Coagulation markers in healthy human subjects exposed to diesel exhaust.
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).


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.


RESULTS
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.
Carlsten
Chris
C
Department of Medicine, University of Washington, 4225 Roosevelt Ave NE, University of Washington, Campus Box 354695, Seattle, WA 98195, United States. carlsten@u.washington.edu
Kaufman
Joel D
JD
Peretz
Alon
A
Trenga
Carol A
CA
Sheppard
Lianne
L
Sullivan
Jeffrey H
JH
D000328:Adult; D015415:Biomarkers / Q000097:blood*; D001777:Blood Coagulation / Q000187:drug effects*; D002097:C-Reactive Protein / Q000378:metabolism; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D008297:Male; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D010976:Platelet Count; D001335:Vehicle Emissions / Q000633:toxicity*; D014841:von Willebrand Factor / Q000378:metabolism
D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; D017395:Plasminogen Activator Inhibitor 1; D001335:Vehicle Emissions; C036309:fibrin fragment D; D014841:von Willebrand Factor; D002097:C-Reactive Protein