OZONE-INDUCED INFLAMMATION IS ATTENUATED WITH MULTIDAY EXPOSURE

It is well known that ozone (O-3) causes acute lung inflammation. What is not known is whether there is progression of the inflammatory resp onse in humans with repeated short-term exposures. Our study was desig ned to test the hypothesis that repeated exposures to a high-ambient c oncentration of O-3 (0.2 ppm) over several days would cause more infla mmation than a single exposure. Fifteen healthy volunteers were expose d in random fashion to 0.2 ppm ozone for 4 h on a single day and to 0. 2 ppm O-3 for 4 h on 4 consecutive days while exercising moderately fo r 30 min of each hour. Pulmonary function tests were obtained immediat ely 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 s how initial progression followed by attenuation of the acute physiolog ic response to O-3 with repeated daily exposures. We found a significa nt difference in percent change in FEV1, FVC, and specific airway resi stance (SRaw) across the single-day exposure when compared with the ch ange across Day 4 of the 4-d exposure. Bronchial fraction (the first 1 5 mi of BAL return) and BAL were analyzed for the following end points : total and differential cell counts, total protein, lactate dehydroge nase (LDH), fibronectin, interleukin-6 (IL-6), interleukin-8 (IL-8), a nd granulocyte-macrophage colony-stimulating factor (CM-CSF). In the b ronchial fraction the number of polymorphonuclear cells (PMN)s and fib ronectin concentration were significantly decreased after 4-d exposure compared with single-day exposure. In BAL, significant decreases in t he number of PMNs, fibronectin, and IL-6 were found after 4-d exposure versus single-day exposure. These results suggest that there is atten uation of the O-3-induced inflammatory response in both proximal airwa ys and distal lung with repeated daily exposures.