title: Profiling of volatile organic compounds in exhaled breath as a strategy to find early predictive signatures of asthma in children.
abstract: 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.
authors.affiliation: Department of Toxicology, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, Maastricht, The Netherlands; Top Institute Food and Nutrition, Wageningen, The Netherlands.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Smolinska
authors.affiliation: Department of Pediatric Pulmonology, School for Public Health and Primary Care (CAPHRI), Maastricht University Medical Center (MUMC), Maastricht, The Netherlands.
authors.forename: Ester M M
authors.initials: EM
authors.lastname: Klaassen
authors.affiliation: Department of Toxicology, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, Maastricht, The Netherlands.
authors.forename: Jan W
authors.initials: JW
authors.lastname: Dallinga
authors.affiliation: Department of Pediatric Pulmonology, School for Public Health and Primary Care (CAPHRI), Maastricht University Medical Center (MUMC), Maastricht, The Netherlands.
authors.forename: Kim D G
authors.initials: KD
authors.lastname: van de Kant
authors.affiliation: Department of Pediatric Pulmonology, School for Public Health and Primary Care (CAPHRI), Maastricht University Medical Center (MUMC), Maastricht, The Netherlands.
authors.forename: Quirijn
authors.initials: Q
authors.lastname: Jobsis
authors.affiliation: Department of Toxicology, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, Maastricht, The Netherlands.
authors.forename: Edwin J C
authors.initials: EJ
authors.lastname: Moonen
authors.affiliation: Department of General Practice, School for Public Health and Primary Care (CAPHRI), Maastricht University Medical Center (MUMC), Maastricht, The Netherlands.
authors.forename: Onno C P
authors.initials: OC
authors.lastname: van Schayck
authors.affiliation: Department of Pediatric Pulmonology, School for Public Health and Primary Care (CAPHRI), Maastricht University Medical Center (MUMC), Maastricht, The Netherlands.
authors.forename: Edward
authors.initials: E
authors.lastname: Dompeling
authors.affiliation: Department of Toxicology, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, Maastricht, The Netherlands.
authors.forename: Frederik J
authors.initials: FJ
authors.lastname: van Schooten
mesh_terms: D001249:Asthma / Q000175:diagnosis* / Q000503:physiopathology; D001944:Breath Tests / Q000379:methods*; D002648:Child; D002675:Child, Preschool; D016002:Discriminant Analysis; D045853:Exhalation; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D016018:Least-Squares Analysis; D008297:Male; D025341:Principal Component Analysis; D012372:ROC Curve; D012135:Respiratory Sounds / Q000175:diagnosis; D055549:Volatile Organic Compounds / Q000032:analysis*
chemical_list: D055549:Volatile Organic Compounds
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