Effects of equipment dead space and pediatric breathing patterns on inhaled mass of nebulized budesonide

Inhaled mass, the quantity of aerosolized drug actually inhaled by a patient, can be estimated in vitro by using a piston pump and an inhaled mass filter in a manner that simulates in vivo aerosol delivery. For pediatric patients, measurement with an inhaled mass filter with a large equipment dead space (V(DEQ)) in relation to a small tidal volume (V(T)) may underestimate the inhaled mass. The present study investigated the impact of V(DEQ) on the accuracy of in vitro measured inhaled mass of budesonide suspension for nebulization using Spira Module 1 jet nebulizers (Respiratory Care Center, Hameenlinna, Finland), inhaled mass filters, V(DEQ)s of different sizes, and pediatric breathing patterns. The V(DEQ) varied between 14 and 108 mL, and the breathing patterns corresponded to a V(T) between 50 and 500 mL, to breathing frequencies of 40 to 12 per min^-1, to a duty cycle of 0.5 for all breathing patterns, and to a nebulization time of 2 minutes. The results showed that the inhaled mass was a function of the V(DEQ) for each breathing pattern as defined by the inspiratory minute volume (V(I)). For a large V(T), a small V(DEQ) affected the inhaled mass of budesonide only marginally, but as the V(DEQ) increased, the measured inhaled mass decreased to the point that for a V(DEQ) larger than the V(T), the inhaled mass was zero. When the inhaled mass was expressed as a function of an effective volume (V(EFF)) (i.e., V(I) corrected for V(DEQ)), the results showed a linear correlation (R² = 0.921) between the volume of aerosol inhaled through the nebulizer and the inhaled mass of budesonide. The results of the study indicate that V(DEQ) has a critical effect on the measurement of inhaled mass in vitro for conventional jet nebulizers using pediatric breathing patterns. This means that the in vitro measured inhaled mass of drug can seriously underestimate the in vivo value. When pediatric breathing patterns are used in vitro, a correction of the V(T) by the V(DEQ) should be made in order to more accurately reflect the in vivo inhaled mass of drug.