Magnesium alginate versus proton pump inhibitors for the treatment of laryngopharyngeal reflux: a non-inferiority randomized controlled trial

Purpose Proton pump inhibitors (PPIs) are commonly prescribed for laryngopharyngeal reflux (LPR), but their efficacy remains debated. Alginates is an option for the treatment of LPR with few adverse effects. The study aimed to investigate the non-inferiority of an alginate suspension (Gastrotuss®) compared to PPIs (Omeprazole) in reducing LPR symptoms and signs. Methods A non-inferiority randomized controlled trial was conducted. Fifty patients with laryngopharyngeal symptoms (Reflux Symptom Index -RSI- ≥ 13) and signs (Reflux Finding Score -RFS- ≥ 7) were randomized in two treatment groups: (A) Gastrotuss® (20 ml, three daily doses) and, (B) Omeprazole (20 mg, once daily). The RSI and the RFS were assessed at baseline and after 2 months of treatment. Results Groups had similar RSI and RFS scores at baseline. From pre- to 2-month posttreatment, the mean RSI significantly decreased (p = 0.001) in alginate and PPI group (p = 0.003). The difference between groups in the RSI change was not significant (95%CI: − 4.2–6.7, p = 0.639). The mean RFS significantly decreased in alginate (p = 0.006) and PPI groups (p = 0.006). The difference between groups in the mean change RFS was not significant (95%CI: − 0.8; 1.4, p = 0.608). Conclusion After 2 months of treatment, LPR symptoms and signs are significantly reduced irrespective of the treatment. Alginate was non-inferior to PPIs and may represent an alternative treatment to PPIs for the treatment of LPR.

Dental Disorders and Salivary Changes in Patients with Laryngopharyngeal Reflux

Background: Laryngopharyngeal reflux (LPR) is a common inflammatory condition of the upper aerodigestive tract tissues related to the effects of gastroduodenal content reflux, characterized by a wide variety of clinical manifestations. The aim of our study was to evaluate the possible association between dental disorders and LRP, focusing on the role of salivary changes. Methods: Patient’s dental status was evaluated according to Schiff Index Sensitivity Scale (SISS), Basic Erosive Wear Examination (BEWE) and Decayed, Missing, and Filled Teeth (DMFT) scores. Reflux-associated symptoms were assessed according to Reflux symptom index (RSI). A qualitative and quantitative examination of saliva was performed. Results: Patients suffering from LPR had a higher incidence of dental disorders, regardless the presence of salivary pepsin, and thus, statistically significant higher scores of RSI (p = 0.0001), SISS (p = 0.001), BEWE (p < 0.001) and VAS (p < 0.001). Moreover, they had lower salivary flow compared with healthy patients. Conclusions: The finding of demineralization and dental caries on intraoral evaluation must raise the suspicion of LRP. Reflux treatments should also be aimed at correcting salivary alterations, in order to preserve the buffering capacity and salivary pH, thus preventing mucosal and dental damage.

Efficiency of treatment of laryngopharyngeal reflux with proton pump inhibitors depending on the CYP2C19 polymorphism

Introduction. A treatment for LFR for many years, the superiority of PPIs over placebos is still controversial. Of particular clinical importance is the metabolic rate of PPIs in hepatocytes using the cytochrome P450 system with the participation of the isoenzyme CYP2C19 and partially CYP3A4Аim. We set a goal to study the efficacy of omeprazole 20 mg in the treatment of LFR symptoms without esophageal syndrome in patients with gastroesophageal reflux (GERD), depending on the polymorphism of the CYP2C19 genotype.Мaterials and мethods. After the exclusion criteria, 100 people took part in the study, 94 people completed the study.Results. According to the results, 26.6% of patients in the study group (residents of the Moscow region) with LFR symptoms without esophageal syndrome belong to fast metabolizers of CYP2C19, 4.2% to ultrafast metabolizers, 52.1% to normal metabolizers, 16% to intermediate metabolizers and 1.1% to slow CYP2C19.Conclusions. In patients with a rapid metabolism, within 1 month after discontinuation of omeprazole, it is necessary to increase the amount of omeprazole 20 mg intake up to 2 times a day in the morning and in the evening and reduce the duration of treatment to 6 weeks.

Matrix metalloproteinase-7 induces E-cadherin cleavage in acid-exposed primary human pharyngeal epithelial cells via the ROS/ERK/c-Jun pathway

Laryngopharyngeal reflux disease (LPRD) is caused by pharyngeal mucosal damage due to the reflux of gastric contents, including acid, pepsin, and bile juice. Our previous study has demonstrated that LPRD is associated with the cleavage of E-cadherin, which is facilitated by the acid-activated matrix metalloproteinase-7 (MMP-7); however, the mechanism by which the acid activates MMP-7 remains unclear. The purpose of this study was to investigate the mechanism by which MMP-7 is activated in the pharyngeal epithelial cells that are exposed to acid. The levels of reactive oxygen species (ROS) were measured in the epithelial cells exposed to acid. To investigate the signaling mechanism of ROS in the expression of MMP-7, the mechanism of action of the mitogen-activated protein kinase was examined. The expression of various signaling factors was determined, according to the presence or absence of each inhibitor in the acid-exposed pharyngeal epithelial cells. To identify changes in the cleavage of E-cadherin, the integrity of the mucosal membrane was assessed using a transepithelial permeability test. We found that acid exposure increased the levels of ROS, phosphorylated-extracellular signal-regulated kinase (p-ERK) 1/2, and phosphorylated-c-Jun (p–c-Jun) in pharyngeal epithelial cells. The ROS inhibitor reduced the expression of p-ERK and MMP-7, while the ERK inhibitor reduced the expression of p–c-Jun and MMP-7. Moreover, the c-Jun inhibitor reduced the expression of MMP-7 and blocked the degradation of E-cadherin. In addition, decrease in the levels of immunostained E-cadherin and increase in transepithelial permeability after acid exposure were collectively alleviated by the inhibitors of ROS, ERK, and c-Jun. The degradation of E-cadherin that occurs after human mucosal cells are exposed to acid appears to be caused by an increase in the expression of MMP-7 via the ROS/ERK/c-Jun pathway, which is thought to be an important mechanism associated with the development of LPRD. Key messages • ROS is triggered when reflux occurs. • ROS regulates the transcription factor c-Jun via the ERK pathway. • The increase in MMP-7 that induces LPRD is induced via the ROS/ERK/c-Jun pathway. • This study revealed for the first time the expression mechanism of MMP-7, which is one of the causes of LPRD.

Evaluation and management of voice disorders: Our experiences

Background: Change in voice is one of the most common complains among patients visiting to ENT outpatient. The causes are numerous and need to be evaluated before approaching to curative intent of treatment. Aims and Objectives: The current study was designed with an aim to analyze the spectrum of voice disorders and their management option. Materials and Methods: Prospective study conducted between June 25, 2020, and November 30, 2021. Clinical, demographic profiles were recorded. Fiber-optic laryngoscopy was performed in all the cases. Radiology examination computed tomography/magnetic resonance imaging was supplemented only in required cases. Treatment was executed based of etiological profile analysis. Minimum 3 months follow-up was collected post-therapy. Statistical analysis was performed using Statistical Package for the Social Sciences version 24. Pearson Chi-square test was used for see the association between parameters. P-value was considered significant while being <0.05. Results: Out of 218 patients, the most patients (approx. 70%) occupied in the age group of 30–50 years. There was male predominance (76.6%). Voice change secondary to laryngopharyngeal reflux was seen in 56.4% of cases. Benign vocal fold lesions (nodule/cyst/polyp) were noticed in 26.5% of cases. Malignant lesions were seen in 1.8% of cases. Benign vocal fold lesions (polyp and cyst) were treated by microlaryngeal surgery (MLS). Pre-malignant lesion (leukoplakia) was treated with MLS stripping. Out of four malignant lesions, one was in early stage and underwent supraglottic laryngectomy while others were in advanced stage (T4) and treated by total laryngectomy. Conclusions: Voice disorders comprise wide etiological profile from reflux to malignant lesion. Timely proper evaluation followed by definitive management achieves good treatment outcomes.

The role of magnesium supplement in laryngopharyngeal reflux disease

<p class="abstract"><strong>Background:</strong> Laryngopharyngeal reflux disease (LPRD) is one of the most prevalent upper gastrointestinal disorder encountered in clinical practice and its optimal treatment is not standardized. The role of magnesium in the human body functions is often underestimated. Since magnesium (Mg) plays a major role in the regulation of smooth muscle contractionby relaxing the pyloric sphincter and enhancing gastric emptying, thereby decreasing the pressure on the LES, it was hypothesized that adding magnesium supplements along with the regular treatment for LPRD, can improve LPRD symptoms. Magnesium has a neutralizing action on the gastric acid and therefore, it may be pertinent to achieve optimal Mg intakes in patients with LPRD.</p><p class="abstract"><strong>Methods:</strong> This is a prospective study done over a period of 1 year conducted in a tertiary care hospital in central India in patients presenting with LPRD of the age group 18-65 years. </p><p class="abstract"><strong>Results:</strong> The study patients were divided into two groups-one treated with esmoprazole 40 mg capsules and alginate syrup and the other with esmoprazole capsules, alginate syrup and magnesium glycinate (250 mg) supplement. Both the groups showed appreciable improvement in their mean reflux symptom index (RSI) and reflux finding score (RFS) at 1 month and 3 months follow-up. Females showed a higher preponderance than males in the disease, symptoms and the mean RSI and RFS score.</p><p class="abstract"><strong>Conclusions:</strong> Addition of magnesium supplements along with the regular treatment for LPRD, can improve LPRD symptoms and should be considered in the treatment protocol of LPRD.</p>

Distribution and Appearance of Ki-67, IL-1α, IL-10, and PGP 9.5 in Reinke’s Oedema-Affected Larynx Tissue Compared with Control Tissue

Smoking, laryngopharyngeal reflux, and vocal fold abuse can promote the development of Reinke’s oedema, leading to vocal fold dysfunction and injury. The aim of the work was to investigate the appearance and distribution of proliferation marker Ki-67 (Ki-67), interleukin 10 (IL-10), interleukin 1 alpha (IL-1α), and protein gene peptide 9.5 (PGP 9.5) in Reinke’s oedema-affected larynx tissue. Methods: A routine histological and immunohistochemical Reinke’s oedema and control group patient analysis was conducted. We used the biotin–streptavidin biochemical method to detect Ki-67, IL-10, IL-1α, and PGP 9.5 The semiquantitative grading method was used to evaluate immunoreactive cells' appearance and local distribution. A Mann–Whitney U test and Spearman’s rank coefficient were performed. Results: A low positive correlation between IL-1α epithelial and subepithelial immunoreactive cells in the patient group was found. Mann–Whitney U tests revealed significant patient and control group immunoreactive marker differences. All examined markers showed a higher number of immunoreactive structures in the patient group. Conclusions: Intensive proliferation of the surface epithelium was observed in patient tissues. The notable increase in IL-10 positive structures indicates the dominant anti-inflammatory tissue response. An increased number of IL-1α structures in the larynx epithelium and subepithelium in the patient group is linked to inflammation, proliferation, and tissue remodelling. The PGP 9.5 expression increase is involved in the morphopathogenesis of Reinke’s oedema.