Pathogenesis of pleural fibrosis

Our plain-English summary of Pathogenesis of pleural fibrosis, by S.E. Mutsaers, C.M. Prele, A.R. Brody, et al (Respirology, 2004).

The study

• Authors: S.E. Mutsaers, C.M. Prele, A.R. Brody, S. Idell
• Journal: Respirology
• Published: 2004;9(4):428-40
• Type of article: Review
• Cited by: 87 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Pleural fibrosis resembles fibrosis in other tissues and can be defined as an excessive deposition of matrix components that results in the destruction of normal pleural tissue architecture and compromised function. Pleural fibrosis may be the consequence of an organised haemorrhagic effusion, tuberculous effusion, empyema or asbestos-related pleurisy and can manifest itself as discrete localised lesions (pleural plaques) or diffuse pleural thickening and fibrosis. Although the pathogenesis is unknown, it is likely that the complex interactions between resident and inflammatory cells, profibrotic mediators and coagulation, and fibrinolytic pathways are integral to pleural remodelling and fibrosis. It is generally considered that the primary target cell for pleural fibrosis is the subpleural fibroblast. However, increasing evidence suggests that mesothelial cells may also play a significant role in the pathogenesis of this condition, both by initiating inflammatory responses and producing matrix components. A greater understanding of the interactions between pleural and inflammatory cells, cytokines and growth factors, and blood derived proteins is required before adequate therapies can be developed to prevent pleural fibrosis from occurring.

In plain English

This article was an invited review, not a new study. The authors reviewed published laboratory, animal and clinical research on how pleural fibrosis develops. Pleural fibrosis is scarring of the membrane lining the lungs and chest wall, and the review included fibrosis linked to asbestos. They described pleural injury and fibrosis as marked by disordered fibrin turnover. Increased local tissue factor starts clotting, while increased PAI-1 and antiplasmins turn down clot breakdown. They wrote that the subpleural fibroblast is considered the main target cell, but that mesothelial cells can also produce matrix components. They described TGF-beta as considered the most potent profibrotic mediator, present at high levels in asbestos-induced fibrosis. On asbestos, they described fibres reaching the pleura by lymphatic flow. They noted that pleural fibrosis and plaques have been recorded in asbestos-exposed workers without lung fibrosis, and that all asbestos varieties have been shown to generate reactive oxygen species. The authors concluded that at least two pathways, cytokines and growth factors on one hand and oxygen radicals on the other, are likely involved in asbestos-induced pleural fibrosis. They stated that very few studies have examined cytokines and growth factors specifically in pleural 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: Invited review of published research (narrative review)
• Who was studied: No study population of its own; the review drew on published cell, animal and patient research on the pleura
• Exposure: Causes of pleural fibrosis including asbestos (all varieties; amphibole, chrysotile and crocidolite are discussed), talc, infection such as tuberculosis, and radiation
• Main results:
  • The review described pleural injury and fibrosis as characterised by disordered fibrin turnover: increased local tissue factor starts clotting, and fibrin breakdown is reduced by increased PAI-1 and antiplasmins
  • The review stated that the subpleural fibroblast is the primary target cell for pleural fibrosis, but that laboratory studies show mesothelial cells can also produce matrix components
  • The review described TGF-beta as considered the most potent profibrotic mediator and as present at high levels in asbestos-induced fibrosis
  • The review described transport of inhaled fibres from the lung interstitium to the subpleural space by lymphatic flow as a key event in asbestos-induced pleural fibrosis
  • The review noted that pleural fibrosis and plaques have been recorded in asbestos-exposed workers who do not have fibrosis of the lung tissue; the authors suggested that as yet undefined susceptibility genes may control this
  • The review stated that all asbestos varieties have been shown to generate reactive oxygen species
  • The review described cited work showing that oxygen radicals from chrysotile and crocidolite activate TGF-beta in the laboratory and in animals. The authors noted it is not yet established whether pleural fibroblasts are affected
• The authors' conclusion: The authors concluded that at least two mechanistic pathways are likely to be involved in asbestos-induced pleural fibrosis: the generation of cytokines and growth factors, and oxygen radicals
• Limitations the authors state:
  • The authors stated that very few studies have specifically examined the role of cytokines and growth factors in pleural fibrosis
  • The authors stated that the pathogenesis of pleural fibrosis is unknown
  • The authors stated that the roles of many mediators implicated in tissue and serosal fibrosis still need to be examined specifically in pleural fibrosis

Topics

The National Library of Medicine indexes this study under subjects our site covers: Pleural plaques and thickening.

Medical terms in this study, explained in our Lexicon: Fibrosis, Deposition, Empyema, Pleurisy, Pleural Plaques, Diffuse Pleural Thickening, Fibroblast, Mesothelial Cells.

Related studies

• Pathogenesis of pleurisy, pleural fibrosis, and mesothelial proliferation — A. Herbert (1986)
• Asbestos-induced pleural fibrosis and impaired lung function — D.A. Schwartz, L.J. Fuortes, et al. (1990)
• Causes and management of pleural fibrosis — J.T. Huggins, S.A. Sahn (2004)
• Diffusing capacity and forced vital capacity in 5,003 asbestos-exposed workers: relationships to interstitial fibrosis (ILO profusion score) and pleural thickening — A. Miller, R. Warshaw, et al. (2013)
• Splicing factor SRSF6 mediates pleural fibrosis — L.M. Liang, L. Xiong, et al. (2021)
• Chronic pleuritic pain in four patients with asbestos induced pleural fibrosis — A. Miller (1990)

Browse more research in Respirology, or return to medical research.