Pleural fluid biomarkers: a narrative review

Our plain-English summary of Pleural fluid biomarkers: a narrative review, by C. Chan, K.K.P. Chan (Journal of Thoracic Disease, 2024).

The study

• Authors: C. Chan, K.K.P. Chan
• Journal: Journal of Thoracic Disease
• Published: 2024;16(7):4764-4771
• Type of article: Review
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background And Objective: Pleural fluid is a source from which various biomarkers can be obtained and measured to facilitate the management and prognostication of various conditions. This narrative review aims to summarise a few selected applications of pleural fluid biomarker analysis based on the latest literature.

Methods: A literature search for articles published in English regarding human subjects from the period January 2000 to December 2023 was performed through PubMed. Publications considered by the authors to be relevant were included in this review, with additional references added based on the authors' judgement. This review considered both prospective and retrospective cohort studies analysing the clinical value of a range of pleural fluid biomarkers.

Key Content And Findings: The biomarkers selected in this narrative review have either established clinical applicability or promising initial results which require further research. Pleural fluid adenosine deaminase, mesothelin and N-terminal pro-B-type natriuretic peptide can optimize the diagnosis of tuberculous pleuritis, malignant mesothelioma and heart failure-related pleural effusion respectively. The detection rate for epidermal growth factor receptor mutations for lung cancer is higher in the pleural fluid than in the pleural tissue or plasma. Suitable targeted therapy in patients with detectable mutations can offer survival benefits. The pleural fluid neutrophil-lymphocyte ratio, soluble urokinase plasminogen activator receptor and plasminogen activator inhibitor 1 carry prognostic implications and can potentially guide subsequent treatment decisions. These biomarkers used individually, or in conjunction with other clinical parameters, should only be utilised in pre-defined, appropriate clinical conditions to maximize their clinical value.

Conclusions: A great variety of different biomarkers are available for analysis in pleural fluid. Further research and development are necessary to widen the spectrum and enhance the clinical utility of pleural fluid biomarkers. Comparison with the diagnostic utilities of serum biomarkers and other investigation parameters, such as radiological findings, could be considered when evaluating the performance of pleural fluid biomarkers.

2024 Journal of Thoracic Disease. All rights reserved.

In plain English

This was a narrative review, not a new study. The authors searched PubMed for English-language studies in humans published from January 2000 to December 2023 on pleural fluid biomarkers. They included publications they judged relevant and summarised selected markers for malignant pleural effusion, pleural infection, tuberculous pleuritis and heart failure. For malignant mesothelioma, the review cited a meta-analysis reporting that mesothelin measured in pleural fluid had a sensitivity of up to 79%, compared with 61% when measured in serum, with similar pooled specificities of 85% to 87%. It noted that pancreatic and ovarian cancers can also limit the specificity of mesothelin testing. It also cited a sensitivity of around 30% for pleural fluid cytology in diagnosing mesothelioma. Other studies it summarised covered EGFR mutation testing in lung cancer, survival prediction in malignant effusion, infection markers, adenosine deaminase in tuberculosis, and NT-proBNP in heart failure. The authors concluded that a variety of pleural fluid biomarkers have been validated to aid diagnosis and treatment decisions, and that more research is needed. The article does not discuss asbestos.

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: English-language, human-based studies found through a PubMed search covering January 2000 to December 2023 (search date 1 February 2024), plus additional articles added by the authors' consensus; the number of studies included is not stated
• Exposure: Not applicable: the review concerned pleural fluid biomarkers, not an exposure. Asbestos and fiber types are not mentioned.
• Main results:
  • Citing a meta-analysis (its reference 10), the review reported that mesothelin had greater sensitivity for diagnosing malignant mesothelioma when measured in pleural fluid than in serum: up to 79% compared with 61%
  • In the same cited meta-analysis, specificities of pleural fluid and serum mesothelin were similar, with pooled estimates of 85% to 87%
  • A cited study by Ashour et al. suggested a pleural fluid mesothelin cutoff of 3.0 nmol/L, giving a sensitivity of 73% and a specificity of 82% for mesothelioma
  • The review stated that other conditions that express mesothelin, such as pancreatic and ovarian cancers, could limit the specificity of mesothelin testing
  • The review cited a sensitivity of around 30% for pleural fluid cytology in diagnosing mesothelioma
  • In a cited Hong Kong review of 5,504 EGFR test results, the EGFR detection rate in pleural fluid was higher than in pleural biopsy (59.8% vs. 50.7%)
  • In a cited study by Popowicz et al. of patients with malignant pleural effusion, a pleural fluid neutrophil-lymphocyte ratio above 0.745 was associated with a median survival of 130 days, compared with 312 days for patients with a ratio below 0.745
  • In a cited study of pleural infection, pleural fluid suPAR at a cutoff of 35 ng/mL had 100% sensitivity and 91% specificity for predicting pleural fluid loculations
  • A cited meta-analysis pooling 44 publications estimated that adenosine deaminase at a cutoff of at least 40 U/L had a sensitivity of 0.88 (95% CI 0.85 to 0.91) and a specificity of 0.91 (95% CI 0.89 to 0.92) for diagnosing tuberculous pleurisy
  • The British Thoracic Society Guideline, in a combined analysis of five studies, reported a sensitivity of 93% and a specificity of 93% for pleural fluid NT-proBNP in diagnosing unilateral pleural effusion due to heart failure
• The authors' conclusion: The authors concluded that a variety of pleural fluid biomarkers have been validated to aid diagnosis and treatment decisions for different types of pleural effusion. They added that many others are currently limited by inconclusive results or by testing costs, and that biomarker analysis is only one part of pleural medicine.
• Limitations the authors state:
  • The turnaround time of pleural fluid mesothelin testing has not been widely reported in the literature
  • For suPAR and PAI1, further prospective, multicenter studies are needed before the findings can be applied to a wider population
  • Pleural fluid biomarkers cannot assess anti-tuberculosis drug sensitivity
  • The literature on pleural fluid NT-proBNP lacks data from Chinese patients and has scarce data on patients of Asian descent

Topics

Medical terms in this study, explained in our Lexicon: Biomarker, Mesothelin, Mesothelioma, Pleural Effusion, Lung Cancer, Targeted Therapy.

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• Pleural fluid microbiota as a biomarker for malignancy and prognosis — B. Kwok, B.G. Wu, et al. (2023)
• The Role of Occupational and Environmental Exposures in the Pathogenesis of Idiopathic Pulmonary Fibrosis: A Narrative Literature Review — S.P. Trethewey, G.I. Walters (2018)
• Asbestos-induced chronic inflammation in malignant pleural mesothelioma and related therapeutic approaches-a narrative review — A.A. Zolondick, G. Gaudino, et al. (2021)
• Epidemiology, diagnosis and treatment of the malignant pleural mesothelioma, a narrative review of literature — S.O. Schumann, G. Kocher, et al. (2021)

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