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Background: Laboratory methods for measuring vaccine potency of nebulized aerosol are required to support clinical trials of measles aerosol vaccination., Methods: Measles vaccine containing the Edmonston Zagreb virus strain was reconstituted in sodium fluoride as tracer and nebulized from three devices. Emitted aerosol was collected using an impinger. Aliquots were removed from the impinger chamber for vaccine virus plaque assay and for fluoride measurement to determine aerosol output., Results: Vaccine potency retention results were adjusted to take into account the effect of aerosol output on estimates. Adjusted potency of nebulized vaccine ranged from 88% to 102%., Conclusions: New laboratory methods to measure aerosol vaccine potency retention were reliable and accurate. The results demonstrated that Edmonston Zagreb vaccine remains robust during aerosolisation and imply that this is a viable candidate for further evaluation in the measles aerosol project.

The delivery of nebulized drugs is poorly controlled and the choice of the most appropriate delivery device is poorly understood, particularly because of off-license prescriptions and a lack of evidence-based medicine. Standardized in vitro methods for measuring nebulizer performance have been adopted in Europe, by the 2001 publication of a European Standard, prEN13544-1. These standardized methods were subsequently incorporated within the European Respiratory Society nebulizer guidelines, which will provide clinicians with useful information to improve nebulizer therapies. Standards for measuring nebulizer performance should be considered in North America and elsewhere. Careful consideration should be given to either adopting the methods embodied in the European Standard or developing the basis for developing that standard further through the International Standards Organization. Either way, confusion among clinicians would be reduced and nebulizer safety and aerosol delivery efficiency increased by standardizing in vitro methods of nebulizer performance assessment.

Standardized methods for the measurement of airway responsiveness may use the Mefar MB3 inhalation dosimeter to generate standard doses of methacholine aerosol. The manufacturer provides calibrated output data for every nebulizer, so that a standard output may be achieved by varying nebulization time. This output is, however, measured by weight loss (WL), which may over-estimate true aerosol output (AO) because of concomitant evaporation. We have used a chemical (fluoride) tracer method to measure AO directly from two batches of Mefar nebulizers (batch 1 n = 5, batch 2 n = 10) and compared results with manufacturer's quoted WL. Mean AO from batch 1 was 10.56 mg.s-1 (range 9.50-11.63, SD = 0.92 mg.s-1), and mean AO from batch 2 was 5.66 mg.s-1 (range 4.92-6.58, SD = 0.57 mg.s-1), implying that AO varied little within, but substantially between, the two nebulizer batches. Manufacturer's quoted WL does not reflect this near two fold difference: mean WL batch 1 = 14.0 mg.s-1 (range 13-15 mg.s-1); mean WL batch 2 = 11.1 mg.s-1 (range 11-12 mg.s-1). The median aerosol fractions (AO/WL) for batches 1 and 2 were 76% (range 65-83%) and 50% (range 43-60%), respectively. Similar results were obtained with our own measurement of weight loss. This implies that if the median nebulizers of batches 1 and 2 were calibrated (as recommended) by the manufacture's WL to deliver a presumed 100 micrograms methacholine dose, the actual doses delivered would be 76 micrograms and 50 micrograms, the range for all 15 nebulizers being 43-83 micrograms.(ABSTRACT TRUNCATED AT 250 WORDS)

Drug nebulizers should be designed to produce an aerosol which efficiently targets drug to the respiratory tract. In this article we review the basic principles of aerosol generation from both jet and ultrasonic nebulizers, and the factors governing respiratory tract penetration and deposition. We review methods for accurate measurement of aerosol dose and size, with emphasis on evaporative effects and the implications to drug nebulizer design. We identify three forms of drug aerosol waste attributable to: generation of non-respirable aerosol, losses to the environment, and dead volume solution; and we consider how each may be minimized through good nebulizer design. Finally, we compare the relative merits of jet and ultrasonic nebulizers, and conclude by predicting a new trend in future drug nebulizer therapy.

Output from jet nebulisers is calibrated traditionally by weighing them before and after nebulisation, but the assumption that the weight difference is a close measure of aerosol generation could be invalidated by the concomitant process of evaporation. A method has been developed for measuring aerosol output directly by using a solute (fluoride) tracer and aerosol impaction, and this has been compared with the traditional weight loss method for two Wright, six Turbo, and four Micro-Cirrus jet nebulisers and two Microinhaler ultrasonic nebulisers. The weight loss method overestimated true aerosol output for all jet nebulisers. The mean aerosol content, expressed as a percentage of the total weight loss, varied from as little as 15% for the Wright jet nebulisers to 54% (range 45-61%) for the Turbo and Micro-Cirrus jet nebulisers under the operating conditions used. In contrast, there was no discrepancy between weight loss and aerosol output for the ultrasonic nebulisers. These findings, along with evidence of both concentrating and cooling effects from jet nebulisation, confirm that total output from jet nebulisers contains two distinct fractions, vapour and aerosol. The vapour fraction, but not the aerosol fraction, was greatly influenced by reservoir temperature within the nebuliser; so the ratio of aerosol output to total weight loss varied considerably with temperature. It is concluded that weight loss is an inappropriate method of calibrating jet nebuliser aerosol output, and that this should be measured directly.