Pepsin and pH of Gastric Juice in Patients With Gastrointestinal Reflux Disease and Subgroups.

GOAL: The aim of this study was to investigate the pepsin values and pH results of gastric juice among the subtypes of gastroesophageal reflux disease (GERD) and functional heartburn. BACKGROUND: The major destructive agents of GERD on the esophageal epithelium are gastric acid and pepsin. No precise information about pepsin concentration in gastric juice exists. STUDY: Ninety patients with GERD, 39 erosive reflux disease (ERD) Los Angeles (LA) grade A/B, 13 ERD LA grade C/D, 19 nonerosive reflux disease (NERD), 8 esophageal hypersensitivity, 11 functional heartburn, and 24 healthy controls were included in the study. During endoscopy gastric juices from the patients were aspirated and their pH readings immediately recorded. Gastric juice samples were analyzed using Peptest, a lateral flow device containing 2 unique human monoclonal antibodies to detect any pepsin present in the gastric juice sample. RESULTS: The highest mean gastric pepsin concentration (0.865 mg/mL) and the lowest median gastric pH (1.4) was observed in the LA grade C/D group compared with the lowest mean gastric pepsin concentration (0.576 mg/mL) and the highest median gastric pH (2.5) seen in the NERD group. Comparing pH, the NERD patient group was significantly higher (P=0.0018 to P=0.0233) when compared with all other GERD patient groups. CONCLUSIONS: The basal gastric pepsin level in the healthy control group was comparable to literature values. There was good correlation and a significant linear relationship between the gastric pepsin level and gastric pH within the patient groups. The severity of the GERD disease is related to the lowest pH and the highest pepsin concentration in gastric juice.

A comparative study on the raft chemical properties of various alginate antacid raft-forming products.

OBJECTIVE: Research to measure the chemical characterization of alginate rafts for good raft performance and ascertain how formulation can affect chemical parameters. SIGNIFICANCE: A selection of alginate formulations was investigated all claiming to be proficient raft formers with significance between products established and ranked. METHODS: Procedures were selected which demonstrated the chemical characterization allowing rafts to effectively impede the reflux into the esophagus or in severe cases to be refluxed preferentially into the esophagus and exert a demulcent effect, with focus of current research on methods which complement previous studies centered on physical properties. The alginate content was analyzed by a newly developed HPLC method. Methods were used to determine the neutralization profile and the acid neutralization within the raft determined along with how raft structure affects neutralization. RESULTS: Alginate content of Gaviscon Double Action (GDA) within the raft was significantly superior (p < .0001) to all competitor products. The two products with the highest raft acid neutralization capacity were GDA and Rennie Duo, the latter product not being a raft former. Raft structure was key and GDA had the right level of porosity to allow for longer duration of neutralization. CONCLUSION: Alginate formulations require three chemical reactions to take place simultaneously: transformation to alginic acid, sodium carbonate reacting to form carbon dioxide, calcium releasing free calcium ions to bind with alginic acid providing strength to raft formation. GDA was significantly superior (p <.0001) to all other comparators.

Pepsin in saliva for the diagnosis of gastro-oesophageal reflux disease.

OBJECTIVE: Current diagnostic methods for gastro-oesophageal reflux disease (GORD) have moderate sensitivity/specificity and can be invasive and expensive. Pepsin detection in saliva has been proposed as an 'office-based' method for GORD diagnosis. The aims of this study were to establish normal values of salivary pepsin in healthy asymptomatic subjects and to determine its value to discriminate patients with reflux-related symptoms (GORD, hypersensitive oesophagus (HO)) from functional heartburn (FH). DESIGN: 100 asymptomatic controls and 111 patients with heartburn underwent MII-pH monitoring and simultaneous salivary pepsin determination on waking, after lunch and dinner. Cut-off value for pepsin positivity was 16 ng/mL. Patients were divided into GORD (increased acid exposure time (AET), n=58); HO (normal AET and + Symptom Association Probability (SAP), n=26) and FH (normal AET and-SAP, n=27). RESULTS: 1/3 of asymptomatic subjects had pepsin in saliva at low concentration (0(0-59)ng/mL). Patients with GORD and HO had higher prevalence and pepsin concentration than controls (HO, 237(52-311)ng/mL and GORD, 121(29-252)ng/mL)(p<0.05). Patients with FH had low prevalence and concentration of pepsin in saliva (0(0-40) ng/mL). A positive test had 78.6% sensitivity and 64.9% specificity for diagnosis of GORD+HO (likelihood ratio: 2.23). However, one positive sample with >210 ng/mL pepsin suggested presence of GORD+HO with 98.2% specificity (likelihood ratio: 25.1). Only 18/84 (21.4%) of GORD+HO patients had 3 negative samples. CONCLUSION: In patients with symptoms suggestive of GORD, salivary pepsin testing may complement questionnaires to assist office-based diagnosis. This may lessen the use of unnecessary antireflux therapy and the need for further invasive and expensive diagnostic methods.

Objective detection of esophagopharyngeal reflux in patients with hoarseness and endoscopic signs of laryngeal inflammation.

GOALS: We aimed to quantify pharyngeal exposure to gastric contents in patients diagnosed with reflux-related hoarseness and healthy controls using new diagnostic techniques. BACKGROUND: Hoarseness with typical signs on laryngoscopy is commonly thought to be caused by esophagopharyngeal reflux. New methods are proposed to assess pharyngeal exposure to gastric contents. They are suggested to measure: (1) liquid or mixed gas-liquid acid and nonacid reflux with impedance pH, (2) aerosolized acid reflux (Dx-pH measuring system), and (3) pepsin in the saliva. STUDY: Twenty-one patients with hoarseness and positive laryngoscopy and 10 controls underwent simultaneous impedance pH, Dx-pH monitoring, and saliva pepsin sampling (5 samples in 24 h). RESULTS: Of the 21 patients, 10 had impedance pH-detected reflux plus at least 1 other test positive. These patients were more likely to have symptomatic relief after proton pump inhibitor therapy. Three of the 21 patients had all 3 tests positive and 4 had all tests negative. None of the controls had impedance pH-detected reflux. Two controls had a positive Dx-pH "RYAN score" and 1 control had >1 saliva sample positive for pepsin. Only 11% of Dx-pH drops to pH<4, 15% pH drops to pH<5, and 10% of pH drops to pH<5.5 coincided with impedance pH-detected reflux in the esophageal body. Positive pepsin saliva samples were preceded by more reflux events [3 (range, 0 to 10)] in the previous 60 minutes than negative samples [0 (range, 0 to 7)] (P<0.0001). CONCLUSION: A subgroup of patients with hoarseness (10/21) had objective detection of the esophagopharyngeal reflux. We propose that these patients are more likely to benefit from further intense antireflux therapy. Detection of pepsin in the saliva may be a useful screening tool in these patients.

Assessment and protection of esophageal mucosal integrity in patients with heartburn without esophagitis.

OBJECTIVES: Intact esophageal mucosal integrity is essential to prevent symptoms during gastroesophageal reflux events. Approximately 70% of patients with heartburn have macroscopically normal esophageal mucosa. In patients with heartburn, persistent functional impairment of esophageal mucosal barrier integrity may underlie remaining symptoms. Topical protection of a functionally vulnerable mucosa may be an attractive therapeutic strategy. We aimed to evaluate esophageal mucosal functional integrity in patients with heartburn without esophagitis, and test the feasibility of an alginate-based topical mucosal protection. METHODS: Three distal esophageal biopsies were obtained from 22 patients with heartburn symptoms, and 22 control subjects. In mini-Ussing chambers, the change in transepithelial electrical resistance (TER) of biopsies when exposed to neutral, weakly acidic, and acidic solutions was measured. The experiment was repeated in a further 10 patients after pretreatment of biopsies with sodium alginate, viscous control, or liquid control "protectant" solutions. RESULTS: Biopsy exposure to neutral solution caused no change in TER. Exposure to weakly acidic and acidic solutions caused a greater reduction in TER in patients than in controls (weakly acid -7.2% (95% confidence interval (CI) -9.9 to -4.5) vs. 3.2% (-2.2 to 8.6), P<0.05; acidic -22.8% (-31.4 to 14.1) vs. -9.4% (-17.2 to -1.6), P<0.01). Topical pretreatment with alginate but not with control solutions prevented the acid-induced decrease in TER (-1% (-5.9 to 3.9) vs. -13.5 (-24.1 to -3.0) vs. -13.2 (-21.7 to -4.8), P<0.05). CONCLUSIONS: Esophageal mucosa in patients with heartburn without esophagitis shows distinct vulnerability to acid and weakly acidic exposures. Experiments in vitro suggest that such vulnerable mucosa may be protected by application of an alginate-containing topical solution.

Gastroesophageal reflux and idiopathic pulmonary fibrosis: a prospective study.

BACKGROUND AND OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) is the most common of the idiopathic interstitial pneumonias. There is evidence of the increased prevalence of gastroesophageal reflux disease in patients with IPF. The aim of this prospective study was to evaluate reflux in patients with IPF by analyzing the scores of the reflux cough questionnaire, measurement of pepsin in exhaled breath condensate (EBC) to detect extraesophageal reflux, and Helicobacter pylori serology to evaluate the prevalence of this stomach bacterium in patients with IPF. MATERIAL AND METHODS: The Hull airway reflux questionnaire (HARQ) was completed by 40 patients with IPF and 50 controls in order to evaluate reflux symptoms. EBC was collected from 23 patients (17 patients with IPF and 6 controls) for measurement of pepsin by the lateral flow technique. A prospective study of 57 subjects (34 patents with IPF and 23 controls) for H. pylori antibody detection by ELISA was preformed. RESULTS: Significantly higher HARQ scores (maximum score, 70) were recorded in patients with IPF compared with controls (19.6 [SD, 12.4] vs. 3 [SD, 2.9], P<0.001). There was no significant difference in EBC pepsin positivity between patients with IPF and controls (2 of the 17 patients vs. none of the 6 controls, P=0.38). There was no significant difference in H. pylori serology between patients with IPF and controls (17 of the 34 patients vs. 14 of the 23 controls, P=0.42). CONCLUSION: Patients with IPF had significantly increased scores of airway reflux symptoms. However, no objective evidence of extraesophageal reflux or H. pylori infection in patients with IPF was obtained in this study. The role of gastroesophageal and extraesophageal reflux in pathogenesis of IPF should be evaluated in a larger prospective study.

Diet and lifestyle as trigger factors for the onset of heartburn.

AIM: To examine prospectively the role of reported trigger factors on symptom onset in patients with heartburn and highlight the role of these factors in the management of heartburn in the primary care setting. METHOD Twenty-two patients with heartburn and 50 controls were recruited in Bedfordshire, UK. A seven-day symptom and trigger diary was completed by patients and controls. RESULTS: Patients reported a collection of heartburn symptoms varying in severity and time of day. Aspects of diet and lifestyle perceived as trigger factors included large meals, time of eating and posture. Multiple trigger factors were reported for heartburn. CONCLUSION: Although symptom onset varies between individuals, consideration should be given to trigger factors in the management of heartburn symptoms.

A Novel In Vitro Model for Determining the Optimum pH and Dose Volume of New Liquid Alginate for Infant Reflux Suppression.

BACKGROUND: Gastroesophageal reflux frequently occurs in infants from birth to 2 years and is characterised by reflux and regurgitation often occurring during or immediately after feeds. These reflux events can range in both frequency and severity, and as the reflux events increase, they become increasingly distressing for both the infant and the parent. The study aimed to characterise the properties of a new infant liquid alginate product, determining the optimum gastric pH and dose volume for maximum reflux suppressant activity. METHODS: An in vitro infant stomach model was designed and developed that allowed products to be assessed for their reflux suppression activity. The validation of the model was completed by three independent operators comparing a milk control with infant Gaviscon to evaluate the models' robustness, reproducibility, and ease of use. The model was used to establish reflux suppression activity of a new liquid alginate infant formulation in comparison with a milk control. Suppression activity was assessed at varying doses and pH within a physiological range. RESULTS: The validation study demonstrated no significant difference in refluxate volumes for the milk control within each reflux event when comparing across the three individual operators. Similarly, no statistical differences were seen during the infant Gaviscon experiments, confirming the robustness and reproducibility of the model. Significant reflux suppression was seen across the pH range (except at pH 5.75); the pH most advantageous for reflux suppression was pH 5.25. The optimum dose volume for consistently suppressing reflux was shown to be 5 ml. An infant stomach model was designed for evaluating reflux suppression activity of a formulation of liquid alginate. The optimum gastric pH and dose volume for demonstrating significant reflux suppression and the thickening of formula milk by the infant liquid alginate formulation were established. CONCLUSION: This study confirms the mode of action of the alginate formula, demonstrating a superior reduction in the retrograde movement of in vitro gastric contents and volume of regurgitation. The study also demonstrates that optimal performance occurs in conditions that are in line physiologically with the target patient. Both actions compliment and support the efficacy of the alginate formulation as a reflux therapy agent.

Physiological parameters governing the action of pancreatic lipase.

The most widely used pharmacological therapies for obesity and weight management are based on inhibition of gastrointestinal lipases, resulting in a reduced energy yield of ingested foods by reducing dietary lipid absorption. Colipase-dependent pancreatic lipase is believed to be the major gastrointestinal enzyme involved in catalysis of lipid ester bonds. There is scant literature on the action of pancreatic lipase under the range of physiological conditions that occur within the human small intestine, and the literature that does exist is often contradictory. Due to the importance of pancreatic lipase activity to nutrition and weight management, the present review aims to assess the current body of knowledge with regards to the physiology behind the action of this unique gastrointestinal enzyme system. Existing data would suggest that pancreatic lipase activity is affected by intestinal pH, the presence of colipase and bile salts, but not by the physiological range of Ca ion concentration (as is commonly assumed). The control of secretion of pancreatic lipase and its associated factors appears to be driven by gastrointestinal luminal content, particularly the presence of acid or digested proteins and fats in the duodenal lumen. Secretion of colipase, bile acids and pancreatic lipase is driven by cholecystokinin and secretin release.

Alginate-antacid combinations: raft formation and gastric retention studies.

BACKGROUND: Alginate-based gastroesophageal reflux disease treatments have been used extensively and fall into two main categories. Those containing alginate as the principle active agent and those containing alginate in combination with a significant amount of antacid. METHOD: The effectiveness of the raft formed by a new alginate/antacid suspension (Gaviscon Double Action Liquid, GDAL), in which calcium carbonate was the main antacid ingredient, was compared with those of existing alginate/antacid suspensions. RESULT: GDAL had similar raft strength and improved raft resilience than Gaviscon Liquid (GL), and both were significantly greater than five other products tested. Gastric retention of GDAL was similar to that of GL. CONCLUSION: the in vitro and in vivo performance is maintained in the new GDAL formulation even with higher antacid levels and the product is as good as, or better than, previous formulations.

Micronutrient intakes of pre-adolescent children living in London.

The aim of the current study was to report on the micronutrient intakes of a sample of pre-adolescent children from a range of socio-economic backgrounds. Eighty-five children aged 7-10 years completed 7-day weighed food diaries, which were used to assess habitual intake of selected micronutrients. Intakes were then compared with the current Department of Health reference values and the findings of the UK National Diet and Nutrition Survey for young people. These children failed to meet the reference values set by the Department of Health for zinc (73% of sample) and potassium (68% of sample), and intakes of calcium, potassium, vitamin B(12), vitamin D and folate were lower than the findings of the UK National Diet and Nutrition Survey. Among this sample, dietary changes are required to ensure that children follow a well-balanced diet for optimum health and development.

Salivary Pepsin as an Intrinsic Marker for Diagnosis of Sub-types of Gastroesophageal Reflux Disease and Gastroesophageal Reflux Disease-related Disorders.

BACKGROUND/AIMS: To determine the value of salivary pepsin in discriminating sub-types of gastroesophageal reflux disease (GERD) and GERD-related disorders. METHODS: Overall, 322 patients with different sub-types of GERD and 45 healthy controls (HC) were studied. All patients took Gastroesophageal Reflux Disease Questionnaire (GerdQ) and underwent endoscopy and 24-hour esophageal pH monitoring and manometry. Salivary pepsin concentration (SPC) was detected by using colloidal gold double-antibody immunological sandwich assay. Oral esomeprazole treatment was administrated in the patients with non-erosive reflux disease (NERD) and extra-esophageal symptoms (EES). RESULTS: Compared to HC, patients with erosive esophagitis, NERD, EES, EES plus typical GERD symptoms, or Barrett's esophagus had a higher prevalence of saliva and SPC (all P < 0.001). There was no significant difference in the positive rate for pepsin in patients with functional heartburn or GERD with anxiety and depression, compared to HC. After esomeprazole treatment, the positive rate and SPC were significantly reduced in NERD (both P < 0.001) and in EES ( P = 0.001 and P = 0.002, respectively). Of the 64 NERD patients, 71.9% (n = 46) were positive for salivary pepsin, which was significantly higher than the rate (43.8%, n = 28) of pathological acid reflux as detected by 24-hour esophageal pH monitoring (P = 0.002). CONCLUSIONS: Salivary pepsin has an important significance for the diagnosis of GERD and GERD-related disorders. Salivary pepsin and 24-hour esophageal pH monitoring may complement with each other to improve the diagnostic efficiency.

The role of an alginate suspension on pepsin and bile acids - key aggressors in the gastric refluxate. Does this have implications for the treatment of gastro-oesophageal reflux disease?

OBJECTIVES: During a reflux event the oesophagus is exposed to a heterogeneous mixture of gastric juice components. The role of non-acid components of the refluxate in causing damage to the oesophagus is now well established but no therapeutic option exists to address this. METHODS: The role of Gaviscon Advance (GA), a raft-forming alginate suspension, in protecting the oesophagus from damage by pepsin and bile acids (aggressors) was investigated using a series of in-vitro models. KEY FINDINGS: GA was able to dose-dependently inhibit pepsin activity over and above the neutralisation effect of the formulation. This was evident against both protein and collagen substrates using two distinct colorimetric assays. GA was able to retard the diffusion of pepsin and multiple bile acids using a Franz cell model. Using the raft-forming mode of action GA was able to remove both pepsin and multiple bile acids from a simulated reflux event. There was capacity in the GA raft to accommodate aggressors from multiple reflux events. CONCLUSIONS: GA can specifically remove both pepsin and bile acids from the refluxate, limit their diffusion and affect enzymatic activity of pepsin. There is a role for GA to reduce the damaging potential of the refluxate and thus protect the oesophagus.

The value of a liquid alginate suspension (Gaviscon Advance) in the management of laryngopharyngeal reflux.

Laryngopharyngeal reflux (LPR) refers to the backflow of stomach contents into the laryngopharynx. Increasing evidence has demonstrated that LPR is a contributing factor in some cases of hoarseness, vocal fatigue, voice breaks, cough and globus and chronic throat clearing. However, several randomised placebo-controlled trials of proton pump inhibitors in the treatment of LPR have been reported with the majority showing no significant benefit in patient symptom scores over placebo. The aim of this pilot clinical study was to investigate whether any improvement in LPR-related symptoms, using the Reflux Symptom Index (RSI), and clinical findings, using the Reflux Finding Score (RFS), could be achieved with treatment with a liquid alginate suspension compared to control (no treatment). Patients presenting with the symptoms of LPR to the Otorhinolaryngology Outpatient Department at the Queen's Medical Centre, Nottingham, UK were considered eligible if they had an RSI of greater than 10 and an RFS greater than 5 based on a fibreoptic examination of the larynx. A total of 49 patients were randomised into the open, parallel group study; 24 patients were randomised to receive 10 ml liquid alginate suspension (Gaviscon Advance) four times daily after meals and at bedtime, and 25 patients into the control group (no treatment). Patients were assessed pre-treatment and at 2, 4 and 6 months post treatment. Mean (SD) RSI and RFS pre-treatment scores were 23.9 (7.0) and 10.4 (3.6) for the treatment group and 24.6 (7.4) and 10.3 (3.3) for the control group, respectively. Significant differences between treatment and control were observed for RSI at the 2-month (11.2 (7.0) vs. 16.8 (6.4), P=0.005) and 6-month (11.2 (8.1) vs. 18.3 (9.4), P=0.008) assessments and for RFS at the 6-month (7.1 (2.8) vs. 9.5 (3.4), P=0.005) assessment. Significant improvement in symptom scores and clinical findings were achieved with liquid alginate suspension (Gaviscon Advance) compared to control and further evaluation for the management of patients presenting with LPR is warranted.

Dietary fibre, fluids and physical activity in relation to constipation symptoms in pre-adolescent children.

Children with constipation are advised frequently to increase their activity levels, fluids and fibre intake. The aim of this study was to examine the prevalence of constipation symptoms in a group of schoolchildren while concurrently assessing their activity levels and fluid and fibre intakes. Eighty-four pre-adolescent children aged 7-10 years were recruited. All children completed a bowel function diary, an activity diary and a weighed food inventory for seven consecutive days. Of the children, 33 percent were found to experience constipation symptoms. Fluid and fibre intakes were higher in the children who did not experience constipation symptoms, but the results were not significant. Physical activity levels were found to be significantly higher in the children reporting constipation symptoms, with the most active children reporting low water intakes. This study has highlighted that constipation symptoms are a prevalent problem in children not seeking medical treatment.

Validation of Peptest™ in Patients with Gastro-Esophageal Reflux Disease and Laryngopharyngeal Reflux Undergoing Impedance Testing.

BACKGROUND AND AIMS: Pepsin in the gastric refluxate is a marker for a prior reflux event and rapid detection might be achieved using the Peptest™, an in vitro diagnostic medical device. The aim of this study was to validate the use of Peptest™ to reliably diagnose reflux in patients with gastro-esophageal reflux disease (GERD) and laryngopharyngeal reflux (LPR) disease diagnosed with multichannel intraluminal impedance/ pHmetry (MII-pH). METHODS: 20 reflux patients were recruited of whom 10 had classical GERD and 10 had LPR. All patients underwent MII-pH and provided expectorated saliva samples when a MII-pH reflux event was observed, or reflux symptoms were experienced, and all were tested for the presence of pepsin using the Peptest™. RESULTS: Pepsin was detected in 31 out of 45 samples (68.9%). At least 1 positive pepsin result was seen in 16 patients (80%) and this was the same, irrespective of the GERD or LPR diagnosis. Peptest™ had a positive predictive value of 69% to detect MII-pH reflux events. CONCLUSIONS: Peptest™ is a good first-line diagnostic procedure to use in reflux sufferers to confirm the presence of reflux.

Validation in China of a non-invasive salivary pepsin biomarker containing two unique human pepsin monoclonal antibodies to diagnose gastroesophageal reflux disease.

OBJECTIVES: Peptest is a new non-invasive reflux diagnostic test based on lateral flow technology that containing two highly specific human pepsin monoclonal antibodies for detecting pepsin, a biomarker for reflux disease. The primary aim of this multicenter clinical study was to validate the efficacy of Peptest in patients diagnosed with gastroesophageal reflux and healthy controls in China. METHODS: Patients with suspected gastroesophageal reflux underwent an endoscopy and were classified into non-erosive reflux disease and erosive esophagitis subgroups. A healthy control group was also recruited. All participants were given a reflux disease questionnaire-patients scoring greater than 12 and controls scoring zero. All participants provided a postprandial saliva sample and most patients gave an additional post-symptom sample for pepsin analysis. RESULTS: Altogether 1032 participants aged between 19 and 78 years were recruited. They consisted of 488 patients with non-erosive reflux disease, 221 with erosive esophagitis and 323 healthy controls. The number of postprandial and post-symptom samples analyzed totaled 1031 and 692, respectively. The results across all centers showed an overall pepsin-positive sensitivity of 85%, a specificity of 60%, a positive predictive value of 82%, a negative predictive value of 65% and a positive likelihood ratio of 2.12. CONCLUSION: The sensitivity of Peptest was high, but the specificity achieved in some centers was low, resulting overall in only a moderate specificity. Further diagnostic investigative studies are warranted.

Pepsin: biomarker, mediator, and therapeutic target for reflux and aspiration.

Extra-esophageal reflux is suspected to cause a wide range of clinical symptoms in the upper airways. Diagnosis and treatment has focused on acid, but realization of the role of nonacid reflux has resulted in research investigating the use of pepsin as a biomarker for gastric reflux and aspiration. Pepsin analysis can complement the use of questionnaires and office-based diagnosis and lessen the dependency on invasive and expensive diagnostic tests. Furthermore, pepsin as a first-line diagnostic biomarker has been shown to improve the accuracy of reflux diagnosis. In addition to its use as a diagnostic biomarker, pepsin has been shown to cause inflammation independent of the pH of the refluxate and thus despite acid suppression therapy. Research is ongoing to develop new therapies for airway reflux that specifically target pepsin.

Action of reactive oxygen species on colonic mucus secretions.

Reactive oxygen species (ROS) have been implicated in the pathogenesis of many colonic diseases. Mucus is the colon's first line of defence against luminal agents. This study has therefore characterised ROS action on colonic mucus secretions. ROS were produced using peroxide-based systems of different concentrations. The effects of these systems were tested on native colonic mucus gels, isolated colonic mucins, and in vivo models. Colonic mucus gels were resistant to ROS breakdown. Mucins were susceptible to ROS attack, causing loss of terminal sugars and protein and mucin fragmentation. The in vivo thickness of the mucus barrier was reduced by up to 50% by ROS (above 5 mM peroxide). A 5 mM peroxide caused a significant increase in resting mucus thickness of ca. 15%. All ROS-generating systems caused mucosal damage once the loosely adherent mucus had been removed. As native mucus gel is more resistant to ROS damage than purified mucin, nonmucin components of mucus may have extensive ROS-scavenging properties. Low levels of luminal colonic ROS increase the protection afforded by the mucus barrier in vivo. Higher levels of ROS significantly reduce this protection. In vitro modeling of mucus degradation by ROS does not necessarily correlate with the dynamic, in vivo situation.