Diesel exhaust and wood smoke : mechanisms, inflammation and intervention

Background Particulate matter (PM) air pollution is associated with increased respiratory and cardiovascular morbidity and mortality. Diesel engine exhaust (DE) and wood combustion are major contributors to ambient air pollution and adverse health effects. The aim of this thesis was to investigate the fate of inhaled combustion-derived PM, the subsequent effects on pulmonary inflammation and symptomatology and to explore the potential for particle filters to improve public health. Additionally, it aimed at increasing the understanding of the pathophysiological mechanisms underlying the adverse vascular effects of PM inhalation in man. Methods In study I, lung deposition of wood smoke-derived particulates from incomplete combustion was determined in healthy and COPD subjects. In study II, airway inflammation was assessed in healthy subjects exposed to wood smoke and filtered air. In study III, vehicle cabin air inlet filters were evaluated regarding filtering capacity for DE and whether they affected the toxicological potential of the filtered PM. Healthy subjects were then exposed to filtered air and unfiltered DE, as well as DE filtered through two selected filters. In study IV, healthy subjects were exposed to filtered air and DE. Nitric oxide bioavailability was assessed by plethysmography in the presence of an NO clamp (NO synthase inhibitor NG-monomethyl locally and systemically administered) with measurements of arterial stiffness, cardiac output and blood pressure (BP). Results Study I: The total PM number deposition fraction of the wood smoke was 0.32 and 0.35 for healthy and COPD subjects respectively. Study II: Inhalation of wood smoke caused CD3+ and mast cell infiltration in the bronchial submucosa along with CD8+ cell recruitment to the epithelium. In bronchial wash, inflammatory cells, myeloperoxidase and matrix metalloproteinase 9 levels decreased. Study III: An efficient cabin air filter with an active charcoal component was most favourable in in-vitro tests and reduced symptoms in the human exposure study. Study IV: Local NO synthase inhibition caused similar vasoconstriction after exposure to DE and filtered air, along with an increase in plasma nitrate concentrations, suggesting an increase in the basal NO release due to oxidative stress. Systemic NO synthase inhibition increased arterial stiffness and blood pressure after DE exposure along with an increase in systemic vascular resistance and reduced cardiac output, implying that the increased basal NO release could not compensate for the reduced NO bioavailability in the conduit vessels. Conclusion Wood smoke particles from incomplete combustion tend to have a greater airway deposition than particles from better combustion. The airway inflammatory responses to the former particles differ from what have been shown for other PM pollutants, which may be of importance for subsequent health effects. The vasomotor dysfunction shown after DE exposure may largely be explained by reduced NO bioavailability. A vehicle cabin air inlet particle filter with active charcoal was effective to reduce DE exposure and subsequent symptoms. This may conceptually be of benefit when it comes to decreasing engine exhaust-related adverse health effects