OZONE-INDUCED AIRWAY INFLAMMATION IN HUMAN-SUBJECTS AS DETERMINED BY AIRWAY LAVAGE AND BIOPSY

Ozone (O-3) is a major constituent of urban air pollution. The acute e ffects of the inhalation of O-3 at ambient or near-ambient concentrati ons on bronchoalveolar ravage (BAL) end points consistent with a dista l lung inflammatory response have been well documented in human subjec ts. Animal toxicologic studies have shown that the airway is also a ma jor site of O-3-induced injury and inflammation. To date, no studies h ave confirmed this finding in human subjects. Effects of O-3 on the pr oximal airways are not adequately studied by BAL, which is primarily i nfluenced by events occurring in the terminal bronchioles and alveoli. We hypothesized that O-3 causes injury and inflammation in the airway s in addition to that previously documented to occur in the distal lun g. We performed isolated lavage of the left mainstem bronchus and forc eps biopsy of the bronchial mucosa in a group of 14 healthy, athletic subjects 18 h after exposure to 0.20 ppm O-3 for 4 h during moderate e xercise in order to assess this possibility. We followed an identical protocol in a similar group of 12 subjects exposed to filtered air. Th e mean (SD) total cell count and the lactate dehydrogenase (LDH) conce ntration in the isolated airway lavage were significantly greater afte r O-3 than after air, 13.9 (20.5) versus 4.9 (5.4) cells/ml x 10(4) an d 18.9 (11.2) versus 9.6 (9.0) U/L, respectively. Morphometry (2,070 n eutrophils/cm(2) of tissue for O-3 and 330 neutrophils/cm(2) of tissue for air) demonstrated that O-3 exposure induced an acute inflammatory cell influx into the airway. These data demonstrate that inhalation o f an ambient concentration of O-3 can cause morphologic evidence of ai rway injury in healthy human subjects. Ozone-induced airway inflammati on may be an important contributing factor to acute exacerbations of a sthma and chronic bronchitis.