Vulnerability to acid reflux of the airway epithelium in severe asthma

BackgroundSevere asthma is associated with multiple co-morbidities, including gastro-oesophageal reflux disease (GORD) which can contribute to exacerbation frequency and poor quality of life. Since epithelial dysfunction is an important feature in asthma, we hypothesised that in severe asthma the bronchial epithelium is more susceptible to the effects of acid reflux.MethodsWe developed an in vitro model of GORD using differentiated bronchial epithelial cells (BECs) from normal or severe asthmatic donors exposed to a combination of pepsin, acid pH, and bile acids using a multiple challenge protocol (MCP-PAB). We also analysed bronchial biopsies and undertook RNA-sequencing of bronchial brushings from controls and severe asthmatics without or with GORD.ResultsExposure of BECs to the MCP-PAB caused structural disruption, increased permeability, IL-33 expression, inflammatory mediator release and changes in gene expression for multiple biological processes. Cultures from severe asthmatics were significantly more affected than those from healthy donors. Analysis of bronchial biopsies confirmed increased IL-33 expression in severe asthmatics with GORD. RNA-sequencing of bronchial brushings from this group identified 15 of the top 37 dysregulated genes found in MCP-PAB treated BECs, including genes involved in oxidative stress responses.ConclusionsBy affecting epithelial permeability, GORD may increase exposure of the airway submucosa to allergens and pathogens, resulting in increased risk of inflammation and exacerbations. Clinical implication: These results suggest the need for research into alternative therapeutic management of GORD in severe asthma.

Scutellariae Radix and Citri Reticulatae Pericarpium Mixture Regulate PPARγ/RXR Signaling in Reflux Esophagitis

Objective. Gastroesophageal reflux disease (GERD) is a gastrointestinal disorder in which stomach contents reflux into the esophagus, causing complications such as mucosal damage. GERD is a very common disease and is on the rise worldwide. The aim of this study was to assess the impact of a Scutellariae Radix and Citri Reticulatae Pericarpium mixture (SC) on esophageal mucosal injury in rats with chronic acid reflux esophagitis (CARE). Methods. After inducing reflux esophagitis through surgery, the group was separated and the drug was administered for 2 weeks: normal rats (Normal, n = 8), CARE-induced rats were treated with distilled water (Control, n = 8), CARE-induced rats were treated with vitamin E 30 mg/kg body weight (VitE, n = 8), CARE-induced rats were treated with SC 100 mg/kg body weight (SC100, n = 8), and CARE-induced rats were treated with SC 200 mg/kg body weight (SC200, n = 8). Results. SC treatment significantly reduced the degree of esophageal mucosal damage, significantly reduced levels of MDA and MPO, and inhibited the activation of the NF-κB inflammatory pathway by activating the PPARγ/RXR pathway. In addition, SC treatment significantly regulated the expression of arachidonic acid-related proteins (COX-1, COX-2, and PGE2) and modulated the MMP/TIMP proteins in reflux esophagitis. Conclusion. Consequently, SC improved the damage to the esophageal mucosa. Also, the anti-inflammatory effects of the SC suggested the inhibition of NF-κB pathway through the activation of the PPARγ/RXR pathway, thereby reducing the expression of inflammation-related cytokines.

Efficient Degradation of Reactive Brilliant Red on the First Open-Framework Borate-Rich Cadmium Borophosphate

A novel open-framework borate-rich cadmium borophosphate has been obtained by the boric acid reflux method. The compound exhibits a complicated network which is composed of CdO6 octahedra and interesting 1D...

Effects of Alkaline-Reduced Water on Gastrointestinal Diseases

Living a healthy lifestyle is the most important need in the world today. However, oxidative stress (OS) is caused by several stress-inducing factors such as smoking, alcohol consumption, chronic diseases, and inflammatory responses, oxygen-free radicals are produced in excess and can damage major organs in the body. This phenomenon has been implicated in the pathogenesis of several gastrointestinal (GI) diseases, including gastritis, constipation, and inflammatory bowel diseases, which include Crohn’s disease, ulcerative colitis, functional dyspepsia, acid reflux, diverticular disease, and irritable bowel syndrome. In this review article, we provide a brief overview of the role of OS in the pathogenesis of GI disorders. Additionally, we discuss the therapeutic role of alkaline-reduced water (ARW) on GI diseases and existing studies on ARW related to GI diseases. Furthermore, we believe that findings from this review article will enhance the knowledge of the readers on the role of ARW on OS and inflammation-based GI diseases.

Effects of acids, pepsin, bile acids, and trypsin on laryngopharyngeal reflux diseases: physiopathology and therapeutic targets

Purpose Laryngopharyngeal reflux disease (LPRD) is a general term for the reflux of gastroduodenal contents into the laryngopharynx, oropharynx and even the nasopharynx, causing a series of symptoms and signs. Currently, little is known regarding the physiopathology of LPRD, and proton pump inhibitors (PPIs) are the drugs of choice for treatment. Although acid reflux plays a critical role in LPRD, PPIs fail to relieve symptoms in up to 40% of patients with LPRD. The influence of other reflux substances on LPRD, including pepsin, bile acid, and trypsin, has received increasing attention. Clarification of the substances involved in LPRD is the basis for LPRD treatment. Methods A review of the effects of acids, pepsin, bile acids, and trypsin on laryngopharyngeal reflux diseases was conducted in PubMed. Results Different reflux substances have different effects on LPRD, which will cause various symptoms, inflammatory diseases and neoplastic diseases of the laryngopharynx. For LPRD caused by different reflux substances, 24-h multichannel intraluminal impedance combined with pH-metry (MII-pH), salivary pepsin, bile acid and other tests should be established so that different drugs and treatment courses can be used to provide patients with more personalized treatment plans. Conclusion This article summarizes the research progress of different reflux substances on the pathogenesis, detection index and treatment of LPRD and lays a theoretical foundation to develop target drugs and clinical diagnosis and treatment.

Proton pump inhibitors associated with rapid eye movement sleep behaviour disorder

We present the case of a 65-year-old woman diagnosed with rapid eye movement sleep behaviour disorder (REMBD) based on typical symptoms and confirmed with an inpatient polysomnogram. She was prescribed clonazepam and later temazepam but continued to have intrusive symptoms. She subsequently recalled that the onset of dream enactment coincided with starting high-dose omeprazole for acid reflux. With this insight, she stopped the omeprazole. Within days, the dream enactment and nocturnal movements subsided. She stopped taking the temazepam and was symptom free for a few months. However, she was started on lansoprazole for recurrent dyspepsia. Once again she experienced violent movements in sleep. This is the first time an association between proton pump inhibitors (PPIs) and REMBD has been reported. PPIs have many effects on the central nervous system and should be considered as a possible provoking factor in people presenting with REMBD.

Evaluating the impact of an enhanced triage process on the performance and diagnostic yield of oesophageal physiology studies post COVID-19

ObjectivesThe COVID-19 pandemic significantly impacted on the provision of oesophageal physiology investigations. During the recovery phase, triaging tools were empirically recommended by national bodies for prioritisation of referrals amidst rising waiting lists and reduced capacity. We evaluated the performance of an enhanced triage process (ETP) consisting of telephone triage combined with the hierarchical ‘traffic light system’ recommended in the UK for prioritising oesophageal physiology referrals.DesignIn a cross-sectional study of patients referred for oesophageal physiology studies at a tertiary centre, data were compared between patients who underwent oesophageal physiology studies 6 months prior to the COVID-19 pandemic and those who were investigated within 6 months after service resumption with implementation of the ETP.Outcome measuresAdjusted time from referral to investigation; non-attendance rates; the detection of Chicago Classification (CC) oesophageal motility disorders on oesophageal manometry and severity of acid reflux on 24 hours pH/impedance monitoring.ResultsFollowing service resumption, the ETP reduced non-attendance rates from 9.1% to 2.8% (p=0.021). Use of the ‘traffic light system’ identified a higher proportion of patients with CC oesophageal motility disorders in the ‘amber’ and ‘red’ triage categories, compared with the ‘green’ category (p=0.011). ETP also reduced the time to test for those who were subsequently found to have a major CC oesophageal motility diagnosis compared with those with minor CC disorders and normal motility (p=0.004). The ETP did not affect the yield or timing of acid reflux studies.ConclusionETPs can effectively prioritise patients with oesophageal motility disorders and may therefore have a role beyond the current pandemic.

Gastroesophageal reflux disease and salivary pepsin in patients with heterotopic gastric mucosa in the upper esophagus

Summary Background Heterotopic gastric mucosa in the upper esophagus (HGMUE) is reported to be related to gastroesophageal reflux disease (GERD). This study investigated the prevalence of GERD and the use of salivary pepsin to diagnose gastroesophageal reflux, especially proximal reflux, in HGMUE patients. Methods One hundred and fifty-three HGMUE patients and 50 healthy volunteers were studied. All subjects took a reflux symptom index questionnaire (RSI); underwent endoscopy, barium esophagogram, high-resolution manometry (HRM), and 24-hour multichannel intraluminal impedance-pH-metry (MII-pH); and salivary pepsin test. Results Ninety-five (62.1%) HGMUE patients but no control subjects were diagnosed with GERD. The salivary pepsin concentration, RSI score, DeMeester score, acid exposure time (AET), total reflux episodes, proximal acidic reflux episodes, and proximal weakly acidic reflux episodes were significantly higher in the HGMUE group than in the control group (P < 0.05). The salivary pepsin test showed a sensitivity of 85.9% and specificity of 56.9% for diagnosing GERD using the optimal cut-off value of 75 ng/mL. One hundred and seven (69.9%) and 46 (30.1%) HGMUE patients were categorized as pepsin (+) and pepsin (−), respectively when 75 ng/mL was used as a cut-off value. Male sex, RSI, AET, and proximal acid reflux episodes were positive predictive factors for the occurrence of pepsin (+) in HGMUE patients. Conclusions GERD, especially GERD with proximal acid reflux and related symptoms, was common in HGMUE patients. The salivary pepsin test could be an additional useful test for testing reflux in HGMUE patients, but it will not replace the MII-pH.