Exhaled breath to screen for malignant pleural mesothelioma: a validation study

Our plain-English summary of Exhaled breath to screen for malignant pleural mesothelioma: a validation study, by K. Lamote, M. Vynck, O. Thas, et al (The European Respiratory Journal, 2017).

The study

• Authors: K. Lamote, M. Vynck, O. Thas, J. Van Cleemput, K. Nackaerts, J.P. van Meerbeeck
• Journal: The European Respiratory Journal
• Published: 2017;50(6)
• Cited by: 34 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant pleural mesothelioma (MPM) is predominantly caused by asbestos exposure and has a poor prognosis. Breath contains volatile organic compounds (VOCs) and can be explored as an early detection tool. Previously, we used multicapillary column/ion mobility spectrometry (MCC/IMS) to discriminate between patients with MPM and asymptomatic high-risk persons with a high rate of accuracy. Here, we aim to validate these findings in different control groups.Breath and background samples were obtained from 52 patients with MPM, 52 healthy controls without asbestos exposure (HC), 59 asymptomatic former asbestos workers (AEx), 41 patients with benign asbestos-related diseases (ARD), 70 patients with benign non-asbestos-related lung diseases (BLD) and 56 patients with lung cancer (LC).After background correction, logistic lasso regression and receiver operating characteristic (ROC) analysis, the MPM group was discriminated from the HC, AEx, ARD, BLD and LC groups with 65%, 88%, 82%, 80% and 72% accuracy, respectively. Combining AEx and ARD patients resulted in 94% sensitivity and 96% negative predictive value (NPV). The most important VOCs selected were P1, P3, P7, P9, P21 and P26.We discriminated MPM patients from at-risk subjects with great accuracy. The high sensitivity and NPV allow breath analysis to be used as a screening tool for ruling out MPM.

Copyright ©ERS 2017.

In plain English

This Belgian multicentre case-control study tested whether a breath analyser could distinguish people with malignant pleural mesothelioma from other groups. Breath came from 330 people: 52 with mesothelioma, 52 unexposed healthy controls, 59 symptom-free former asbestos workers, 41 with benign asbestos-related diseases, 70 with benign lung diseases unrelated to asbestos, and 56 with lung cancer. Accuracy in distinguishing mesothelioma patients, with 95% confidence intervals, was 88.3% (81.3 to 93.3) against former asbestos workers, 81.7% (72.9 to 88.6) against benign asbestos-related disease, 80.3% (72.6 to 86.7) against benign lung disease, 72.2% (63.3 to 80.0) against lung cancer and 65.4% (55.9 to 74.0) against healthy controls. Against all 100 asbestos-exposed people pooled, sensitivity was 94.2% (85.1 to 98.5) and negative predictive value 96.4% (90.5 to 99.1). The test could not separate the two asbestos-exposed groups. The breath compounds used were not chemically identified. The authors concluded the test could serve as a step-up screening tool in asbestos-exposed people. They noted the groups were not matched for age, gender or smoking, and called for blinded prospective validation.

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: Multicentre, cross-sectional, case-control study of exhaled breath analysis using multicapillary column/ion mobility spectrometry (MCC/IMS), with lasso logistic regression and ROC analysis
• Who was studied: 330 participants were recruited from hospitals in Ghent, Leuven, Antwerp and Aalst (Belgium) and from a company occupational health service. They were 52 healthy controls without asbestos exposure, 59 asymptomatic former asbestos-exposed persons, 41 patients with benign asbestos-related diseases, 70 with benign non-asbestos-related lung diseases, 56 with primary lung cancer and 52 with malignant pleural mesothelioma. Breath samples were taken from January 2012 to December 2014.
• Exposure: The study measured volatile organic compounds in exhaled breath. Asbestos exposure defined some of the groups: former asbestos-exposed persons and some patients with benign asbestos-related diseases were recruited via the occupational health service of a company that used asbestos until 1997. Exposure history came from questionnaires. No fiber types or doses are given.
• Main results:
  • Mesothelioma patients compared with healthy controls (52 versus 52): accuracy 65.4% (95% CI 55.9 to 74.0), sensitivity 88.5% (77.6 to 95.2), specificity 42.3% (29.5 to 56.0) and NPV 78.7% (60.7 to 90.8).
  • Mesothelioma patients compared with asymptomatic former asbestos-exposed persons (52 versus 59): accuracy 88.3% (95% CI 81.3 to 93.3), sensitivity 86.5% (75.2 to 93.9), specificity 89.8% (80.1 to 95.8), PPV 88.2% (77.2 to 95.1) and NPV 88.3% (78.3 to 94.7). The area under the ROC curve was 0.879 (0.799 to 0.948).
  • Mesothelioma patients compared with patients with benign asbestos-related diseases (52 versus 41): accuracy 81.7% (95% CI 72.9 to 88.6), sensitivity 88.5% (77.6 to 95.2), specificity 73.2% (58.2 to 85.0), PPV 80.7% (69.0 to 89.4) and NPV 83.3% (68.6 to 92.9). The area under the ROC curve was 0.850 (0.764 to 0.927).
  • Mesothelioma patients (52) compared with the combined asbestos-exposed and benign asbestos-related disease groups (100): accuracy 84.9% (95% CI 78.5 to 89.9), sensitivity 94.2% (85.1 to 98.5), specificity 80.0% (71.3 to 87.0), PPV 71.0% (59.6 to 80.8) and NPV 96.4% (90.5 to 99.1). The area under the ROC curve was 0.890 (0.832 to 0.942).
  • Mesothelioma patients compared with patients with benign non-asbestos-related lung diseases (52 versus 70): accuracy 80.3% (95% CI 72.6 to 86.7).
  • Mesothelioma patients compared with lung cancer patients (52 versus 56): accuracy 72.2% (95% CI 63.3 to 80.0), sensitivity 73.1% (59.9 to 83.8), specificity 71.4% (58.7 to 82.1), PPV 70.4% (57.3 to 81.4) and NPV 74.1% (61.2 to 84.4). The area under the ROC curve was 0.770 (0.678 to 0.855).
  • The asymptomatic asbestos-exposed group could not be distinguished from the benign asbestos-related disease group. Accuracy was 55.0% (95% CI 45.2 to 64.5) and the area under the ROC curve was 0.522.
  • The breath compounds labelled P1, P3, P7, P9, P21 and P26 were the most important for separating mesothelioma from the at-risk and benign lung disease groups. These compounds have not been chemically identified.
• The authors' conclusion: The authors concluded that, given the high sensitivity and NPV, breath analysis could be used as a step-up tool in mesothelioma screening. Under this approach, only asbestos-exposed people with an abnormal breath signature would be investigated further. They stated that validation in an independent, blinded prospective study is needed.
• Limitations the authors state:
  • The study was not randomised, and the groups were not matched for age, gender or smoking status.
  • Patients with secondary malignant pleural effusions were not included.
  • Compounds from the environment may have affected the breath samples despite correction using background samples.
  • The selected breath compounds have not been chemically identified.
  • External validation is still needed, in independent prospective cohorts with blinded investigators and follow-up of at-risk people.

Topics

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

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Asbestos Exposure, Prognosis, Lung Cancer.

Related studies

• Detection of malignant pleural mesothelioma in exhaled breath by multicapillary column/ion mobility spectrometry (MCC/IMS) — K. Lamote, M. Vynck, et al. (2016)
• 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 Analysis in Diagnosis of Malignant Pleural Mesothelioma: Systematic Review — Z.N. Töreyin, M. Ghosh, et al. (2020)
• An electronic nose distinguishes exhaled breath of patients with Malignant Pleural Mesothelioma from controls — S. Dragonieri, M.P. van der Schee, et al. (2012)
• A breath test for malignant mesothelioma using an electronic nose — E.A. Chapman, P.S. Thomas, et al. (2012)
• Use of exhaled breath condensate to investigate occupational lung diseases — M. Corradi, P. Gergelova, et al. (2010)

Browse more research in The European Respiratory Journal, or return to medical research.