A breath test for malignant mesothelioma using an electronic nose

Our plain-English summary of A breath test for malignant mesothelioma using an electronic nose, by E.A. Chapman, P.S. Thomas, E. Stone, et al (The European Respiratory Journal, 2012).

The study

• Authors: E.A. Chapman, P.S. Thomas, E. Stone, C. Lewis, D.H. Yates
• Journal: The European Respiratory Journal
• Published: 2012;40(2):448-54
• Cited by: 82 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant mesothelioma (MM) is a rare tumour which is difficult to diagnose in its early stages. Earlier detection of MM could potentially improve survival. Exhaled breath sampling of volatile organic compounds (VOCs) using a carbon polymer array (CPA) electronic nose recognises specific breath profiles characteristic of different diseases, and can distinguish between patients with lung cancer and controls. With MM, the potential confounding effect of other asbestos-related diseases (ARDs) needs to be considered. We hypothesised that as CPA electronic nose would distinguish patients with MM, patients with benign ARDs, and controls with high sensitivity and specificity. 20 MM, 18 ARD and 42 control subjects participated in a cross-sectional, case-control study. Breath samples were analysed using the Cyranose 320 (Smiths Detection, Pasadena, CA, USA), using canonical discriminant analysis and principal component reduction. 10 MM subjects created the training set. Smell prints from 10 new MM patients were distinguished from control subjects with an accuracy of 95%. Patients with MM, ARDs and control subjects were correctly identified in 88% of cases. Exhaled breath VOC profiling can accurately distinguish between patients with MM, ARDs and controls using a CPA electronic nose. This could eventually translate into a screening tool for high-risk populations.

In plain English

This Australian study tested whether a handheld 'electronic nose' (the Cyranose 320), which reads chemical patterns in exhaled breath, could tell malignant mesothelioma apart from benign asbestos-related disease and from health. It was a small cross-sectional case-control study of 80 people recruited from two Sydney hospital clinics and the community: 20 with mesothelioma, 18 with benign asbestos-related disease (5 asbestosis, 13 pleural disease) and 42 controls. The device was trained on 10 mesothelioma patients and 10 controls. It then correctly classified 9 of 10 further mesothelioma patients and 29 of 32 controls. Of the 18 patients with benign disease, 15 were classed as healthy: 12 of 13 with pleural disease but only 3 of 5 with asbestosis. Across all groups the authors reported 90% sensitivity, 88% specificity and a positive predictive value of 60%. The authors called this an early pilot. They noted the small numbers and that their mesothelioma patients had advanced disease. They also noted that accuracy usually falls when such tests move to prospective screening.

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: Cross-sectional case-control study in two phases: a training phase and a blinded identification (validation) phase
• Who was studied: 80 subjects in Sydney, Australia: 20 with histologically diagnosed malignant mesothelioma (19 at IMIG stage 2, 1 at stage 1b), 18 with benign asbestos-related disease (5 asbestosis, 13 pleural disease including pleural plaques and diffuse pleural thickening), and 42 healthy controls. Controls were matched for age, sex and smoking status. All subjects were never-smokers or ex-smokers. Patients came from outpatient clinics at St Vincent's Hospital and the Prince of Wales Hospital, and controls were community volunteers. Study dates are not given.
• Exposure: The study measured volatile organic compounds in exhaled breath with a 32-sensor carbon polymer array electronic nose (Cyranose 320). All mesothelioma patients had previous asbestos exposure, and benign disease required an occupational history of asbestos exposure. Controls reported no asbestos exposure. No fiber types or doses are given.
• Main results:
  • In the training phase (10 mesothelioma patients and 10 controls), canonical discriminant analysis gave a cross-validated accuracy of 95%. The Mahalanobis distance between the two groups was 4.59.
  • In validation, 38 of 42 subjects were correctly identified: 9 of 10 mesothelioma patients and 29 of 32 controls (sensitivity 90%, specificity 91%). The incorrectly classified samples were correctly identified when re-measured within 2 hours.
  • Among the 18 patients with benign asbestos-related disease, 15 were correctly identified as healthy (specificity 83.3%).
  • In the pleural disease subgroup, 12 of 13 patients were correctly identified as healthy (92% specificity). In the asbestosis subgroup, 3 of 5 were correctly identified (60% specificity).
  • Across mesothelioma, benign asbestos-related disease and control subjects, the device had sensitivity of 90% and specificity of 88%. Positive predictive value was 60% and negative predictive value was 97.8%, compared with histologically proven mesothelioma.
  • In reproducibility testing (2 mesothelioma patients and 3 controls, each tested three times), subjects were assigned to the correct class in 13 of 15 trials (86%).
• The authors' conclusion: The authors concluded that their early pilot study showed mesothelioma could be distinguished from normal controls and from subjects with benign asbestos-related disease with promising accuracy. They said the data require further evaluation in larger studies.
• Limitations the authors state:
  • The number of mesothelioma cases was small, because the device allows only 10 subjects per class in training and validation.
  • The mesothelioma patients had advanced disease, so the results might be less accurate for early-stage mesothelioma.
  • No VOC filter was used, so background environmental contamination was possible.
  • The possible confounding effect of smoking was not formally assessed.
  • The device does not identify which specific chemicals cause the differences in breath patterns.
  • This was a case-control study, and diagnostic accuracy usually falls when such studies move to prospective screening.

Topics

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

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Lung Cancer, Confounding, Case-Control Study.

Related studies

• An electronic nose distinguishes exhaled breath of patients with Malignant Pleural Mesothelioma from controls — S. Dragonieri, M.P. van der Schee, et al. (2012)
• 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)
• Use of exhaled breath condensate to investigate occupational lung diseases — M. Corradi, P. Gergelova, et al. (2010)
• Exhaled breath to screen for malignant pleural mesothelioma: a validation study — K. Lamote, M. Vynck, et al. (2017)
• Electronic Nose Technology in Respiratory Diseases — S. Dragonieri, G. Pennazza, et al. (2017)
• Breath analysis by gas chromatography-mass spectrometry and electronic nose to screen for pleural mesothelioma: a cross-sectional case-control study — K. Lamote, P. Brinkman, et al. (2017)

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