The effect of breathing pattern on nebulizer drug delivery

The significance of using breathing patterns with simplified functional shapes in vented jet nebulizer research is examined. This study is comprised of three parts: (1) The measurement and analysis of human breathing patterns, (2) the subsequent in vitro testing of the effects of breathing pattern differences using a consistent bench test method, and (3) a computer modeling of these effects on the estimated regional drug deposition in the human lung. Breathing through a Pari LC-Star nebulizer caused statistically significant changes (p < or = 0.05) in measured human breathing patterns when compared to normal breathing. Observed changes included an increase in the tidal volume (34%) and period (39%). Additionally, the average duty cycle shifted 12% towards a more symmetrical breath due to the unequal increase in the inhalation and exhalation times (55% and 28%, respectively). The position of the point of maximum flow in each breath phase shifted towards the beginning and end of the breath for the inhale and exhale by 28% and 48%, respectively. The bench testing revealed that breathing pattern shape variation caused statistically significant differences in nebulizer output only in two cases. Decreasing duty cycles and shifting the point of maximum flow towards the beginning of the breath both result in a decrease in output efficiency. Square flow patterns produced slight but consistently higher output efficiencies (average 2.1% higher) and a constant output particle size over the course of each breath, different from the other non-square patterns. Numerical simulations revealed no significant dosage differences resulting from breathing pattern shape variations. However, square wave patterns consistently produced slight overpredictions in comparison with real nebulizer patterns. In contrast, sine wave patterns were found to produce essentially the same results as nebulizer patterns in both the bench tests and in the deposition simulations. This suggests that sine wave shapes are preferable for simulating breathing when bench testing drug delivery using vented jet nebulizers.