Coagulation markers in healthy human subjects exposed to diesel exhaust

Abstract

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 (>or=2 weeks washout) to diesel exhaust at 0 (filtered air), 100 microg PM(2.5)/m(3) and 200 microg PM(2.5)/m(3). 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 microg PM(2.5)/m(3)) effect on PAI-1 levels at 22 h was of borderline significance, with a 1.32-fold decrease after exposure to diesel exhaust (200 microg PM(2.5)/m(3)), 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 microg PM(2.5)/m(3) 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.

Figure 1

Coagulation marker changes from 0 to 6 hours* post-exposure, by exposure level. Each panel depicts medians (bars) and interquartile ranges (whiskers) for each marker associated with given dose and time point (see legend); † 0 versus 6 hour* fold-change significant at p<0.05 (paired t-test); * Except hsCRP (22h); open circles represent data points outside of interquartile range; FA = filtered air; DE = 200μg/m³ (PM_2.5) diesel exhaust.