Breath analysis as a diagnostic and screening tool for malignant pleural mesothelioma: a systematic review

Our plain-English summary of Breath analysis as a diagnostic and screening tool for malignant pleural mesothelioma: a systematic review, by L. Brusselmans, L. Arnouts, C. Millevert, et al (Translational Lung Cancer Research, 2018).

The study

• Authors: L. Brusselmans, L. Arnouts, C. Millevert, J. Vandersnickt, J.P. van Meerbeeck, K. Lamote
• Journal: Translational Lung Cancer Research
• Published: 2018;7(5):520-536
• Type of article: Review
• Cited by: 30 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is a tumour related to a historical exposure to asbestos fibres. Currently, the definite diagnosis is made only by the histological examination of a biopsy obtained through an invasive thoracoscopy. However, diagnosis is made too late for curative treatment because of non-specific symptoms mainly appearing at advanced stage disease. Hence, due to its biologic aggressiveness and the late diagnosis, survival rate is low and the patients' outcome poor. In addition, radiological imaging, like computed tomographic scans, and blood biomarkers are found not to be sensitive enough to be used as an early diagnostic tool. Detection in an early stage is assumed to improve the patients' outcome but is hampered due to non-specific and late symptomology. Hence, there is a need for a new screening and diagnostic test which could improve the patients' outcome. Despite extensive research has focused on blood biomarkers, not a single has been shown clinically useful, and therefore research recently shifted to "breathomics" techniques to recognize specific volatile organic compounds (VOCs) in the breath of the patient as potential non-invasive biomarkers for disease. In this review, we summarize the acquired knowledge about using breath analysis for diagnosing and monitoring MPM and asbestos-related disorders (ARD). Gas chromatography-mass spectrometry (GC-MS), the gold standard of breath analysis, appears to be the method with the highest accuracy (97%) to differentiate MPM patients from at risk asbestos-exposed subjects. There have already been found some interesting biomarkers that are significantly elevated in asbestosis (NO, 8-isoprostane, leukotriene B4, α-Pinene…) and MPM (cyclohexane) patients. Regrettably, the different techniques and the plethora of studies suffer some limitations. Most studies are pilot studies with the inclusion of a limited number of patients. Nevertheless, given the promising results and easy sampling methods, we can conclude that breath analysis may become a useful tool in the future to screen for MPM, but further research is warranted.

In plain English

This was a systematic review of published studies. The authors searched MEDLINE and Web of Science for research on breath tests for malignant pleural mesothelioma (MPM) and benign asbestos-related diseases such as asbestosis, and included 12 primary studies. Because the studies differed, no meta-analysis was run. In the reviewed studies, separating MPM patients from asymptomatic asbestos-exposed people reached 73% to 81% accuracy with electronic noses, 88% with ion mobility spectrometry, and 97% with gas chromatography-mass spectrometry. The 97% figure came from one study. One reviewed study found that cyclohexane set MPM patients apart from former asbestos workers and healthy controls. The authors noted that this compound also reflects other inflammation. Several studies found 8-isoprostane higher in people with asbestosis or asbestos exposure than in healthy controls. The authors said most studies were small pilot studies with likely overoptimistic results, and that none could test whether breath analysis tells asbestos-exposed people apart from patients with early-stage MPM. They concluded that breath analysis may become a useful tool to screen for MPM, but that further research is warranted.

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 primary studies, done following Cochrane Collaboration recommendations for diagnostic research; no meta-analysis
• Who was studied: 12 primary studies (oldest from 2006) found by searching MEDLINE (PubMed) and Web of Science between September 26, 2017 and March 7, 2018. The 204 records found became 150 after duplicates were removed, 23 were read in full, and 12 were included. The studies compared people with MPM or asbestosis (or other benign asbestos-related disease) with healthy controls or with asymptomatic asbestos-exposed subjects. Only pleural mesothelioma was included.
• Exposure: Breath analysis methods (gas chromatography-mass spectrometry, electronic noses, multicapillary column-ion mobility spectrometry, and exhaled breath condensate or exhaled nitric oxide measurement) used in people with MPM, asbestosis or other benign asbestos-related disease, asymptomatic asbestos-exposed subjects, and healthy controls who were never occupationally exposed to asbestos
• Main results:
  • MPM patients versus asymptomatic asbestos-exposed subjects, across the reviewed studies: electronic nose accuracy 73% to 81%, gas chromatography-mass spectrometry 97% (one study, Lamote et al. 2017: 14 MPM, 19 asbestos-exposed), ion mobility spectrometry 88%
  • MPM patients versus subjects with benign asbestos-related disease: accuracy 70% with electronic nose, 82% with ion mobility spectrometry, 79% with gas chromatography-mass spectrometry
  • MPM patients versus pooled asbestos-exposed and asbestos-related disease groups: lowest accuracy with electronic nose (74%), highest with gas chromatography-mass spectrometry (94%), and 85% with ion mobility spectrometry
  • MPM patients versus healthy controls: lowest accuracy 65% with ion mobility spectrometry, highest 95% with an electronic nose. The authors considered this comparison of less clinical importance because healthy people are not the at-risk group for screening.
  • One reviewed study (de Gennaro et al.) found cyclopentane as a marker of long-term asbestos exposure and cyclohexane as the only compound distinguishing MPM patients from former asbestos workers and healthy controls. The authors noted that cyclohexane also appears in pneumonia animal models and in lung cancer patients, so it is not specific for MPM.
  • In breath condensate studies, 8-isoprostane was significantly higher than in healthy controls in patients with asbestosis, asbestos-exposed subjects, and asbestos-exposed subjects with borderline lung tissue changes (P values 0.0001 to 0.0480). The authors noted that such markers reflect chronic inflammation and are not specific for asbestos-related disease or MPM.
  • Because the studies used different instruments, criteria, groups and sample sizes, the authors did not perform a meta-analysis
• The authors' conclusion: The authors concluded that breath analysis may become a useful tool in the future to screen for MPM, but that further research is warranted. They advised blinded, prospective studies that follow asbestos-exposed subjects over time.
• Limitations the authors state:
  • Most reviewed studies were small cross-sectional pilot studies
  • The data were likely overfitted and the results overoptimistic
  • No reviewed study could test whether breath analysis distinguishes asbestos-exposed people from early-stage MPM patients, because such patients are hard to find
  • The studies were not blinded and needed histological confirmation of MPM
  • Most studies did not correct for background (environmental) contamination of breath samples
  • MPM patients were significantly older than healthy controls, making age-matching difficult
  • Breath condensate markers reflect chronic inflammation and are not specific for asbestos-related disease or MPM

Topics

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

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