Delivery of glucocorticoids by jet nebulization: aerosol characteristics and output.

BACKGROUND: Since inflammation has been identified as a critical factor in the pathogenesis of asthma, use of inhaled glucocorticoids has increased. Because young children are often unable to coordinate properly the use of metered-dose inhalers and no glucocorticoids preparations for nebulization have been approved in the United States, parenteral and intranasal glucocorticoids preparations are occasionally administered by nebulization. METHODS: We examined whether a parenteral preparation (triamcinolone acetonide [TAA]; Kenalog) could be delivered by nebulization. TAA, 1000 micrograms (0.1 ml), was placed in the nebulizer bowl (MB5 [MeFar, Brescia, Italy] or Pari-Jet [Dura Pharmaceuticals, San Diego, Calif.]), then diluted with 2.9 ml normal saline solution for a total volume fill of 3 ml. Using a laser particle analyzer, high-performance liquid chromatography, and cascade impactor, we examined the percentage of aerosol volume produced with particles in the respirable range of 1 to 5 microns in diameter, actual TAA output (in micrograms) and concentration of TAA contained in the particles within the respirable range. RESULTS: Laser particle analysis indicated that 34% +/- 3% (mean +/- SEM) (MB5) and 47 +/- 3% (Pari-Jet) of the total aerosol volume produced were within the respirable range of 1 to 5 microns in diameter, and this remained consistent throughout nebulization. The nebulizer was stopped serially for determination of TAA output with high-performance liquid chromatography. TAA output (1000 micrograms less the amount in micrograms remaining after nebulization) was essentially complete after 2 minutes with the Pari-Jet and within 4 minutes with the MB5 and totaled 352 +/- 19 micrograms and 367 +/- 9 micrograms, respectively. Finally, cascade impactor studies confirmed that 33.4% of the TAA aerosol generated by the MB5 nebulizer was contained in particles in the respirable range. CONCLUSION: Approximately 35% (Pari-Jet) and 37% (MB5) of the initial 1000 micrograms of TAA was delivered with the two nebulizers tested. The particles generated within the respirable range were limited to 34% (MB5) and 47% (Pari-Jet) of the amount delivered. TAA was equally distributed in the particles generated. The theoretic amount delivered in the respirable range was approximately 12.5% for the MB5 nebulizer on the basis of the cascade impactor and 16.5% for the Pari-Jet (assuming TAA distribution equivalence) of the TAA placed in each of the nebulizers. Additional clinical studies are needed to define efficacy and safety in view of the excipients used in preparing the parenteral preparation.

A comparison of commercial jet nebulizers.

Seventeen commercially available jet nebulizers from 15 commercial sources were studied (Acorn-I, Acorn-II, AquaTower, AVA-NEB, Cirrhus, Dart, DeVilbiss 646, Downdraft, Fan Jet, MB-5, Misty Neb, PARI LC JET, PARI-JET, Salter 8900, Sidestream, Updraft-II, Whisper Jet). All nebulizers were filled with 2 ml of saline solution plus 0.5 ml of albuterol and powered with the same source (DeVilbiss PulmoAide). We compared total output (TO), time for total output (TTO), and percent output in respirable range (PORR). The TO was obtained by weighing before nebulization and at the point of eight-fold decline in output. The TTO was calculated from initiation of nebulization to the point of eightfold decline in output. The PORR was measured by a laser particle analyzer in continuous nebulization to the same point of abrupt drop in output. The TO varied from 0.98 To 1.86 ml (p < 0.0001) with the Acorn-I, Acorn-II, Updraft-II, and Sidestream, significantly greater than the others (p < 0.05). The TTO varied from 2.28 to 20.95 min (p < 0.0001). The AquaTower, PARI LC JET and PARI-JET, DeVilbiss, and Dart were significantly shorter than the others (p < 0.05). The PORR varied from 21.89 to 71.95 percent (p < 0.0001). The Sidestream was significantly greater than all others (p < 0.05). The PARI LC JET and PARI-JET were, in turn, significantly greater than the remaining models (p < 0.05). To combine these characteristics, we calculated respirable particle delivery rate (RPDR) by dividing TO by TTO and multiplying by PORR. The RPDR varied from 0.03 ml/min to 0.26 ml/min (p < 0.0001). The PARI LC JET (0.24 ml/min) and the PARI-JET (0.26 mg/min) had a RPDR that was significantly greater than the other models except the AquaTower, which, however, had a markedly variable performance. The Sidestream (0.19 mg/ml) did not differ significantly from the above group, nor from the DeVilbiss and Downdraft. All other models had significantly lower outputs (p < 0.05). We conclude that the output characteristics of commercial nebulizers vary greatly and will impact on the time required for treatment as well as the total amount of drug delivered to the lungs.

Comparison of the bronchodilator response to albuterol administered by the OptiHaler, the AeroChamber, or by metered dose inhaler alone.

Eighteen subjects with moderate asthma participated in this double-blind study comparing the bronchodilator response to albuterol or placebo used in conjunction with three inhalation devices; the metered dose inhaler (MDI) actuator alone, the AeroChamber, and the OptiHaler. The principal comparison was the increase in FEV1 over 30 minutes. Also recorded were heart rate, time required to use each device, and patient acceptance of each device. There was a large bronchodilator response with albuterol with each of the devices, but there was no difference in the promptness or the magnitude of the bronchodilator response among the three devices. There was a small but statistically significant increase in heart rate which did not differ among devices. Subject ratings of acceptability were MDI alone best, followed by OptiHaler, then AeroChamber. We conclude (1) the bronchodilator response obtained with use of the MDI alone, the AeroChamber and OptiHaler were not significantly different; (2) patients, as a group, found the MDI required less time to use and they favored it over either spacer; (3) while in subjects employing good MDI technique, the addition of either an AeroChamber or an OptiHaler did not improve bronchodilator response. Spacers may have a role in those with poor inhaler technique or in conjunction with inhaled corticosteroids.