Defining control reference ranges in biologic samples in analytical laboratories

Our plain-English summary of Defining control reference ranges in biologic samples in analytical laboratories, by B. Vrugt, B.K. Kuhn, R. Attanoos (Frontiers in Public Health, 2025).

The study

• Authors: B. Vrugt, B.K. Kuhn, R. Attanoos
• Journal: Frontiers in Public Health
• Published: 2025;13:1618114
• Type of article: Review
• Read it: PubMed · Publisher · Free full text

Abstract

Mineral analytic laboratories define control reference ranges to interpret the significance of an individual's prior exposures. Control reference ranges are internally compiled and defined for two scenarios: background controls-only subjects with ambient asbestos exposure and no increased risk of asbestos related disease, and asbestosis range controls, utilized for the diagnosis of asbestos-related lung fibrosis/asbestosis and for asbestos-related lung cancer causation. The objective of this study was to evaluate how different analytic laboratories have established their internal control reference ranges and to comment on their significance. The study comprised a review of the scientific literature generated from a Pubmed search of mineral analytic data from lung tissue in laboratories determining background exposures to asbestos and other elongate minerals. Twenty-six publications were found from 17 laboratories across Europe, North America, and Asia which had internally defined background control populations. The studies showed marked heterogeneity having been conducted over decades, using different criteria, different microscopic methodologies, and assessment of different fiber dimension. The most common criterion to define background control subjects was to establish individuals with no known occupational history of asbestos exposure and/or no evidence of asbestos-related diseases. In background controls with no disease, chrysotile was reported most frequently. Chrysotile and amphiboles were variably detected in lung tissue from control subjects in virtually all studies. Interlaboratory variations exist so individual results obtained in one laboratory do not transfer significance to another laboratory. The use of negative control groups in case-control studies is discussed alongside their relevance in ensuring the validity of results related to asbestos exposure and its diseases.

Copyright © 2025 Vrugt, Kuhn and Attanoos.

In plain English

This article was a review of published research. The authors searched PubMed for studies reporting asbestos in the lung tissue of 'control' subjects, meaning people without known significant asbestos exposure who are used for comparison. Of 1,349 search results, they selected 26 publications from 17 laboratories in Europe, North America and Asia, published from 1977 to 2023. The most common ways of choosing controls were no documented occupational asbestos exposure and no known asbestos-related disease. Control groups ranged from 5 to 262 people (median 23). Laboratories used different microscopes and different minimum fiber lengths, from 0.2 to 6 micrometres. Four studies reported possible asbestos exposure in some controls, and one confirmed that it had included occupationally exposed people. Chrysotile was the fiber most often found in controls without disease. Non-commercial amphiboles were reported in 14 studies, and amosite and crocidolite were also found in 11 of those. The authors concluded that each laboratory should set its own control ranges, update them periodically and standardize its methods.

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: Literature review of published studies, based on a PubMed search
• Who was studied: 26 publications (1977 to 2023), selected from 1,349 PubMed hits, from 17 laboratories in Europe, North America and Asia that reported asbestos levels in lung tissue of control subjects
• Exposure: Background (ambient) asbestos in the lungs of control subjects, reported as total asbestos fibers, amphibole asbestos fibers or chrysotile fibers per gram of lung tissue
• Main results:
  • No documented occupational asbestos exposure was the primary criterion for choosing controls in 11 studies and a secondary criterion in 6.
  • Absence of known asbestos-related disease was the primary criterion in 6 studies and a secondary criterion in 8.
  • The number of control subjects per study ranged from 5 to 262 (median 23).
  • Gender was reported in only 13 studies.
  • Four studies mentioned possible asbestos exposure in some of their control subjects after lung tissue analysis.
  • One study confirmed that its control group included people with occupational asbestos exposure.
  • Eighteen studies used transmission electron microscopy (TEM) and seven used scanning electron microscopy (SEM).
  • The minimum fiber length counted varied from 0.2 to 6 micrometres.
  • In the studies that used SEM, total asbestos content in controls showed a decrease over three decades.
  • Chrysotile was the fiber type most frequently detected in many control studies of subjects without disease.
  • Fourteen studies reported non-commercial amphibole asbestos (actinolite, anthophyllite, tremolite) in controls. In 11 of these, amosite and crocidolite were also detected.
  • Using the Helsinki criteria threshold, the authors found an overlap between control subjects and occupationally exposed patients in 6 of the 26 reviewed studies (23%).
• The authors' conclusion: The authors concluded that each laboratory should establish its own control groups, using its local setting and methods. They added that these controls should be periodically updated and that laboratories need standardization.
• Limitations the authors state:
  • Marked differences between laboratories made it problematic to compare control values across laboratories.
  • Fiber numbers from the TEM studies could not be compared because different minimum fiber lengths were used.
  • None of the reviewed studies provided information on genetic variability in controls.

Topics

Medical terms in this study, explained in our Lexicon: Asbestos Exposure, Fibrosis, Lung Cancer, Causation, Background Exposure, Fiber Dimensions, Occupational History, Chrysotile.

Related studies

• Analysis of the analytical performance of laboratories participating in two major U.S. bulk asbestos proficiency testing programs — B.W. Harvey, W.G. Winstead (2008)
• Letter: Hazards in laboratories — C.L. Lavelle, A.D. Landman (1976)
• Within-laboratory quality control of asbestos counting — T.L. Ogden, T. Shenton-Taylor, et al. (1986)
• A PC-based quality control (QC) program for an industrial hygiene laboratory — D.K. Verma, K. Ferguson, et al. (2006)
• Quantitative assessment of inorganic fibrous particulates in dust samples with an analytical transmission electron microscope — F.D. Pooley, N.J. Clark (1979)
• UICC standard reference samples of asbestos — V. Timbrell, J.C. Gibson, et al. (1968)

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