Morphologic features and function of the airways in early asbestosis in the sheep model

Our plain-English summary of Morphologic features and function of the airways in early asbestosis in the sheep model, by R. Bégin, S. Massé, M.A. Bureau (The American Review of Respiratory Disease, 1982).

The study

• Authors: R. Bégin, S. Massé, M.A. Bureau
• Journal: The American Review of Respiratory Disease
• Published: 1982;126(5):870-6
• Cited by: 65 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Previous studies of asbestos exposure in humans and small animals have suggested that air flow limitation associated with small airway disease may be an early manifestation of asbestosis, but the subject is still controversial. In this report, we present the airway morphologic aspects and function of our sheep model of the disease. Three groups of 6 sheep were exposed to repeated intratracheal injections of either saline (control group), 2 mg of UICC Canadian chrysotile asbestos in saline (low exposure group), or 128 mg of the same fibers (high exposure group). At the end of the twelfth month of exposure, an alveolitis had developed in the high exposure group only. Detailed pulmonary function tests were followed within 48 by lung biopsies according to methods described, to which were added air-helium flow-volume curves. Lung biopsies in control and low exposure groups did not demonstrate significant morphologic changes, whereas all biopsies in the high exposure group showed alveolitis characterized by an alveolar and interstitial accumulation of macrophages and mononuclear cells without interstitial fibrosis. On all biopsies, over half of the airways were altered by a similar peribronchiolar process, which at times compressed the peripheral airways. Functionally there was no significant difference between low exposure and control groups. However, compared with the control group, the high exposure group had significantly lower vital capacity (2.0 +/- 0.1 versus 2.9 + 0.1 L, p less than 0.01), lower static lung compliance (91 + 13 versus 132 + 9 ml/cmH2O, p less than 0.05), higher isoflow volume (2.15 + 0.08 versus 1.4 + 0.1 L, p less than 0.01), and higher upstream resistance below the isoflow volume (3.3 + 0.2 versus 1.3 + 0.3 cmH2O L/s, p less than 0.02). These data demonstrate that in the early asbestos-induced peribronchiolar alveolitis of the sheep, which restricts lung volumes, there is a concomitant small airway disease that significantly limits air flow.

In plain English

This was an animal experiment. Eighteen male sheep were split into three groups of 6 and given injections of liquid directly into the windpipe for 12 months: saline only (controls), a low dose of UICC Canadian chrysotile asbestos, or a high dose. The methods give cumulative doses of 328 mg and 2282 mg. After exposure stopped, the sheep had lung function tests and lung biopsies. All high-dose sheep showed alveolitis, an inflammation of the air sacs made mostly of macrophages. It was concentrated around the small airways and often narrowed them. Low-dose sheep showed only occasional mild changes. Compared with controls, the high-dose group had lower vital capacity, lower static lung compliance (91 versus 132 ml/cmH2O), lower blood oxygen and a higher isoflow volume. Their upstream airway resistance at low lung volumes was 2 to 3 times that of the other groups. The low-dose group had a 15% lower forced vital capacity than controls. The authors concluded that this early inflammation around small airways can narrow them and limit air flow. They noted that their injected doses do not strictly relate to low inhaled exposures.

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: a sheep model of asbestosis with control, low-exposure and high-exposure groups, studied with lung function tests, transbronchial lung biopsies and autopsy of one animal per group
• Who was studied: 18 male sheep weighing 25 to 50 kg, in three groups of 6, studied at the Unité de Recherche Pulmonaire, Centre Hospitalier Universitaire de Sherbrooke, Québec, Canada
• Exposure: Repeated intratracheal injections over 12 months (monthly for 6 months, then weekly for 6 months). Controls received 50-ml saline injections. The low exposure group received a cumulative dose of 328 mg of UICC Canadian chrysotile fibers in saline, and the high exposure group a cumulative dose of 2282 mg. The article's summary describes the groups as receiving 2 mg and 128 mg.
• Main results:
  • In the high exposure group, all biopsies showed pathologic changes. These were cellular infiltrates, more than 90% macrophages, located mainly around the noncartilaginous bronchioles.
  • In the high exposure group, the infiltrates often compressed the bronchiolar walls and narrowed the airway lumen.
  • In the low exposure group, only a few biopsies showed occasional mild increases in cellularity. Control biopsies remained normal.
  • Mean static lung compliance was 132 ml/cmH2O in controls, 124 in the low exposure group and 91 in the high exposure group. The difference was significant in the high exposure group only (p less than 0.05).
  • The high exposure group had a lower vital capacity than controls: 2.0 plus or minus 0.1 versus 2.9 plus or minus 0.1 L, p less than 0.01.
  • In the low exposure group, forced vital capacity (FVC) was significantly reduced by 15% compared with controls (p less than 0.05).
  • Compared with controls, the high exposure group had lower tidal volume, higher respiratory rate, lower arterial Po2, lower diffusing capacity and lower mixing efficiency (p less than 0.05). The low exposure group did not differ significantly from controls on these measures.
  • The high exposure group had a higher isoflow volume than controls: 2.15 plus or minus 0.08 versus 1.4 plus or minus 0.1 L, p less than 0.01.
  • Below the isoflow volume, upstream resistance in the high exposure group was 2 to 3 times that of the other two groups (p less than 0.01).
  • Lung resistance did not differ significantly between the groups. The control mean was 1.9 cmH2O/L/s.
  • In the autopsy lung of the high exposure sheep, the alveolitis was mainly around the bronchioles and unevenly distributed. It was similar in all lung zones, though somewhat more intense in the lower zones.
• The authors' conclusion: The authors concluded that during the early macrophage alveolitis of the sheep model, which restricts lung volumes, the inflammation lies mainly around the peripheral airways. They found it can compress and narrow small airways, resulting in air flow limitation.
• Limitations the authors state:
  • The study was designed mainly to test whether the disease could be produced in sheep. Because of the mode and intensity of exposure (intratracheal injection), the authors state the data do not strictly relate to very early reactions to low inhaled asbestos exposure in humans or animals.

Topics

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

Medical terms in this study, explained in our Lexicon: Asbestos Exposure, UICC, Chrysotile, Pulmonary Function Test (PFT), Interstitial, Macrophage, Interstitial Fibrosis.

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)
• Biochemical components of bronchoalveolar lavage in early experimental asbestosis of the sheep: phospholipase A2 activity, prostaglandin E2 and proteins — P. Sirois, G. Drapeau, et al. (1983)
• Asbestos-induced lung injury in the sheep model: the initial alveolitis — R. Bégin, M. Rola-Pleszczynski, et al. (1983)
• Mass, number and size of lung fibres in the pathogenesis of asbestosis in sheep — P. Sébastien, R. Bégin, et al. (1990)
• 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)
• Immunohistochemical localization of transforming growth factor-beta and insulin-like growth factor-I in asbestosis in the sheep model — T.C. Lee, L.I. Gold, et al. (1997)

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