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

Agnieszka Smolinska,Agnieszka Smolinska,Quirijn Jobsis,Kim D G Van De Kant,Edward Dompeling,Frederik J Van Schooten,Jan W Dallinga,Edwin J C Moonen,Onno C P Van Schayck,Ester M M Klaassen,Heinz Fehrenbach

doi:10.1371/journal.pone.0095668

Agnieszka Smolinska, Agnieszka Smolinska + Show 9 more

Open Access

https://doi.org/10.1371/journal.pone.0095668

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Journal: PloS one	Publication Date: Apr 21, 2014
Citations: 160	License type: CC BY 4.0

Affiliation: Maastricht University, TiFN

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.

Highlights

During the few last decades biomarker discovery has become a significant area in biomedical research
The metabolites detected in exhaled breath originate from normal and deviant metabolic processes occurring in the body [4,5]
These processes produce volatile products, Volatile Organic Compounds (VOCs), which are first released into the blood and in the lungs into exhaled breath

Summary

Introduction

During the few last decades biomarker discovery has become a significant area in biomedical research. Breathomics or the analysis of the exhaled breath is used less as a biological medium for metabolomics testing biofluids [2,3]. To other types of biological samples, exhaled breath can be used to define biomarkers (or breath prints) related to abnormal health status in humans. The metabolites detected in exhaled breath originate from normal and deviant (for instance inflammatory) metabolic processes occurring in the body [4,5]. These processes produce volatile products, Volatile Organic Compounds (VOCs), which are first released into the blood and in the lungs into exhaled breath. Several applications of breathomics have been demonstrated for monitoring and diagnosing diseases, such as asthma [7,8], lung cancer [9], chronic obstructive pulmonary disease [10,11,12], cystic fibrosis [13,14], inflammatory bowel disease [15] and non-alcoholic steatohepatitis [16]

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