Asbestos-induced lung disease

Our plain-English summary of Asbestos-induced lung disease, by A.R. Brody (Environmental Health Perspectives, 1993).

The study

• Author: A.R. Brody
• Journal: Environmental Health Perspectives
• Published: 1993;100:21-30
• Type of article: Review
• Cited by: 50 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

This review attempts to deal with two major questions concerning asbestos-induced lung disease: How does inhaled asbestos cause cell proliferation and fibrosis? and Will there continue to be risk from exposure to asbestos in schools and public buildings? The first is a scientific question that has spawned many interesting new experiments over the past 10 years, and there appear to be two hypothetical schemes which could explain, at least in part, the fibroproliferative effects of asbestos fibers. One supports the view that toxic oxygen radicals generated on fiber surfaces and/or intracellularly are the central mediators of disease. The second hypothesis is not mutually exclusive of the first, but, in my opinion, may be integral to it, i.e., the cellular injury induced by oxygen radicals stimulates the elaboration of multiple varieties of growth factors and cytokines that mediate the pathogenesis of asbestosis. There is increasing evidence that molecules such as platelet-derived growth factor and transforming growth factor beta, both synthesized and secreted by activated lung macrophages, are responsible, respectively, for the increased interstitial cell populations and extracellular matrix proteins that are the hallmarks of asbestos-induced fibrosis. The challenge today is to establish which combinations of the many factors released actually are playing a role in disease pathogenesis. The issue of continued risk currently is more a question of policy and perception than science because a sufficient database has not yet been established to allow full knowledge of the circumstances under which asbestos in buildings constitutes an ongoing health hazard. The litigious nature of this question does not help its resolution. In as much as public policy statements and risk assessment are not within my purview, I have focused on the state-of-the-art of asbestos as a complete carcinogen. It appears to be generally nongenotoxic, but all asbestos fiber types can induce chromosomal mutations and aneuploidy, perhaps through their ability to disrupt normal chromosome segregation.

In plain English

This 1993 review asked how inhaled asbestos causes cell growth and scarring (fibrosis) in the lung, and whether asbestos in schools and public buildings will remain a risk. It described two proposed explanations for fibrosis. One is that reactive oxygen molecules formed on or in response to fibers injure cells. The other, which the author linked to the first, is that this injury prompts cells, mainly lung macrophages, to release growth factors, such as platelet-derived growth factor and transforming growth factor beta, that may drive the scarring; the author wrote that the actual mediators were unknown. In the author's studies in rats and mice, brief chrysotile exposure was followed by an almost 30-fold increase in the percentages of dividing cells in the small airways, and by scars where those airways meet the air sacs. On cancer, the author wrote that the most consistent experimental evidence pointed to fibers disrupting normal chromosome separation. The author stated that risk in buildings was unsettled because likely exposures were poorly defined, but concluded that asbestos, including chrysotile, was likely to remain a risk.

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: narrative review of laboratory (cell culture and animal) research and of literature on asbestos in buildings
• Who was studied: No new study population. The review covered cell culture and animal (rat and mouse) studies, including the author's own laboratory work, plus reports on exposure in buildings.
• Exposure: Asbestos in general, especially chrysotile in the animal studies described (for example, 1-hour exposure to approximately 1000 fibers/cc), and asbestos-containing building material
• Main results:
  • The review described two main explanations for asbestos-induced fibrosis: the oxygen radical hypothesis and the growth factor hypothesis.
  • The author suggested, as a hypothesis, that growth factors are responsible for the cell proliferation and matrix production, possibly stimulated by cytotoxic oxygen radicals.
  • A study from another laboratory (Mossman and colleagues) reported that continuous catalase, an antioxidant enzyme, blocked part of the inflammatory and fibrogenic responses in rats that inhaled crocidolite asbestos for 2 weeks.
  • In the author's laboratory studies in rats and mice exposed to chrysotile, there was an almost 30-fold increase in the percentages of proliferating cells in the terminal bronchioles and alveolar ducts.
  • In the animal studies described, chrysotile exposure led to well-defined scars at the bronchiolar-alveolar duct junctions.
  • In unpublished observations, chrysotile treatment of rat lung fibroblasts in culture increased the number of PDGF alpha receptors on their membranes by about 45%.
  • On cancer, the author wrote that the most consistent experimental evidence supported fibers interfering with normal chromosome segregation, leading to chromosomal mutations and aneuploidy.
  • The question of risk from asbestos in buildings had not been settled because the exposures that might occur in a given building were not well defined.
  • The author suggested that early cell proliferation could be an integral event in asbestos-caused cancer.
• The authors' conclusion: The author concluded that asbestos is likely to remain a risk, partly because asbestos, including chrysotile, is a proven carcinogen.
• Limitations the authors state:
  • The author stated that what mediates the cell proliferation and matrix production was not known.
  • Whether the receptor increase seen in cultured fibroblasts happens in living animals was not yet known.
  • The fiber concentrations that can cause cancer-related cell transformation were not known.
  • Differences between particles in cell culture experiments were hard to interpret.
  • The author did not address public policy or risk assessment.

Topics

Medical terms in this study, explained in our Lexicon: Fibrosis, Cytokine, Platelet-Derived Growth Factor (PDGF), Macrophage, Interstitial.

Related studies

• Relative release of interleukin-1 beta and interleukin-1 receptor antagonist by alveolar macrophages. A study in asbestos-induced lung disease, sarcoidosis, and idiopathic pulmonary fibrosis — J.N. Kline, D.A. Schwartz, et al. (1993)
• Susceptibility to asbestos-induced and transforming growth factor-beta1-induced fibroproliferative lung disease in two strains of mice — G.S. Warshamana, D.A. Pociask, et al. (2002)
• Fiber levels and disease in workers from a factory predominantly using amosite — A.R. Gibbs, M.J. Gardner, et al. (1994)
• Global perspectives of emerging occupational and environmental lung diseases — S. Moitra, R. Puri, et al. (2015)
• Relationships of Lower Lung Fibrosis, Pleural Disease, and Lung Mass with Occupational, Household, Neighborhood, and Slate Roof-Dense Area Residential Asbestos Exposure — D. Kang, Y.Y. Kim, et al. (2018)
• The pathobiology of asbestos-induced lung disease: a proposed role for macrophage-derived growth factors — J.A. Lasky, J.C. Bonner, et al. (1991)

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