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.

Altered exhaled biomarker profiles in children during and after rhinovirus-induced wheeze

“…Longitudinal follow-up of the children in the present study, which is currently on-going, is necessary to establish the long-term predictive potential of exhaled markers for the development of asthma, as recently established for GC-MS [37].…”

Asthma Metabolomics and the Potential for Integrative Omics in Research and the Clinic

“…Twenty-one studies using metabolomic profiling of exhaled breathe condensate (EBC) (n ¼ 11), [3][4][5][6][7][8][9][10][11][12][13] urine (n ¼ 4), [14][15][16][17] serum (n ¼ 3), [18][19][20] and plasma (n ¼ 3) [21][22][23] were identified (Table 1). Twelve studies evaluated children, [3][4][5][6][7][8][9][10]14,15,21,22 eight evaluated adults, 12,13,[16][17][18][19][20]23 and one included both. 11 The majority used MS-based methods; six used NMR.…”

“…[10][11][12][13]15,20 All but four 16,17,21,22 were case-control in design, and the total number of people with asthma ranged from 10 16 to 343. 9 The primary aim of most studies was to examine the differences between asthma cases and healthy control patients, with a smaller number of studies examining disease severity or phenotypes. One study of recurrent wheeze was also included.…”

“…In the search for biomarkers several possible validation strategies can be used, including: (1) testing on a separately recruited and ascertained validation cohort; (2) using a hold-out data set; and (3) performing permutation testing by label shuffling. 24,25 Eight 5,7,8,14,15,17,19,21 and four 9,12,13,20 studies used permutation and a hold-out dataset, respectively. Both approaches provided support for accuracy of the reported biomarkers.…”

“…Fifteen of the included studies were targeted or semitargeted in nature: three focused on volatile organic compounds (VOCs) 7,9,13 ; three on a combination of alkanes, alkenes, aldehydes, and ketones 6,16,17 ; one on ; and the rest on a variety of metabolites from specific panels. A targeted approach allows for optimal sensitivity in the measurement of these metabolites because it uses tailored and calibrated methods; however, it lacks the broad range of an untargeted approach and may miss novel but important metabolites without an a priori biological hypothesis.…”