Inflammatory bowel disease and patterns of volatile organic compounds in the exhaled breath of children: A case-control study using Ion Molecule Reaction-Mass Spectrometry

Abstract

Inflammatory bowel diseases (IBD) profoundly affect quality of life and have been gradually increasing in incidence, prevalence and severity in many areas of the world, and in children in particular. Patients with suspected IBD require careful history and clinical examination, while definitive diagnosis relies on endoscopic and histological findings. The aim of the present study was to investigate whether the alveolar air of pediatric patients with IBD presents a specific volatile organic compounds’ (VOCs) pattern when compared to controls. Patients 10–17 years of age, were divided into four groups: Crohn’s disease (CD), ulcerative colitis (UC), controls with gastrointestinal symptomatology, and surgical controls with no evidence of gastrointestinal problems. Alveolar breath was analyzed by ion molecule reaction mass spectrometry. Four models were built starting from 81 molecules plus the age of subjects as independent variables, adopting a penalizing LASSO logistic regression approach: 1) IBDs vs. controls, finally based on 18 VOCs plus age (sensitivity = 95%, specificity = 69%, AUC = 0.925); 2) CD vs. UC, finally based on 13 VOCs plus age (sensitivity = 94%, specificity = 76%, AUC = 0.934); 3) IBDs vs. gastroenterological controls, finally based on 15 VOCs plus age (sensitivity = 94%, specificity = 65%, AUC = 0.918); 4) IBDs vs. controls, built starting from the 21 directly or indirectly calibrated molecules only, and finally based on 12 VOCs plus age (sensitivity = 94%, specificity = 71%, AUC = 0.888). The molecules identified by the models were carefully studied in relation to the concerned outcomes. This study, with the creation of models based on VOCs profiles, precise instrumentation and advanced statistical methods, can contribute to the development of new non–invasive, fast and relatively inexpensive diagnostic tools, with high sensitivity and specificity. It also represents a crucial step towards gaining further insights on the etiology of IBD through the analysis of specific molecules which are the expression of the particular metabolism that characterizes these patients.

Oxidative Stress Markers in Inflammatory Bowel Diseases: Systematic Review

“…Gaseous alkanes, determined in exhaled air, have been elevated in CD as reported by Wendland et al [43]. They were also core components of the diagnostic model devised by Monasta et al [98] (Table 1) for differentiating IBD patients from non-IBD controls and characterized by very high accuracy, as discussed in the section dedicated to the differential markers. Circulating lipoproteins are susceptible to lipid peroxidation as well, especially in conditions associated with the diminished activity of PON1.…”

“…Boehm, et al [45] analyzed arylesterase activity of paraoxonase (PON1) in plasma and found it to better differentiate CD and UC than CRP but the overall accuracy as well as sensitivity of the enzyme were poor despite good specificity (Table 1). Monasta et al [98], in turn, analyzed VOCs in alveolar breath of children with IBD and found the presence of 13 to differ between CD and UC. The model based on those compounds, including reactive nitrogen species, reactive aldehydes, gaseous alkens, and child's age was characterized by remarkably high (93%) accuracy and ability to correctly classify 87% of children (Table 1).…”

“…Of the reviewed papers, an attempt to compare the oxidative stress markers between patients with IBD and other diseases of the gastrointestinal tract that may potentially interfere with proper diagnosis has been undertaken in seven, of which only Monasta et al [98] employed ROC analysis to determine diagnostic accuracy of examined markers. In their study, a panel of 15 VOCs and children's age were capable of correctly classifying 94% of IBD patients with 65% specificity (Table 1).…”

“…As discussed above, both, the limited number of papers and the reported lack of association of markers seemingly promising in adults, clearly support the provocative thesis of Savage et al [9] and Shores et al [127] on children being "biomarker orphans". However, the only two more sophisticated studies which were retrieved using the specified search terms, that is, metaproteomic analysis of aspirates of mucosal-luminal interface by Zhang et al [106] and alveolar breath analysis by Monasta et al [98], were conducted on pediatric populations. While the sample collection in the former one remains invasive, the breath analysis successfully implemented by Monasta et al [98] is addressing the more restrictive requirements for pediatric biomarker for the "non-invasiveness" is a relative term regarding pediatric testing.…”

Applications of Electronic-Nose Technologies for Noninvasive Early Detection of Plant, Animal and Human Diseases

“…Studies involving VOC-profile model development are providing critical information towards better understanding the etiology of IBD through analysis of specific VOCs produced as a result of disease-modifications of host metabolic processes. Analysis of VOC patterns in alveolar air of pediatric patients with IBD was investigated in a recent study of young CD and UC patients compared to controls with and without gastrointestinal symptomatology [196]. Alveolar breath was analyzed by ion molecule reaction mass spectrometry (IMR-MS).…”