Nebulizer calibration using lithium chloride: an accurate, reproducible and user-friendly method

Abstract

Jet nebulizers are used clinically and in research in the measurement of airway responsiveness [1][2][3]. Drug output from nebulizers has traditionally been calibrated by weighing the units before and after nebulization. Variations in the design of nebulizers means that aerosol output cannot be predicted by conventional weight loss calibration [4]. Several methods of measuring true aerosol output have been attempted [5][6][7] with some success, but these methods have tended to be confined to specialist research centres because of their complexity.There are two components represented in the gravimetric method, evaporative loss of water vapour and aerosol. Of these two components only the aerosol carries drug and, therefore, it is only this component that is relevant for dose assessment. The gravimetric method, though easy to perform, overestimates true drug output by 25-85% [4][5][6]. DENNIS et al. [4] developed a chemical tracer technique using sodium fluoride (the NaF method) which measured true aerosol output. NaF solution was placed in a nebulizer and the nebulizer activated. The resultant NaF aerosol was collected onto a filter paper and recovered. The concentration of NaF was measured electrochemically with a fluoride electrode and the amount present represented the aerosol fraction of the concomitant weight loss. Solute tracer methods, in particular the NaF assay, have proved useful in research studies needing accurate assessment of nebulizer output. However, the NaF method is time consuming, difficult and requires sensitive specialist equipment and dedicated staff. This has resulted in only a few centres, with the appropriate resources, adopting the method.We present a simple, repeatable method of nebulizer calibration which can be carried out either in the respiratory laboratory or in hospital biochemistry departments on routine analysers that employ low detection limits. The method is similar to the NaF method, but uses lithium chloride (LiCl) as the tracer. LiCl is ideal for this purpose because it is readily soluble, uncommon in the environment (unlike other salts such as Na + and K + ) and has a low molecular weight, maximizing the molar concentration of a weight/volume solution.When introducing a new method it is necessary to validate it against an existing established method. We compared the NaF tracer method and the new LiCl tracer method using 10 Mefar jet nebulizers (Mefar, Brescia, Italy). These nebulizers were chosen for relative aerosol output assessment, because of the international importance they have achieved through selection for use in the European Community Respiratory Health Survey (ECRHS) [1]. Methods Nebulizers and dosimeterAerosol output and weight loss from a Mefar dosimeter (driving pressure 180 kPa) was assessed for each of two A new adaptation of a widely available clinical assay for lithium (determined by flame photometry, LiCl method) was compared to an existing electrochemical method based on fluoride detection (NaF method). The agreement between the two methods and the rep...

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“…Nebulizer output was measured gravimetrically on an analytical balance (sensitivity 0.0001 g) and by an aerosol tracer method using lithium chloride (LiCl) [10]. Briefly, the nebulizer was filled with 4 mL of LiCl solution and activated five times with a 6 s pause between activations.…”

European Community Respiratory Health Survey calibration project of dosimeter driving pressures

“…The overall mean output of all the nebulizers was 6.4¡0.8 mg?s -1 , with a range of 3.1-8.4 mg?s -1 . The coefficient of repeatability for the lithium analysis was 0.8 mg [3,7].…”

“…The coefficient of repeatability (i.e. the value below which the difference between two measurements will lie, with probability 0.95) of the nebulizer calibrations was examined in previous publications [3,7] using the BLAND and ALTMAN method [9].…”

“…Nebulizer output measurements: variation of nebulizers used in the European Community Respiratory Health Survey phase II A previously validated method was used for determining true solute as opposed to gravimetric nebulizer output, because the latter is markedly affected by evaporative loss [6,7]. Briefly, each nebulizer was filled with 4 mL of LiCl 0.24 M solution and activated five times with a 6-s pause between activations.…”

“…Briefly, each nebulizer was filled with 4 mL of LiCl 0.24 M solution and activated five times with a 6-s pause between activations. Aerosol was entrained onto a glass fibre filter paper and the LiCl subsequently desorbed in 5 mL of purified water and measured by flame photometry [6,7].…”