No abstract

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, con Glass fibre filter onto which NaF laden aerosols impact jet nebuliser reservoir containing 1 % w/v NaF mm GF/A filters, through which air was drawn at 25 1/min. A higher flow rate and larger filter were used for the ultrasonic nebulisers because the filter could not be positioned as close to the source of nebulisation. After aerosol collection GF/A filters were removed and stored for later analysis. For flow rates of 15 1/min and above and for aerosols having a mass median diameter of 0 3 gm or more the collection efficiency of GF/A filters exceeds 99 9%.18 When a second filter was placed in series we detected no aerosol breakthrough.Analysis of aerosol output Total ionic strength adjustment buffer (TISAB; BDH Chemicals Ltd) was prepared as a 50% solution in distilled water, and 20 ml were added to each Whatman filter within 25 ml plastic Universal bottles. The bottles were then sealed and fluoride was allowed to desorb overnight. The recovery of fluoride from filters was complete (> 98%) and no fluoride was detected in unused filters. Fluoride analysis followed well established protocols.'9 Fluoride standards were prepared by microlitre injections of 5 0, 10-0, and 15-0 pl of 1 00% sodium fluoride into 20 ml aliquots of 50% TISAB buffer, resulting in 5-95E-5M, 1 19E'M, and 1 *78E'M fluoride solutions. Both standard and test solutions were equilibrated to 25°C in a water bath. Fluoride concentrations within the buffered solutions were then measured electrochemically with a fluoride specific ion electrode (Corning Ltd, Halstead) on a Corning 255 pH/ ion meter with a calomel reference electrode. This electrochemical system had a log-linear relation between concentration and activity (mV) from 10-'M to 10'M F. All solutions were continually agitated during analysis with an electromagnetic stirrer. An internal two point calibration was established with the 5 and 15 pl fluoride standards and its accuracy was checked with the 10 p1 standard....

Background The value of measuring airway responsiveness in asthma research is currently limited by the number of different methods used by different investigators, by the lack of a standardised method of expressing precision, and by an inability to equate the results of one method with those of another. Methods Two pairs of measurements of airway responsiveness to methacholine were performed in 20 asthmatic subjects, one pair using a dosimeter method (AR-D) and one pair using the conventional Wright nebuliser tidal breathing method (AR-W). The two methods normally use different techniques for quantifying changing levels in forced expiratory volume in one second (FEV,) after each dose of methacholine (the mean of the highest three of six measurements for AR-D, the lower of two measurements for AR-W), and different techniques for expressing measurements of airway responsiveness (the provoking dose (PD20) and the provoking concentration (PCQ0) respectively responsible for a 20% decrement in FEV,). Results The coefficient of repeatability (and hence precision) for the measurement of airway responsiveness was significantly better for AR-D (3.0) than for AR-W (10.9), but the technique for quantifying FEV, contributed more to this than the technique for delivering methacholine. A PCQ0 of 1 mg/ml with AR-W was equivalent to a PD,0 of 103 pg withConclusions It is practical as well as desirable to compare the precision of different techniques for the measurement of airway responsiveness and to derive conversion factors so that results may be equated. (Thorax 1993;48:239-243) Airway responsiveness provides a useful concept in understanding asthma and its measurement is valuable in asthma research. Of the various bronchoconstrictor stimuli used, nebulised methacholine is probably the most popular. At present several different methods of methacholine delivery are employed together with various different methods of expressing or measuring airway responsiveness. This limits the value of such measurements because the results from one laboratory cannot readily be compared with those from another. There is consequently a need to establish some means of defining precision in measurement-for example, coefficient of repeatability-and of equating results between methods.Of the two measurement methods which are currently most popular, that using the Wright nebuliser has become the conventional one throughout much of Canada, Australasia and Europe.' Aerosol is generated continuously over successive periods of two minutes from doubling concentrations of methacholine and is inhaled by the test subject during tidal breathing. The dose delivered consequently depends on tidal volume and ventilatory frequency as well as on aerosol output and so is not readily quantified, although it may be closely repeatable for the individual subject. As a result airway responsiveness is expressed by the provoking concentration of methacholine (rather than the delivered dose) which is estimated to provoke a 20% decrement in the forced expirator...

Late asthmatic reactions can be difficult to recognize because of their prolonged time course and the confounding effects of superimposed circadian rhythms of ventilatory function. Conventional methods of analysis are rather arbitrary. They depend for example on a 15 or 20% fall in forced expiratory volume in one second (FEV 1 ) from baseline or from time-matched control measurements. We have, therefore, investigated whether statistical approaches applied to individual subjects can assist in the identification of late asthmatic reactions.In two separate series of aerosol inhalation tests, three symptomatic workers, three asthmatic controls and three nonasthmatic controls were challenged blindly with increasing doses of two chemical agents, and saline. One of the agents, sodium isononanoyl oxybenzene sulphonate (SINOS) was a suspected cause of occupational asthma. Prior to the challenges, FEV 1 was measured hourly on three control days. Cumulative late changes on both control and active challenge days were quantified as the area between a line extrapolated from a 10.00 h baseline and the actual measurements from 12.00-22.00 h (the 2-12 h area decrement). The area decrement measurements on control and active challenge days were compared using Student's t-tests. The sensitivity of this method for detecting late asthmatic reactions among potentially positive tests (SINOS challenge tests in the workers) was examined, as was its specificity. The latter was determined from the false positive rate among the negative tests. A second statistical method based on the pooled standard deviation of serial (hourly) FEV 1 measurements was investigated in the same way. In total, the data from 220 challenge and 30 control days were available for analysis.Late responses associated with falls in FEV 1 of 8-16% were statistically significant when a t-test was used to compare area decrement on each active challenge day with three control days. This approach was, therefore, potentially more sensitive than conventional techniques for identifying late asthmatic reactions. The false positive rate was 4%. The serial FEV 1 method was more sensitive, identifying a further five positive tests, but was less specific, with a false positive rate of 7%.These results suggest that when the day-to-day variability of lung function has been estimated from at least three control days, statistical tests can be applied to potential late asthmatic reactions, allowing them to be identified with greater precision than conventional clinical techniques.