Effects of short-term exposure to nitrogen dioxide and ozone on human airways

Abstract

The studies presented in this thesis have examined the plausible mechanisms underlying development of airway inflammation soon after short-term exposure to ozone at peak ambient levels and NO2 at peak indoor levels on human airways.The study presented in chapter 3 has shown that short-term exposure of healthy human subjects to 2 ppm NO2 induces an acute inflammatory response characterised by secretion of IL-8 at 1.5 hours and this is followed by influx of PMNs at 6 hours in the bronchial wash (BW) following exposure. No changes were seen in the inflammatory cell numbers or in the expression of leucocyte endothelial adhesion molecules (LECAMs) in the bronchial mucosa suggesting that NO2 induces an inflammatory response mainly in the peripheral conducting airways.In order to study (chapter 4) the role of the LECAMs in ozone-induced acute inflammatory response, fibre-optic bronchoscopy (FOB) was performed 1.5 hours following exposure to ozone (0.12 ppm). No changes were seen in total and differential cell counts, albumin and total protein in BW and bronchoalveolar lavage (BAL) fluid. A significant increase was seen in the expression of P-selectin staining blood vessels in the bronchial submucosa following ozone exposure. However, no changes were seen in the numbers of neutrophils and the expression of other LECAMs including ICAM-1, E-selectin and VCAM-1 in bronchial submucosa. In the absence of an overt inflammatory response the upregulation of P-selectin could represent one of the earliest events in the inflammatory response such as 'rolling' of neutrophils on the vessel wall prior to transendothelial migration.In conclusion, these studies have shown that short-term exposure to ozone (healthy and asthmatic airways) and NO2 (in healthy airways) induces an acute inflammatory response characterised by PMN influx and at least at the dose and time points studied the inflammatory response occurs mainly in the peripheral conducting airways. In addition, exposure to ozone in healthy subjects induces epithelial damage, stimulates subepithelial sensory nerves to release SP and secretion of chemokines which contribute to development of inflammation.</p