A Critique of Helsinki Criteria for Using Lung Fiber Levels to Determine Causation in Mesothelioma Cases

Our plain-English summary of A Critique of Helsinki Criteria for Using Lung Fiber Levels to Determine Causation in Mesothelioma Cases, by T. Tran, D. Egilman, M. Rigler, et al (Annals of Global Health, 2021).

The study

• Authors: T. Tran, D. Egilman, M. Rigler, T. Emory
• Journal: Annals of Global Health
• Published: 2021;87(1):73
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Asbestos is a known human carcinogen and the chief known cause of mesothelioma. In 1997, a group of experts developed the Helsinki Criteria, which established criteria for attribution of mesothelioma to asbestos. The criteria include two methods for causation attribution: 1) a history of significant occupational, domestic, or environmental exposure and/or 2) pathologic evidence of exposure to asbestos. In 2014, the Helsinki Criteria were updated, and these attribution criteria were not changed. However, since the Helsinki Criteria were first released in 1997, some pathologists, cell biologists, and others have claimed that a history of exposure cannot establish causation unless the lung asbestos fiber burden exceeds "the background range for the laboratory in question to attribute mesothelioma cases to exposure to asbestos." This practice ignores the impact on fiber burden of clearance/translocation over time, which in part is why the Helsinki Criteria concluded that a history of exposure to asbestos was independently sufficient to attribute causation to asbestos. After reviewing the Helsinki Criteria, we conclude that their methodology is fatally flawed because a quantitative assessment of a background lung tissue fiber level cannot be established. The flaws of the Helsinki Criteria are both technical and substantive. The 1995 paper that served as the scientific basis for establishing background levels used inconsistent methods to determine exposures in controls and cases. In addition, historic controls cannot be used to establish background fiber levels for current cases because ambient exposures to asbestos have decreased over time and control cases pre-date current cases by decades. The use of scanning electron microscope (SEM) compounded the non-compatibility problem; the applied SEM cannot distinguish talc from anthophyllite because it cannot perform selected area electron diffraction, which is a crucial identifier in ATEM for distinguishing the difference between serpentine asbestos, amphibole asbestos, and talc.

Copyright: © 2021 The Author(s).

In plain English

In this critique, the authors reviewed the methods behind the "background" lung fiber ranges used with the 1997 and 2014 Helsinki Criteria for mesothelioma. They focused on a 1995 paper by Srebro and colleagues, using depositions and laboratory records. They reported that the 1995 paper dropped one control after learning he had installed furnaces. It did not search other controls' histories that way, though at least thirteen held jobs with potential asbestos exposure. The authors stated that a two-tailed test showed no statistically significant difference between control and case fiber counts. They stated that asbestos bodies and uncoated fibers showed almost no relationship (R-squared 0.0099 to 0.0769) and that the microscope used could not reliably distinguish talc from anthophyllite. They criticized later use of control Case #24 as a talc background: its 10,160 non-asbestos mineral fibers per gram were extrapolated to be all talc after only 5 of 26 fibers were typed. That figure was almost four standard deviations above the control mean talc count of 981.8 fibers per gram. The authors concluded that the method for setting background lung fiber levels was fatally flawed.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Critique of the methods behind the Helsinki Criteria pathologic criteria, based on published papers, depositions and laboratory records. It is labelled "Original Research" in the header and called a "commentary" in the competing-interests statement.
• Who was studied: No new patients. The authors reviewed the 1995 Srebro and colleagues paper, whose mesothelioma cases were litigation referrals and whose controls were male veterans from a VA hospital examined 1980 to 1995. They also reviewed depositions and laboratory records for those cases and controls.
• Exposure: Lung asbestos body counts and lung fiber levels as measured by scanning electron microscope (SEM) in the 1995 paper. Fiber types included amosite, chrysotile, tremolite, actinolite, anthophyllite, and talc.
• Main results:
  • In the 1995 paper, one control with high amosite levels was found to have installed furnaces, after a records search and calls to relatives. That case was excluded.
  • The 1995 paper did not apply the same extensive history search to any other control.
  • Based on medical records alone, at least thirteen of the 1995 paper's controls worked in occupations with potential asbestos exposure.
  • The authors stated that the 1995 paper should have used a two-tailed test. With a two-tailed test, even excluding the outlier control, control and case fiber counts were not statistically significantly different.
  • In the 1995 paper's data, there was almost no relationship between asbestos bodies and uncoated fibers (R-squared 0.0099 to 0.0769).
  • One control (Case #19) in the 1995 paper had 22 asbestos bodies per gram of wet lung, above the 0 to 20 range the paper described as normal.
  • The 1995 paper classified iron-free fibers with magnesium and silicon peaks on SEM as talc, and reported no anthophyllite in any case or control.
  • Control Case #24, later used by Pavlisko and colleagues and Roggli and colleagues as the talc background, had a non-asbestos mineral fiber (NAMF) level of 10,160 f/gm that Roggli extrapolated to be all talc fibers.
  • For Case #24, fiber type was analyzed for only 5 of 26 non-asbestos mineral fibers.
  • Case #24's level of 10,160 f/gm was almost four standard deviations above the controls' mean talc count of 981.8 f/gm (standard deviation 2,354 f/gm).
• The authors' conclusion: The authors concluded that the method used to determine background lung fiber levels was fatally flawed. They also concluded that a background level of asbestos exposure cannot be quantitatively established by tissue analysis as performed.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Helsinki Criteria, Causation, Mesothelioma, Attribution, Environmental Exposure, Fiber Burden, Translocation, Talc.

Related studies

• An inter-laboratory study to determine the effectiveness of procedures for discriminating amphibole asbestos fibers from amphibole cleavage fragments in fiber counting by phase-contrast microscopy — M. Harper, E.G. Lee, et al. (2012)
• Man-made mineral fibers and interstitial lung diseases — E. Fireman (2014)
• Asbestos, asbestosis, and cancer: The Helsinki criteria for diagnosis and attribution. Critical need for revision of the 2014 update — X. Baur, H.J. Woitowitz, et al. (2017)
• The analysis of asbestos count data with "nondetects": the example of asbestos fiber concentrations in the lungs of brake workers — M.M. Finkelstein (2013)
• Asbestos fiber burden in lung tissues of occupationally exposed workers — D.K. Verma, N.E. Clark (2012)
• Health effects of asbestos and nonasbestos fibers — O.Y. Osinubi, M. Gochfeld, et al. (2000)

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