The Unusual Suspects: Air Pollution Components and Associated Health Effects

Abstract

The aim of the thesis was to investigate which physical, chemical or oxidative characteristics of ambient PM have the most consistent associations with acute cardio-respiratory effects in human volunteers. During the first phase of the RAPTES project (“Risk of Airborne Particles: a Toxicological-Epidemiological hybrid Study”) eight sites in the Netherlands that differed in local PM emission sources were chosen for extensive air pollution characterization. The measured air pollutants included PM10, PM2.5, PM2.5-10, particle number concentrations (PNC, a proxy for ultrafine particles), PM absorbance, elemental (EC) and organic carbon (OC), trace metals (Fe, Cu, Ni, V), secondary inorganic components (nitrate and sulfate), endotoxin content, OP, and the gaseous air pollutants – ozone and nitrogen oxides (O3, NO2, NOX). The selected sites were: an underground train station, three different road traffic sites, a livestock farm, a sea harbor, a site located in the vicinity of a large steelworks, and an urban background site. Chapter 2 presents a detailed characterization of air pollution at these sites. The underground train station had substantially higher concentrations of nearly every PM characteristic, especially Fe, Cu and OP. PNC showed the highest concentrations at the continuous traffic site. Substantially increased levels of endotoxin were measured at the farm. These results showed that it was possible to identify real-world locations where several PM characteristics had high contrast and correlations sufficiently low to investigate their independent health effects. In the second, semi-experimental phase, healthy, non-smoking, young adults were repeatedly exposed for five hours at each of the sites. Measurements took place on 30 days between March and October 2009, resulting in 170 observations in 31 volunteers. Markers of respiratory and cardiovascular health were measured prior to exposure, directly after, two hours after and in the following morning. Two-pollutant linear regression models were used to investigate which air pollution component(s) were most consistently associated with health effects. Chapter 3 investigated which ambient air pollutants had the most consistent associations with acute respiratory effects. An increase in PNC was associated with acute airway inflammation (FENO). The association was robust and insensitive to adjustment for other pollutants. Similarly consistent associations were seen between impaired lung function (FVC and FEV1) and PNC and NO2. PM mass concentration and OP were not predictive of the observed acute responses, neither were other measured PM characteristics. Associations with acute cardiovascular effects were studied in chapter 4. OC, sulfate and nitrate were most consistently associated with different blood biomarkers predictive of the risk of cardiovascular events – C-reactive protein, fibrinogen, platelet counts and von Willebrand Factor. Associations for PM mass concentrations and OP were less consistent, whereas PNC, EC, trace metals and NO2, were not associated with the biomarkers after adjustment for other pollutants. In chapter 5 thrombin generation ex vivo was measured using blood samples collected during the study. Increases in thrombin generation in the intrinsic (FXII-dependent) blood coagulation pathway were associated with exposure to NO2, nitrate and sulfate, but not PM mass, OP or other measured air pollutants.