Sniffing Out Paediatric Gastrointestinal Diseases: The Potential of Volatile Organic Compounds as Biomarkers for Disease.

The diagnostic work-up and follow-up of paediatric functional gastrointestinal disorders and organic conditions usually includes invasive tests, carrying a high burden on patients. There is a place, therefore, for novel, noninvasive disease-specific biomarkers. Volatile organic compounds (VOCs), originating from (patho)physiological metabolic processes in the human body, are excreted as waste products through all conceivable bodily excrements. The spectrum of VOCs harbours a magnificent source of information, with the potential to serve as noninvasive diagnostic biomarkers and to monitor disease activity. VOC analysis has been studied in children and infants with a variety of gastrointestinal diseases, including inflammatory bowel disease, liver diseases, irritable bowel syndrome, necrotizing enterocolitis and infectious diarrhoea. Most of these studies, although limited in sample size, show that patients can be discriminated from controls based on their VOC profiles, underscoring the potential of VOC analysis in diagnosis and follow-up. Currently, however, the application of VOC analysis in clinical practice is limited; substantial challenges, including methodological, biological, and analytical problems, still need to be met. In this review we provide an overview of the available literature on the potential of VOCs as biomarkers for paediatric gastrointestinal diseases. We discuss the available techniques to analyse VOCs and provide topics for VOC-related research, which need to be addressed before VOC diagnostics can be implemented in daily clinical practice.

Early Detection of Necrotizing Enterocolitis by Fecal Volatile Organic Compounds Analysis.

OBJECTIVES: To test the hypothesis that fecal volatile organic compounds (VOCs) analysis by electronic nose (eNose) allows for early detection of necrotizing enterocolitis (NEC). STUDY DESIGN: In 3 neonatal intensive care units, fecal samples of infants born at gestational age ≤ 30 weeks were collected daily, up to the 28th day of life. Included infants were allocated in 3 subgroups: NEC, sepsis, and matched controls. Three time windows were defined: (1) T-5,-4 (5 and 4 days before diagnosis); (2) T-3,-2 (3 and 2 days before diagnosis); and (3) T-1,0 (day before and day of diagnosis). Three subgroups were analyzed by eNose. RESULTS: Fecal VOC profiles of infants with NEC (n = 13) could significantly be discriminated from matched controls (n = 14) at T-3,-2 (area under the curve ± 95% CI, P value, sensitivity, specificity: 0.77 ± 0.21, P = .02, 83%, 75%); the accuracy increased at T-1,0 (0.99 ± 0.04, P ≤ .001, 89%, 89%). VOC profiles of infants with NEC were also significantly different from those with sepsis (n = 31) at T-3,-2 (0.80 ± 0.17, P = .004, 83%, 75%), but not at T-1,0 (0.64 ± 0.18, P = .216, 89%, 57%). CONCLUSIONS: In this proof of principle study, we observed that fecal VOC profiles of infants with NEC could be discriminated from controls, from 2-3 days predating onset of clinical symptoms. Our observations suggest that VOC-profiling by eNose has potential as a noninvasive tool for the early prediction of NEC.

An electronic nose in the discrimination of patients with non-small cell lung cancer and COPD.

BACKGROUND: Exhaled breath contains thousands of gaseous volatile organic compounds (VOCs) that may be used as non-invasive markers of lung disease. The electronic nose analyzes VOCs by composite nano-sensor arrays with learning algorithms. It has been shown that an electronic nose can distinguish the VOCs pattern in exhaled breath of lung cancer patients from healthy controls. We hypothesized that an electronic nose can discriminate patients with lung cancer from COPD patients and healthy controls by analyzing the VOC-profile in exhaled breath. METHODS: 30 subjects participated in a cross-sectional study: 10 patients with non-small cell lung cancer (NSCLC, [age 66.4+/-9.0, FEV(1) 86.3+/-20.7]), 10 patients with COPD (age 61.4+/-5.5, FEV(1) 70.0+/-14.8) and 10 healthy controls (age 58.3+/-8.1, FEV(1) 108.9+/-14.6). After 5 min tidal breathing through a non-rebreathing valve with inspiratory VOC-filter, subjects performed a single vital capacity maneuver to collect dried exhaled air into a Tedlar bag. The bag was connected to the electronic nose (Cyranose 320) within 10 min, with VOC-filtered room air as baseline. The smellprints were analyzed by onboard statistical software. RESULTS: Smellprints from NSCLC patients clustered distinctly from those of COPD subjects (cross validation value [CVV]: 85%; M-distance: 3.73). NSCLC patients could also be discriminated from healthy controls in duplicate measurements (CVV: 90% and 80%, respectively; M-distance: 2.96 and 2.26). CONCLUSION: VOC-patterns of exhaled breath discriminates patients with lung cancer from COPD patients as well as healthy controls. The electronic nose may qualify as a non-invasive diagnostic tool for lung cancer in the future.