Profiling of volatile organic compounds in exhaled breath as a strategy to find early predictive signatures of asthma in children

• Published in: PloS one Vol. 9; no. 4; p. e95668
• Main Authors: Smolinska, Agnieszka, Klaassen, Ester M M, Dallinga, Jan W, van de Kant, Kim D G, Jobsis, Quirijn, Moonen, Edwin J C, van Schayck, Onno C P, Dompeling, Edward, van Schooten, Frederik J
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.04.2014; Public Library of Science (PLoS)
• Subjects: Adults; Allergies; Asthma; Asthma - diagnosis; Asthma - physiopathology; Asthma in children; Biology and Life Sciences; Biomarkers; Breath Tests - methods; Chemical properties; Child; Child, Preschool; Children; Chromatography; Chronic illnesses; Computer and Information Sciences; Data analysis; Diagnostic systems; Discriminant Analysis; Drug therapy; Engineering and Technology; Exhalation; Female; Gas chromatography; Gas Chromatography-Mass Spectrometry; Humans; Identification methods; Least-Squares Analysis; Lipid peroxidation; Lung cancer; Lungs; Male; Mass spectrometry; Mass spectroscopy; Medicine and Health Sciences; Metabolism; Metabolites; Multivariate analysis; Nutrition; Organic compounds; Oxidative stress; Pediatrics; Peroxidation; Physical Sciences; Predictions; Preschool children; Primary care; Principal Component Analysis; Public health; Respiratory Sounds - diagnosis; ROC Curve; Scientific imaging; Toxicology; VOCs; Volatile organic compounds; Volatile Organic Compounds - analysis; Wheezing; Netherlands
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0095668

Wheezing is one of the most common respiratory symptoms in preschool children under six years old. Currently, no tests are available that predict at early stage who will develop asthma and who will be a transient wheezer. Diagnostic tests of asthma are reliable in adults but the same tests are difficult to use in children, because they are invasive and require active cooperation of the patient. A non-invasive alternative is needed for children. Volatile Organic Compounds (VOCs) excreted in breath could yield such non-invasive and patient-friendly diagnostic. The aim of this study was to identify VOCs in the breath of preschool children (inclusion at age 2-4 years) that indicate preclinical asthma. For that purpose we analyzed the total array of exhaled VOCs with Gas Chromatography time of flight Mass Spectrometry of 252 children between 2 and 6 years of age. Breath samples were collected at multiple time points of each child. Each breath-o-gram contained between 300 and 500 VOCs; in total 3256 different compounds were identified across all samples. Using two multivariate methods, Random Forests and dissimilarity Partial Least Squares Discriminant Analysis, we were able to select a set of 17 VOCs which discriminated preschool asthmatic children from transient wheezing children. The correct prediction rate was equal to 80% in an independent test set. These VOCs are related to oxidative stress caused by inflammation in the lungs and consequently lipid peroxidation. In conclusion, we showed that VOCs in the exhaled breath predict the subsequent development of asthma which might guide early treatment.