Asbestos-induced lung injury in the sheep model: the initial alveolitis

Our plain-English summary of Asbestos-induced lung injury in the sheep model: the initial alveolitis, by R. Bégin, M. Rola-Pleszczynski, S. Massé, et al (Environmental Research, 1983).

The study

• Authors: R. Bégin, M. Rola-Pleszczynski, S. Massé, I. Lemaire, P. Sirois, M. Boctor, D. Nadeau, G. Drapeau, M.A. Bureau
• Journal: Environmental Research
• Published: 1983;30(1):195-210
• Cited by: 56 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

In order to study the cellular and biochemical changes in early asbestosis, three groups of sheep were repeatedly exposed to intratracheal instillations of either saline (controls), low doses of UICC chrysotile asbestos (LD), or high doses of the fibers (HD) until an alveolitis was observed in all HD sheep during the twelfth month of exposure. All sheep were studied bimonthly by transbronchial lung biopsy (LB), bronchoalveolar lavage (BAL), pulmonary function tests (PFT), and chest roentgenograms (CXR). While LBs of the HD sheep demonstrated large accumulations of monocyte-macrophages in the alveolar and interstitial spaces, those of controls and LD sheep did not. In BAL, there was no difference in total and differential cell counts between groups, but the BAL lymphocyte proliferative capacity was clearly depressed in all asbestos-exposed sheep. In the BAL supernatant, total proteins (mainly albumin, beta + gamma globulins) and lactate dehydrogenase were significantly elevated in the HD group only. This alveolitis was associated with a fall in vital capacity, lung compliance, diffusing capacity, and arterial PO2. Abnormalities on CXR appeared 3 months later. Thus, the cellular and biochemical features of early asbestosis are clearly distinct from those reported in idiopathic pulmonary fibrosis.

In plain English

In this animal experiment, researchers put UICC chrysotile asbestos directly into sheep windpipes to study early asbestosis. After six months of monthly doses, six low-exposure sheep then received 2 mg weekly and six high-exposure sheep 128 mg weekly. A control group received saline only. Every two months, all sheep had lung biopsies, lung washings (bronchoalveolar lavage), lung function tests and chest X-rays. During the twelfth month, all biopsies from high-exposure sheep showed cell build-up, mostly macrophages, with no increase in collagen or fibrosis. In the last six months of exposure, lung-washing cell counts did not differ between groups. Within two months of weekly dosing, lymphocyte growth responses were depressed in both asbestos groups. Only the high-exposure group showed raised proteins and lactate dehydrogenase in the washings, along with lower lung compliance, vital capacity, diffusing capacity and arterial oxygen. Four of six high-exposure sheep showed ill-defined vascular markings on X-ray, and three months later all had small diffuse opacities. The low-dose sheep showed no X-ray abnormality. The authors concluded that this early alveolitis was distinct from that of idiopathic pulmonary fibrosis.

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: Animal experiment: repeated intratracheal instillation of asbestos in conscious sheep, with sequential lung biopsy, bronchoalveolar lavage, pulmonary function tests and chest X-rays
• Who was studied: Three groups of sheep: controls given saline (number not stated), six low-dose sheep and six high-dose sheep. Location of the animals and study dates are not stated.
• Exposure: UICC Canadian chrysotile asbestos given by intratracheal instillation. The first 6 months were monthly doses (average cumulative 36 mg in the low-exposure group and 328 mg in the high-exposure group). After that, the low-exposure group received 2 mg weekly and the high-exposure group 128 mg weekly. Controls received saline only.
• Main results:
  • In high-exposure sheep, all lung biopsies showed pathological changes during the twelfth month (sixth month of weekly exposure). The cellular infiltrates were mostly alveolar macrophages.
  • Masson staining of these high-exposure biopsies showed no increase in interstitial collagen or fibrosis.
  • Total cell yield from lung washings averaged 19.6 million, with no significant difference between groups (P greater than 0.05).
  • The lung-washing cell mix (on average 75% macrophages, 13% lymphocytes, 3% neutrophils) did not differ significantly between groups during the last 6 months of asbestos exposure, including when alveolitis was seen on biopsy in high-exposure sheep.
  • Within 2 months of weekly exposure, lymphocytes from lung washings in both the low- and high-exposure groups had significantly depressed proliferative capacity.
  • In the high-exposure group only, total proteins, albumin, beta + gamma globulins and lactate dehydrogenase in the lung washings increased significantly during the last 4 months of the study.
  • Static lung compliance averaged 130 ml per cm H2O in controls, 120 in the low-exposure group and 89 in the high-exposure group. It was significantly lower than control values only in the high-exposure group (P less than 0.01).
  • At the twelfth month, vital capacity was 45 ml/kg (standard error 2) in the high-exposure group versus 52 ml/kg (standard error 3) in controls (P less than 0.05).
  • Compared with controls, the high-exposure group had significantly lower arterial PO2, a higher alveolar-arterial PO2 gradient and lower diffusing capacity for carbon monoxide (P less than 0.01).
  • For most of these lung function measurements, differences between the low-dose group and controls were not significant (P greater than 0.05).
  • On chest X-ray, the first changes in the high-exposure group were ill-defined vascular markings, seen in four of the six sheep at the twelfth month. No abnormality was seen in the low-dose group.
  • Three months later, all high-exposure sheep had abnormal chest X-rays, described as diffuse irregular small opacities of 1-2 mm diameter.
• The authors' conclusion: The authors concluded that the asbestos-induced initial alveolitis was clearly distinct from the immune complex-induced alveolitis of idiopathic pulmonary fibrosis.
• Limitations the authors state:
  • The distribution within the lung of the asbestos instilled into the trachea was not studied.
  • Whether the increase in globulins came from the blood or was produced locally in the lung remained speculative.

Topics

Medical terms in this study, explained in our Lexicon: UICC, Chrysotile, Biopsy, Bronchoalveolar Lavage (BAL), Pulmonary Function Test (PFT), Macrophage, Interstitial, Lactate Dehydrogenase (LDH).

Related studies

• Assessment of progression of asbestosis in the sheep model by bronchoalveolar lavage and pulmonary function tests — R. Bégin, M. Rola-Pleszczynski, et al. (1983)
• Selective exposure and analysis of the sheep tracheal lobe as a model for toxicological studies of respirable particles — R. Bégin, S. Massé, et al. (1985)
• Morphologic features and function of the airways in early asbestosis in the sheep model — R. Bégin, S. Massé, et al. (1982)
• Pulmonary uptake of gallium-67 in asbestos-exposed humans and sheep — R. Bégin, A. Cantin, et al. (1983)
• Fibronectin and procollagen 3 levels in bronchoalveolar lavage of asbestos-exposed human subjects and sheep — R. Bégin, M. Martel, et al. (1986)
• Clinical features to stage alveolitis in asbestos workers — R. Bégin, A. Cantin, et al. (1985)

Browse more research in Environmental Research, or return to medical research.