Exhaled Breath Analysis in Diagnosis of Malignant Pleural Mesothelioma: Systematic Review

Our plain-English summary of Exhaled Breath Analysis in Diagnosis of Malignant Pleural Mesothelioma: Systematic Review, by Z.N. Töreyin, M. Ghosh, Ö. Göksel, et al (International Journal of Environmental Research and Public Health, 2020).

The study

• Authors: Z.N. Töreyin, M. Ghosh, Ö. Göksel, T. Göksel, L. Godderis
• Journal: International Journal of Environmental Research and Public Health
• Published: 2020;17(3)
• Type of article: Systematic review
• Cited by: 20 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is mainly related to previous asbestos exposure. There is still dearth of information on non-invasive biomarkers to detect MPM at early stages. Human studies on exhaled breath biomarkers of cancer and asbestos-related diseases show encouraging results. The aim of this systematic review was to provide an overview on the current knowledge about exhaled breath analysis in MPM diagnosis. A systematic review was conducted on MEDLINE (PubMed), EMBASE and Web of Science databases to identify relevant studies. Quality assessment was done by the Newcastle-Ottawa Scale. Six studies were identified, all of which showed fair quality and explored volatile organic compounds (VOC) based breath profile using Gas Chromatography Coupled to Mass Spectrometry (GC-MS), Ion Mobility Spectrometry Coupled to Multi-capillary Columns (IMS-MCC) or pattern-recognition technologies. Sample sizes varied between 39 and 330. Some compounds (i.e, cyclohexane, P3, P5, P50, P71, diethyl ether, limonene, nonanal, VOC IK 1287) that can be indicative of MPM development in asbestos exposed population were identified with high diagnostic accuracy rates. E-nose studies reported breathprints being able to distinguish MPM from asbestos exposed individuals with high sensitivity and a negative predictive value. Small sample sizes and methodological diversities among studies limit the translation of results into clinical practice. More prospective studies with standardized methodologies should be conducted on larger populations.

In plain English

This was a systematic review, not a new study of patients. The authors searched three databases for papers from 2000 to September 2019 on breath tests for diagnosing malignant pleural mesothelioma (MPM). Six studies, published 2010 to 2017, met their criteria. Each compared the breath of MPM patients (13 to 52 per study) with groups such as asbestos-exposed people, people with benign asbestos-related disease, and healthy unexposed people. The studies used chemical analysis or 'electronic nose' devices. The authors rated all six as fair quality. Results varied widely. Sensitivity (the share of MPM patients correctly identified) against healthy controls ranged across studies from 0.62 (95% confidence interval 0.32 to 0.86) to 0.96 (95% confidence interval 0.78 to 1.0). Two studies reported that breath cyclohexane could tell MPM patients apart from healthy people. The authors did not pool the results in a meta-analysis because the studies were few and small. They concluded that this research was at an early stage, that small samples and differing methods limited its clinical use, and that larger, standardized prospective studies were 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: Systematic review following PRISMA guidelines. Papers from 2000 to September 2019 were searched in MEDLINE (PubMed), EMBASE and Web of Science. Study quality was rated with the Newcastle–Ottawa Scale. No meta-analysis was done.
• Who was studied: Six cross-sectional case-control studies published between 2010 and 2017. Each included 13 to 52 patients with biopsy-confirmed malignant pleural mesothelioma. Comparison groups were asbestos-exposed workers, people with benign asbestos-related diseases, healthy people never exposed to asbestos, and, in one study, lung cancer and non-asbestos benign lung disease patients.
• Exposure: Past asbestos exposure; no fiber types are named. For the MPM patients, exposure came from self-reports or questionnaires. For the asbestos-exposed control groups, it came mainly from company records. None of the studies used structured exposure assessment or accounted for duration of exposure.
• Main results:
  • All six included studies scored 4 to 6 out of 9 on the quality scale, rated as fair quality.
  • In forest plots of breath-compound (VOC) methods for distinguishing MPM patients from healthy controls, sensitivity ranged across studies from 0.62 (95% CI 0.32 to 0.86) to 0.96 (0.78 to 1.0). Specificity ranged from 0.42 (0.29 to 0.57) to 1.0 (0.74 to 1.0).
  • The authors observed heterogeneity across studies by visually comparing confidence intervals.
  • Two included studies reported that cyclohexane in breath distinguished MPM patients from healthy subjects. In one of them (Gennaro et al.), median cyclohexane was 251.79 ng/L in MPM patients, 69.31 ng/L in long-term asbestos-exposed subjects and 33.08 ng/L in healthy controls.
  • In one electronic-nose study (Dragonieri et al.), MPM patients were distinguished from asbestos-exposed subjects with a cross-validated accuracy of 80.8%, sensitivity of 92.3% and specificity of 85.7%.
  • In another electronic-nose study (Chapman et al.), the device had a sensitivity of 90%, a specificity of 88%, and positive and negative predictive values of 60% and 97.8%. These figures were for identifying breath prints among MPM, asbestos-related diseases and healthy controls.
  • In a validation study (Lamote et al., 2017), MPM was distinguished from a pooled group of asbestos-exposed people and people with benign asbestos-related diseases with a sensitivity of 95% and a negative predictive value of 96%.
  • The search found no studies of exhaled breath condensate in MPM patients.
• The authors' conclusion: The authors concluded that research on breath markers of MPM was at an early phase but encouraging. They said small sample sizes and differing methods limited its translation into clinical practice, and that larger prospective studies with standardized methods and external validation were needed.
• Limitations the authors state:
  • The authors could not conduct a meta-analysis because there were too few studies to address heterogeneity rigorously.
  • All included studies were small, which the authors said may limit internal validity and generalizability.
  • None of the included studies used structured asbestos exposure assessment or accounted for exposure duration.
  • None of the included studies ensured that investigators were blinded.
  • Cases and controls were not matched for age in some studies.
  • Most of the included studies lacked external validation.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Systematic Review, Asbestos Exposure, Biomarker.

Related studies

• Chemical characterization of exhaled breath to differentiate between patients with malignant plueral mesothelioma from subjects with similar professional asbestos exposure — G. de Gennaro, S. Dragonieri, et al. (2010)
• Exhaled breath to screen for malignant pleural mesothelioma: a validation study — K. Lamote, M. Vynck, et al. (2017)
• Detection of malignant pleural mesothelioma in exhaled breath by multicapillary column/ion mobility spectrometry (MCC/IMS) — K. Lamote, M. Vynck, et al. (2016)
• An electronic nose distinguishes exhaled breath of patients with Malignant Pleural Mesothelioma from controls — S. Dragonieri, M.P. van der Schee, et al. (2012)
• Use of exhaled breath condensate to investigate occupational lung diseases — M. Corradi, P. Gergelova, et al. (2010)
• Leukotrienes B4, C4, D4 and E4 in the exhaled breath condensate (EBC), blood and urine in patients with pneumoconiosis — D. Pelclová, Z. Fenclová, et al. (2012)

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