracic deposition (p=0.0037), and 24-hr clearance (p<0.0001), contrary to the inhalation parameters, which showed no effect.

Conclusions: This article presents the results of an analysis of the in vivo deposition data, obtained in a clinical study designed to provide data for model validation. This study has demonstrated the value of SPECT imaging over planar, the influence of particle size on regional distribution within the lung, and differences in deposition between the left and right lungs.

Keywords: SPECT; aerosol deposition distribution; gamma camera imaging; helium.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aerosols / administration & dosage*
  • Aged
  • Equipment Design / standards*
  • Humans
  • Inhalation / physiology
  • Lung / diagnostic imaging*
  • Lung / physiology
  • Male
  • Middle Aged
  • Nebulizers and Vaporizers / standards*
  • Particle Size*
  • Pilot Projects
  • Reproducibility of Results
  • Respiratory Mechanics / physiology
  • Technetium
  • Tomography, Emission-Computed, Single-Photon*
  • Tomography, X-Ray Computed
  • Young Adult

Substances

  • Aerosols
  • Technetium