Predicting Long-Term Asbestos Prevalence in Human Lungs, Lymph Nodes, and Remote Organs from Short-Term Murine Experiments

Our plain-English summary of Predicting Long-Term Asbestos Prevalence in Human Lungs, Lymph Nodes, and Remote Organs from Short-Term Murine Experiments, by A. DeStefano, C. Martin, A. Huang, et al (Bulletin of Mathematical Biology, 2021).

The study

• Authors: A. DeStefano, C. Martin, A. Huang, D. Wallace
• Journal: Bulletin of Mathematical Biology
• Published: 2021;83(5):54
• Cited by: 2 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Inhalation of asbestos fibers leads to a suite of fatal diseases that can manifest years, if not decades, after cessation of exposure. The first phase of disease progression occurs as fibers are transported from point of entry in the lungs throughout the entire body. A mathematical model is developed for the disposition of non-chrysotile asbestos in the body and, except for exposure levels, is parameterized by published data on short-term rat experiments. Asbestos exposure in individual humans is determined by matching published long-term lung data for nine patients. The resulting model predicts transport of fibers within the lymphatic system and prevalence of fibers in lymph nodes for these patients with reasonable accuracy. Model predictions for remote organs are compared against published observations. The model consists of a system of globally stable differential equations, and a sensitivity analysis was conducted. The model indicates that fiber density in lymph nodes is correlated with total exposure, level times duration, no matter whether there is a long-term, low-level exposure or short-term, high-level exposure. The model predicts that levels of sequestered asbestos reach steady state within five years of cessation of exposure, a timeline previously not known. The model suggests that the time to steady state is short compared to onset of disease, and that delayed onset of related disease may be a function of chemical and biological processes not in this model.

In plain English

This was a mathematical modeling study, not a study of new patients or animals. The authors built a model of how inhaled non-chrysotile asbestos fibers move through the lungs, pleura, lymph system, blood and other organs. Model settings were estimated from a published experiment in which rats inhaled crocidolite asbestos for five days, plus other published data. Using published autopsy data on nine men with occupational asbestos exposure, the authors set each man's exposure level so the model matched his lung fiber count. They then compared predicted and measured lymph node fiber levels. All nine men had more asbestos in lymph nodes than in lungs, and the model's average predicted lymph-to-lung ratio was 3.131. Predictions fell within the measured lymph node range for six of nine men and were of the same order of magnitude for the rest. In the model, fiber levels settled within a few years after exposure ended. The authors concluded that the model predicts lymph node fiber density well from lung fiber density. Chrysotile and fiber chemistry were not modeled.

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: Mathematical modeling study: a compartment model built from ordinary differential equations. Its settings were estimated from a published short-term rat experiment and other published sources, and it was tested against published human autopsy data. A sensitivity analysis and a stability analysis were included.
• Who was studied: No new subjects. The study used published autopsy data (Dodson et al. 2007) on eleven male patients with reported occupational asbestos exposure. Nine were modeled; patients 7 and 8 were excluded because their duration of exposure was not clear. Age at death was 60 to 82 years, and every death was from cancer in the lung or mesothelioma. Model settings came mainly from a published experiment in weanling male Wistar rats (Bernstein et al. 2014).
• Exposure: Non-chrysotile asbestos. The rat data came from crocidolite exposure for six hours per day on five consecutive days. For the nine patients, total exposure duration ranged from 1825 to 14965 days. Exposure level was not known and was fitted so that the model matched each patient's lung fiber density. Chrysotile was not modeled.
• Main results:
  • In the autopsy data, all nine patients had a substantially higher asbestos burden in lymph nodes than in lungs.
  • For these nine patients, the model's average predicted lymph-to-lung ratio was 3.131.
  • The model's predicted lymph node fiber density fell within the observed range between the highest and lowest lymph nodes for six of the nine patients. For the other three it was of the same order of magnitude.
  • The model could either underestimate or overestimate average fiber density in lymph tissue for individual patients.
  • The model predicted a much lower asbestos burden in remote organs, with an average organ-to-lung ratio of 0.002217 for these patients.
  • In the model, fiber levels reached equilibrium within a few years after exposure ended.
  • In the sensitivity analysis, the settings with the biggest effect were duration of exposure, exposure rates, and the macrophage production and death rates. The lymph-to-lung ratio was robust to most of the other settings.
• The authors' conclusion: The authors concluded that, although the model was not tailored to individuals and was inferred from rat studies, it gives a good prediction of fiber density in thoracic lymph nodes given the fiber density in lung tissue. They also concluded that the movement of asbestos fibers through the body appears to be rapid compared with how long disease takes to develop.
• Limitations the authors state:
  • The model covers only how fibers move, not their chemical properties.
  • Variation in fiber size and differences between individuals were not addressed.
  • Chrysotile was not modeled, and patients 2 to 5 had chrysotile in their lungs that the model did not account for.
  • Each patient's level of exposure was not known and had to be fitted from lung data.
  • The autopsy data have sources of error, including whether the measurements from a given lymph node are representative.
  • Remote organs were treated as a single category, even though measured burdens vary widely between organs.

Topics

Medical terms in this study, explained in our Lexicon: Disease Progression, Chrysotile, Asbestos Exposure.

Related studies

• The prevalence of enlarged mediastinal lymph nodes in asbestos-exposed individuals: a CT study — C. Sampson, D.M. Hansell (1992)
• Extrapleural and cardiophrenic lymph nodes: prevalence, clinical significance and diagnostic value — B. Feragalli, C. Mantini, et al. (2014)
• Monitoring of fluoro-edenite fibre pollution through the study of sheep lymph nodes as a model of a biological indicator — V. Rapisarda, G. Rapisarda, et al. (2005)
• Asbestos content of lung tissue, lymph nodes, and pleural plaques from former shipyard workers — R.F. Dodson, M.G. Williams, et al. (1990)
• Intrapulmonary lymph nodes. Clinical, radiologic, and pathologic features — R.L. Kradin, P.W. Spirn, et al. (1985)
• A comparison of asbestos burden in lung parenchyma, lymph nodes, and plaques — R.F. Dodson, M.G. Williams, et al. (1991)

Browse return to medical research.