A breath test for malignant mesothelioma using an electronic nose

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.

[1]  Olaf Tietje,et al.  Prediction of lung cancer using volatile biomarkers in breath , 2005 .

[2]  Heng Tao Shen,et al.  Principal Component Analysis , 2009, Encyclopedia of Biometrics.

[3]  S. Skates,et al.  Comparison of Osteopontin, Megakaryocyte Potentiating Factor, and Mesothelin Proteins as Markers in the Serum of Patients with Malignant Mesothelioma , 2008, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[4]  A. Savitzky,et al.  Smoothing and Differentiation of Data by Simplified Least Squares Procedures. , 1964 .

[5]  P. Sterk,et al.  An electronic nose distinguishes exhaled breath of patients with Malignant Pleural Mesothelioma from controls. , 2012, Lung cancer.

[6]  H. Pass,et al.  Current status of screening for malignant pleural mesothelioma. , 2009, Seminars in thoracic and cardiovascular surgery.

[7]  S. Weitzman,et al.  The molecular basis of asbestos induced lung injury , 1999, Thorax.

[8]  M. Phillips,et al.  Metabolic and environmental origins of volatile organic compounds in breath. , 1994, Journal of clinical pathology.

[9]  Kevin Gleeson,et al.  Detection of lung cancer with volatile markers in the breath. , 2003, Chest.

[10]  L. Trizio,et al.  Chemical characterization of exhaled breath to differentiate between patients with malignant plueral mesothelioma from subjects with similar professional asbestos exposure , 2010, Analytical and bioanalytical chemistry.

[11]  M. Copin,et al.  Soluble mesothelin-related peptides in the diagnosis of malignant pleural mesothelioma. , 2006, American journal of respiratory and critical care medicine.

[12]  Onofrio Resta,et al.  An electronic nose in the discrimination of patients with non-small cell lung cancer and COPD. , 2009, Lung cancer.

[13]  H. Pass,et al.  Soluble mesothelin-related peptide level elevation in mesothelioma serum and pleural effusions. , 2008, The Annals of thoracic surgery.

[14]  S. Anderson,et al.  Airway responsiveness : standardized challenge testing with pharmacological, physical and sensitizing stimuli in adults , 1993 .

[15]  D. Yates,et al.  Incidence trends and gender differences in malignant mesothelioma in New South Wales, Australia. , 2007, Scandinavian journal of work, environment & health.

[16]  Eun‐Kee Park,et al.  Asbestos-related occupational lung diseases in NSW, Australia and potential exposure of the general population. , 2008, Industrial health.

[17]  Anton Amann,et al.  Lung cancer detection by proton transfer reaction mass-spectrometric analysis of human breath gas , 2007 .

[18]  M. Mcculloch,et al.  Diagnostic Accuracy of Canine Scent Detection in Early- and Late-Stage Lung and Breast Cancers , 2006, Integrative cancer therapies.

[19]  D. Yates,et al.  An electronic nose in the discrimination of breath from smokers and non-smokers: a model for toxin exposure , 2009, Journal of breath research.

[20]  Tarek Mekhail,et al.  Diagnosis of lung cancer by the analysis of exhaled breath with a colorimetric sensor array , 2007, Thorax.

[21]  Deborah H Yates,et al.  Exhaled breath condensate biomarkers in asbestos-related lung disorders. , 2009, Respiratory medicine.

[22]  J. Hankinson,et al.  Standardisation of spirometry , 2005, European Respiratory Journal.

[23]  J. Leigh,et al.  After Helsinki: a multidisciplinary review of the relationship between asbestos exposure and lung cancer, with emphasis on studies published during 1997-2004. , 2004, Pathology.

[24]  M. Robinson,et al.  Statement on malignant mesothelioma in the UK , 2002, Thorax.

[25]  I. Horváth,et al.  Exhaled biomarkers in lung cancer , 2009, European Respiratory Journal.

[26]  Peter J Sterk,et al.  An electronic nose in the discrimination of patients with asthma and controls. , 2007, The Journal of allergy and clinical immunology.

[27]  L. Garneau The diagnosis of nonmalignant diseases related to asbestos , 1986 .

[28]  D. Yates,et al.  Breath analysis in asbestos-related disorders: a review of the literature and potential future applications , 2010, Journal of breath research.

[29]  Niki Fens,et al.  Exhaled breath profiling enables discrimination of chronic obstructive pulmonary disease and asthma. , 2009, American journal of respiratory and critical care medicine.

[30]  R. Welsh,et al.  Age, tumor size, type of surgery, and gender predict survival in early stage (stage I and II) non-small cell lung cancer after surgical resection. , 2010, Lung cancer.

[31]  P. Mazzone,et al.  Detection of lung cancer by sensor array analyses of exhaled breath. , 2005, American journal of respiratory and critical care medicine.

[32]  J. Austin,et al.  Detection of lung cancer using weighted digital analysis of breath biomarkers. , 2008, Clinica chimica acta; international journal of clinical chemistry.

[33]  R. Cataneo,et al.  Volatile organic compounds in breath as markers of lung cancer: a cross-sectional study , 1999, The Lancet.

[34]  J. Roca,et al.  Standardization of the measurement of transfer factor (diffusing capacity). Report Working Party Standardization of Lung Function Tests, European Community for Steel and Coal. Official Statement of the European Respiratory Society. , 1993, The European respiratory journal. Supplement.

[35]  J. Austin,et al.  Prediction of lung cancer using volatile biomarkers in breath. , 2007, Cancer biomarkers : section A of Disease markers.

[36]  Eun‐Kee Park,et al.  Soluble mesothelin-related protein in an asbestos-exposed population: the dust diseases board cohort study. , 2008, American journal of respiratory and critical care medicine.

[37]  A. Musk,et al.  Soluble mesothelin-related protein--a blood test for mesothelioma. , 2005, Lung cancer.

[38]  A. Tossavainen Asbestos , asbestosis , and cancer : the Helsinki criteria for diagnosis and altribu tion , 2022 .

[39]  Linda Humphrey,et al.  Lung Cancer Screening with Sputum Cytologic Examination, Chest Radiography, and Computed Tomography: An Update for the U.S. Preventive Services Task Force , 2004, Annals of Internal Medicine.

[40]  D. Yates,et al.  Projected mesothelioma incidence in men in New South Wales , 2007, Occupational and Environmental Medicine.

[41]  Philipp Lirk,et al.  Mass spectrometric profile of exhaled breath—field study by PTR-MS , 2005, Respiratory Physiology & Neurobiology.

[42]  J. Roca,et al.  Standardization of the measurement of transfer factor (diffusing capacity) , 1993, European Respiratory Journal.