Ozone exposure in humans: Inflammatory, small and peripheral airway responses

We exposed eight normal adults to filtered air (FA) and 0.35 ppm ozone (O₃) and compared responses in spirometry, including isovolume (isoV) flows at intermediate-to-low lung volumes, against levels of inflammatory markers in bronchoalveolar lavage fluid (BALF) and peripheral lung resistance (Rp) measured through a wedged bronchoscope. Spirometry was performed at the end, 25 min and 24 h after exposure, bronchoscopy at 24 h after exposure. The percentages of neutrophils, fibrinogen, albumin, PGE₂, PGF(2α), and kinins were elevated in BALF after O₃ compared with FA. The percentage reduction in (isoV) FEF_25-75 at 25 min and 24 h after administration of O₃ correlated closely with the rise in fibrinogen concentrations in BALF, a marker of altered vascular permeability. Rp, a measurement dominated by very small or peripheral airways, was unaffected in 7 of 8 subjects. The absence of change in Rp might have reflected insufficient penetration of O₃ into these airways to produce or sustain an effect for 24 h; alternatively, the bronchoscopic procedure which included atropine and lidocaine pretreatment may have reversed an O₃ effect. An unexpected finding was the significant association between baseline Rp (after FA) and the magnitude of the spirometric response to O₃. Our results suggest that small airway dysfunction in the immediate post-O₃ period is a marker of lung inflammation.