Project at a Glance

Title: Study of air pollution: effects of ozone on neuropeptide-mediated responses in human subjects

Principal Investigator / Author(s): Boushey Jr, H. A.

Contractor: University of California

Contract Number: A833-158

Research Program Area: Health & Exposure

Topic Areas: Health Effects of Air Pollution


We examined the effects of exposure to 0.2, 0.4, and 0.6 ppm of ozone on the cough response to capsaicin aerosol in healthy human subjects to examine the hypothesis that ozone inactivates the enzyme, neutral endopeptidase, responsible for limiting the effects of neuropeptides released from afferent nerve endings. Cough response was measured by delivering single inhalations of serially increasing concentrations of capsaicin solution delivered from a nebulizer (10-8 to 10-4 M) at two-minute intervals until two or more coughs were produced. Other endpoints measured included irritative symptoms as rated by the subjects on a nonparametric scale, spirometry, and specific airway resistance as determined by body plethysmography. The effects of each concentration or ozone were compared to those of filtered air in a single-Mind randomized sequence. Our first study was of four subjects exposed to air or 0.6 ppm of ozone for two hours while performing intermittent exercise. Ozone caused a significant increase in specific airway resistance, an increase in symptoms of borderline significance, and a decrease in cough threshold (i.e. cough occurred on inhaling a lower concentration of capsaicin) in two subjects. Six subjects were then exposed to air and to 0.4 ppm of ozone in a similar protocol. Ozone caused significantly greater changes (p < 0.05 by paired t-test) in cough threshold, symptoms, and specific airway resistance and a marginally greater (0.05 < p < 0.10) fail in FEV1.Nine subjects were exposed to 0.2 ppm ozone and to air for two hours, and eight subjects were exposed to 0.2 ppm ozone and to air for three hours. Neither duration IX exposure to this tower concentration or ozone had a significant effect on cough threshold, symptoms, or tests of pulmonary function. These results indicate that a two-hour exposure IO 0.4 ppm of ozone with intermittent light exercise alters the sensitivity of airway nerves that mediate the cough response to inhaled materials. This dose of ozone also caused a change in FEV. A lower level of ozone, 0.2 ppm, caused a change in neither cough threshold nor FEV1, even when the duration of exposure was extended to three hours. These findings are consistent with our hypothesis that ozone may sensitize nerve endings in the airways by inactivating neutral endopeptidase, an enzyme that regulates their activity, but they do not demonstrate that directly examining an effect directly mediated by airway nerves allows detection of effects of ozone at doses below those causing effects detected by standard tests of pulmonary function.

For questions regarding this research project, including available data and progress status, contact: Research Division staff at (916) 445-0753

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