Isoprene is a major hydrocarbon found in human breath. This study was conducted to evaluate whether respiratory isoprene output could serve as a monitor for ozone exposure. Healthy young adult subjects (n = 10) underwent chamber exposure on separate days to filtered air and to a variable concentration of ozone. Exposures had durations of 130 min that included alternate periods of rest and light treadmill exercise; breath was sampled pre- and postexposure. For six subjects, breath was resampled 19 +/- 1 h postexposure. Breath samples were concentrated cryogenically and analyzed by capillary gas chromatography. Isoprene output immediately postexposure was significantly reduced by ozone or filtered air (17 and 19%, respectively). These results suggest that exercise alone reduces isoprene levels in breath without an additive ozone effect. However, in the six subjects restudied 19 +/- 1 h postexposure to ozone, breath isoprene concentrations were now increased above the preexposure output by 99% (P < 0.01) and exceeded the 51% increase in output of isoprene at this time point after filtered-air exposure (P < 0.01). Therefore, breath isoprene is proposed as a noninvasive marker of a physiological response to oxidant-induced injury to epithelial membranes and fluid linings of the lower respiratory tract by ozone.

Exposure of humans to ambient levels of ozone causes inflammatory changes within lung tissues. These changes have been reported for the "initial" (1- to 3-h) and "late" (18- to 20-h) postexposure periods. We hypothesized that at the late period when protein and cellular markers of inflammation in bronchoalveolar lavage remain abnormal, permeability of respiratory epithelia would be altered. To test this, we measured by gamma-camera imagery the clearance kinetics in healthy subjects (n = 9) of 99mTc-labeled solute [diethylenetriaminepentaacetic acid (DTPA)] that was deposited by aerosol onto epithelial surfaces 19 +/- 1 h after a single exposure to ozone (O3; 130 min at ambient levels between 150 and 350 parts per billion and alternate periods of rest and moderate exercise) or filtered air. At the late period, the lung clearance of 99mTc-DTPA over a 120-min period was significantly increased, i.e., 0.732%/min for O3 exposures compared with 0.661%/min for filtered-air exposures (P < 0.05). Regional analysis demonstrated that 99mTc-DTPA clearance from the periphery (excluding the lung hilum) and lung apexes were significantly increased by O3 but changes in clearance for the base of the lung were not significant. The forced expiratory volume in 1 s at the late time after O3 was slightly but significantly reduced (-2.1%) from preexposure levels. There was no relationship between the functional changes observed acutely after exposure to O3 and subsequent changes in 99mTc-DTPA clearance or forced expiratory volume in 1 s observed at the late period. These results suggest that epithelial permeability of the lung is altered 18-20 h post-O3; this injury is regional, and the lung base appears to have a different time course of response or is in an adapted state with respect to O3 exposure.

Clearance of low-molecular-weight solutes, e.g., radiolabeled chelate diethylenetriaminepentaacetate (DTPA), across epithelial surfaces of distal airways and the lung parenchyma is a broadly used technique to assess epithelial integrity. It has been generally assumed that clearance of solute follows a simple first-order process and that DTPA clearance through the respiratory epithelium and into blood and lymphatic channels is complete within a few hours. Using gamma-camera imaging and a radiolabeled aerosol of 99mTc-labeled DTPA, we observed in eight healthy subjects lung retention of radioisotope approximately 24 h postdeposition of the 99mTc-DTPA. Residual lung retention at the 24-h end point averaged 6.0 +/- 1.8 (SD)% of the amount of radioisotope initially deposited in the lung. This suggests that for normal healthy subjects a small amount of the 99mTc radioisotope, either in a dissociated or chelated form, is nonpermeable or slowly cleared from respiratory tisssues.