Inhalation and deposition of nebulized sodium cromoglycate in two different particle size distributions in children with asthma.

Abstract

The relative deposition of two inhaled droplet size distributions of sodium cromoglycate produced by a Hudson Updraft II nebulizer was evaluated, using a setup modified from the proposed Comité Européen Normalisé (CEN) standard prEN 13544-1. The modified setup comprised an Andersen 296 impactor and a Spira Electro 2 dosimeter. The setup was characterized prior to use in children with sodium cromoglycate (SCG) and sodium fluoride as tracer aerosol. The main in vivo study was designed to allow nine children with a mean age of 10 years to inhale SCG aerosol at two different relative humidities (RH), a high RH (> 90%) and a low RH (13%), which in turn resulted in two different droplet size distributions. The nebulizer/dosimeter was set to provide 1-sec nebulization during 50 inhalations. Throughout the exposures, the children were instructed to inhale in a consistent manner with target tidal volumes (0.5 L) and inhalation flows (0.4 L/sec). Blood samples were taken at predefined time intervals, and the area under the curve (AUC) was calculated. A lung deposition program, TGLD2, was used to calculate the expected deposition, using the droplet sizes and inhalation parameters obtained during in vivo exposures. The in vivo monitoring of droplet size distribution during the exposure showed that the low, intermediate (room air), and high RHs gave a mean droplet size distribution with a mass median aerosol diameter (MMAD) of 1.2, 1.7, and 2.0 microm, respectively. The average tidal volume over all exposures was 0.51 +/- 0.12 L. The total deposition fraction was 33.4% of the estimated nebulizer output. A correlation was found between tidal volume and the calculated deposited fraction. The results indicate that there is a difference in total deposition, depending on the size of the droplet size distribution, with the larger droplet size distribution (MMAD, 2.0 microm) having a higher total deposition than the smaller droplet size distribution (MMAD, 1.2 microm). The deposition results were in good agreement with the deposition fractions estimated using the TGLD2 software for the inhalation parameters found in the study. The obtained study results can arise from differences in regional deposition, but may also be explained by differences in extrathoracic deposition.