The overall goals of this project are to improve and advance the current criteria established by the International Labor Organization (ILO) to evaluate chest wall abnormalities and to understand the determinants of restrictive lung function in asbestos-induced pleural fibrosis. Together, circumscribed pleural plaques and diffuse pleural thickening are the most frequent radiographic abnormality among exposed workers. The radiographic criteria established by the ILO to define and classify circumscribed pleural plaques and diffuse pleural thickening have not been adequately evaluated. Moreover, the association between pleural fibrosis and restrictive lung function were not considered when establishing these radiographic criteria. Although several groups have established a relationship between restrictive lung function both and circumscribed pleural plaques and diffuse pleural thickening, the determinants accounting for this association have not been adequately addressed. Our preliminary studies indicate that restrictive lung function among those with asbestos-induced pleural fibrosis is, in part, caused by subradiographic inflammation and fibrosis of the lung parenchyma. These findings lead us to hypothesize that more sensitive indicators of parenchymal injury will allow us to fully understand the determinants of restrictive lung function in persons with asbestos-induced pleural fibrosis. The theses put forth in this proposal are designed to investigate the accuracy of the diagnostic criteria established by the ILO, evaluate the anatomic and functional validity of these criteria, and identify the determinants of restrictive lung function among individuals with asbestos-induced pleural plaques and diffuse pleural thickening. We will use a nested case-control study design with 120 subjects randomly selected from a large cohort (N-1,223) of sheet metal workers who have recently undergone a screening medical evaluation. Using chest x-rays, chest CT scans, and physiologic measures of lung function, we will evaluate the reliability and validity (anatomic and functional) of the current ILO criteria for pleural fibrosis. We will also use sensitive physiologic (progressive cycle ergometry and lung and chest wall compliance), radiographic (high resolution CT scans), and biologic (bronchoalveolar lavage cellularity) measures to control for the presence of parenchymal fibrosis while investigating the relationship between asbestos-induced pleural fibrosis and restrictive lung function.
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