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

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.

Regional deposition of inhaled Evans blue dye in mechanically ventilated rabbits with air or helium oxygen mixture.

An animal model has been used and further developed to examine and evaluate differences in regional deposition patterns of an Evans Blue dye (EB) tracer aerosol. This was done by using different carrier gas composition of either He-O2 (80% helium, 20% oxygen) or air (79% nitrogen, 21% oxygen) in histamine-provoked and nonprovoked rabbits. The ratio of peripheral deposition to total deposition (central + peripheral), in relation to percentage increase in intratracheal pressure (ITP delta %), was used as an evaluation tool. The animals were tracheostomized, cannulated, and ventilated in a volume-controlled mode until they were stable. Saline or histamine was then administrated for 2 min before the tracer aerosol EB was given. The percentage increase in intratracheal pressure before and after provocation was calculated (ITP delta %) and was, on average, 51 +/- 20% for air and 51 +/- 20% for He-O2. EB was extracted from lung tissues and measured with a spectrophotometer. The absorbance in different lung regions was used as a measure of the distribution of aerosol. Bronchial provocation gave a central deposition 0.55 +/- 0.11 (mean +/- SD, ratio = peripheral deposition/central + peripheral deposition) compared to 0.80 +/- 0.09 in the control group. He-O2-ventilated rabbits showed significantly higher peripheral deposition ratio (0.67 +/- 0.12) compared with air-ventilated rabbits (0.55 +/- 0.11). The latter finding may be due to the difference in the degree of turbulent flow. There were significant correlations between intratracheal peak pressure and peripheral deposition, r = -.60 and r = -.71 for air and He-O2, respectively. This study demonstrates the possibility of using a rabbit model and different carrier gases for evaluation of effects of bronchial provocation.

Clearance in smaller airways of inhaled 6-microm particles in subjects with immotile-cilia syndrome.

In subjects with an inherited lack of mucociliary transport, so called immotile-cilia syndrome (ICS), coughing effectively clears particles deposited in larger airways of the tracheobronchial region. The present study investigated clearance in smaller airways of 111In-labeled 6-microm (aerodynamic diameter) monodisperse Teflon particles in six subjects with ICS. The particles were inhaled at an extremely slow flow, 0.05 L/s. Theoretical calculations and experimental data in healthy subjects using this slow flow support particle deposition mainly in smaller ciliated airways, i.e., in bronchioli (generations 12-16). This contrasts with the more centrally deposited pattern obtained using a normal inhalation flow, 0.5 L/s. Lung retention was measured at 0, 24, 48,72 and 96 h. Clearance was significant every 24 h measured over the first 72 h, whereupon it slowed down. The fractions of retained particles were significantly (p < .01) larger than those found for healthy subjects using the slow inhalation flow and those found for ICS subjects using a normal inhalation flow. The results indicate that clearance of particles in smaller airways is incomplete and that cough cannot fully compensate for the lack of mucociliary transport in this region.

Basic nebulizer function.

The main function of a jet nebulizer is to aerosolize the contained liquid. The primary generation point is the orifice where the compressed air expands and increases in velocity. At this point the expanding air induces an underpressure and liquid is sucked up to the air orifice where it meets the rapidly expanding air. Droplets from the liquid surface are carried away with the airstream towards the baffle system. After cut-off by impaction on the baffle surface, secondary generation occurs on the baffle as droplets are produced due to high air velocity. Several different designs of nebulizer are available. The differences cause variation in the output characteristics; for example, in the liquid output and droplet size distribution. There is also disparity between individual nebulizers of the same brand. This is due to manufacturing errors. Repeated use of a single nebulizer over time causes ageing. This, in turn, causes the critical points of droplet generation to change. The most significant changes are the small increases in the diameter of the air orifice. This may be due to mechanical wear from the compressed air source or to extensive cleaning procedures. The effect of the increasing diameter, as seen by the user, is decreased driving pressure at a constant rate of air flow. There is also an effect on the output characteristic of the nebulizer. With decreasing driving pressure the air velocity decreases. This in turn, increases the droplet size generated at the air orifice.(ABSTRACT TRUNCATED AT 250 WORDS)

Why do medical nebulizers differ in their output and particle size characteristics?

Previous work done on the characterisation of nebulizers has focused on gravimetrical output and particle/droplet size distribution at various air flow rates. This paper investigates six different nebulizers, with regard to droplet generation and separation properties, at a single air flow rate. Droplet generation and separation properties were measured with laser diffraction and impactor techniques. For each of the nebulizers the air velocity was calculated and both liquid and air volumetric flow rate was measured. The primary generated droplets (nebulizer without impaction baffle) had a mean size of between 15 microns and > 500 microns. The secondary generated droplets (nebulizer with baffle) were in the size range of 1 to 10 microns. It was found that the baffle system of the investigated nebulizers could be described according to ordinary impaction theory. The mass median diameters (MMD) of these nebulizers were found to be dependent on air velocity (vg), and ratio of liquid to air volumetric flow rate (Ql/Qa). In all of the nebulizers, between 93% and 99% of the generated primary droplets were caught by the baffle system which resulted in a very low output. Thus, the nebulizers examined do not appear to be optimised, with regard to observed droplet generation and baffle arrangements, if secondary droplets with a size approximately 1 micron are desired. By changing the design at the primary generation point, air velocity (vg) and liquid to air flow rate (Ql/Qa), the primary generated droplet size could be decreased. This would result in an increase in the number concentration of smaller droplets that pass the baffle system.(ABSTRACT TRUNCATED AT 250 WORDS)

Human tracheobronchial deposition and effect of two cholinergic aerosols.

The effects of two methacholine aerosols with mass median diameters congruent to 7 and 3 microns were measured in 10 healthy subjects. The concentrations of the two aerosols were increased until forced expiratory volume in 1 s (FEV1) decreased with about 20%. Pulmonary fraction (FEV1, FVC, FEV25-75%, FEF75-85%, R(aw), and phase III of single breath O2 test) and deposition of 3.6-microns radiolabeled Teflon particles were studied before and after bronchial challenge with the two aerosols. Output from the nebulizers and size distribution were measured and from these data and from data on deposition of Teflon particles from this and seven earlier studies the doses of the two methacholine aerosols to the tracheobronchial region were calculated. The changes in all pulmonary function parameters and deposition of 3.6-microns particles were similar for the two aerosols. The calculated dose for the aerosol with the large particles was 3-4 times higher than that with the smaller particles. The results indicate greater effect of a certain dose to the tracheobronchial part of the lung if the mass is spread on many small particles than on fewer large ones.