We describe a laboratory investigation comparing the delivery of chlorofluorocarbon (CFC)- and hydrofluoroalkane (HFA)-formulated beclomethasone dipropionate (BDP) by metered-dose inhaler and holding chamber (AeroChamber HC MV) in a simulation of a mechanically ventilated adult patient.
Methods: We equipped each HC MV (n = 5) with an 8.0 mm diameter endotracheal tube (ETT), locating the HC MV in the inspiratory limb of a breathing circuit linked to a mechanical ventilator set to simulate tidal breathing at tidal volume = 830 mL, respiratory rate = 15 breaths/min, inspiratory-expiratory ratio of 1:2.1, peak inspiratory pressure = 20 cm H(2)O. Temperature and humidity settings were 35+/-1 degrees C and 100% relative humidity (close to body conditions). We compared delivery of 5-actuations of CFC- and HFA-BDP (both 50 microg/actuation), measuring total emitted mass captured by a filter at the distal end of the ETT. In a separate study, we inserted the distal end of the ETT within the entry cone of a cascade impactor so that the aerosol particle size distribution could be determined with the circuit at similar environmental conditions as described previously. We made benchmark measurements with circuit temperature and humidity at room ambient conditions (21+/-1 degrees C and 54+/-5% RH respectively).
Results: Total emitted mass (5 measurements/device) was significantly greater for HFA-BDP (14.1+/-1.1 microg/actuation) compared with CFC-BDP (2.4+/-0.8 microg/actuation) (paired t test, p < 0.001). More HFA-BDP (2.7 +/- 0.2 microg/actuation) was lost from the delivery system during exhalation (0.9 +/- 0.4 microg/actuation for CFC-BDP) (p < 0.001). The mass median aerodynamic diameter (MMAD) increased from 1.2 microm (room ambient) to 2.8 microm (higher temperature and humidity conditions) for HFA-BDP. In contrast, MMAD for CFC-BDP remained close to 4.6 microm under either condition, but particles finer than about 4.0 microm increased in size when the circuit was saturated.
Conclusions: Total emitted mass for HFA-BDP was increased by a factor of 5.8 compared with CFC-BDP, due largely to the finer particle size distribution of the HFA-based solution formulation. Additional water vapor required to operate the breathing circuit at close to body conditions resulted in fine particle growth with both formulations.