The physical properties of a jet-nebulizer and their relevance for the histamine provocation test

We have examined the physical properties of eight specimens of a frequently used jet-nebulizer (Wiesbadener Doppelinhalator). For each nebulizer, under various conditions we measured driving pressure, solution output, solute output, particle concentration and size distribution in the aerosol, and the change of solute concentration in the storage vessel. Using histamine acid phosphate solutions in distilled water, there was considerable variability between the nebulizers in solute output (range about a factor 3). Solute output was strongly related to driving pressure (r2 = 0.89), to solution output (r2 = 0.96) and to particle concentration (r2 = 0.87). The particle size distributions of the eight nebulizers were very similar. The volume median aerodynamic diameter (VMAD) of the stable evaporated particles was on average 0.33 micrograms (geometric standard deviation of 1.78), which implies a VMAD of the primary droplets of about 3.2 micrograms. In fifteen subjects with bronchial hyperreactivity, a twofold increase of histamine output of the nebulizer without a change in particle size resulted on average in a twofold decrease of the histamine concentration that caused a 20 per cent fall (PC20) in FEV1. At constant histamine output the administration of dry particles instead of direct nebulization of (partly) saturated droplets into the mouth increased PC20 by a factor 2. This difference could not be explained by a changed deposition in the hypopharynx. There were large interindividual differences in the response to the altered aerosol characteristics. We conclude that the physical properties of the administered aerosols should be carefully controlled since they influence the biological response to inhaled histamine. The solute output of the investigated jet-nebulizer can satisfactorily be validated by weighing, for which an equation is given. In bronchial provocation testing, administration of dry particles is recommended.