The effects of air pollution on health have become a major concern for politicians and an almost daily topic for newspapers. A Google search using ‘air pollution and health’ provides over 18 000 000 entries. Air pollution has been linked not only to pulmonary disease, but also to cardiovascular disease. Both acute [1,2] and chronic  exposure to polluted air are associated with an increased incidence of acute myocardial infarction. Mechanistic explanations for this association are actively being sought .
The current issue of this Journal contains a remarkable piece of detective work that took place in the region of Lombardy, northern Italy. This region contains both the often heavily polluted industrial area around Milan, and idyllic places such as the Como lake and the southern Alpine slopes. The A. Bianchi Bonomi Haemophilia and Thrombosis Centre in Milan collected blood over a period of 10 years from 1218 healthy individuals from this region, who were partners or friends of patients with thrombosis, and who agreed to undergo thrombophilia testing. The very original feature of this study by Baccarelli et al.  is that it relates the results of the clotting tests to the degree of air pollution, in the hours and days before sampling, in the area where the subject lived. Surprisingly, a weak but significant negative correlation was found between the prothrombin time and the degree of air pollution at the time of sampling or the average air pollution in the 30 days prior to sampling. The degree of air pollution had no effect on the activated partial thromboplastin time or on the levels of fibrinogen, antithrombin, protein C or protein S. In a separate paper on the same healthy subjects, Baccarelli et al.  report that particulate air pollution interacts with cigarette smoking to increase plasma homocysteine levels.
Until now, relatively little attention has been paid to slight shortenings of the prothrombin time, a very frequently performed global coagulation test. Infusion of recombinant factor VIIa, however, results in a markedly shortened prothrombin time . As Baccarelli et al.  suggest, the somewhat shortened prothrombin time following exposure to polluted air could well result from an increased FVIIa level, in view of the absence of any shortening of the activated partial thromboplastin time. Measurement of FVIIa was, however, not included in the screening of these healthy individuals.
An increase in FVIIa levels may reflect exposure of the blood to tissue factor. What could be the link between air pollution and tissue factor? Associations have already been found between smoking and circulating tissue factor activity  and FVIIa levels . Exposure to polluted air causes pulmonary inflammation in humans, as evidenced by the presence of inflammatory cells in sputum  and in bronchoalveolar lavage fluid . Following intratracheal instillation of diesel exhaust particles in hamsters, there is a strict link between the degree of lung inflammation and the extent of thrombosis following minor vascular injury . Inflamed pulmonary endothelial cells would expose adhesion molecules, including P-selectin and von Willebrand factor , resulting in binding and mutual activation of leukocytes and platelets, which could then lead to the release of leukocyte-derived tissue factor-containing microparticles into the circulation . Alternatively, pulmonary inflammation because of air pollution is known to be associated with release of proinflammatory cytokines into the circulation, namely interleukin-1β, interleukin-6 and granulocyte–macrophage colony-stimulating factor . Exposure to polluted air further stimulates the release of neutrophils [16,17] and monocytes  from the bone marrow. One could assume that inhalation of pollutants may also release hematopoietic cell-derived microparticles carrying tissue factor  from the bone marrow into the circulation.
Tissue factor-bearing microparticles derived from leukocytes deposit on a layer of activated platelets [20,21]. Activated platelets accumulate clotting factors [22–26]. The interaction of tissue factor with clotting factors concentrated on a platelet layer overlying a vascular lesion would result in a local burst of thrombin activity that could readily lead to an occlusive thrombosis. It thus becomes understandable how exposure to polluted air may trigger within hours a myocardial infarction in a susceptible individual [27–29].
But enough speculation! The time has come to verify whether circulating tissue factor activity and FVIIa level do indeed rise in humans following acute exposure to polluted air, and whether this is related to the gaseous or the particulate matter in the inhaled air, and to the extent of the resulting inflammation.