Chemical characterization of exhaled breath to differentiate between patients with malignant plueral mesothelioma from subjects with similar professional asbestos exposure

Malignant pleural mesothelioma (MPM) is an aggressive tumour whose main aetiology is the long-term exposure to asbestos fibres. The diagnostic procedure of MPM is difficult and often requires invasive approaches; therefore, it is clinically important to find accurate markers for MPM by new noninvasive methods that may facilitate the diagnostic process and identify patients at an earlier stage. In the present study, the exhaled breath of 13 patients with histology-established diagnosis of MPM, 13 subjects with long-term certified professional exposure to asbestos (EXP) and 13 healthy subjects without exposure to asbestos (healthy controls, HC) were analysed. An analytical procedure to determine volatile organic compounds by sampling of air on a bed of solid sorbent and thermal desorption GC-MS analysis was developed in order to identify the compounds capable of discriminating among the three groups. The application of univariate (ANOVA) and multivariate statistical treatments (PCA, DFA and CP-ANN) showed that cyclopentane and cyclohexane were the dominant variables able to discriminate among the three groups. In particular, it was found that cyclohexane is the only compound able to differentiate the MPM group from the other two; therefore, it can be a possible marker of MPM. Cyclopentane is the dominant compound in the discrimination between EXP and the other groups (MPM and HC); then, it can be considered a good indicator for long-term asbestos exposure. This result suggests the need to perform frequent and thorough investigations on people exposed to asbestos in order to constantly monitor their state of health or possibly to study the evolution of disease over time.

[1]  Teuvo Kohonen,et al.  Self-organization and associative memory: 3rd edition , 1989 .

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

[3]  M. Friedrich,et al.  Scientists seek to sniff out diseases: electronic "noses" may someday be diagnostic tools. , 2009, JAMA.

[4]  H. Pass,et al.  Current concepts in malignant pleural mesothelioma , 2008, Expert review of anticancer therapy.

[5]  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.

[6]  B. Robinson,et al.  Advances in malignant mesothelioma. , 2005, The New England journal of medicine.

[7]  J. Zahn,et al.  Bias of Tedlar bags in the measurement of agricultural odorants. , 2006, Journal of environmental quality.

[8]  D. Rice,et al.  Diagnosis, Staging, and Surgical Treatment of Malignant Pleural Mesothelioma , 2008, Current treatment options in oncology.

[9]  Jure Zupan,et al.  Kohonen and counterpropagation artificial neural networks in analytical chemistry , 1997 .

[10]  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.

[11]  L. Greillier,et al.  Mesothelioma and Asbestos-Related Pleural Diseases , 2008, Respiration.

[12]  P. Gross Biologic activity of epsilon-caprolactam. , 1984, Critical reviews in toxicology.

[13]  P. Gross Biologic Activity of ε-Caprolactam , 1984 .

[14]  P. Baas,et al.  Biomarkers for Malignant Pleural Mesothelioma , 2008, Molecular Diagnosis & Therapy.

[15]  P. Španěl,et al.  The challenge of breath analysis for clinical diagnosis and therapeutic monitoring. , 2007, The Analyst.

[16]  Simona M Cristescu,et al.  The suitability of Tedlar bags for breath sampling in medical diagnostic research , 2007, Physiological measurement.

[17]  L. Sobin,et al.  TNM Classification of Malignant Tumours , 1987, UICC International Union Against Cancer.

[18]  Johann Gasteiger,et al.  Neural networks in chemistry and drug design , 1999 .

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

[20]  R. Fall,et al.  Human breath isoprene and its relation to blood cholesterol levels: new measurements and modeling. , 2001, Journal of applied physiology.

[21]  G. Giaccone,et al.  Prognostic factors in patients with pleural mesothelioma: the European Organization for Research and Treatment of Cancer experience. , 1998, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[22]  M. Tutino,et al.  Monitoring of volatile organic compounds in non-residential indoor environments. , 2008, Indoor air.

[23]  G. Rooth,et al.  Acetone in alveolar air, and the control of diabetes. , 1966, Lancet.

[24]  S. Wacholder,et al.  Environment And Genetics in Lung cancer Etiology (EAGLE) study: An integrative population-based case-control study of lung cancer , 2008, BMC public health.

[25]  J D Pleil,et al.  Exhaled human breath measurement method for assessing exposure to halogenated volatile organic compounds. , 1997, Clinical chemistry.

[26]  M. Phillips,et al.  Volatile organic compounds in the breath of patients with schizophrenia. , 1995, Journal of clinical pathology.

[27]  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.

[28]  F. G. Río,et al.  New screening method for lung cancer by detecting volatile organic compounds in breath , 2007, Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico.

[29]  Dall Jl,et al.  MORE ACID/BASE DISTURBANCES. , 1963 .