Fine and ultrafine particle exposure: Health effects and biomarkers

University dissertation from Lund University, Faculty of Medicine

Abstract: Particle, especially fine and ultrafine particle exposure has been linked to lower airway infections, asthma, chronic obstructive pulmonary disease (COPD), ischemic heart disease, stroke and cancer. The underlying mechanisms are under active investigation, and are still not fully understood. Several mechanisms have been proposed such as oxidative stress, inflammatory response and genotoxicity.Different biomarkers have been developed to investigate the mechanisms. This thesis includes exposure to fine and ultrafine particles from three different exposure sources: diesel exhaust, asphalt fumes and welding fumes. The main aim is to investigate adverse health effectscaused by airborne fine and ultrafine particle exposure, and to analyze biomarkers that are hypothesized to be in the causal pathway from exposure to pulmonary and cardiovascular disease.The thesis is based on three studies (four papers): i) a human experimental exposure study with 18 volunteers; ii) a field study with 167 asphalt workers and 100 controls; iii) a field study with 101 welders and 127 controls. We investigated airway symptoms and lung function as health outcomes,and measured different biomarkers: cytokines (as biomarkers for inflammatory response), mitochondrial DNA copy number (as biomarker for oxidative stress) and telomere length (as biomarker for genotoxicity) to explore mechanisms.The exposure levels in our studies were lower than the current occupational exposure limits. However, we still found exposure related eyes and airway irritation and transient decrease in lung function. Changes in cytokines after exposures were not statistically clear, but may indicate a mild inflammatory response. Higher mitochondrial DNA copy number together with lower methylation suggests possible exposure related oxidative stress. No difference in telomere length was found between exposure groups and controls, but telomere length was positively associated with PAH metabolites, indicating more PAH exposure was associated with longer telomere length.This thesis shows health effects and change of biomarkers under low to moderate exposure to particles. Although the effects seem to be in the compensatory stage, reconsideration is still called for regarding current occupational exposure limits.