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STUDIES TO ADDRESS THE ASSOCIATION BETWEEN PARTICULATE MATTER (PM) EXPOSURE AND DEVELOPMENT/EXACERBATION OF LUNG INJURY, INFLAMMATION, AND INCREASED AIRWAY RESPONSIVENESS.
Impact/Purpose:
The overall goal of this project is to establish the relative lung/airway toxicity of PM collected under different ambient conditions. These and analogous studies focusing on health effects of PM from specific airsheds may serve to specify proximate PM toxicants beyond that of a simple mass-based metric. These studies also provide mechanistic support for the conclusions from the epidemiological studies conducted in Utah Valley "natural experiment," which pointed to emissions from the steel mill as a factor affecting the incidence of morbidity and mortality in this population.
Description:
Asthma, an inflammatory airways disease, has become an urgent health problem affecting an estimated 17 million persons in the United States alone (CDC 1998 MMWR 47). Since 1979, the death rate from asthma has increased by almost 56%. Epidemiologic studies have demonstrated positive associations with ambient air particulate matter (PM) exposure and daily respiratory morbidity C including exacerbations of asthma. Still other studies have associated asthma exacerbations with exposure to air pollutants such as ozone and NOx. To better understand why asthmatics appear to be at increased risk for exposure to air pollutants, in particular particulate matter and irritant gases, data are needed to define mechanisms by which pollutant exposure relates to inflammatory airways disease and to identify which pollutants (or in the case of PM, which PM subcomponents) appear to be predominately mediating these effects. Because the airway epithelium contains some of the first cells to come in direct contact with inhaled gases and particles and represents a critical effector cell population within the lung, we are using rodent-derived primary, differentiated epithelial cultures as a "model" airway system to compare and contrast the effects of a variety of PM samples. On a more limited basis, we follow up our in vitro testing results with animal studies to validate the in vitro results and to assess the pulmonary functional significance of the observed epithelial effects. Our overall interest is to understand how exposure to certain PM results in: (1) lung / airway injury, (2) airway inflammation, and (3) increased airway responsiveness, hallmark features of asthma in humans. In addition, we are attempting to elucidate how PM-induced changes in these three pathologic or pathophysiologic effects may (or may not) relate to each other. There are 2 components to this project: 1) to establish the toxicity of hi-vol filter extracts obtained from filters collected in the Utah Valley during winter months when the Geneva steel mill was and was not operational. In brief, we observed that administration of equal masses of water-based extracts from plant "on" 1986 and 1988 filters (but not plant "off" 1987 filters) to healthy adult rats resulted in acute, but transient, pulmonary injury and neutrophilic inflammation. We further observed that CD rats instilled with the 1986 or 1988 extracts developed histologic evidence of alveolar and airway cell damage and that up to 50% of rats developed transient but significant increases in non-specific airway responsiveness. In addition, we confirmed the differential airway toxicity of these PM extracts in primary airway cultures, demonstrating that extracted material from the steel mill operational periods was in fact significantly more epitheliotoxic. Also, epithelial injury elicited by Zinc + Copper + Vanadium surrogate metal mixtures closely paralleled that of the extracts themselves. Moreover, metal interactions appeared to play critical but complex roles in the overall epithelial effects induced. 2) to establish that on an equimass basis, ambient PM largely related to crustal material is significantly less toxic than PM related to anthropogenic, in particular emission sources. Based on a series of hi-vol filter extraction studies, it became apparent that effective removal of PM-associated metals (and quite possibly other organic material) from archived hi-vol filters is exceedingly difficult. Only minor quantities of PM-associated metals were recovered from exposed hi-vol filters obtained via the water extraction procedure used in the studies noted above. The low metallic yield of these and other similarly extracted Utah PM filter samples is, in part, related to difficulties in physically separating ambient PM (and its associated metals) from the filter matrices upon which it was deposited. Not surprisingly therefore, the total metal content of the above Utah PM filter extracts above was considerably lower than that of other bulk (e.g., cyclone) collected ambient PM samples. We are currently modulating the resultant pH of the "wash" liquid in an effort to increase metal extraction efficiency. However, it will also be important to establish whether a consistent amount of deposited metallic elements can be uniformly extracted. Portions of this project have been completed. Contact the PI for more information.