Variation in nebulizer aerosol output and weight output from the dosimeter: Implications for multicentre studies

The active aerosol component of nebulizers is less than 100% of output by weight, and may vary between nebulizers in different batches from the same manufacturer. A measure of bronchial responsiveness to methacholine, which can overcome this problem, is required. One hundred and sixty nebulizers from 21 centres in the European Community Respiratory Health Survey (ECRHS) were calibrated for aerosol and weight output. Methacholine challenge data were obtained for 1,021 subjects in three English centres of the ECRHS. The dose producing a 20% fall in forced expiratory volume in one second (PD20), and log-slope, the regression slope of percentage decline in FEV1 with log (dose), were calculated, with and without calibration of nebulizers by weight. Within-centre variation in nebulizer percentage aerosol output had a coefficient of variation of less than 10%. Unlike PD20, log-slope is unaffected by constant percentage overestimation of nebulizer output. Variation in output by weight of nebulizers of 10% had little affect on log-slope. It is, however, affected by the scheduled range of doses. Log-slope shows advantages in analysis, and is less affected by variation in nebulizer output. It can be used for multicentre comparisons, with restriction to a common dose protocol.