The pathogenesis of asbestos-associated diseases

Our plain-English summary of The pathogenesis of asbestos-associated diseases, by J.E. Craighead, B.T. Mossman (The New England Journal of Medicine, 1982).

The study

• Authors: J.E. Craighead, B.T. Mossman
• Journal: The New England Journal of Medicine
• Published: 1982;306(24):1446-55
• Type of article: Review
• Cited by: 316 articles, as counted by NIH iCite
• Read it: PubMed · Publisher
• In J-M's library: Johns-Manville's company medical library held a copy (J-M no. 000665).

In plain English

This article, by two University of Vermont pathology researchers, was a review of published knowledge on how asbestos causes disease, not a new study of patients. It covered mineral types (chrysotile, a serpentine; crocidolite, amosite and anthophyllite, amphiboles), their uses, and how fibers deposit in and clear from the lungs. It then covered asbestosis, pleural plaques, pleural and peritoneal mesothelioma, lung cancer and digestive-system cancers. The review stated that plaques did not appear to develop into mesothelioma. It reported that mesothelioma prevalence in workers heavily exposed over extended periods was about 2 to 3 per cent and had been reported to approach 10 per cent. It described the combined effects of asbestos and smoking on lung cancer as appearing multiplicative rather than additive, and the cancer-causing potential of asbestos in the digestive tract as appearing low. The authors cited their own unpublished laboratory data on chrysotile and cultured cells. They noted that disease mechanisms were not established and that fiber characteristics had been fully defined in only a few studies. They added that the long latency of mesothelioma clouded most epidemiologic studies of whether asbestos types differ in causing it.

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: Review article ('Medical Progress') summarizing published research on asbestos-associated diseases and their mechanisms
• Who was studied: No study population of its own. The review drew on published human epidemiologic and pathology studies, animal experiments and cell-culture work. It also cited one piece of the authors' own unpublished cell-culture data.
• Exposure: Asbestos of different mineral types: chrysotile (serpentine), crocidolite, amosite and anthophyllite (amphiboles), and tremolite as a contaminant of Canadian chrysotile. Also covered were the fibrous zeolite erionite and asbestos-like fibers in drinking water.
• Main results:
  • The review described diffuse pulmonary fibrosis (asbestosis) as the typical lesion associated with prolonged, heavy exposure to asbestos.
  • The authors reported their own unpublished observation that superoxide dismutase protected cultured respiratory epithelial cells from the cytotoxic effects of chrysotile.
  • The review stated that pleural plaques are benign and do not appear to develop into malignant mesotheliomas.
  • The review stated that mesothelioma prevalence in workers with heavy exposure over extended periods is about 2 to 3 per cent and has been reported to approach 10 per cent. It gave the latency period as usually 20 years or longer, and often as long as 40 to 50 years.
  • The review described rat experiments by Stanton and colleagues. In those experiments, fiber dimensions rather than chemical composition were the critical factor in mesothelioma development. Long, thin fibers placed in the pleural space proved carcinogenic.
  • The review stated that peritoneal mesotheliomas occur only in persons exposed to amphibole asbestos.
  • On fiber type and mesothelioma, the review said crocidolite is clearly the most strongly associated type. It said the bulk of evidence indicated chrysotile is not an important cause of mesothelioma in chrysotile miners and millers in Quebec and Italy, although the results are debated.
  • On lung cancer, the review reported that mortality was increased 2.4-fold among chrysotile workers and five times higher than normal among miners of both chrysotile and crocidolite.
  • The review reported that asbestos-exposed nonsmokers show only a slight increase in lung cancer. Heavy smokers (more than 20 cigarettes per day) have an 80-fold to 90-fold greater predisposition. The combined effects appear multiplicative rather than additive.
  • The review stated that the mechanism of asbestos-associated lung cancer is unclear, although asbestos appears to act like a classic tumor promoter.
  • The review judged that the carcinogenic potential of asbestos in the gastrointestinal tract appears to be low.
  • Fibers with the properties of serpentine and amphibole asbestos were reported in over half of the US water supply samples studied.
• The authors' conclusion: The authors concluded that the pathogenesis of asbestosis in humans remains to be established. They considered that dust concentrations permitted under the regulations then in force would probably not induce substantial pulmonary fibrosis during a worker's lifetime. They said questions about thresholds for mesothelioma cannot be answered with contemporary methods and must be resolved by practical rather than theoretical considerations.
• Limitations the authors state:
  • Counting fibers or asbestos bodies in lung tissue is only a crude measure of exposure.
  • Fiber characteristics have been fully defined in only a few epidemiologic and experimental studies.
  • Most studies of digestive-tract cancer relied on death certificates, so peritoneal mesotheliomas may have been confused with metastatic gastrointestinal carcinomas.
  • No experimental models exist for pleural plaques, because plaques occur only in human beings.
  • Most epidemiologic studies of whether asbestos types differ in causing mesothelioma are clouded by uncertainty because of the long latency period of mesothelioma.

Related studies

• Multiple roles of oxidants in the pathogenesis of asbestos-induced diseases — A. Shukla, M. Gulumian, et al. (2003)
• Pathogenesis of asbestos-associated diseases — M.E. Meeks (1982)
• Mass and number of fibres in the pathogenesis of asbestos-related lung disease in rats — J.M. Davis, S.T. Beckett, et al. (1978)
• How the industrial physician can reduce mortality from asbestos-related diseases — R.J. Levine (1978)
• Recommendations for the Diagnosis and Management of Asbestos-Related Pleural and Pulmonary Disease — C. Diego Roza, M.J. Cruz Carmona, et al. (2017)
• IDO-Mediated Tryptophan Degradation in the Pathogenesis of Malignant Tumor Disease — R. Sucher, K. Kurz, et al. (2010)

Browse more research in The New England Journal of Medicine, or return to medical research.