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 effects of the inhalation of O-3 at ambient or near-ambient concentrations on bronchoalveolar ravage (BAL) end points consistent with a distal lung inflammatory response have been well documented in human subjects. Animal toxicologic studies have shown that the airway is also a major site of O-3-induced injury and inflammation. To date, no studies have confirmed this finding in human subjects. Effects of O-3 on the proximal airways are not adequately studied by BAL, which is primarily influenced by events occurring in the terminal bronchioles and alveoli. We hypothesized that O-3 causes injury and inflammation in the airways in addition to that previously documented to occur in the distal lung. We performed isolated lavage of the left mainstem bronchus and forceps 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 exercise in order to assess this possibility. We followed an identical protocol in a similar group of 12 subjects exposed to filtered air. The mean (SD) total cell count and the lactate dehydrogenase (LDH) concentration in the isolated airway lavage were significantly greater after O-3 than after air, 13.9 (20.5) versus 4.9 (5.4) cells/ml x 10(4) and 18.9 (11.2) versus 9.6 (9.0) U/L, respectively. Morphometry (2,070 neutrophils/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 of an ambient concentration of O-3 can cause morphologic evidence of airway injury in healthy human subjects. Ozone-induced airway inflammation may be an important contributing factor to acute exacerbations of asthma and chronic bronchitis.