Exhaled breath analysis for lung cancer.

Early diagnosis of lung cancer results in improved survival compared to diagnosis with more advanced disease. Early disease is not reliably indicated by symptoms. Because investigations such as bronchoscopy and needle biopsy have associated risks and substantial costs, they are not suitable for population screening. Hence new easily applicable tests, which can be used to screen individuals at risk, are required. Biomarker testing in exhaled breath samples is a simple, relatively inexpensive, non-invasive approach. Exhaled breath contains volatile and non-volatile organic compounds produced as end-products of metabolic processes and the composition of such compounds varies between healthy subjects and subjects with lung cancer. Many studies have analysed the patterns of these compounds in exhaled breath. In addition studies have also reported that the exhaled breath condensate (EBC) can reveal gene mutations or DNA abnormalities in patients with lung cancer. This review has summarised the scientific evidence demonstrating that lung cancer has distinct chemical profiles in exhaled breath and characteristic genetic changes in EBC. It is not yet possible to accurately identify individuals with lung cancer in at risk populations by any of these techniques. However, analysis of both volatile organic compounds in exhaled breath and of EBC have great potential to become clinically useful diagnostic and screening tools for early stage lung cancer detection.

[1]  C. Kneepkens,et al.  The potential of the hydrocarbon breath test as a measure of lipid peroxidation. , 1994, Free radical biology & medicine.

[2]  György Horvath,et al.  Human Ovarian Carcinomas Detected by Specific Odor , 2008, Integrative cancer therapies.

[3]  M. Phillips.  Method for the collection and assay of volatile organic compounds in breath. , 1997, Analytical biochemistry.

[4]  R. Dweik,et al.  Biomarkers in exhaled breath condensate: a review of collection, processing and analysis , 2008, Journal of breath research.

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

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

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

[8]  Ping Wang,et al.  A study of the volatile organic compounds exhaled by lung cancer cells in vitro for breath diagnosis , 2007, Cancer.

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

[10]  HywelC. Williams,et al.  SNIFFER DOGS IN THE MELANOMA CLINIC? , 1989, The Lancet.

[11]  Tarek Mekhail,et al.  Exhaled Breath Analysis with a Colorimetric Sensor Array for the Identification and Characterization of Lung Cancer , 2012, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[12]  Bogusław Buszewski,et al.  Human exhaled air analytics: biomarkers of diseases. , 2007, Biomedical chromatography : BMC.

[13]  A. Jemal,et al.  Global Patterns of Cancer Incidence and Mortality Rates and Trends , 2010, Cancer Epidemiology, Biomarkers & Prevention.

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

[15]  L. Freitag,et al.  Ion mobility spectrometry for the detection of volatile organic compounds in exhaled breath of patients with lung cancer: results of a pilot study , 2009, Thorax.

[16]  Ping Wang,et al.  The analysis of volatile organic compounds biomarkers for lung cancer in exhaled breath, tissues and cell lines. , 2012, Cancer biomarkers : section A of Disease markers.

[17]  HywelC. Williams,et al.  Another sniffer dog for the clinic? , 2001, The Lancet.

[18]  O. Resta,et al.  Endothelin-1 Is Increased in the Breath Condensate of Patients with Non-Small-Cell Lung Cancer , 2004, Oncology.

[19]  A. Jemal,et al.  Global cancer statistics , 2011, CA: a cancer journal for clinicians.

[20]  T. Walles,et al.  Canine scent detection in the diagnosis of lung cancer: revisiting a puzzling phenomenon , 2011, European Respiratory Journal.

[21]  G. E. Carpagnano,et al.  Microsatellite alterations and cell-free DNA analysis: could they increase the cytology sensitivity in the diagnosis of malignant pleural effusion? , 2012, Rejuvenation research.

[22]  C. Willis,et al.  Olfactory detection of human bladder cancer by dogs: proof of principle study , 2004, BMJ : British Medical Journal.

[23]  H. Haick,et al.  Detection of lung, breast, colorectal, and prostate cancers from exhaled breath using a single array of nanosensors , 2010, British Journal of Cancer.

[24]  Dianne B. Walker,et al.  Evidence for canine olfactory detection of melanoma , 2004 .

[25]  C. Mountain,et al.  Revisions in the International System for Staging Lung Cancer. , 1997, Chest.

[26]  M. Gare,et al.  Dilution of respiratory solutes in exhaled condensates. , 2002, American journal of respiratory and critical care medicine.

[27]  James L Mulshine,et al.  Lung cancer screening. , 2005, The oncologist.

[28]  D. Klemp,et al.  Volatile organic compounds in the exhaled breath of young patients with cystic fibrosis , 2006, European Respiratory Journal.

[29]  P. Mazzone,et al.  Analysis of volatile organic compounds in the exhaled breath for the diagnosis of lung cancer. , 2008, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[30]  Giorgio Pennazza,et al.  An investigation on electronic nose diagnosis of lung cancer. , 2010, Lung cancer.

[31]  M. Broffman,et al.  Lung cancer detection by canine scent: will there be a lab in the lab? , 2012, European Respiratory Journal.

[32]  B. Buszewski,et al.  Identification of volatile lung cancer markers by gas chromatography–mass spectrometry: comparison with discrimination by canines , 2012, Analytical and Bioanalytical Chemistry.

[33]  A. Spanevello,et al.  Prognostic value of exhaled microsatellite alterations at 3p in NSCLC patients. , 2009, Lung cancer.

[34]  H. Haick,et al.  Non-invasive Breath Analysis of Pulmonary Nodules , 2012, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

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

[36]  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.

[37]  H. J. O’neill,et al.  Volatile organic compounds in exhaled air from patients with lung cancer. , 1985, Clinical chemistry.

[38]  E. Martinelli,et al.  Lung cancer identification by the analysis of breath by means of an array of non-selective gas sensors. , 2003, Biosensors & bioelectronics.

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

[40]  R. Rosenfeld.  Patients , 2012, Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery.

[41]  Zsofia Lazar,et al.  Electronic Nose Breathprints Are Independent of Acute Changes in Airway Caliber in Asthma , 2010, Sensors.

[42]  A. B. Robinson,et al.  Quantitative analysis of urine vapor and breath by gas-liquid partition chromatography. , 1971, Proceedings of the National Academy of Sciences of the United States of America.

[43]  M. Phillips,et al.  Effect of age on the breath methylated alkane contour, a display of apparent new markers of oxidative stress. , 2000, The Journal of laboratory and clinical medicine.

[44]  Characteristic odour in the blood reveals ovarian carcinoma , 2010, BMC Cancer.

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

[46]  W. Miekisch,et al.  Breath gas aldehydes as biomarkers of lung cancer , 2009, International journal of cancer.

[47]  M. Fiegl,et al.  Noninvasive detection of lung cancer by analysis of exhaled breath , 2009, BMC Cancer.

[48]  L. Bianchi,et al.  Exhaled volatile organic compounds in patients with non-small cell lung cancer: cross sectional and nested short-term follow-up study , 2005, Respiratory research.

[49]  M. Corradi,et al.  Breath analysis in non small cell lung cancer patients after surgical tumour resection. , 2008, Acta bio-medica : Atenei Parmensis.

[50]  M. Kumar,et al.  Olfactory detection of prostate cancer by dogs sniffing urine: A step forward in early diagnosis , 2011 .

[51]  H. Kuhn,et al.  Detection of p53 gene mutations in exhaled breath condensate of non-small cell lung cancer patients. , 2004, Lung cancer.

[52]  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.

[53]  G. E. Carpagnano,et al.  Exhaled matrix metalloproteinase-9 in lung cancer. , 2012, Rejuvenation research.

[54]  M. Phillips,et al.  Variation in volatile organic compounds in the breath of normal humans. , 1999, Journal of chromatography. B, Biomedical sciences and applications.

[55]  Yoshihiro Kakeji,et al.  Colorectal cancer screening with odour material by canine scent detection , 2011, Gut.

[56]  P. J. Callahan,et al.  Volatile organic compounds as breath biomarkers for active and passive smoking. , 2002, Environmental health perspectives.

[57]  Bradford G. Stone,et al.  Effect of regulating cholesterol biosynthesis on breath isoprene excretion in men , 1993, Lipids.

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

[59]  R. Shaker,et al.  The promise and perils of exhaled breath condensates. , 2004, American journal of physiology. Lung cellular and molecular physiology.