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PI: T. Gordon; Co-I.: J. Fine; Consultants: L.C. Chen and J. Reibman.
Our objective is to determine whether co-exposure
to ozone influences the acute cardiopulmonary effects from controlled
exposures to particulate matter (PM) in human volunteers. Co-exposure
of human subjects to PM and O3 is likely to produce
changes in pulmonary function and inflammation that are greater
than that from exposure to PM or O3 alone.
A pilot study, funded by the Health Effects Institute, is
currently underway, examining the adverse effects of exposure to concentrated
ambient PM alone in normal and asthmatic subjects. The experiments proposed
here will build on these studies by enabling the controlled testing of exposure
to concentrated ambient PM with and without O3 in normal and asthmatic
subjects. Normal subjects (n = 12, ages 18 to 45) will be exposed for 2 hours
by face mask to filtered air, 150 µg/m3 concentrated ambient
PM alone, 0.12 ppm O3 alone, or 150 µg/m3 concentrated
ambient PM and 0.12 ppm O3 together. Biochemical and cellular
parameters in sputum, coagulability indices in blood, electrocardiogram and
heart rate/heart rate variability changes, and pulmonary function will be
measured up to 18 hours after each exposure. Careful chemical characterization
of the exposure atmospheres will insure that day-to-day variability in PM
composition will be considered in the interpretation of results. Asthmatic
subjects (n = 12) will be exposed to test atmospheres as described above.
The same endpoints will be examined in addition to studying the TH2 cytokine
profile and eosinophil-derived products in recovered sputum. Strict inclusion/exclusion
criteria for study participants will ensure that the variability of asthmatics
is kept to a minimum, and that medication usage is controlled during the
study.
It is anticipated that concentrated ambient PM alone will
not produce statistically significant adverse effects in healthy individuals.
This project, however, will address the potential synergism that may occur
between concentrated ambient PM and O3. The study of human subjects
with pre-existing cardiac or pulmonary disease will be an important focus.
It is expected that our experiments will demonstrate that asthmatics are
made more susceptible to the adverse effects of PM by co-exposure to O3,
suggesting that the health effects of very low concentrations PM on this
sensitive subpopulation should be considered in the setting of PM air quality
standards.
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