Analytical methods based on exhaled breath for early detection of lung cancer

Abstract Lung cancer is among the most common malignancies and among the most difficult to treat, mainly due to the lack of symptoms, which means that the vast majority of tumors to be diagnosed are at an advanced stage. After reviewing the literature on this subject, with special emphasis on both canine smell and the potential of omics biomarkers for detecting lung cancer, we discuss the role of analytical chemists in the new steps to be taken for early detection. We also comment on the steps to be developed (from sampling to full validation of the biomarkers found).

[1]  H. Rammensee,et al.  “Electronic nose” detects major histocompatibility complex-dependent prerenal and postrenal odor components , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[2]  A. Modak Single time point diagnostic breath tests: a review , 2010, Journal of breath research.

[3]  H. Haick,et al.  Diagnosing lung cancer in exhaled breath using gold nanoparticles. , 2009, Nature nanotechnology.

[4]  S. Balseiro,et al.  Is olfactory detection of human cancer by dogs based on major histocompatibility complex-dependent odour components?--A possible cure and a precocious diagnosis of cancer. , 2006, Medical hypotheses.

[5]  M. Carvalho,et al.  Differential proteomic serum pattern of low molecular weight proteins expressed by adenocarcinoma lung cancer patients. , 2005, Journal of experimental therapeutics & oncology.

[6]  T. Byers,et al.  Multi-target interphase fluorescence in situ hybridization assay increases sensitivity of sputum cytology as a predictor of lung cancer. , 2004, Cancer Detection and Prevention.

[7]  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.

[8]  K. Kostikas,et al.  VEGF, TNF-alpha and 8-isoprostane levels in exhaled breath condensate and serum of patients with lung cancer. , 2009, Lung cancer.

[9]  D. Postma,et al.  Pulmonary biomarkers in chronic obstructive pulmonary disease. , 2006, American journal of respiratory and critical care medicine.

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

[11]  E. Patz,et al.  Identification of small lung nodules at autopsy: implications for lung cancer screening and overdiagnosis bias. , 2001, Lung cancer.

[12]  Peter B Bach,et al.  Screening for lung cancer: the guidelines. , 2003, Chest.

[13]  R. Greil,et al.  Biomarkers in non-small cell lung cancer prevention , 2004, European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation.

[14]  D. Carbone,et al.  Proteomics analysis in lung cancer: Challenges and opportunities , 2007, Respirology.

[15]  William L. Bigbee,et al.  Diagnostic Accuracy of MALDI Mass Spectrometric Analysis of Unfractionated Serum in Lung Cancer , 2007, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

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

[17]  J. Aisner CT Screening for Lung Cancer: Are We Ready for Wide-Scale Application? , 2007, Clinical Cancer Research.

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

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

[20]  C. Claussen,et al.  Tumor Detection by Diffusion-Weighted MRI and ADC-Mapping—Initial Clinical Experiences in Comparison to PET-CT , 2007, Investigative radiology.

[21]  H. Pashler,et al.  Puzzlingly High Correlations in fMRI Studies of Emotion, Personality, and Social Cognition 1 , 2009, Perspectives on psychological science : a journal of the Association for Psychological Science.

[22]  J. Mulshine,et al.  Molecular markers in early cancer detection. New screening tools. , 1995, Chest.

[23]  A. Jemal,et al.  Cancer Statistics, 2009 , 2009, CA: a cancer journal for clinicians.

[24]  F. Hirsch,et al.  Using molecular markers in sputum for the early detection of lung cancer: a review. , 2004, Lung cancer.

[25]  H. Frijlink,et al.  Applications of stable isotopes in clinical pharmacology. , 2011, British journal of clinical pharmacology.

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

[27]  A. Paradiso,et al.  3p microsatellite signature in exhaled breath condensate and tumor tissue of patients with lung cancer. , 2008, American journal of respiratory and critical care medicine.

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

[29]  P. Thomas,et al.  Exhaled breath analysis: novel approach for early detection of lung cancer. , 2009, Lung cancer.

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

[31]  A. Paradiso,et al.  3p microsatellite alterations in exhaled breath condensate from patients with non-small cell lung cancer. , 2005, American journal of respiratory and critical care medicine.

[32]  Massimo Corradi,et al.  Lung cancer biomarkers in exhaled breath , 2011, Expert review of molecular diagnostics.

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

[34]  G. Teschl,et al.  Isoprene and acetone concentration profiles during exercise on an ergometer , 2009, Journal of breath research.

[35]  Byung-Tae Kim,et al.  Non-small cell lung cancer: prospective comparison of integrated FDG PET/CT and CT alone for preoperative staging. , 2005, Radiology.

[36]  Terence H Risby,et al.  Effects of ventilation on the collection of exhaled breath in humans. , 2004, Journal of applied physiology.

[37]  W. Miekisch,et al.  Breath biomarkers for lung cancer detection and assessment of smoking related effects--confounding variables, influence of normalization and statistical algorithms. , 2010, Clinica chimica acta; international journal of clinical chemistry.

[38]  G. Teschl,et al.  A modeling-based evaluation of isothermal rebreathing for breath gas analyses of highly soluble volatile organic compounds , 2011, Journal of breath research.

[39]  R. Diasio,et al.  13C-5-FU breath test current status and future directions: a comprehensive review , 2009, Journal of breath research.

[40]  K. Fiedler Voodoo Correlations Are Everywhere—Not Only in Neuroscience , 2011, Perspectives on psychological science : a journal of the Association for Psychological Science.

[41]  Eric Edell,et al.  Detection and Localization of Intraepithelial Neoplasia and Invasive Carcinoma Using Fluorescence-Reflectance Bronchoscopy: An International, Multicenter Clinical Trial , 2009, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[42]  P. Barnes,et al.  Exhaled biomarkers. , 2006, Chest.

[43]  A. Hershey,et al.  Inhalation chemotherapy for macroscopic primary or metastatic lung tumors: proof of principle using dogs with spontaneously occurring tumors as a model. , 1999, Clinical cancer research : an official journal of the American Association for Cancer Research.

[44]  P. J. Barnes,et al.  Exhaled breath condensate: methodological recommendations and unresolved questions , 2005, European Respiratory Journal.

[45]  Antoine Flahault,et al.  Baseline results of the Depiscan study: a French randomized pilot trial of lung cancer screening comparing low dose CT scan (LDCT) and chest X-ray (CXR). , 2007, Lung cancer.

[46]  G. Gioia,et al.  IL-2, TNF-α, and leptin : Local versus systemic concentrations in NSCLC patients , 2006 .

[47]  U. Sack,et al.  Angiogenic markers in breath condensate identify non-small cell lung cancer. , 2010, Lung cancer.

[48]  Vitor Sousa,et al.  Metabolic signatures of lung cancer in biofluids: NMR-based metabonomics of urine. , 2011, Journal of proteome research.

[49]  A. Prasse,et al.  Inflammatory markers in exhaled breath condensate following lung resection for bronchial carcinoma , 2008, Respirology.

[50]  Martin R. Johnson,et al.  Rapid Identification of Dihydropyrimidine Dehydrogenase Deficiency by Using a Novel 2-13C-Uracil Breath Test , 2004, Clinical Cancer Research.

[51]  G. Preti,et al.  Analysis of lung air from patients with bronchogenic carcinoma and controls using gas chromatography-mass spectrometry. , 1988, Journal of chromatography.

[52]  H. Hinterhuber,et al.  Dynamic profiles of volatile organic compounds in exhaled breath as determined by a coupled PTR-MS/GC-MS study , 2010, Physiological measurement.

[53]  A. A. Reilly,et al.  Gene promoter methylation assayed in exhaled breath, with differences in smokers and lung cancer patients , 2009, Respiratory research.

[54]  Robert A. Smith,et al.  American Cancer Society Guidelines for the Early Detection of Cancer, 2003 , 2003, CA: a cancer journal for clinicians.

[55]  A. Dzien,et al.  The analysis of healthy volunteers' exhaled breath by the use of solid-phase microextraction and GC-MS , 2008, Journal of breath research.

[56]  Z. Borrill,et al.  Exhaled breath condensate biomarkers in COPD , 2008, European Respiratory Journal.

[57]  P. Howell Stereological methods vol. 2: Theoretical foundation: By E. R. Weibel Academic Press Inc., London, 1980 340 pages, many figures and tables ISBN 0‐12‐742202‐1 , 1981 .

[58]  Ildikó Horváth,et al.  Differential Cytokine Pattern in the Exhaled Breath of Patients with Lung Cancer , 2008, Pathology & Oncology Research.

[59]  Joachim Schneider,et al.  Oncogene and tumor-suppressor gene products as serum biomarkers in occupational-derived lung cancer , 2007, Expert review of molecular diagnostics.

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

[61]  Tarek Mekhail,et al.  Lung cancer screening , 2007, Current oncology reports.

[62]  Julian King,et al.  Physiological modeling of isoprene dynamics in exhaled breath. , 2010, Journal of theoretical biology.

[63]  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.

[64]  Peter B Bach,et al.  Screening for lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition). , 2007, Chest.

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

[66]  M. Corradi,et al.  Chromium in exhaled breath condensate and pulmonary tissue of non-small cell lung cancer patients , 2008, International archives of occupational and environmental health.

[67]  S. Diederich CT screening for lung cancer , 2008, Cancer imaging : the official publication of the International Cancer Imaging Society.

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

[69]  Julian King,et al.  A mathematical model for breath gas analysis of volatile organic compounds with special emphasis on acetone , 2010, Journal of mathematical biology.

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

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

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