Early detection and follow‐up of colorectal neoplasia based on faecal volatile organic compounds

Aim: Early detection and removal of colorectal cancer (CRC) and advanced adenomas (AAs) decreases the incidence of and mortality from the disease. We aimed to evaluate the potential of faecal volatile organic compounds (VOCs) for detection and follow‐up of colorectal adenoma using advanced electronic nose technology. Method: This was a prospective multi‐centre case–control cohort including two district hospitals and one tertiary referral hospital. Patients undergoing colonoscopy were instructed to collect a faecal sample prior to bowel cleansing and were included in the study when CRC, AAs, large adenomas (LAs; 0.5–1.0 cm), small adenomas (SAs; 0.1–0.5 cm) or no endoscopic abnormalities (controls) were observed. Patients undergoing polypectomy and controls were asked for a second sample after 3 months. Faecal VOCs were measured with gas chromatography–ion mobility spectrometry. Random forest, support vector machine, Gaussian process and neural net classification were used to evaluate accuracy. Results: In total, 14 patients with CRC, 64 with AAs, 69 with LAs, 127 with SAs and 227 controls were included. A second sample was collected from 32 polypectomy patients and 32 controls. Faecal VOCs discriminated CRC and adenomas from control [AUC (95% CI): CRC vs control 0.96 (0.89–1); AA vs control 0.96 (0.93–1); LA vs control 0.96 (0.92–0.99); SA vs control 0.96 (0.94–0.99)]. There were no significant differences between CRC and adenoma groups. Patients with adenomas and controls were discriminated prior to polypectomy, whereas 3 months after polypectomy VOC profiles were similar [T0 adenoma vs control 0.98 (0.95–1); T1 adenoma vs control 0.55 (0.40–0.69)]. Conclusions: Faecal VOC profiles may be useful for early detection of CRC and adenomas and the timing of polyp surveillance as polypectomy led to a normalization of the VOC profile

Urinary Volatile Organic Compound Testing in Fast-Track Patients with Suspected Colorectal Cancer

Colorectal symptoms are common but only infrequently represent serious pathology, including colorectal cancer (CRC). A large number of invasive tests are presently performed for reassurance. We investigated the feasibility of urinary volatile organic compound (VOC) testing as a potential triage tool in patients fast-tracked for assessment for possible CRC. A prospective, multicenter, observational feasibility study was performed across three sites. Patients referred to NHS fast-track pathways for potential CRC provided a urine sample that underwent Gas Chromatography-Mass Spectrometry (GC-MS), Field Asymmetric Ion Mobility Spectrometry (FAIMS), and Selected Ion Flow Tube Mass Spectrometry (SIFT-MS) analysis. Patients underwent colonoscopy and/or CT colonography and were grouped as either CRC, adenomatous polyp(s), or controls to explore the diagnostic accuracy of VOC output data supported by an artificial neural network (ANN) model. 558 patients participated with 23 (4%) CRC diagnosed. 59% of colonoscopies and 86% of CT colonographies showed no abnormalities. Urinary VOC testing was feasible, acceptable to patients, and applicable within the clinical fast track pathway. GC-MS showed the highest clinical utility for CRC and polyp detection vs. controls (sensitivity = 0.878, specificity = 0.882, AUROC = 0.896) but it is labour intensive. Urinary VOC testing and analysis are feasible within NHS fast-track CRC pathways. Clinically meaningful differences between patients with cancer, polyps, or no pathology were identified suggesting VOC analysis may have future utility as a triage tool

Detection of spontaneous preterm birth by maternal urinary volatile organic compound analysis : a prospective cohort study

Accurate prediction of preterm birth is currently challenging, resulting in unnecessary maternal hospital admittance and fetal overexposure to antenatal corticosteroids. Novel biomarkers like volatile organic compounds (VOCs) hold potential for predictive, bed-side clinical applicability. In a proof of principle study, we aimed to assess the predictive potential of urinary volatile organic compounds in the identification of pregnant women at risk for preterm birth. Urine samples of women with a high risk for preterm birth (≧24 + 0 until 36 + 6 weeks) were collected prospectively and analyzed for VOCs using gas chromatography coupled with an ion mobility spectrometer (GS-IMS). Urinary VOCs of women delivering preterm were compared with urine samples of women with suspicion of preterm birth collected at the same gestation period but delivering at term. Additionally, the results were also interpreted in combination with patient characteristics, such as physical examination at admission, microbial cultures, and placental pathology. In our cohort, we found that urinary VOCs of women admitted for imminent preterm birth were not significantly different in the overall group of women delivering preterm vs. term. However, urinary VOCs of women admitted for imminent preterm birth and delivering between 28 + 0 until 36 + 6 weeks compared to women with a high risk for preterm birth during the same gestation period and eventually delivering at term (>37 + 0 weeks) differed significantly (area under the curve: 0.70). In addition, based on the same urinary VOCs, we could identify women with a confirmed chorioamnionitis (area under the curve: 0.72) and urinary tract infection (area under the curve: 0.97). In conclusion, urinary VOCs hold potential for non-invasive, bedside prediction of preterm birth and on the spot identification of intra-uterine infection and urinary tract infections. We suggest these observations are further explored in larger populations

Discriminatory ability of gas chromatography-ion mobility spectrometry to identify patients hospitalised with COVID-19 and predict prognosis

Objectives Rapid diagnostic and prognostic tests for COVID-19 are urgently required. We aimed to evaluate the diagnostic and prognostic ability of breath analysis using gas chromatography-ion mobility spectrometry (GC-IMS) in hospitalised patients with COVID-19. Methods Between February and May 2021, we took one breath sample for analysis using GC-IMS from participants who were admitted to hospital for COVID-19, participants who were admitted to hospital for other respiratory infections, and symptom-free controls, at the University Hospitals of Leicester NHS Trust, UK. Demographic, clinical, and radiological data, including requirement for continuous positive airway pressure (CPAP) ventilation as a marker for severe disease in the COVID-19 group, was collected. Results 113 participants were recruited into the study. 72 (64%) were diagnosed with COVID-19; 20 (18%) diagnosed with another respiratory infection, and 21 (19%) healthy controls. Differentiation between participants with COVID-19 and those with other respiratory tract infections with GC-IMS was highly accurate (sensitivity/specificity: 0.80/0.88; [AUROC] 0.85; 95% confidence intervals: CI [0.74-0.96]). GC-IMS was also moderately accurate at identifying those who subsequently required CPAP (sensitivity/specificity 0.62/0.80; [AUROC] 0.70; 95% CI [0.53-0.87]). Conclusions GC-IMS shows promise as both a diagnostic tool and a predictor of prognosis in hospitalised patients with COVID-19 and should be assessed further in larger studies

Determining the Geographical Origin of Crude Palm Oil with the Combined Use of GC-IMS Fingerprinting and Chemometrics

Current administrative controls used to verify geographical provenance within palm oil supply chains require enhancement and strengthening by more robust analytical methods. In this study, the application of volatile organic compound fingerprinting, in combination with five different analytical classification models, has been used to verify the regional geographical provenance of crude palm oil samples. For this purpose, 108 crude palm oil samples were collected from two regions within Malaysia, namely Peninsular Malaysia (32) and Sabah (76). Samples were analysed by gas chromatography-ion mobility spectrometry (GC-IMS) and the five predictive models (Sparse Logistic Regression, Random Forests, Gaussian Processes, Support Vector Machines, and Artificial Neural Networks) were built and applied. Models were validated using 10-fold cross-validation. The Area Under Curve (AUC) measure was used as a summary indicator of the performance of each classifier. All models performed well (AUC 0.96) with the Sparse Logistic Regression model giving best performance (AUC = 0.98). This demonstrates that the verification of the geographical origin of crude palm oil is feasible by volatile organic compound fingerprinting, using GC-IMS supported by chemometric analysis. </p

Optimized Sampling Conditions for Fecal Volatile Organic Compound Analysis by Means of Field Asymmetric Ion Mobility Spectrometry

Fecal volatile organic compounds (VOCs) are increasingly considered to be potential noninvasive, diagnostic biomarkers for various gastrointestinal diseases. Knowledge of the influence of sampling conditions on VOC outcomes is limited. We aimed to evaluate the effects of sampling conditions on fecal VOC profiles and to assess under which conditions an optimal diagnostic accuracy in the discrimination between pediatric inflammatory bowel disease (IBD) and controls could be obtained. Fecal samples from de novo treatment-naïve pediatric IBD patients and healthy controls (HC) were used to assess the effects of sampling conditions compared to the standard operating procedure (reference standard), defined as 500 mg of sample mass diluted with 10 mL tap water, using field asymmetric ion mobility spectrometry (FAIMS). A total of 17 IBD (15 CD (Crohn's disease) and 2 UC (ulcerative colitis)) and 25 HC were included. IBD and HC could be discriminated with high accuracy (accuracy = 0.93, AUC = 0.99, <i>p</i> < 0.0001). A smaller fecal sample mass resulted in a decreased diagnostic accuracy (300 mg accuracy = 0.77, AUC = 0.69, <i>p</i> = 0.02; 100 mg accuracy = 0.70, AUC = 0.74, <i>p</i> = 0.003). A loss of diagnostic accuracy was seen toward increased numbers of thaw–freeze cycles (one cycle, accuracy = 0.61, AUC = 0.80, <i>p</i> = 0.0004; two cycles, accuracy = 0.64, AUC = 0.56, <i>p</i> = 0.753; and three cycles, accuracy = 0.57, AUC = 0.50, <i>p</i> = 0.5101) and when samples were kept at room temperature for 180 min prior to analysis (accuracy = 0.60, AUC = 0.51, <i>p</i> = 0.46). Diagnostic accuracy of VOC profiles was not significantly influenced by storage duration differences of 20 months. The application of a 500 mg sample mass analyzed after one thaw–freeze cycle showed the best discriminative accuracy for the differentiation of IBD and HC. VOC profiles and diagnostic accuracy were significantly affected by sampling conditions, underlining the need for the implementation of standardized protocols in fecal VOC analysis

Preclinical Detection of Non-catheter Related Late-onset Sepsis in Preterm Infants by Fecal Volatile Compounds Analysis A Prospective, Multi-center Cohort Study

BACKGROUND: Late onset sepsis (LOS) in preterm infants is preceded by fecal volatile organic compound (VOC) alterations, suggesting an etiologic role of gut microbiota in LOS rather than being primarily caused by central venous catheters (CVC). To increase our knowledge about the involvement of the gut microbiota in LOS, we analyzed fecal samples from septic infants without a CVC. METHODS: In this prospective multicenter study, fecal samples were collected daily from all infants born at ≤30 weeks gestation. Fecal VOC profiles up to 3 days prior to sepsis onset from infants with non-catheter-related LOS were compared with profiles from non-septic controls by means of High-Field Asymmetric Waveform Ion Mobility Spectrometry. RESULTS: In total, 104 fecal samples were analyzed. Fecal VOC profiles allowed for discrimination between non-catheter-related LOS cases (n = 24) and matched controls (n = 25). Discriminative accuracy increased after focusing on center of origin (area under the curve, sensitivity, specificity; 0.95, 100%, 83%) and after focusing on LOS cases caused by Staphylococcus epidermidis (0.95, 100%, 78%), the most cultured pathogen (n = 11). CONCLUSIONS: Fecal VOC profiles of preterm LOS infants without a CVC differed from matched controls underlining the increasing notion that aberrations in gut microbiota composition and activity may play a role in LOS etiology.status: publishe

Preclinical detection of non-catheter related late-onset sepsis in preterm infants by fecal volatile compounds analysis:A prospective, multi-center cohort study

\u3cp\u3eBACKGROUND: Late onset sepsis (LOS) in preterm infants is preceded by fecal volatile organic compound (VOC) alterations, suggesting an etiologic role of gut microbiota in LOS rather than being primarily caused by central venous catheters (CVC). To increase our knowledge about the involvement of the gut microbiota in LOS, we analyzed fecal samples from septic infants without a CVC. METHODS: In this prospective multicenter study, fecal samples were collected daily from all infants born at ≤30 weeks gestation. Fecal VOC profiles up to 3 days prior to sepsis onset from infants with non-catheter-related LOS were compared with profiles from non-septic controls by means of High-Field Asymmetric Waveform Ion Mobility Spectrometry. RESULTS: In total, 104 fecal samples were analyzed. Fecal VOC profiles allowed for discrimination between non-catheter-related LOS cases (n = 24) and matched controls (n = 25). Discriminative accuracy increased after focusing on center of origin (area under the curve, sensitivity, specificity; 0.95, 100%, 83%) and after focusing on LOS cases caused by Staphylococcus epidermidis (0.95, 100%, 78%), the most cultured pathogen (n = 11). CONCLUSIONS: Fecal VOC profiles of preterm LOS infants without a CVC differed from matched controls underlining the increasing notion that aberrations in gut microbiota composition and activity may play a role in LOS etiology.\u3c/p\u3