Cigarette smoke makes airway and early parenchymal asbestos-induced lung disease worse in the guinea pig

Our plain-English summary of Cigarette smoke makes airway and early parenchymal asbestos-induced lung disease worse in the guinea pig, by V. Tron, J.L. Wright, N. Harrison, et al (The American Review of Respiratory Disease, 1987).

The study

• Authors: V. Tron, J.L. Wright, N. Harrison, B. Wiggs, A. Churg
• Journal: The American Review of Respiratory Disease
• Published: 1987;136(2):271-5
• Cited by: 23 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. 000363).

Abstract

In order to assess the effects of cigarette smoke and asbestos exposure, we divided guinea pigs into 4 groups: smoking or nonsmoking, and asbestos-exposed or not asbestos-exposed groups. Asbestos-exposed animals were given a single intratracheal instillation of 5 mg UICC amosite, a dose and method of administration that we have previously shown produces morphologic changes in the small airways as well as minimal interstitial fibrosis. Animals were smoked 5 days per week for 6 months. By itself, smoking did not affect lung collagen content, small airways wall thickness, or the volume fraction of tissue surrounding airways, but it did cause a significant increase in alveolar mean linear intercept (Lm). Asbestos alone increased collagen content, airway wall thickness, and tissue volume fraction surrounding airways, the latter measure used to assess interstitial fibrosis. An unexpected finding was that asbestos also increased Lm. The two agents administered together caused more severe changes of all types than were produced by either agent alone, and the interaction between the 2 was generally synergistic. Smoke-exposed animals retained 3 times the asbestos fiber burden of those not smoke-exposed; the increase in retention was greater for short than for long fibers. We conclude that cigarette smoke can potentiate the fibrosis induced by asbestos, possibly because of increased fiber retention. As well, in this model, asbestos or asbestos plus cigarette smoke produces increases in alveolar size.(ABSTRACT TRUNCATED AT 250 WORDS)

In plain English

In this animal experiment, female guinea pigs were split into four groups: no exposure, cigarette smoke only, amosite asbestos only, or both. Asbestos groups received a single 5 mg dose of UICC amosite placed into the windpipe. Smoked groups were exposed to cigarette smoke 5 days a week for 6 months. Twelve animals per group were then examined. Smoke alone did not significantly change small-airway wall thickness or lung collagen, but it did enlarge the air spaces. Amosite alone thickened small-airway walls, increased alveolar wall tissue around the small airways, raised collagen and also enlarged air spaces. Animals given both showed the largest changes. The authors reported a more-than-additive (multiplicative) effect for tissue around airways and for collagen; for airway wall thickness this effect was not statistically significant. Smoke-exposed animals retained about three times as many fibers (700 million versus 250 million per gram of dry lung). The authors concluded that the two agents together increased lung damage beyond either alone, but cautioned against treating the results as events in humans without human data.

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 with four groups: no exposure, cigarette smoke only, amosite asbestos only, or both smoke and amosite.
• Who was studied: Female Hartley strain guinea pigs of about 500 g, studied at the University of British Columbia, Vancouver. Twelve animals started in the saline control group and 16 in each other group. At 6 months 12, 13, 14 and 12 were alive, and 12 animals per group were analyzed.
• Exposure: Asbestos groups received a single 5 mg intratracheal instillation (placed directly into the windpipe) of UICC amosite. Smoked groups were exposed to cigarette smoke 5 days per week for 6 months. The methods specify whole smoke of 10 non-filter cigarettes per day.
• Main results:
  • Small-airway (respiratory bronchiole) wall thickness was 0.038 mm in the amosite nonsmokers and 0.048 mm in the amosite smokers, compared with 0.014 mm in the nonsmoking controls and 0.017 mm in the smoking controls. The comparison of each amosite group with each control group had p less than 0.001.
  • Smoking controls had slightly thicker airway walls than nonsmoking controls, but the difference was not statistically significant.
  • For airway wall thickness, smoking did not show a statistically significant multiplicative effect with asbestos (p = 0.25), although the authors wrote that the data suggest a more than additive effect may be present.
  • Volume proportion of alveolar wall around respiratory bronchioles was 26 in nonsmoking controls and 29 in smoking controls. It was 32 in amosite nonsmokers (p less than 0.001 versus both control groups) and 41 in amosite smokers (p less than 0.001 versus both control groups and versus amosite nonsmokers).
  • For alveolar wall volume proportion, smoking showed a multiplicative effect on the asbestos effect (p = 0.07). The authors had set an interaction term of p less than 0.10 as indicating a multiplicative effect.
  • Mean linear intercept (a measure of alveolar size) was 0.046 mm in nonsmoking controls. It was 0.054 mm with smoking alone (p less than 0.05) and 0.056 mm with amosite alone (p less than 0.001).
  • In animals exposed to both asbestos and smoke, mean linear intercept rose to 0.066 mm (p less than 0.001 compared with all other groups).
  • Lung hydroxyproline (collagen measure) averaged 9.9 mg/g dry lung in nonsmoking controls and 11.6 in smoking controls. These two values were not significantly different.
  • Hydroxyproline was 12.8 in amosite nonsmokers (p less than 0.01 versus nonsmoking controls). It was 17.3 in amosite smokers, which differed from both control groups and from amosite nonsmokers (p less than 0.001; the text's scanned p values are confirmed by Table 1).
  • For hydroxyproline, cigarette smoke plus amosite appeared to act in a multiplicative fashion (p = 0.05).
  • Animals exposed to asbestos and smoke retained about 3 times the fiber burden of animals exposed to asbestos alone: 700 × 10^6 versus 250 × 10^6 fibers per gram of dry lung (p less than 0.02).
  • In both lung tissue and lavage fluid, smokers had shorter mean fiber lengths than nonsmokers.
• The authors' conclusion: The authors concluded that asbestos plus cigarette smoke increased structural lung damage beyond that produced by either agent alone, and that for the most part the two agents acted synergistically. They also suggested that greater fiber retention caused by smoke may be one underlying cause.
• Limitations the authors state:
  • Intratracheal instillation produces much more unevenly distributed lesions than inhalation.
  • Intratracheal instillation tends to exaggerate airway changes while producing relatively less parenchymal damage.
  • The UICC amosite used produces relatively little alveolar wall interstitial fibrosis, even when inhaled.
  • The asbestos-induced lesions were qualitatively similar to, but quantitatively somewhat different from, what is usually seen in humans.
  • The authors knew of no long- or medium-term studies of cigarette smoke effects in guinea pigs.
  • Without actual human data, the model should not be interpreted as representing events that actually occur in humans.
  • The observations were based on rather mild disease.

Topics

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

Medical terms in this study, explained in our Lexicon: Asbestos Exposure, UICC, Amosite, Interstitial Fibrosis, Collagen, Fiber Burden, Fibrosis.

Related studies

• Cigarette smoke increases the penetration of asbestos fibers into airway walls — D. McFadden, J. Wright, et al. (1986)
• Effects of cigarette smoke and asbestos on airway, vascular and mesothelial cell proliferation — H. Sekhon, J. Wright, et al. (1995)
• Cigarette smoke, asbestos, and small irregular opacities — W. Weiss (1984)
• Synergistic effects of mineral fibres and cigarette smoke on the production of tumour necrosis factor by alveolar macrophages of rats — Y. Morimoto, M. Kido, et al. (1993)
• Effects of cigarette smoke exposure on retention of asbestos fibers in various morphologic compartments of the guinea pig lung — A. Churg, V. Tron, et al. (1987)
• Cigarette smoke potentiates asbestos-induced airflow abnormalities — J.L. Wright, V. Tron, et al. (1988)

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