Fiona Sands

Project title: The Effects of Exposure to Diesel Exhaust on Endothelial Function as Measured by Brachial Artery Reactivity

Degree: MPH | Program: Environmental and Occupational Health (EOH) | Project type: Thesis/Dissertation
Completed in: 2005 | Faculty advisor: Joel D. Kaufman


Diesel engines are widely used and emit significant amounts of fine and ultrafine particulate matter. Exposure to such particles may have serious health consequences including an increase in cardiovascular diseases, observed in epidemiologic studies of both acute and chronic exposures. The mechanism for this increase in cardiovascular disease is unknown, but may include endothelial dysfunction. Endothelial dysfunction is associated with both acute and chronic processes involved in cardiovascular diseases, including the regulation of vascular tone, homeostasis, immune and inflammatory responses. To evaluate the potential mechanism by which particulate matter (PM) might cause cardiovascular health effects, we assessed endothelial function through measurement of brachial artery reactivity.

Ultrasonographic assessment of flow-mediated dilation (FMD) of the brachial artery is a non-invasive way to characterize endothelial dependent responses in humans, and thus determine if the endothelium is affected by exposure to diesel exhaust (DE). The overall hypothesis is that exposure to inhaled DE will result in concentration-related changes in endothelial homeostasis as reflected in FMD following two hours at 0, 50, 100, and 200 μg/m3 of DE. The hypothesis is being evaluated in a series of experiments including completed pilot studies and an ongoing main study. Methods development pilot studies included one study assessing the variability of FMD using proximal verses distal cuff placement in repeated measurements. The other pilot study evaluated software for image analysis in interpreting ultrasonographic FMD data.

FMD is assessed by the degree of brachial artery dilation following inflation and deflation of a blood pressure cuff on the arm, but the placement of the cuff (forearm vs. upper arm) has not been standardized in existing protocols. Pilot study results showed that upper arm cuff placement had a lower coefficient of variation and was associated with better test characteristics.

Automated image analysis is becoming a common way of interpreting ultrasound images for FMD assessment. We evaluated two software packages, and determined that one had superior characteristics for our study, further determining that provided software defaults and instructions were inadequately detailed to produce reliable research quality data. Additional guidance was developed to reduce measurement error in FMD assessment. We are now evaluating the effect of DE on FMD, and will present preliminary data analysis from human subjects.