Are pleural plaques an appropriate endpoint for risk analyses?

Abstract

This review summarizes the literature on the relation between the development of pleural plaques and non-malignant and malignant disease in cohorts exposed to asbestos and other fibers. The available evidence indicates that, absent any other pleural disease, the presence of pleural plaques does not result in respiratory symptoms or clinically significant impacts on lung function. For certain types of asbestos, the development of pleural plaques is statistically correlated with malignant disease, but the evidence is consistent with the hypothesis that pleural plaques without other pleural disease are a marker of exposure, rather than an independent risk factor. Pleural plaques have also developed in cohorts exposed to other fibers that have not proven to be carcinogenic. Risk analyses should be based on the avoidance of known adverse conditions, rather than pleural plaques per se.

• Asbestos
• lung cancer
• lung function
• mesothelioma
• non-malignant respiratory disease
• other natural and synthetic fibers
• pleural plaques
• respiratory symptoms
• risk analysis

Acknowledgements

We acknowledge the constructive comments of the anonymous reviewers of this manuscript in draft. Their comments were useful and improved the quality of this work.

Declaration of interest

This research was sponsored by Unifrax 1 LLC, a major producer of several synthetic high temperature fibers. The findings and opinions expressed herein are those of the authors alone, however, and do not necessarily reflect the views of the sponsor.

Notes

¹In a critical review, Moolgavkar et al. (2014) argued that the EPA analysis sets a poor precedent and, moreover, the technical features of the BMD analysis to establish the RfC were flawed. Zu et al. (2015) also concluded that the EPA choice of pleural plaques as an endpoint was flawed.

²We used various search engines and databases (e.g. PubMed, Google Scholar) to locate relevant articles.

³Via a surgical incision in the chest wall.

⁴Via use of a thin, lighted tube (called an endoscope) to examine the inside of the chest.

⁵For example, there is evidence that asbestosis (while not the sole cause of certain respiratory cancers) is an independent risk factor for malignant diseases and, moreover (Moolgavkar et al., 2014), may result in fatality absent malignancy. Asbestosis is a legitimate endpoint for risk analysis.

⁶For example, Bar-Shai et al. (2012) found no correlation between duration of exposure and extent of pleural plaques.

⁷The same is true for the second model of Paris et al. (2008) wherein cumulative exposure (f-year/ml) is substituted for mean exposure.

⁸This finding is not unprecedented. Ehrlich et al. (1992) found, in a study (short-term, high-exposure) of employees in a plant in Paterson, NJ, that time since first employment was a useful predictor of pleural abnormalities, whereas cumulative exposure was not. Jakobsson et al. (1995) also highlighted the importance of time, even after brief exposures.

⁹This is presumably meant as a statistical fact; pleural plaques are also associated with exposure to other materials. As noted by Sargent et al. (1978): “Although asbestos dust inhalation is not the sole cause of pleural plaques, it is certainly the most common”.

¹⁰Some investigators [see, e.g. Thomas et al. (2011) in a study of Australians exposed to secondary product rather than mining or milling] have noted that pleural plaques were more extensive in those reporting past asbestos exposure and more frequent in those with higher asbestos body counts, but the observed strength of the association does not support their use as a marker of risk for asbestos-related disease.

¹¹The study of Sandén et al. (1992) was negative in terms of the relation between plaques and lung cancer, but positive for mesothelioma. They used one subgroup of workers with 20+ years of asbestos exposure for this comparison, but did not explicitly correct for possible exposure differences among this cohort.

¹²In one study (Järvholm & Sandén, 1987) asbestos exposures were estimated by the exposed male shipyard workers and by a panel of experts whose judgment was based only on occupational title. The analysis was restricted to men with at least 20 years of exposure. These investigators found that there was a much closer correlation between the occurrence of pleural plaques and the men’s own estimates of exposure than between the occurrence and the experts’ estimates. This is a cautionary tale as many studies use job titles for estimating exposure.

¹³Another example of lack of precision in exposure estimates is reported by Finkelstein & Vingilis (1984) who carefully calculated cumulative exposure of various members of a cohort of asbestos-cement workers (f-year/ml) and noted that these estimates were estimated to be accurate within a factor of 3–5. Many studies have not reported estimates of the precision of the exposure estimates.

¹⁴See, for example, remarks contained in Welch et al. (2007).