Reflux Revisited: Advancing the Role of Pepsin

Gastroesophageal reflux disease is mediated principally by acid. Today, we recognise reflux reaches beyond the esophagus, where pepsin, not acid, causes damage. Extraesophageal reflux occurs both as liquid and probably aerosol, the latter with a further reach. Pepsin is stable up to pH 7 and regains activity after reacidification. The enzyme adheres to laryngeal cells, depletes its defences, and causes further damage internally after its endocytosis. Extraesophageal reflux can today be detected by recognising pharyngeal acidification using a miniaturised pH probe and by the identification of pepsin in saliva and in exhaled breath condensate by a rapid, sensitive, and specific immunoassay. Proton pump inhibitors do not help the majority with extraesophageal reflux but specifically formulated alginates, which sieve pepsin, give benefit. These new insights may lead to the development of novel drugs that dramatically reduce pepsinogen secretion, block the effects of adherent pepsin, and give corresponding clinical benefit

The detection of patients at risk of gastrointestinal toxicity during pelvic radiotherapy by electronic nose and FAIMS : a pilot study

It is well known that the electronic nose can be used to identify differences between human health and disease for a range of disorders. We present a pilot study to investigate if the electronic nose and a newer technology, FAIMS (Field Asymmetric Ion Mobility Spectrometry), can be used to identify and help inform the treatment pathway for patients receiving pelvic radiotherapy, which frequently causes gastrointestinal side-effects, severe in some. From a larger group, 23 radiotherapy patients were selected where half had the highest levels of toxicity and the others the lowest. Stool samples were obtained before and four weeks after radiotherapy and the volatiles and gases emitted analysed by both methods; these chemicals are products of fermentation caused by gut microflora. Principal component analysis of the electronic nose data and wavelet transform followed by Fisher discriminant analysis of FAIMS data indicated that it was possible to separate patients after treatment by their toxicity levels. More interestingly, differences were also identified in their pre-treatment samples. We believe these patterns arise from differences in gut microflora where some combinations of bacteria result to give this olfactory signature. In the future our approach may result in a technique that will help identify patients at “high risk” even before radiation treatment is started

OC-163 identification of inflammatory bowel disease (IBD) using field asymmetric ion mobility spectrometry (FAIMS)

Introduction Resident colonic bacteria, principally anaerobes and firmicutes, ferment undigested fibre. The resultant volatile organic compounds (VOCs) formed are dissolved in the faeces but also absorbed and excreted in the urine. We have previously shown that electronic nose (E-nose) analysis of urine VOCs distinguishes between Crohn's disease (CD), ulcerative colitis (UC) and healthy volunteers (HV): the underlying principle is pattern recognition of disease-specific “chemical fingerprint”. High-Field Asymmetric Waveform Ion Mobility Spectrometry (FAIMS) offers a possible alternative. The underlying principle is separation of VOC chemical components based on their different ion mobilties in high electric fields. We performed a pilot study in the above groups, the patients in remission (Rem) or with active disease (AD), to assess if this technology could achieve separation between the groups. The results were validated against E-nose analysis. Methods 59 subjects were studied; HV n=14, UC (Rem) n=18, UC (AD) n=4; CD (Rem) n=19, CD (AD) n=4. Urine samples (7 ml) in universal containers (25 ml) were heated to 40±0.1 C. The headspace (the air above the sample) was then analysed using FAIMS. The data were analysed by Fisher Discriminant Analysis. Results The technique distinguished between the three groups. Additionally, patients with active disease could be distinguished from those in remission. These results were concordant with E-nose analysis. Conclusion This pilot shows that urine VOCs, analysed by the different approaches of E-nose and FAIMS, the latter a novel application, can distinguish the healthy from those with UC and CD when disease is active or in remission. The two technologies together offer a non-invasive approach to diagnosis and follow-up in inflammatory bowel disease

Breathomics—exhaled volatile organic compound analysis to detect hepatic encephalopathy : a pilot study

he current diagnostic challenge with diagnosing hepatic encephalopathy (HE) is identifying those with minimal HE as opposed to the more clinically apparent covert/overt HE. Rifaximin, is an effective therapy but earlier identification and treatment of HE could prevent liver disease progression and hospitalization. Our pilot study aimed to analyse breath samples of patients with different HE grades, and controls, using a portable electronic (e) nose. 42 patients were enrolled; 22 with HE and 20 controls. Bedside breath samples were captured and analysed using an uvFAIMS machine (portable e-nose). West Haven criteria applied and MELD scores calculated. We classify HE patients from controls with a sensitivity and specificity of 0.88 (0.73-0.95) and 0.68 (0.51-0.81) respectively, AUROC 0.84 (0.75-0.93). Minimal HE was distinguishable from covert/overt HE with sensitivity of 0.79 and specificity of 0.5, AUROC 0.71 (0.57-0.84). This pilot study has highlighted the potential of breathomics to identify VOCs signatures in HE patients for diagnostic purposes. Importantly this was performed utilizing a non-invasive, portable bedside device and holds potential for future early HE diagnosis

The Construction of a New Evaluative GERD Questionnaire – Methods and State of the Art

Gastroesophageal reflux disease (GERD) is one of the most prevalent diseases worldwide, and it is becoming increasingly important to monitor the effect of various interventions on GERD symptoms. There can be rapid temporal changes in the severity and frequency of patients' symptoms as well as their health status and well-being, all of which could, theoretically, be monitored using diaries or questionnaires. However, current GERD monitoring instruments are not appropriate because they do not assess symptoms daily, they are not sufficiently responsive to short-term changes in health status or they are not adequately validated. To address these problems, the conceptual and psychometric requirements for a GERD symptom assessment questionnaire were identified. A dimension-based scale was designed to reduce the number of symptoms monitored on a daily basis, and the validation process was defined to produce parallel long and short forms of a scale for patients' self-assessment of their GERD symptom response to therapy. These basic principles which underlie the successful development of a new, self-assessed symptomatic reflux questionnaire (ReQuestTM) are also applicable to the development of validated questionnaires for daily symptom self-assessment in other disease areas

Electronic nose versus canine nose : clash of the titans

We read with great interest the article by Sonoda et al published on line (Gut doi:10.1136/gut.2010.218305) of canine scent detection in those with colorectal cancer. The concept of using a dog to detect diseases is not new; there are many reported incidents of dogs barking at their owners (or even trying to bite the leg off of an owner with melanoma!) who are later shown to have the disease