The objective of this investigation was to study the relation between size and position of a mask leak on spacer output and lung dose. An upper-airway model (SAINT model, Erasmus MC) was connected to a breathing simulator. Facemasks with leaks ranging between 0 and 1.5 cm(2) were examined. Leaks were located close to the nose or close to the chin. During simulated breathing, 200 microg budesonide (Pulmicort, AstraZeneca) was delivered to the model via NebuChamber (AstraZeneca) with facemask. Spacer output and lung dose were measured by placing a filter between spacer and facemask or between model and breathing simulator, respectively. Budesonide trapped on the filter was quantified by means of HPLC, and expressed as percentage of the nominal dose. Mean spacer output doses for the nose position were 50, 38, 28, 12, 10, 6, and 0%, and for the chin position were 50, 40, 31, 11, 9, 4, and 0% for leaks of 0, 0.05, 0.1, 0.16, 0.2, 0.3, and larger than 0.4 cm(2), respectively. Mean lung doses for the nose position were 10, 8, 6, 3, 3, 1, 0, 0, 0, and 0%, and for the chin position were 10, 9, 8, 6, 6, 5, 1, 1, 0, and 0% for leaks of 0, 0.05, 0.1, 0.16, 0.2, 0.3, 0.4, 0.5, 1, and 1.5 cm(2). Efficiency of a pMDI-spacer facemask strongly depends on the size of a facemask leak. Spacer output did not depend on the position of the leak. Lung dose was higher for leaks near the chin than for leaks near the nose.

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This study aimed at identifying in a daily-life setting the influence of facemask design on drug delivery via a spacer to young children. In a 4-week randomized crossover study, 24 children (7-23-months old) with recurrent wheeze tested the AstraZeneca, Galemed, and Hans Rudolph facemask combined with the NebuChamber at home. Each mask was tested twice daily for seven consecutive days. Filters positioned between the NebuChamber and facemask trapped the budesonide aerosol (200 microg, Pulmicort). Parents were asked to score the child's degree of cooperation during administration on diary cards. The administration procedure was evaluated through video recordings. Mean filter dose (standard deviation (s.d.)), expressed as % of nominal dose, was 39% (14), 47% (12), and 42% (11) for the AstraZeneca, the Galemed and the Hans Rudolph mask, respectively. Irrespective of the degree of cooperation, the Galemed mask gave significantly higher mean filter doses than the other masks (level of significance) (p < 0.045). Median (range) within-subject dose variability, expressed, as coefficient of variation (CV), was 37% (19-255), 32% (9-114), and 30% (9-115) for the AstraZeneca mask, the Galemed mask and the Hans Rudolph mask, respectively, not significant. Dose variability increased with decreasing cooperation for all three masks (p = 0.007). Drug delivery to young children with recurrent wheeze by means of the NebuChamber can be enhanced using the Galemed facemask. Dose variability seems to be independent of facemask design but mainly depends on cooperation.

What is already known about this subject • For asthmatic adults, bronchodilators with a MMAD between 3 and 6 mm were shown to give the best improvement in lung function and the least systemic side-effects.• It is not known, however, what is the most efficacious particle size for inhaled steroids in asthmatic adults. Clinical efficacy and systemic side-effects of inhaled steroids should be measured to define the optimal particle size.What this study adds • Our study investigated the systemic absorption of inhaled steroids. We found that a particle size of 2.5 mm and 4.5 mm gave a higher pulmonary bioavailability compared with the 1.5 mm monodisperse aerosols in adults with mild asthma and therefore were more likely to elicit systemic adverse effects. AimsFor optimal efficacy, antiasthma drugs should be delivered to the desired region in the airways. To date, the optimal particle size for steroids in adults is not known. The aim of the study was to evaluate the pulmonary bioavailability for inhaled beclomethasone dipropionate (BDP) aerosols of different particle sizes. MethodsIn a randomized single-blind crossover trial, 10 mild asthmatic patients inhaled monodisperse BDP aerosols with mass median aerodynamic diameters (MMADs) of 1.5, 2.5 and 4.5 mm. Gastrointestinal absorption was blocked by activated charcoal. Plasma concentrations of 17-beclomethasone monopropionate (17-BMP) were measured by liquid chromatography plus mass spectrometry. ResultsAerosols with MMADs of 1.5 mm, 2.5 mm, and 4.5 mm gave mean maximum concentrations (Cmax) of 17-BMP of 475 pg ml -1 , 1300 pg ml -1 , and 1161 pg ml -1 , respectively. The area under the curve (AUC) values of 17-BMP for MMADs of 1.5 mm, 2.5 mm, and 4.5 mm were 825 pg ml -1 h, 2629 pg ml -1 h, and 2276 pg ml -1 h, respectively. The mean terminal half-time of 17-BMP for all three aerosol sizes was around 1.5 h. ConclusionsMonodisperse BDP aerosols with a MMAD of 1.5 mm gave two-three fold lower values for Cmax and AUC than those with MMADs of 2.5 and 4.5 mm.