Metabolomics pilot study to identify volatile organic compound markers of childhood asthma in exhaled breath.

BACKGROUND In-community non-invasive identification of asthma-specific volatile organic compounds (VOCs) in exhaled breath presents opportunities to characterize phenotypes, and monitor disease state and therapies. The feasibility of breath sampling with children and the preliminary identification of childhood asthma markers were studied. METHOD End-tidal exhaled breath was sampled (2.5 dm³) from 11 children with asthma and 12 healthy children with an adaptive breath sampler. VOCs were collected onto a Tenax®/Carbotrap hydrophobic adsorbent trap, and analyzed by GC-MS. Classification was by retention-index and mass spectra in a 'breath matrix' followed by multivariate analysis. RESULTS A panel of eight candidate markers (1-(methylsulfanyl)propane, ethylbenzene, 1,4-dichlorobenzene, 4-isopropenyl-1-methylcyclohexene, 2-octenal, octadecyne, 1-isopropyl-3-methylbenzene and 1,7-dimethylnaphtalene) were found to differentiate between the asthmatic and healthy children in the test cohort with complete separation by 2D principal components analysis (2D PCA). Furthermore, the breath sampling protocol was found to be acceptable to children and young people. CONCLUSION This method was found to be acceptable for children, and healthy and asthmatic individuals were distinguished on the basis of eight VOCs at elevated levels in the breath of asthmatic children.

[1]  I. Wilson,et al.  A workflow for the metabolomic/metabonomic investigation of exhaled breath using thermal desorption GC-MS. , 2012, Bioanalysis.

[2]  Graham Bothamley,et al.  Point-of-care breath test for biomarkers of active pulmonary tuberculosis. , 2012, Tuberculosis.

[3]  Ashley Woodcock,et al.  Non-invasive phenotyping using exhaled volatile organic compounds in asthma , 2011, Thorax.

[4]  Q. Jöbsis,et al.  Metabolomics of Volatile Organic Compounds in Cystic Fibrosis Patients and Controls , 2010, Pediatric Research.

[5]  Royston Goodacre,et al.  Non-invasive Metabolomic Analysis of Breath Using Differential Mobility Spectrometry in Patients with Chronic Obstructive Pulmonary Disease and Healthy Smokers , 2022 .

[6]  E. Wouters,et al.  Volatile organic compounds in exhaled breath as a diagnostic tool for asthma in children , 2009, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[7]  H. Pandya,et al.  Towards a metabolomic approach to respiratory disease in childhood: Feasibility and acceptability of a novel breath-sampling procedure and initial breath analysis data , 2009 .

[8]  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.

[9]  F. Guarneri,et al.  Allergic contact dermatitis and asthma caused by limonene in a labourer handling citrus fruits , 2008, Contact dermatitis.

[10]  R. Barton.  Inoperable brain metastases from non-small cell lung cancer: what part does whole brain radiotherapy play in standard treatment? , 2007, Thorax.

[11]  E. Wouters,et al.  Development of accurate classification method based on the analysis of volatile organic compounds from human exhaled air. , 2008, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[12]  D. Blake,et al.  Exhaled methyl nitrate as a noninvasive marker of hyperglycemia in type 1 diabetes , 2007, Proceedings of the National Academy of Sciences.

[13]  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.

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

[15]  C L P Thomas,et al.  An adaptive breath sampler for use with human subjects with an impaired respiratory function. , 2007, The Analyst.

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

[17]  M. Longnecker,et al.  Volatile Organic Compounds and Pulmonary Function in the Third National Health and Nutrition Examination Survey, 1988–1994 , 2006, Environmental health perspectives.

[18]  M. Bulsara,et al.  Association of domestic exposure to volatile organic compounds with asthma in young children , 2004, Thorax.

[19]  R. Delfino,et al.  Respiratory symptoms and peak expiratory flow in children with asthma in relation to volatile organic compounds in exhaled breath and ambient air , 2003, Journal of Exposure Analysis and Environmental Epidemiology.

[20]  P J Lioy,et al.  Ozone and limonene in indoor air: a source of submicron particle exposure. , 2000, Environmental health perspectives.

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

[22]  J. Trottier,et al.  Book Review: Mass Spectrometry: Principles and Applications. E. de Hoffman, J. Charette and W. Stroobant. Wiley, Chichester 1996. ISBN 0 471 96697 5 , 1997 .

[23]  R. Jackson,et al.  Multiple lipid oxidation products in low density lipoproteins induce interleukin-1 beta release from human blood mononuclear cells. , 1994, Journal of lipid research.