Effect of nebulizer configuration on delivery of aerosolized tobramycin.

Abstract

Differences in the reported efficacy of aerosolized aminoglycosides may be due, in part, to differences in aerosol delivery. Optimization of delivery systems of bench testing of nebulizers in a manner that simulates clinical conditions can lead to enhanced lung deposition in subsequent clinical studies. In the present study, we assessed the effects of varying nebulizer configuration on the performance of ultrasonic and jet nebulizers. Tobramycin was mixed with a radiotracer (99mTc) to facilitate measurement of nebulizer output and particle size. A piston ventilator provided a simulated breathing pattern, and the dose delivered to a filter corresponded to what would have been inhaled by a patient (percentage of nebulizer charge inhaled). Particle size was measured using a cascade impactor, sampling at 1 L/min. An ultrasonic nebulizer (Ultra-Neb; DeVilbiss, Somerset, PA), ventilated at 20 breaths per minute, charged with 600 mg of tobramycin (in 30-mL volume) and fitted with its standard tubing, was tested with and without the addition of one-way valves to the inspiratory and expiratory ports of the mouthpiece. In order to assess the degree of environmental contamination associated with jet nebulizer therapy, a filter was placed at the expiratory port of all jet nebulizer experiments. The addition of the valves reduced the percentage of charge inhaled from a mean +/- standard deviation (SD) of 29.2% +/- 1.4% to 7.6% +/- 2.3% and reduced mass median aerodynamic diameter [MMAD (sigma g) from 4.3 microns (2.1) to 1.45 microns (1.65)]. A Circulaire (Westmed, Tucson, AZ) jet nebulizer (7 L/min flow, 50 pounds per square inch gauge (psig), 20 breaths per minute, containing 160 mg of tobramycin in a 4-mL volume) was tested in two configurations: using a plain T-piece and using a valved inflatable aerosol chamber. The use of the holding chamber resulted in an almost twofold reduction in MMAD [MMAD (sigma g) = 2.45 microns (2.0); T-piece; 1.25 microns (2.0), holding chamber]. A slight reduction in the percentage of nebulizer charge inhaled using the holding chamber, compared to the plain T-piece, was not statistically significant (mean +/- SD of percentage inhaled with holding chamber = 20.8% +/- 1.6%; with T-piece = 23.6% +/- 0.5%). With both the jet and ultrasonic nebulizers, breathing frequency influenced percentage inhaled, with a higher percentage inhaled at 20 breaths per minute compared to 15 breaths per minute. The use of the plain T-piece at 20 breaths per minute was associated with more environmental contamination than the use of the holding chamber with the same breathing pattern (26.7% +/- 1.0%, T-piece; 4.5% +/- 0.3%, holding chamber, P < 0.0001). We conclude that nebulizer configuration can potentially affect both the amount of aerosol inhaled and the particle size, and needs to be specified precisely in treatment protocols.