Breath Analysis: A Systematic Review of Volatile Organic Compounds (VOCs) in Diagnostic and Therapeutic Management of Pleural Mesothelioma

Our plain-English summary of Breath Analysis: A Systematic Review of Volatile Organic Compounds (VOCs) in Diagnostic and Therapeutic Management of Pleural Mesothelioma, by A. Catino, G. de Gennaro, A. Di Gilio, et al (Cancers, 2019).

The study

• Authors: A. Catino, G. de Gennaro, A. Di Gilio, L. Facchini, D. Galetta, J. Palmisani, F. Porcelli, N. Varesano
• Journal: Cancers
• Published: 2019;11(6)
• Type of article: Review
• Cited by: 29 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is a rare neoplasm related to asbestos exposure and with high mortality rate. The management of patients with MPM is complex and controversial, particularly with regard to early diagnosis. In the last few years, breath analysis has been greatly implemented with this aim. In this review the strengths of breath analysis and preliminary results in searching breath biomarkers of MPM are highlighted and discussed, respectively. Through a systematic electronic literature search, collecting papers published from 2000 until December 2018, fifteen relevant scientific papers were selected. All papers considered were prospective, comparative, observational case-control studies although every single one pilot and based on a relatively small number of samples. The identification of diagnostic VOCs pattern, through breath sample characterization and the statistical data treatment, allows to obtain a strategic information for clinical diagnostics. To date the collected data provide just preliminary information and, despite the promising results and diagnostic accuracy, conclusions cannot be generalized due to the limited number of individuals included in each cohort study. Furthermore none of studies was externally validated, although validation process is a necessary step towards clinical implementation. Breathomics-based biomarker approach should be further explored to confirm and validate preliminary findings and to evaluate its potential role in monitoring the therapeutic response.

In plain English

This article was a systematic review, not a new study. The authors searched medical databases for English-language papers on human subjects published from 2000 to December 2018 on breath analysis in malignant pleural mesothelioma and asbestos-related diseases. They included 15 papers, all small case-control studies.

Among the reviewed studies, a 2017 study by Lamote and colleagues used gas chromatography-mass spectrometry with 14 mesothelioma patients and comparison groups. It reported identifying the mesothelioma patients with 94% accuracy. A 2014 study by the same group used ion mobility spectrometry with 20 patients and reported 85% sensitivity (64 to 96%) and 90% specificity (71 to 98%). That group's larger 2017 validation study included 52 mesothelioma patients. It reported accuracies from 65% (versus healthy controls) to 88% (versus asymptomatic former asbestos-exposed people).

Two reviewed studies of exhaled breath condensate reported higher oxidative stress or inflammation markers in people with asbestosis than in healthy controls.

The authors concluded that breath analysis is promising. They also concluded that the results are preliminary and cannot be generalized because the studies were small, and that none of the studies had been externally validated.

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 of published breath-analysis studies
• Who was studied: 15 published papers, all prospective, comparative, observational case-control studies with small numbers of subjects. They included people with malignant pleural mesothelioma, people with asbestos-related diseases, asbestos-exposed people and healthy controls.
• Exposure: Not a single exposure. The review covered breath tests (volatile organic compounds, exhaled breath condensate markers, exhaled nitric oxide) in mesothelioma, asbestosis and asbestos-exposed groups. No fiber types are analysed.
• Main results:
  • All included studies were prospective, comparative, observational case-control studies with relatively small numbers of samples.
  • Reviewed study by Lamote et al. 2017 (gas chromatography-mass spectrometry; 14 mesothelioma patients, 19 asymptomatic former exposed, 15 benign asbestos-related disease, 14 healthy controls): mesothelioma patients were identified with 94% accuracy, with sensitivity 100%, specificity 91%, positive predictive value 82% and negative predictive value 100%.
  • Reviewed study by de Gennaro et al. 2010 (13 mesothelioma patients, 13 asbestos-exposed subjects, 13 healthy controls): cyclopentane and cyclohexane were the main compounds separating the three groups.
  • Reviewed study by Lamote et al. 2014 (ion mobility spectrometry; 20 mesothelioma patients, 10 asbestos-exposed, 10 healthy controls): 85% sensitivity (64 to 96%) and 90% specificity (71 to 98%).
  • Reviewed validation study by Lamote et al. 2017 (52 mesothelioma, 56 lung cancer, 70 benign non-asbestos lung disease, 41 benign asbestos-related disease, 59 asymptomatic former exposed, 52 healthy controls): mesothelioma was separated from healthy controls, former exposed, benign asbestos-related disease, benign non-asbestos lung disease and lung cancer with 65%, 88%, 82%, 80% and 72% accuracy respectively.
  • Reviewed study by Cakir et al. (25 mesothelioma patients, 12 healthy controls): sensitivity 96%, specificity 50%. The review authors noted that one of the compounds, alpha-pinene, comes from outside the body and could reflect contamination.
  • Reviewed electronic-nose study by Dragonieri et al. (13 mesothelioma, 13 asbestos-exposed, 13 healthy controls): cross-validated accuracy 79.5% and area under the ROC curve 0.885 for the three-way classification.
  • Reviewed study by Chow et al. (18 asbestosis, 26 pleural plaques, 16 diffuse pleural thickening, 26 healthy controls): markers of inflammation and oxidative stress in breath condensate were elevated in asbestosis but not in pleural diseases.
  • Reviewed study by Lehtonen et al. (15 asbestosis patients, 15 healthy controls): LTB4 and 8-isoprostane in breath condensate were higher in the asbestosis patients.
• The authors' conclusion: The authors concluded that breath analysis is a promising technique for early diagnosis of mesothelioma. They also concluded that the available data are only preliminary and cannot be generalized because of the small numbers of subjects.
• Limitations the authors state:
  • None of the reviewed studies externally validated their findings.
  • In the ion mobility studies, uncertain chemical identification of the compounds prevented a full comparison of results.
  • The field lacks standardized analytical methods.

Topics

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

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