Airborne endotoxin in the work environment was associated with acute declines in lung function. A history of longer duration of exposure to endotoxin was also associated with evidence of variable airflow obstruction - the physiologic signature of asthma. We found that the association held up when controlled for other exposures in the fiberglass-manufacturing environment. This finding was the first time, and to date the only time, that endotoxin exposure in a non-agricultural work environment has been clearly implicated as a causal factor for acute and chronic effects on pulmonary function. Studies in agricultural environments implicating endotoxin have the fundamental problem, that endotoxin exposure in these settings is associated with exposure to other components of organic dust that may have been the actual causal factor. By providing evidence of a causal association in a non-agricultural environment, this project gives significant new weight to the hypothesis that endotoxin is an important cause of occupational airway disease. The endotoxin measurement validation studies demonstrated that measured endotoxin potency of environmental samples was determined by several factors. Potency was in part a function of Lipopolysaccharide (LPS) composition, but assay factors also contributed importantly to measured potency. A major problem identified by this project is that the commercially available Limulus amebocyte lysate preparations produce inconsistent results from lot-to-lot and manufacturer-to-manufacturer. This project demonstrated that interference with environmental endotoxin measurements can be severe, and that routine application of parallel-line bioassay analysis can compensate for most of these interferences. We showed that the increased cost of the parallel-line assay design is asymptotically more efficient than use of less expensive but less precise methods to determine exposure for epidemiologic studies. Finally, we conducted aerosol chamber studies to validate endotoxin sample collection and assay methods. These studies demonstrate that sample extraction methods, especially use of detergents, can have profound effects on the levels of endotoxin activity measured, and that these effects result from interference with the assay and do not represent improved recovery of LPS or endotoxin from the filter media.
Endotoxins; Epidemiology; Airborne particles; Work environment; Lung disease; Lung function; Air flow; Airway obstruction; Bronchial asthma; Pulmonary system disorders; Bioassays; Environmental factors
Final Grant Report
Pulmonary System Disorders
National Institute for Occupational Safety and Health
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