Ozone-induced Inflammation Is Attenuated with Multiday Exposure

Abstract

It is well known that ozone (O3) causes acute lung inflammation. What is not known is whether there is progression of the inflammatory response in humans with repeated short-term exposures. Our study was designed to test the hypothesis that repeated exposures to a high-ambient concentration of O3 (0.2 ppm) over several days would cause more inflammation than a single exposure. Fifteen healthy volunteers were exposed in random fashion to 0.2 ppm ozone for 4 h on a single day and to 0.2 ppm O3 for 4 h on 4 consecutive days while exercising moderately for 30 min of each hour. Pulmonary function tests were obtained immediately before and after each 4-h exposure. Bronchoscopy was performed 20 h after the completion of each exposure arm to obtain bronchoalveolar lavage (BAL) for measurement of markers of inflammation. Our results show initial progression followed by attenuation of the acute physiologic response to O3 with repeated daily exposures. We found a significant difference in percent change in FEV1, FVC, and specific airway resistance (SRaw) across the single-day exposure when compared with the change across Day 4 of the 4-d exposure. Bronchial fraction (the first 15 ml of BAL return) and BAL were analyzed for the following end points: total and differential cell counts, total protein, lactate dehydrogenase (LDH), fibronectin, interleukin-6 (IL-6), interleukin-8 (IL-8), and granulocyte-macrophage colony-stimulating factor (GM-CSF). In the bronchial fraction the number of polymorphonuclear cells (PMN)s and fibronectin concentration were significantly decreased after 4-d exposure compared with single-day exposure. In BAL, significant decreases in the number of PMNs, fibronectin, and IL-6 were found after 4-d exposure versus single-day exposure. These results suggest that there is attenuation of the O3-induced inflammatory response in both proximal airways and distal lung with repeated daily exposures.

Outdoor air pollution, climatic changes and allergic bronchial asthma

“…O 3 decreases exercise tolerance in well-trained nonasthmatic athletes [69][70][71][72]. Repeated daily, shortterm exposures of healthy subjects to O 3 attenuates the acute lung function and inflammatory responses [73,74]. It is important to establish whether the enhanced O 3 -induced inflammatory responses of asthmatic persons also become attenuated with repeated daily exposures, particularly in view of the fact that exposure to high O 3 concentrations may occur for several consecutive days during smog episodes.…”

Effects of antioxidant enzyme polymorphisms on ozone-induced lung function changes

“…O 3 reacts with respiratory tract lining fluid constituents and cellular membrane components to generate lipid ozonation products (LOP) and reactive oxygen species (ROS), which in turn can cause oxidative damage to other biological molecules [4][5][6]. Acute exposure to ambient levels of O 3 can induce short-term lung function abnormalities and airway inflammation, while chronic exposure may lead to remodelling of the small airways, where deposition is the greatest [7][8][9][10][11][12].…”

Toxicologic methods: controlled human exposures.

“…Bronchoscopy was first used by Seltzer and colleagues (18) to detect airway inflammation in response to 03 exposure. Since then, bronchoscopy has allowed investigators to characterize the nature of the airway inflammatory response to single and repeated exposures to 03 in healthy, allergic, and asthmatic subjects (19)(20)(21)(22). It has been used to study the effects of exposure to many pollutants in addition to 03, including NO2 (23-25), SO2, (26), acid aerosols (27)(28)(29), and diesel exhaust (30).…”