Aerosol inhalation from spacers and valved holding chambers requires few tidal breaths for children.

OBJECTIVE: The goal was to determine the number of breaths required to inhale salbutamol from different spacers/valved holding chambers (VHCs). METHODS: Breathing patterns were recorded for 2- to 7-year-old children inhaling placebo from 4 different spacers/VHCs and were simulated by a flow generator. Drug delivery with different numbers of tidal breaths and with a single maximal breath was compared. RESULTS: With tidal breathing, mean inhalation volumes were large, ranging from 384 mL to 445 mL. Mean values for drug delivery with an Aerochamber Plus (Trudell, London, Canada) were 40% (95% confidence interval [CI]: 34%-46%) and 41% (95% CI: 36%-47%) of the total dose with 2 and 9 tidal breaths, respectively. Mean drug delivery values with these breath numbers with a Funhaler (Visiomed, Perth, Australia) were 39% (95% CI: 34%-43%) and 38% (95% CI: 35%-42%), respectively. With a Volumatic (GlaxoSmithKline, Melbourne, Australia), mean drug delivery values with 2 and 9 tidal breaths were 37% (95% CI: 33%-41%) and 43% (95% CI: 40%-46%), respectively (P = .02); there was no significant difference in drug delivery with 3 versus 9 tidal breaths. With the modified soft drink bottle, drug delivery. Drug delivery was not improved with a single maximal breath with any device. CONCLUSION: For young children, tidal breaths through a spacer/VHC were much larger than expected. Two tidal breaths were adequate for small-volume VHCs and a 500-mL modified soft drink bottle, and 3 tidal breaths were adequate for the larger Volumatic VHC.

Validation of methodology for recording breathing and simulating drug delivery through spacers and valved holding chambers.

BACKGROUND: Output from spacers (or valved holding chambers) is sensitive to changes in breathing pattern. Different spacers have unique characteristics that may influence breathing. A method used for breathing simulation, where the simulated breathing can be recorded on subjects while they are using spacers, may allow for more accurate in vitro estimation of drug delivery in specific populations, using specific spacers. METHODS: A flow chamber was used to record breathing while salbutamol was administered to two adult subjects through different spacers. Each subject performed a series of breathing patterns over a range of different inhalation volumes and flows. Salbutamol "inhaled" by subjects was captured on inspiratory filters and quantified by ultraviolet spectrophotometry. Recorded breathing patterns were simulated and ex vivo drug delivery was compared to in vitro drug delivery. Three equipment configurations were used to validate different aspects of the methodology. Configuration 1: breathing recorded by pneumotachometer placed directly between a human subject and the spacer. Breathing simulation performed with an identical setup. Configuration 2: spacer enclosed within a flow-chamber while breathing was recorded. Breathing simulation performed with an identical setup. Configuration 3: spacer enclosed in flow chamber to record breathing, but not when simulating breathing. In each configuration, the ex vivo and in vitro (simulated) filter doses were compared. RESULTS: Configuration 1: the median difference between ex vivo and in vitro filter doses was 0.4% (range: -12.2 to 6.9%). Configuration 2: the median difference was -2.3% (range: -9.0 to 5.0%). Configuration 3: the median difference was 1.7% (range: -11.5 to 3.9%). CONCLUSION: Our results indicate that in vitro simulated drug delivery using this method of recording using a flow chamber, closely approximates ex vivo total drug delivery. This technique allows for recording of breathing on patients while they are using spacers, with minimum increase in dead space or resistance, and no physical alteration in the patient-device interface.