Nebulizer aerosol output

A draft European Nebulizer Standard (30) has been submitted for formal approval to CEN (Comite Europeen de Normalisation European Committee for Standardization). CEN is responsible for European standardization in all fields except Electrotechnical (CENELEC) and Telecommunications (ETSl). Publication of the European Nebulizer Standard is expected during 2001. Included within the European standard are detailed descriptions of two test methods for (1) assessing nebulizer aerosol output inhaled using breath simulation similar to that described previously and (2) assessing nebulized aerosol droplet size using low-flow cascade impaction. Because this standard is expected to be adopted throughout Europe (and possibly more widely), a summary of its contents may be useful to readers. 

During nebulization from airjet nebulizers, cooling of the reservoir solution occurs which, together with vapor loss, results in concentration of the dmg solution. This in turn produces an aerosol output in which the drag concentration increases with time. Concentration of the dmg solution in the reservoir can lead to drug recrystallization with subsequent blockage within the device or variation in aerosol particle size. 

Commercially available nebulizers have different performance characteristics, including aerosol output and the mean size and range of particle sizes generated [5,37]. The volume of fluid being nebulized and the flowrates generated also influence output. 

Once these modifications have been performed, the exact output (milliliters per minute) of the nebulizer is measured (characterized nebulizer nSpire Health). With the exact nebulizer output known, modulation of the duration of aerosol delivery by the dosimeter allows the determination of aerosol output per inhalation. For example, the author currently uses a characterized nebulizer with an output of 1.007ml min with a dosimeter programmed to deliver pressurized air for 1.2 s, thus allowing the nebulizer to deliver exactly 0.02 ml aerosol per inhalation. Since investigators worldwide will likely continue to use different equipment for the performance of cough challenge studies, one way to achieve a measure of standardization would be to control nebulizer output per breath, with the aforementioned... 

Figure 17 Schematic describing experiments measuring aerosol output from Fisoneb ultrasonic nebulizer. (From Ref. 10.)...

Figure 21 Influence of ventilator choice on aerosol output expressed as inhaled mass (%) versus time for four ventilators utilizing the Misty-Neb nebulizer. (Baxter Healthcare Corp., Valencia CA from Ref. 32.)...

Since the 1970s laser sizers have offered convenient and rapid estimation of the optical size distributions of nebulized aerosol size distributions. However, just as weight loss as a measure of aerosol output is confounded by evaporation, droplet size distributions are now clearly understood also to be affected by evaporation once the aerosol cloud is mixed with drier ambient air. The methodology adopted within the European standard was inevitably a compromise but may arguably present the most representative clinical compromise. 

During development of the European standard, an interlaboratory trial was organized involving six laboratories within Europe to follow a defined protocol to assess aerosol output and size from two fundamentally different nebulizer systems. Results demonstrated that the methods were repeatable within +/- 10% of mean return for both aerosol output and aerosol size (unpublished data). Results of preliminary research investigating the correlation between in vivo response and in vitro estimate of aerosol output and size show a promising correlation (33), though further work is needed in this area. 

Table 1 Summary of Relative Designed Aerosol Output Characteristics of New Nebulizer Technologies Compared with a Traditional Nebulizer and a Typical pMDI...

Dennis JH, Stenton SC, Beach JR, Avery AJ, Walters EH, Hendrick DJ. Jet and ultrasonic nebulizer output use of a new method to measure aerosol output directly. Thorax 1990 45 728-732. 

For all fluids, Ghazanfari et al. [71] found that the Omron nebulizer generated aerosols with slightly larger droplet size and similar or smaller fine particle fraction (FPF) than those of the Aeroneb Pro device. The total aerosol output was generally independent of fluid properties. However, increased fluid viscosity resulted in a decrease in droplet size and a consequent increase in the FPF, but the nebulization time was prolonged and output rate decreased (Fig. 33.12). 

The presence of low ion concentrations in the nebulizer fluid was desirable as it enhanced the aerosol generation and reduced the variability of droplet size and aerosol output. Increased ion concentration also resulted in a decrease in droplet size and a subsequent increase in the FPF, particularly for the Omron nebulizer. 

Many reviews on the relevant technical aspects for drug nebulization are available (e.g. [43 5]. The greatest disadvantages of nebulizers are their poor deposition efficiency (see Section 3.11) and low output rate (e.g. [46]). Several developments have been reported to improve their efficacy, like the use of open vents or breath-assisted open vents [47] and adapted aerosol delivery [48]. A renewed interest in nebulizer therapy may also come from the generation of special aerosols, such as hposomes [49]. 

There are many commercially available nebulizers with differing mass output rates and aerosol size distributions which will be a function of operating conditions, such as compressed air flow rate. As described above, for maximum efficacy, the drug-loaded droplets need to be less than 5 pm. In the treatment or prophylaxis of P.carinii pneumonia with nebulized pentamidine where the target is the alveolar space it is preferable to use nebulizers capable of generating droplets of less than 2 pm. 

Nerbrink, O., Dahlback, M., and Hansson, H. C. (1994), Why do medical nebulizers differ in their output and particle size characteristics J. Aerosol Med., 7,259-276. 

The delivery efficiency, or the nebulizer output, can be expressed in many different ways, as widely documented in the literature. Sometimes it is represented as the volume output, or solution mass output. However, it is more practical to use the drug mass emitted from the nebulizer at or near the mouthpiece to estimate the nebulizer output, because the amount of aerosolized drug mass at this point in the system is the best measure of how much drug the patient has available to inhale. 

Nebulizers fitted with a T-mouthpiece have an unrestricted flow of ambient air passing through the nebulizer output, supplying inhaled air flow, which effectively increases drug output. In vented nebulizers, the inhaled air must flow through the droplet production region. Therefore, the breathing pattern of the patient has an effect on the aerosol characteristics produced by such devices. The delivery efficiency of... 

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