Hyaluronic acid in viscous malignant mesothelioma pleural effusion

Our plain-English summary of Hyaluronic acid in viscous malignant mesothelioma pleural effusion, by H.M. Cheah, D. Fitzgerald, A. Louw, et al (Respirology Case Reports, 2021).

The study

• Authors: H.M. Cheah, D. Fitzgerald, A. Louw, J. Creaney, Y.C.G. Lee
• Journal: Respirology Case Reports
• Published: 2021;9(1):e00694
• Type of article: Case report
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural effusion (MPE) is common with mesothelioma. We report two cases of extraordinarily viscous MPEs associated with mesothelioma. The viscosity prohibited spontaneous gravity-dependent drainage via indwelling pleural catheters. Our ex vivo experiments found very high hyaluronic acid (HA) content within the fluid. Treatment of the fluid with hyaluronidase, but not with deoxyribonucleases, significantly reduced fluid viscosity. The results provide proof that HA can contribute to high viscosity of pleural fluid in mesothelioma. Research into strategies of counteracting HA properties in the management of MPEs may provide further insight.

© 2020 The Authors. Respirology Case Reports published by John Wiley & Sons Australia, Ltd on behalf of The Asian Pacific Society of Respirology.

In plain English

This case report described two people with mesothelioma, a 79-year-old man and a 79-year-old woman. The fluid that built up around their lungs (malignant pleural effusion) was so thick that it would not drain on its own through indwelling pleural catheters, so manual suction was needed. Intrapleural tissue plasminogen activator (tPA) with deoxyribonuclease (DNase) improved drainage at times in both patients. In the man, the fluid re-accumulated within two weeks. The authors then tested the fluid in the laboratory. All three samples had very high hyaluronic acid (HA) levels, from 2.31 to 5.39 million ng/mL. The enzyme hyaluronidase reduced the fluid's thickness in a dose-dependent manner. In one sample, viscosity fell from 800.21 to 2.94 mPas. The enzyme rhDNase lowered the same sample only from 780.56 to 567.38 mPas. The authors concluded that HA can contribute to high viscosity of pleural fluid in mesothelioma. They said that whether hyaluronidase can be used safely inside the chest needs investigation. The article does not report the patients' asbestos exposure.

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: Case report of two patients, combined with ex vivo (laboratory) experiments on their pleural fluid samples
• Who was studied: Two patients with mesothelioma and malignant pleural effusion referred to the authors' centre in Perth, Western Australia: Patient 1, a 79-year-old man with a left-sided effusion; Patient 2, a 79-year-old woman with a right-sided effusion. Three fluid samples were tested (two from Patient 1, taken about 38 days apart, and one from Patient 2).
• Exposure: Not reported. The article gives no information on asbestos exposure, fiber type or occupation for either patient. The laboratory treatments tested on the fluid were hyaluronidase (0 to 100 U/mL for 10 minutes) and recombinant human DNase (rhDNase; 2.5 to 10 micrograms per mL for 4 hours).
• Main results:
  • The pleural fluid from both patients had very high hyaluronic acid (HA) concentrations.
  • Patient 1, Sample 1: HA concentration 2.66 × 10^6 ng/mL. Viscosity was 800.21 mPas untreated, 54.62 after hyaluronidase 1 U/mL, 21.91 after 10 U/mL, and 2.94 after 100 U/mL.
  • Patient 1, Sample 2: HA concentration 5.39 × 10^6 ng/mL. The fluid was too viscous to measure untreated and after hyaluronidase 1 U/mL. Viscosity was 153.67 mPas after 10 U/mL and 18.61 after 100 U/mL.
  • Patient 2, Sample 3: HA concentration 2.31 × 10^6 ng/mL. Viscosity was 303.03 mPas untreated, 168.01 after hyaluronidase 1 U/mL, 6.59 after 10 U/mL, and 2.87 after 100 U/mL.
  • Patient 1, Sample 1 treated with rhDNase: viscosity was 780.56 mPas untreated, 690.93 at 2.5 micrograms per mL, 627.61 at 5, and 567.38 at 10.
  • Hyaluronidase, but not rhDNase, reduced the viscosity of the fluid in a dose-dependent manner.
  • Cytology of Patient 1's fluid showed material consistent with HA.
  • Patient 1: intrapleural tPA/DNase drained a total of 2.8 L with radiographic improvement, but the fluid re-accumulated within two weeks. Later, escalated doses had little effect.
  • Patient 2: after IPC drainage failed, a trial of intrapleural tPA 2.5 mg/DNase 5 mg drained 1.5 L.
• The authors' conclusion: The authors concluded that the results provide proof that HA can contribute to high viscosity of pleural fluid in mesothelioma. In the discussion they described HA as likely contributing to the high viscosity. They said strategies to counteract HA production or enhance its breakdown warrant exploration.
• Limitations the authors state:
  • It is not yet known whether hyaluronidase can be applied safely inside the chest, in a large enough quantity, to break down HA in human malignant pleural effusions.
  • Whether tPA itself affects the viscosity of the fluid is unknown. The authors suggest the early drainage benefit may have come from dilution by fluid that tPA stimulates.

Topics

Medical terms in this study, explained in our Lexicon: Hyaluronic Acid, Malignant Mesothelioma, Pleural Effusion, Mesothelioma, Indwelling Pleural Catheter.

Related studies

• Pleural effusion hyaluronic acid as a prognostic marker in pleural malignant mesothelioma — J. Creaney, I.M. Dick, et al. (2013)
• Utility of hyaluronic acid in pleural fluid for differential diagnosis of pleural effusions: likelihood ratios for malignant mesothelioma — S. Atagi, M. Ogawara, et al. (1997)
• Histochemical demonstration of hyaluronic acid in pleural mesotheliomas — J.C. Wagner, D.E. Munday, et al. (1962)
• Complement Protein C1q Binds to Hyaluronic Acid in the Malignant Pleural Mesothelioma Microenvironment and Promotes Tumor Growth — C. Agostinis, R. Vidergar, et al. (2017)
• Hyaluronic acid in the pleural fluid of patients with malignant pleural mesothelioma — N. Fujimoto, K. Gemba, et al. (2013)
• Serum mesothelin has a higher diagnostic utility than hyaluronic acid in malignant mesothelioma — B. Grigoriu, B. Chahine, et al. (2009)

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