The role of nitric oxide in pleural disease

Our plain-English summary of The role of nitric oxide in pleural disease, by O.S. Kotsiou, K.I. Gourgoulianis, S.G. Zarogiannis (Respiratory Medicine, 2021).

The study

• Authors: O.S. Kotsiou, K.I. Gourgoulianis, S.G. Zarogiannis
• Journal: Respiratory Medicine
• Published: 2021;179:106350
• Type of article: Review
• Cited by: 8 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Nitric oxide (NO) regulates various physiological and pathophysiological functions in the lungs. However, there is much less information about the effects of NO in the pleura. The present review aimed to explore the available evidence regarding the role of NO in pleural disease. NO, has a double-edged role in the pleural cavity. It is an essential signaling molecule mediating various physiological cell functions such as lymphatic drainage of the serous cavities, the immune response to intracellular multiplication of pathogens, and downregulation of neutrophil migration, but also induces genocytotoxic and mutagenic effects when present in excess. NO is implicated in the pathogenesis of asbestos-related or exudative pleural disease and mesothelioma. From a clinical point of view, the fraction of exhaled NO has been suggested as a potential non-invasive tool for the diagnosis of benign asbestos-related disorders. Under experimental conditions, NO-mimetics were found to attenuate hypoxia-induced therapy resistance in mesothelioma. Similarly, hybrid agents consisting of an NO donor coupled with a parent anti-inflammatory drug showed an enhancement of the anti-inflammatory activity of anti-inflammatory drugs. However, given the paucity of research work performed over the last years in this area, further research should be undertaken to establish reliable conclusions with respect to the feasibility of determining or targeting the NO signaling pathway for pleural disease diagnosis and therapeutic management.

Copyright © 2021 Elsevier Ltd. All rights reserved.

In plain English

This article was a narrative review, not a new study. The authors gathered published research on nitric oxide (NO), a molecule the body makes, in diseases of the pleura, the lining around the lungs. It does not say how many studies were reviewed or how they were chosen. The authors reported that, although data conflict, most published studies suggest NO produced after inhaling asbestos fibers in sufficient concentrations plays a dominant role in lung and pleural damage. Cited studies found that adding crocidolite or chrysotile fibers to cytokine-stimulated cell cultures raised NO production by rat alveolar macrophages and parietal pleural mesothelial cells. On exhaled NO, a breath test, results were mixed: one cited study found higher levels in people with asbestosis than controls, but not in people with asbestos-related pleural plaques. Asbestos was reported to raise NO levels in mesothelioma cells. In experiments, NO-mimetics were reported to reduce hypoxia-induced therapy resistance in mesothelioma, and NO donors coupled with anti-inflammatory drugs enhanced their anti-inflammatory activity. The authors concluded that NO plays a double-edged role in the pleura and that more research is needed.

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: Narrative review of published literature
• Who was studied: Published studies (human, animal and cell-culture) on nitric oxide in pleural disease. The article does not describe how many studies were reviewed or how they were selected; one author performed the literature search.
• Exposure: Nitric oxide in pleural disease, including asbestos-related disease (pleural plaques, asbestosis, mesothelioma) and tuberculous, malignant and parapneumonic pleural effusions. Cited cell-culture studies added crocidolite or chrysotile fibers to cytokine-stimulated cultures. Carbon nanotubes were also discussed.
• Main results:
  • The authors reported that, despite conflicting data, most published studies suggest NO production induced by inhaling asbestos fibers in sufficient concentrations plays a dominant role in lung and pleura damage.
  • Cited studies found that adding crocidolite or chrysotile fibers to cytokine-stimulated cell cultures increased NO production by rat alveolar macrophages and rat parietal pleural mesothelial cells.
  • The authors described evidence on exhaled NO (FeNO) in pleural plaques as contradictory. One cited study (Chow et al.) found significantly elevated FeNO in subjects with asbestosis compared with controls, but not in subjects with asbestos-related pleural plaques.
  • Asbestos was reported to increase NO levels in mesothelioma cells by modulating both the eNOS and iNOS enzymes. Previous research found that human mesothelioma cells overexpress iNOS.
  • Under experimental conditions, NO-mimetics were reported to reduce hypoxia-induced therapy resistance in mesothelioma.
  • In a mouse model of pleurisy, hybrid agents combining an NO donor with a nonsteroidal anti-inflammatory drug reduced leukocyte recruitment and production of inflammatory mediators.
• The authors' conclusion: The authors concluded that NO plays a double-edged role in the pleura. It is needed for normal functions but may contribute to asbestos-related and exudative pleural disease and mesothelioma when present in excess. They concluded that further studies are needed before reliable conclusions can be drawn about measuring or targeting NO for the diagnosis and treatment of pleural disease.
• Limitations the authors state:
  • The authors stated that few studies have investigated NO and exhaled NO in benign asbestos-related disease over the past decade.
  • The authors stated that only a few published studies exist on NO and exhaled NO in pleural diseases.

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: Pleura, Pleural Cavity, Serous Cavities, Mesothelioma, Hypoxia.

Related studies

• Fractional exhaled nitric oxide concentration is increased in asbestosis and pleural plaques — A. Sandrini, A.R. Johnson, et al. (2006)
• Asbestos redirects nitric oxide signaling through rapid catalytic conversion to nitrite — D.D. Thomas, M.G. Espey, et al. (2006)
• Chronic infections and inflammatory processes as cancer risk factors: possible role of nitric oxide in carcinogenesis — H. Ohshima, H. Bartsch (1994)
• Participation of nitric oxide and iron in the oxidation of DNA in asbestos-treated human lung epithelial cells — C.C. Chao, S.H. Park, et al. (1996)
• Increased alveolar nitric oxide concentration and high levels of leukotriene B(4) and 8-isoprostane in exhaled breath condensate in patients with asbestosis — H. Lehtonen, P. Oksa, et al. (2007)
• Asbestos fibers and interferon-gamma up-regulate nitric oxide production in rat alveolar macrophages — G. Thomas, T. Ando, et al. (1994)

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