Volatile organic compounds in exhaled human breath for the diagnosis of malignant pleural mesothelioma: a meta-analysis

Our plain-English summary of Volatile organic compounds in exhaled human breath for the diagnosis of malignant pleural mesothelioma: a meta-analysis, by T. Zhao, X. Hu, M. Peng, et al (Frontiers in Oncology, 2025).

The study

• Authors: T. Zhao, X. Hu, M. Peng, W. Wei, N. Fu, C. Chen, Z. Chen
• Journal: Frontiers in Oncology
• Published: 2025;15:1537767
• Type of article: Systematic review
• Cited by: 2 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Objective: Malignant pleural mesothelioma (MPM) is a relatively rare thoracic tumor with a high mortality rate, making early diagnosis and treatment challenging. The present study evaluated the utility of exhaled volatile organic compounds (VOCs) in diagnosing MPM.

Methods: The Cochrane Library, PubMed, EMBASE, and Web of Science were systematically searched for clinical trials assessing the diagnostic ability of VOCs for MPM through August 30, 2024. Quality was evaluated using the QUADAS-2 tool. A meta-analysis was performed with a bivariate model for sensitivity and specificity using Stata MP 17.0 software.

Results: Eight trials with 859 subjects were included. VOCs were found to have a pooled sensitivity of 0.86 (95% confidence interval [CI] 0.75-0.93), a pooled specificity of 0.73 (95% CI 0.58-0.84), and an area under the curve (AUC) of 0.88 (95% CI 0.85-0.90) in differentiating MPM patients from healthy controls. In addition VOCs had a pooled sensitivity of 0.89 (95% CI 0.83-0.93), a pooled specificity of 0.79 (95% CI 0.57-0.91), and an AUC of 0.91 (95% CI 0.88-0.93) in differentiating MPM patients from asymptomatic individuals formerly exposed to asbestos (AEx).

Conclusions: Although the utility of VOCs in diagnosing MPM varied among clinical trials, VOCs in exhaled human breath may have a potential role in the diagnosis of MPM. Large-scale randomized clinical trials are warranted.

Copyright © 2025 Zhao, Hu, Peng, Wei, Fu, Chen and Chen.

In plain English

This article was a systematic review and meta-analysis. The authors did not test anyone themselves. They pooled results from eight earlier studies, published between 2012 and 2023, on whether chemicals in exhaled breath (volatile organic compounds, or VOCs) could identify malignant pleural mesothelioma. Those studies covered 859 people: 189 with the disease and 670 without, including healthy people and asymptomatic former asbestos workers. Breath was analyzed with several kinds of equipment, including electronic noses. Compared with healthy controls, breath tests had a pooled sensitivity of 86% (95% CI 75 to 93%) and specificity of 73% (95% CI 58 to 84%). Compared with people formerly exposed to asbestos, the figures were 0.89 (95% CI 0.83 to 0.93) and 0.79 (95% CI 0.57 to 0.91). Results varied widely between studies. The authors concluded that breath VOCs may have a potential role in diagnosing the disease. They called for large trials. They noted small samples, five studies from one research team, mostly retrospective and case-control designs, and English-only studies.

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: Systematic review and meta-analysis of diagnostic accuracy studies on exhaled breath volatile organic compounds (VOCs) for malignant pleural mesothelioma (MPM)
• Who was studied: Eight published studies (2012 to 2023; from Australia, Italy and Belgium) with 859 subjects in total: 189 MPM patients and 670 non-MPM controls. The controls included healthy controls, asymptomatic former asbestos workers, patients with benign asbestos-related diseases, patients with benign non-asbestos-related lung diseases, and patients with lung cancer.
• Exposure: The index test was VOCs in exhaled breath, analyzed by multicapillary column/ion mobility spectrometry (MCC/IMS) in four studies, by electronic nose (Cyranose 320) in three studies, and by gas chromatography-mass spectrometry in others. MPM patients were compared with healthy controls and with asymptomatic individuals formerly exposed to asbestos (AEx). No fiber types or doses are reported.
• Main results:
  • MPM patients vs healthy controls (six studies): pooled sensitivity 86% (95% CI 75 to 93%) and pooled specificity 73% (95% CI 58 to 84%)
  • MPM patients vs healthy controls: area under the curve (AUC) 0.88. The confidence interval is printed in the body as 85 to 90%; the article's abstract gives it as 0.85 to 0.90.
  • MPM patients vs healthy controls: both specificity (I2 = 78.50%) and sensitivity (I2 = 66.68%) were heterogeneous across studies
  • MPM patients vs asbestos-exposed subjects (six studies): pooled sensitivity 0.89 (95% CI 0.83 to 0.93), pooled specificity 0.79 (95% CI 0.57 to 0.91), and AUC 0.91 (95% CI 0.88 to 0.93)
  • MPM patients vs asbestos-exposed subjects: specificity was highly heterogeneous (I2 = 95.78%)
  • Subgroup of European studies, MPM patients vs healthy controls: sensitivity 0.85 (95% CI 0.76 to 0.94) and specificity 0.67 (95% CI 0.54 to 0.81)
  • Deeks funnel plots showed no marked publication bias (MPM vs healthy controls, P = 0.33; MPM vs asbestos-exposed subjects, P = 0.98)
• The authors' conclusion: The authors concluded that, although results varied among studies, VOCs in exhaled breath may have a potential role in diagnosing MPM, and that large-scale randomized clinical trials are warranted.
• Limitations the authors state:
  • Limited sample size, which may have reduced statistical power
  • Five of the included studies came from the same research team, possibly introducing selection bias
  • Seven of the eight studies had a case-control design, which may have introduced selection bias; these were rated high risk of bias for patient selection
  • Interfering factors in breath samples (such as diet, medication, exercise and sample collection environment) varied across studies
  • Most included studies were retrospective
  • All included studies were published in English, possibly adding selection bias
  • The publication bias assessment was limited by the small number of studies

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Meta-Analysis, Clinical Trial, confidence interval.

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• Breath Analysis: A Systematic Review of Volatile Organic Compounds (VOCs) in Diagnostic and Therapeutic Management of Pleural Mesothelioma — A. Catino, G. de Gennaro, et al. (2019)
• Headspace Volatile Organic Compound Profiling of Pleural Mesothelioma and Lung Cancer Cell Lines as Translational Bridge for Breath Research — E. Janssens, Z. Mol, et al. (2022)
• Assessing truck driver exposure at the World Trade Center disaster site: personal and area monitoring for particulate matter and volatile organic compounds during October 2001 and April 2002 — A.S. Geyh, S. Chillrud, et al. (2005)
• Volatile organic compound analysis of malignant pleural mesothelioma chorioallantoic membrane xenografts — L.D. Little, S.E. Barnett, et al. (2024)
• Asbestos mineral fibre exposure significantly affects volatile organic compound profiles of mesothelial cell lines in vitro — S. Bonsall, T. Issitt, et al. (2026)

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