Serum Clara cell protein: A sensitive biomarker of increased lung epithelium permeability caused by ambient ozone

Ozone in ambient air may cause various effects on human health, including d ecreased lung Function, asthma exacerbation, and even premature mortality. These effects have been evidenced using various clinical indicators that, a lthough sensitive, do not specifically evaluate the O-3-increased lung epit helium permeability. In the present study, we assessed the acute effects of ambient O-3 on the pulmonary epithelium by a new approach relying on the a ssay in serum of the lung-specific Clara cell protein (CC16; or CC10). We a pplied this test to cyclists who exercised for 2 hr during episodes of phot ochemical smog and found that O-3 induces an early leakage of lung Clara ce ll protein. The protein levels increased significantly into the serum from exposure levels as low as 0.060-0.084 ppm. Our findings, confirmed in mice exposed to the current U.S. National Ambient Air Quality Standards for O-3 (0.08 ppm for 8 hr) indicate that above the present natural background leve ls, there is almost no safety margin for the effects of ambient O-3 on airw ay permeability. The assay of CC16 in the serum represents a new sensitive noninvasive test allowing the detection of early effects of ambient O-3 on the lung epithelial barrier.