Characterization and comparison of oxidative potential of real-world biodiesel and petroleum diesel particulate matter emitted from a nonroad heavy duty diesel engine.

Little is known regarding the oxidative potential of biodiesel particulate matter (PM) relative to diesel PM emitted from heavy duty diesel (HDD) nonroad engines generated in real-world occupational settings. The composition of biodiesel and diesel PM can include transition metals, polar, and nonpolar organic species which can increase oxidative potential via production of reactive oxygen species (ROS). Elevated ROS can lead to oxidative stress and induce antioxidant defense, inflammation, and toxicity. This study characterized the chemical composition of PM (water soluble organic carbon and elemental metals) collected in a real-world occupational setting. ROS production in a human epithelial cell line (BEAS-2B) treated with biodiesel and diesel PM extracts was compared to oxidative potential measured by an acellular dithiothreitol (DTT) assay. The oxidative potential (DTT consumption rate) of diesel PM was 21% greater than biodiesel PM at the highest treatment concentration (60 µg/mL), yet the ROS generated in vitro were similar between fuel types. Average concentrations of Cu, Cr and Zn were higher in diesel PM compared to biodiesel PM. Additionally, there was a significant correlation between DTT consumption and Cu in diesel PM (r = 0.98), but not B20 PM. There was a strong correlation between WSOC content in diesel PM and ROS generated in vitro (r = 0.83), but no correlation between WSOC content in biodiesel PM and ROS. Taken together, the results indicate the influence of fuel type on the chemical composition and oxidative potential of PM generated by a nonroad HDD engine operated at a recycling center. While acknowledging the potential influence of other species of interest not measured (i.e., quinones), real-world petroleum diesel PM emissions had higher oxidative potential compared to biodiesel PM suggesting that biodiesel use may reduce risk to human health.

Pharmacokinetics of a novel submicron budesonide dispersion for nebulized delivery in asthma.

The objective of this study was to evaluate the safety and pharmacokinetics of unit dose budesonide (UDB), an aqueous dispersion of submicron-sized budesonide particles, and a commercially available budesonide suspension formulation. This was a randomized, double-blind, active-controlled, 4-period, 4-way crossover trial in 16 healthy, adult volunteers. Subjects received UDB 0.24, 0.12, and 0.06 mg or commercial budesonide 0.25 mg via a jet nebulizer. T(max) was significantly (p<0.05) earlier for UDB 0.06, 0.12, and 0.24 mg (4.5+/-3.3, 3.1+/-1.5, 3.7+/-1.5 min) vs. commercial budesonide (9.1+/-7.1 min). C(max) was significantly (p<0.05) higher for UDB 0.24 mg vs. commercial budesonide 0.25 mg (434.5+/-246.9 pg/mL vs. 303.5+/-177.4 pg/mL) but not between UDB 0.12 mg (239.9+/-140 pg/mL) and commercial budesonide 0.25 mg (p=0.448). AUC(0-infinity) was marginally, but significantly lower for UDB 0.24 mg than commercial budesonide 0.25 mg. AUCs for UDB 0.12 mg were lower than commercial budesonide 0.25 mg. UDB 0.24 mg was absorbed more rapidly and achieved higher peak concentrations than commercial budesonide 0.25 mg, but had a lower AUC(0-infinity). UDB 0.12 mg also was absorbed more rapidly but had lower C(max) and AUCs than commercial budesonide 0.25 mg.

In vitro estimations of in vivo jet nebulizer efficiency using actual and simulated tidal breathing patterns.

In vivo aerosol delivery efficiency was estimated in vitro for two jet nebulizers using a breath monitor (Breathe!; Pari GmbH, Germany) and breath simulator (COMPAS; Pari GmbH) to reproduce subject tidal breathing patterns. The AeroEclipse (Trudell Medical International, Canada), a breath-actuated nebulizer, and the LC Star (Pari GmbH), a breath-enhanced nebulizer, were filled with levalbuterol HCl solution (Sepracor, USA) and operated with compressed O(2) at 8 lpm. Tidal breathing patterns of 20 adult subjects were digitally recorded with the Breathe! Breath Monitor. Subjects then breathed tidally from each nebulizer separately for 1 minute and to nebulizer dryness. Levalbuterol aerosol collected on filters placed between the nebulizer and mouth was chemically assayed to determine the inspired mass (IM), wasted mass (WM) and total emitted mass (TM). Measurements were repeated using the COMPAS Breath Simulator to simulate each subject's tidal breathing pattern. IM, WM, and TM measurements using actual versus simulated tidal breathing were highly comparable for each nebulizer, except the IM (p < 0.05) from LC Star measured at nebulizer dryness. Breath simulation was an inaccurate tool for estimating the time to nebulizer dryness as simulated measurements to nebulizer dryness took significantly longer than measurements preformed with actual tidal breathing (p < 0.001). While breath simulation provides an accurate in vitro tool for estimating in vivo aerosol delivery, it should not completely replace in vivo measurements until inherent limitations in simulator operation can be overcome to provide a more clinically realistic simulation.