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BIOMARKERS OF HEALTH EFFECTS IN THE HUMAN LUNG
Impact/Purpose:
This research directly affects the determination of health effects associated with long-term particulate matter (PM) exposure. Data are needed to determine the fate/dose and ultimately health effects and elucidating the mechanisms by which particles cause these effects. Results will be used to improve the understanding of patho-physiological mechanism by which PM causes diseases in humans. Our multi-disciplinary approach provides a means toward establishing dose levels in specific anatomical sites in human lung required to produce adverse health outcomes.
Description:
Little information exists about retained particle/metal burden in human lung and associated biomarkers of internal dose/indicators of health effects. We have shown that anatomical remodeling of the terminal and respiratory bronchioles occur at sites of particle deposition. We extend the value of these findings in our studies by providing information on lung particle and metal content in relation to indicators of effect as classified by standard diagnostic criteria for 1) chronic bronchitis 2) asthma 3) mineral dust disease and 4) smoking-related disease. Lung autopsies have been examined from 40 male Hispanics from the Central Valley of California who had died from non-respiratory related causes. Computer-controlled scanning electron microscopy is used to determine particle concentration (No. particles/mg tissue) and inductively coupled plasma emission spectrometry (ICP) for metal analysis. We have observed significant increases in number of particles/mg of material and metal levels for all 4 health indicators (except asthma) relative to normal tissue have. We have acquired an additional 40 lung samples and will evaluate identical health indicators in relation to particle concentration, composition and size. Recently we have been asked to provide identical data for several autopsy samples with fatal and non-fatal asthma from the Prairie Provinces. Pending funding direct comparison will be made between these and the Fresno lung samples. We have added an additional internal dose measurement through our collaboration with Klaus Whittmaker (GSF) who will apply PIXIE methodology commonly used for trace metal analysis for ambient air exposure to human lung samples.