Pulmonary endpoints (lung carcinomas and asbestosis) following inhalation exposure to asbestos

Our plain-English summary of Pulmonary endpoints (lung carcinomas and asbestosis) following inhalation exposure to asbestos, by B.T. Mossman, M. Lippmann, T.W. Hesterberg, et al (Journal of Toxicology and Environmental Health. Part B, Critical Reviews, 2011).

The study

• Authors: B.T. Mossman, M. Lippmann, T.W. Hesterberg, K.T. Kelsey, A. Barchowsky, J.C. Bonner
• Journal: Journal of Toxicology and Environmental Health. Part B, Critical Reviews
• Published: 2011;14(1-4):76-121
• Type of article: Review
• Cited by: 139 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Lung carcinomas and pulmonary fibrosis (asbestosis) occur in asbestos workers. Understanding the pathogenesis of these diseases is complicated because of potential confounding factors, such as smoking, which is not a risk factor in mesothelioma. The modes of action (MOA) of various types of asbestos in the development of lung cancers, asbestosis, and mesotheliomas appear to be different. Moreover, asbestos fibers may act differentially at various stages of these diseases, and have different potencies as compared to other naturally occurring and synthetic fibers. This literature review describes patterns of deposition and retention of various types of asbestos and other fibers after inhalation, methods of translocation within the lung, and dissolution of various fiber types in lung compartments and cells in vitro. Comprehensive dose-response studies at fiber concentrations inhaled by humans as well as bivariate size distributions (lengths and widths), types, and sources of fibers are rarely defined in published studies and are needed. Species-specific responses may occur. Mechanistic studies have some of these limitations, but have suggested that changes in gene expression (either fiber-catalyzed directly or by cell elaboration of oxidants), epigenetic changes, and receptor-mediated or other intracellular signaling cascades may play roles in various stages of the development of lung cancers or asbestosis.

In plain English

This article was a literature review, not a new study. The authors reviewed published work on how inhaled asbestos and other fibers deposit in, are retained in, move through and dissolve in the lung, and on how asbestos may lead to lung carcinomas and asbestosis. They drew on in vitro (cell) studies, analyses of human lungs and rodent inhalation experiments. The authors stated that they did not discuss studies that gave fibers by intratracheal instillation or pharyngeal administration, or that injected asbestos into the lung. In the work reviewed, chrysotile fibers were less biopersistent than ceramic and special-purpose glass fibers and considerably less than amphibole fibers. Even so, all asbestos types were noted in animal models and epidemiological studies to induce asbestosis and lung cancer, especially in smokers. Increased lung cancer risks were described in both nonsmokers and smokers exposed to asbestos. The review described oxidant-driven cell signaling in asbestosis and evidence that molecular changes in lung tumors may be independent of fibrosis. The authors concluded that the dose, dimension and durability paradigm applies to asbestos fibers. They noted that dose-response studies were lacking in most work.

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
• Who was studied: Published studies using in vitro models, analyses of human lungs, and inhalation experiments in rodents
• Exposure: Inhalation of various types of asbestos (chrysotile and amphiboles such as crocidolite, amosite and tremolite) and other fibers, including synthetic vitreous fibers. The authors stated that studies giving fibers by intratracheal instillation, by pharyngeal administration, or by injection into the lung were not discussed.
• Main results:
  • In the studies reviewed, chrysotile fibers were less biopersistent in the lung than ceramic and special-purpose glass fibers, and considerably less biopersistent than amphibole fibers.
  • The review stated that all asbestos types were noted in animal models and in epidemiological studies to induce asbestosis and lung cancer, especially in smokers.
  • According to the epidemiological work cited, increased lung cancer risks were observed in both nonsmokers and smokers exposed to asbestos. Tobacco smoke was described as the single greatest risk factor for lung cancer.
  • In most in vitro assays reviewed, chrysotile produced toxicity similar to or greater than that of amphiboles. The authors noted this does not agree with in vivo laboratory studies and human epidemiology.
  • Molecular studies of lung tumors reviewed suggested that asbestos-associated molecular changes may be independent of fibrosis.
  • The review described reactive oxygen species generated by asbestos, or by asbestos–cell interactions, as possible signaling intermediates that activate pathways involved in inflammation and fibrosis.
• The authors' conclusion: The authors concluded that recent well-designed inhalation toxicity studies showed that the fiber toxicity paradigm of dose, dimension and durability in the lung applies to asbestos fibers.
• Limitations the authors state:
  • The authors stated that the expression of fiber dose (dosimetry) is often the weakest component of published studies.
  • The authors stated that dose-response studies are lacking in most in vivo and in vitro studies.
  • The authors stated that in human studies of epigenetic changes it is difficult to determine the effects of specific asbestos types because of mixed exposures.

Topics

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

Medical terms in this study, explained in our Lexicon: Carcinoma, Pulmonary Fibrosis, Confounding, Mesothelioma, Lung Cancer, Deposition, Translocation, Dose-response relationship.

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