Background: Ambient particulate matter (PM) is associated with cardiovascular morbidity and mortality. It has been proposed that PM induces a pro-thrombotic process, increasing the risk of cardiovascular events, with some support from epidemiological and laboratory-based models. Diesel exhaust is a major contributor to urban PM, and we conducted a controlled human exposure of diesel exhaust in healthy subjects. Objective: To evaluate diesel exhaust exposure effects on fibrinolytic burden (D-dimer), platelet number, and endothelial injury (von Willebrand's factor, VWF), inhibition of the fibrinolytic pathway (plasminogen activator inhibitor-1 [PAI-1]), and inflammation (C-reactive protein, CRP). Materials and methods: Randomized, crossover, double-blinded design, with 13 healthy participants exposed on three different days (≥ 2 weeks washout) to diesel exhaust at 0 (filtered air), 100 μg PM2.5/m3 and 200 μg PM2.5/m3. We assessed diesel exhaust-associated changes in D-dimer, VWF, PAI-1 and platelets at 3, 6 and 22 h, and CRP at 22 h, after exposure initiation. Result: Significant changes did not occur in any primary endpoints. Among secondary endpoints, diesel exhaust (200 μg PM2.5/m3) effect on PAI-1 levels at 22 h was of borderline significance, with a 1.32-fold decrease after exposure to diesel exhaust (200 μg PM2.5/m3), relative to filtered air (CI 1.00 to 1.54). Diurnal patterns in D-dimer and PAI-1 were observed. Conclusions: In healthy individuals, exposure to 200 μg PM2.5/m3 diesel exhaust did not affect primary pro-thrombotic endpoints. Thus, these data do not support a diesel exhaust-induced pro-thrombotic phenomenon. Replication of these studies should be carried out to ascertain whether or not they inform our mechanistic understanding of air pollution's cardiovascular effects.
Bibliographical noteFunding Information:
We would like to thank Mary Aulet, Timothy Gould, Karen Jansen, Sara Jarvis, Jim Stewart, and the University of Washington's General Clinical Research Center staff for invaluable assistance with the conduct of this study. Support for this study was provided by grants R830954 and R827355 from the Environmental Protection Agency, M01RR-00037 from the National Institutes of Health (Uniõversity of Washington — General Clinical Research Center), and ES013195, ES011139, and P30ES07033 (University of Washington — Center for Ecogenetics and Environmental Health) from the National Institute for Environmental Health Sciences.
- Inhalation exposure
- Vehicle emissions
ASJC Scopus subject areas