Cumulative Retrospective Exposure Assessment (REA) as a predictor of amphibole asbestos lung burden: validation procedures and results for industrial hygiene and pathology estimates

Abstract

Context: A detailed evaluation of the correlation and linearity of industrial hygiene retrospective exposure assessment (REA) for cumulative asbestos exposure with asbestos lung burden analysis (LBA) has not been previously performed, but both methods are utilized for case-control and cohort studies and other applications such as setting occupational exposure limits.

Objective: (a) To correlate REA with asbestos LBA for a large number of cases from varied industries and exposure scenarios; (b) to evaluate the linearity, precision, and applicability of both industrial hygiene exposure reconstruction and LBA; and (c) to demonstrate validation methods for REA.

Methods: A panel of four experienced industrial hygiene raters independently estimated the cumulative asbestos exposure for 363 cases with limited exposure details in which asbestos LBA had been independently determined. LBA for asbestos bodies was performed by a pathologist by both light microscopy and scanning electron microscopy (SEM) and free asbestos fibers by SEM. Precision, reliability, correlation and linearity were evaluated via intraclass correlation, regression analysis and analysis of covariance. Plaintiff’s answers to interrogatories, work history sheets, work summaries or plaintiff’s discovery depositions that were obtained in court cases involving asbestos were utilized by the pathologist to provide a summarized brief asbestos exposure and work history for each of the 363 cases.

Results: Linear relationships between REA and LBA were found when adjustment was made for asbestos fiber-type exposure differences. Significant correlation between REA and LBA was found with amphibole asbestos lung burden and mixed fiber-types, but not with chrysotile. The intraclass correlation coefficients (ICC) for the precision of the industrial hygiene rater cumulative asbestos exposure estimates and the precision of repeated laboratory analysis were found to be in the excellent range. The ICC estimates were performed independent of specific asbestos fiber-type.

Conclusions: Both REA and pathology assessment are reliable and complementary predictive methods to characterize asbestos exposures. Correlation analysis between the two methods effectively validates both REA methodology and LBA procedures within the determined precision, particularly for cumulative amphibole asbestos exposures since chrysotile fibers, for the most part, are not retained in the lung for an extended period of time.

• ANCOVA
• asbestos
• asbestos-bodies
• assessment
• case-control
• dose-response
• exposure
• fiber-burden
• mesothelioma
• retrospective
• reconstruction
• SEM
• validation

Acknowledgements

We especially want to acknowledge the contributions of the late Lawrence Birkner, CIH who provided much of the inspiration, initial direction and management for the rater correlation. Without his dedication to this project, the work would never have been completed. William Dyson, Ph.D, CIH along with Mr. Birkner participated as industrial hygiene raters. Thanks to Dalmon Larson, Ph.D., who suggested and performed many of our initial correlations of asbestos body concentrations as a function of estimated cumulative exposure. Special thanks are also due to Matthew Strand, Ph.D, of National Jewish Hospital and the University of Colorado who provided advance advice and review of the statistical procedures that were utilized. In addition, Andrey Korchevskiy, Ph.D, provided additional statistical analysis and quality control and also provided invaluable advice. Heartfelt thanks to David Ostrowski, D.Phil, for related research and critical reviews and to Debbie Vaughan for her preparation of the manuscript for publication.