Am. J. Respir. Crit. Care Med., Volume 161, Number 6, June 2000, 1855-1861

The Effect of Repeated Ozone Exposures on Inflammatory Markers in Bronchoalveolar Lavage Fluid and Mucosal Biopsies

RUDOLF A. JÖRRES, OLAF HOLZ, WOLFGANG ZACHGO, PETRA TIMM, SILKE KOSCHYK, BERND MÜLLER, FRIEDRICH GRIMMINGER, WERNER SEEGER, FRANK J. KELLY, CHRISTINE DUNSTER, THOMAS FRISCHER, GERD LUBEC, MARC WASCHEWSKI, AXEL NIENDORF, and HELGO MAGNUSSEN

Krankenhaus Grosshansdorf, Zentrum für Pneumologie und Thoraxchirurgie, Grosshansdorf; Laboratory of Respiratory Cell Biology, Policlinic - Department of Internal Medicine, Philipps-University, Marburg; Justus-Liebig Universität Giessen, Zentrum für Innere Medizin, Gieen; Universitäts-Krankenhaus Eppendorf, Institut für Pathologie, Hamburg, Germany; Cardiovascular Research, The Rayne Institute, St. Thomas' Hospital, London, United Kingdom; and University Children's Hospital Vienna, Vienna, Austria

The aim of this study was to investigate the cellular and biochemical events associated with repeated exposures to ozone. Twenty-three healthy subjects underwent single exposures to 200 ppb ozone and to filtered air (FA), as well as repeated exposures to 200 ppb ozone on 4 consecutive days, each for 4 h of intermittent exercise. Bronchoalveolar lavage was performed and mucosal biopsies were taken 20 h after the single or the last of the repeated exposures. As compared with FA, the single exposure to ozone caused a decrease in FEV₁, an increase in the percentages of neutrophils and lymphocytes, the concentrations of total protein, IL-6, IL-8, reduced glutathione, urate, and ortho-tyrosine in BAL fluid (BALF), but no changes in the cellular composition of biopsy. After the repeated exposure, the effect on lung function was abolished and differential cell counts in BALF were not significantly different from those after FA. However, the concentrations of total protein, IL-6, IL-8, reduced glutathione, and ortho-tyrosine were still increased. IL-10 could only be detected in BALF after repeated ozone exposures. Furthermore, macroscopic scores for bronchitis, erythema, and hypervulnerability of airway mucosa were increased, as well as numbers of neutrophils in bronchial mucosal biopsies. Our data demonstrate that airway inflammation persists after repeated ozone exposure, despite attenuation of some inflammatory markers in BALF and adaptation of lung function.

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