Prediction of the efficacy of proton-pump inhibitors in patients with contact granuloma using 24-hour combined dual channel pH/impedance monitoring.

OBJECTIVES: We aimed to evaluate the treatment outcomes of proton-pump inhibitors (PPIs) in patients with contact granuloma (CG) and to investigate the parameters of 24 h combined dual channel pH/impedance (24 h pH/MII) monitoring, which are reliable for predicting the response to PPI of CG patients. METHODS: We reviewed the medical records of patients with CG who had been treated with PPIs and had completed more than 6 months of follow-up. We classified the patients into two groups (cured vs. persistent), according to their PPI treatment outcomes. Reflux events were categorized into three groups based on pharyngeal pH during reflux: 1) acid reflux (pH < 4), 2) weak acid reflux (4 < pH < 7), and 3) weak alkaline reflux (pH >7), as detected by a proximal probe. We compared the results of 24h-pH/MII between the two groups and used receiver operating characteristic curve (ROC) analysis to determine the cutoff values of significant parameters for predicting responses to PPIs. RESULTS: Among 22 patients who completed at least 6 months of PPI treatment and follow-up, weak acid reflux events were more frequently observed in persistent group than in the cured group (p = 0.046), and the proportion of weak acid reflux was also higher in the persistent group (p = 0.031) than in the cured group. Reliable parameters predictive of a poor response to PPIs were a number of weak acid reflux events ≥ 11 (area under the curve [AUC], 0.775; p = 0.03) and a proportion of weak acid reflux events ≥ 56.7 % (AUC, 0.763; p = 0.038) in ROC analyses. CONCLUSION: Weak acid reflux was identified as a significant factor associated with the treatment outcomes of PPIs in patients with CG. A number of weak acid reflux events ≥ 11 is considered to be the most reliable predictor of a poor response to PPIs in patients with CG.

ChatGPT-4 accuracy for patient education in laryngopharyngeal reflux.

INTRODUCTION: Chatbot Generative Pre-trained Transformer (ChatGPT) is an artificial intelligence-powered language model chatbot able to help otolaryngologists in practice and research. The ability of ChatGPT in generating patient-centered information related to laryngopharyngeal reflux disease (LPRD) was evaluated. METHODS: Twenty-five questions dedicated to definition, clinical presentation, diagnosis, and treatment of LPRD were developed from the Dubai definition and management of LPRD consensus and recent reviews. Questions about the four aforementioned categories were entered into ChatGPT-4. Four board-certified laryngologists evaluated the accuracy of ChatGPT-4 with a 5-point Likert scale. Interrater reliability was evaluated. RESULTS: The mean scores (SD) of ChatGPT-4 answers for definition, clinical presentation, additional examination, and treatments were 4.13 (0.52), 4.50 (0.72), 3.75 (0.61), and 4.18 (0.47), respectively. Experts reported high interrater reliability for sub-scores (ICC = 0.973). The lowest performances of ChatGPT-4 were on answers about the most prevalent LPR signs, the most reliable objective tool for the diagnosis (hypopharyngeal-esophageal multichannel intraluminal impedance-pH monitoring (HEMII-pH)), and the criteria for the diagnosis of LPR using HEMII-pH. CONCLUSION: ChatGPT-4 may provide adequate information on the definition of LPR, differences compared to GERD (gastroesophageal reflux disease), and clinical presentation. Information provided upon extra-laryngeal manifestations and HEMII-pH may need further optimization. Regarding the recent trends identifying increasing patient use of internet sources for self-education, the findings of the present study may help draw attention to ChatGPT-4's accuracy on the topic of LPR.

Effect of Laryngopharyngeal Reflux and Potassium-Competitive Acid Blocker (P-CAB) on the Microbiological Comprise of the Laryngopharynx.

OBJECTIVE: To probe the microbiota composition progressing from healthy individuals to those with laryngopharyngeal reflux disease (LPRD) and subsequently undergoing potassium-competitive acid inhibitor (P-CAB) therapy. STUDY DESIGN: Prospective case-control study. SETTING: Academic Medical Center. METHODS: Forty patients with LPRD and 51 patients without LPRD were recruited. An 8-week P-CAB therapy was initiated (post-T-LPRD), and 39 had return visits. In total, 130 laryngopharyngeal saliva samples were collected and sequenced by targeting the V3-V4 region of the 16S ribosomal RNA (rRNA) gene using an Illumina MiSeq. Amplicon sequence variants (ASVs) and clinical indices were analyzed. RESULTS: Alpha and beta diversities were compared among the non-LPRD, LPRD, and post-T-LPRD groups, and the Observed_ASVs were not significantly different. At the same time, the Shannon and Simpson indices, unweighted Unifrac, weighted Unifrac, and binary Jaccard distance were significantly different between non-LPRD and LPRD groups. In addition, significant differences were found in the abundance of Streptococcus, Prevotella, and Prevotellaceae in the LPRD versus non-LPRD groups, and Neisseria, Leptotrichia, and Allprevotella in the LPRD versus post-T-LPRD groups. The genera model was used to distinguish patients with LPRD from those without, and a better receiver operating characteristic curve was formed after combining the clinical indices of reflux symptom index, reflux finding score, and pepsin, with an area under the curve of 0.960. CONCLUSION: Laryngopharyngeal microbial communities changed after laryngopharyngeal reflux and were modified further after P-CAB treatment, which provides a potential diagnostic value for LPRD, especially when combined with clinical indices.

Is there a role for voice therapy in the treatment of laryngopharyngeal reflux? A pilot study.

Objective: The aim of this study was to compare the efficacy of voice therapy combined with standard anti-reflux therapy in reducing symptoms and signs of laryngopharyngeal reflux (LPR). Methods: A randomised clinical trial was conducted. Fifty-two patients with LPR diagnosed by 24 h multichannel intraluminal impedance-pH monitoring were randomly allocated in two groups: medical treatment (MT) and medical plus voice therapy (VT). Clinical symptoms and laryngeal signs were assessed at baseline and after 3 months of treatment with the Reflux Symptom Index (RSI), Reflux Finding Score (RFS), Voice Handicap Index (VHI) and GRBAS scales. Results: Groups had similar scores at baseline. At 3-month follow-up, a significant decrease in RSI and RFS total scores were found in both groups although it appeared to be more robust in the VT group. G and R scores of the GRBAS scale significantly improved after treatment in both groups, with better results in the VT group. The VHI total score at 3 months improved more in the VT group (VHI delta 9.54) than in the MT group (VHI delta 5.38) (p < 0.001). Conclusions: The addition of voice therapy to medications and diet appears to be more effective in improving treatment outcomes in subjects with LPR. Voice therapy warrants consideration in addition to medication and diet when treating patients with LPR.

The Tibetan Formula Cong zhi 6 in the ORL (ENT) Practice: Experiences with Laryngopharyngeal Reflux.

BACKGROUND: Laryngopharyngeal reflux (LPR) is a frequent condition; in European countries, the prevalence can be estimated as 10-30% of the general population. Treatment includes lifestyle measures and highly dosed proton pump inhibitors (PPIs) over at least 4 weeks. However, PPIs are not unproblematic due to their potential side effects and the known phenomenon of rebound acid hypersecretion. Cong zhi 6 is a multi-herbal Tibetan formula additionally containing calcium carbonate and is available in several European countries as a food supplement Padma Aciben/Padma AciTib. CASE REPORT: Ten patients with LPR took Cong zhi 6. The course of the complaints was documented, and the data were retrospectively analysed. Clinical symptoms as assessed with the Reflux Symptom Index (RSI) questionnaire and the findings in laryngoscopy with the Reflux Finding Score (RFS) both showed marked improvement of several symptoms. The number of patients with pathological LPR sum score was significantly reduced from 8 to 2 patients and from 10 to 1 patient in RSI and RFS, respectively. The mean sum scores were reduced from 18.1 to 8.4 (RSI) and from 12.9 to 4.4 (RFS), respectively. Also, other gastrointestinal symptoms, such as abdominal pain, bloating, feeling of fullness, and nausea, which are usually associated with functional dyspepsia and irritable bowel syndrome, were markedly improved (reduction of mean score of the 3 most frequent symptoms by 77-87%). CONCLUSION: Standard medical treatment for LPR consists in high dosed PPI for at least 4 weeks, which is known for several side effects and does not treat reliable the nonacid component of LPR of pepsin or other gastric enzymes. Therefore, other medical treatment options are urgently needed. The promising data of this case series suggest that the Tibetan herbal formula Cong zhi 6 may be a treatment option in LPR and related gastrointestinal symptoms and warrant further research.Der laryngopharyngeale Reflux (LPR) ist eine häufige Erkrankung. In europäischen Ländern wird die Prävalenz in der Gesamtbevölkerung auf 10­30% geschätzt. Die Behandlung beinhaltet Ernährungs- und Verhaltensänderung sowie die Gabe hochdosierter Protonen-Pumpen-Hemmer (PPI) über mindestens 4 Wochen. PPI sind jedoch aufgrund ihrer hohen potenziellen Nebenwirkungen und des bekannten Rebound-Phänomens der sauren Magensafthypersekretion nicht unproblematisch. Cong zhi 6 ist eine tibetische Rezeptur aus einem Vielpflanzengemisch sowie zusätzlich Calciumcarbonat und ist in einigen europäischen Ländern als Nahrungsergänzungsmittel Padma Aciben/Padma AciTib erhältlich.Zehn Patienten mit laryngo-pharyngealem Reflux (LPR) nahmen Cong zhi 6 ein. Der Beschwerdeverlauf wurde dokumentiert und die Daten retrospektiv analysiert. Die klinischen Symptome, die mithilfe des Reflux Symptom Index (RSI) Fragebogens erfasst wurden und die mittels des Reflux Finding Score (RFS) beurteilten laryngoskopischen Befunde zeigten beide eine deutliche Verbesserung verschiedener Symptome. Die Zahl der Patienten mit pathologischen LPR-Summenscore reduzierte sich signifikant, im RSI von 8 auf 2 und im RFS von 10 auf 1 Patienten. Der mittlere Summenwert sank von 18.1 auf 8.4 (RSI) und von 12.9 auf 4.4 (RFS). Des Weiteren zeigte sich auch bei anderen gastrointestinalen Beschwerden, wie Bauchschmerzen, Blähungen, Völlegefühl und Übelkeit, die normalerweise mit funktioneller Dyspepsie oder Reizdarm zusammenhängen, eine deutliche Verbesserung (durchschnittliche Verringerung des Scores der drei häufigsten Symptome um 77­87%).Die medikamentöse Standardbehandlung bei LPR besteht aus der hochdosierten PPI-Gabe über mindestens 4 Wochen, die jedoch für verschiedene Nebenwirkungen bekannt ist und die nicht-saure Komponente von LPR, wie Pepsin oder andere digestive Enzyme, nicht mitbehandelt. Daher sind andere medikamentöse Behandlungsmöglichkeiten dringend erforderlich. Die vielversprechenden Daten dieser Fallserie deuten darauf hin, dass die tibetische Pflanzenrezeptur Cong zhi 6 eine Behandlungsoption bei LPR sowie deren gastrointestinalen Symptome darstellt und rechtfertigen weitere Studien.

Ocular Surface Disease as Extraesophageal Gastroesophageal Reflux Disease Manifestation: A Specific Therapeutic Strategy.

PURPOSE: Gastroesophageal reflux disease (GERD) and laryngopharyngeal reflux (LPR) are common gastrointestinal disorders with extraesophageal manifestations (EGERD). Studies showed a correlation between GERD/LPR and ocular discomfort. Our aim was to report the prevalence of ocular involvement in patients with GERD/LPR, describe clinical and biomolecular manifestations, and provide a treatment strategy for this novel EGERD comorbidity. METHODS: Fifty-three patients with LPR and 25 healthy controls were enrolled in this masked randomized controlled study. Fifteen naive patients with LPR were treated with magnesium alginate eye drops and oral therapy (magnesium alginate and simethicone tablets) with a 1-month follow-up. Clinical ocular surface evaluation, Ocular Surface Disease Index questionnaire, tear sampling, and conjunctival imprints were performed. Tear pepsin levels were quantified by ELISA. Imprints were processed for human leukocyte antigen-DR isotype (HLA-DR) immunodetection and for HLA-DR, IL8, mucin 5AC (MUC5AC), nicotine adenine dinucleotide phosphate (NADPH), vasoactive intestinal peptide (VIP), and neuropeptide Y (NPY) transcript expression (PCR). RESULTS: Patients with LPR had significantly increased Ocular Surface Disease Index ( P < 0.05), reduced T-BUT ( P < 0.05), and higher meibomian gland dysfunction ( P < 0.001) compared with controls. After treatment, tear break-up time (T-BUT) and meibomian gland dysfunction scores improved to normal values. Pepsin concentration increased in patients with EGERD ( P = 0.01) and decreased with topical treatment ( P = 0.0025), significantly. HLA-DR, IL8, and NADPH transcripts were significantly increased in the untreated versus controls and comparable significant values were obtained after treatment ( P < 0.05). MUC5AC expression significantly increased with treatment ( P = 0.005). VIP transcripts were significantly higher in EGERD than in controls and decreased with the topical treatment ( P < 0.05). No significant changes were observed in NPY. CONCLUSIONS: We report an increase in prevalence of ocular discomfort in patients with GERD/LPR. The observations of VIP and NPY transcripts demonstrate the potential neurogenic nature of the inflammatory state. Restoration of the ocular surface parameters suggests the potential usefulness of topical alginate therapy.

Salivary pepsin as an independent predictor of treatment response for laryngopharyngeal reflux: prospective cohort study with multivariate analysis.

To analyze the predictive value of salivary pepsin for treatment outcomes in laryngopharyngeal reflux (LPR) using multivariate analysis that includes various associated factors. This prospective cohort study was conducted between August 2020 and August 2022. Patients with LPR who had symptoms lasting more than 1 month and a reflux symptom index (RSI) of 14 or higher were enrolled. The participants received a 2-month regimen of proton pump inhibitors (PPIs) treatment and lifestyle modification. Salivary pepsin was checked using fasting saliva before treatment. Salivary pepsin was detected more frequently in the good treatment response group (61.1%), compared to 14.3% in the poor response group. Similarly, patients with higher compliance to lifestyle modifications (> 90%) had a higher chance of a good response (91.7%) compared to those with lower compliance, who had a 53.8% chance of a good response. Other clinical factors have no significant association with treatment response. In multivariate analysis, both pretreatment salivary pepsin and higher compliance with lifestyle modification were found to be independent factors for treatment response (OR 14.457, CI 1.075 ~ 194.37 for both). This study found that positive salivary pepsin and strict lifestyle modification are independent predictors of treatment outcomes in LPR.

Is empiric proton pump inhibition in patients with symptoms of extraesophageal gastroesophageal reflux justified?

BACKGROUND: The prevalence of gastroesophageal reflux disease (GERD) has had a marked increase in Western countries with a paralleling interest in extraesophageal (EE) manifestations of GERD, including laryngopharyngeal reflux (LPR). There are considerable differences in clinical practice between gastroenterologists, otolaryngologists and pulmonologists. METHODS: In this narrative review we address some of these controversies concerning EE manifestations of GERD and LPR. RESULTS: It is disputed whether there is causal relationship between reflux and the numerous symptoms and conditions suggested to be EE manifestations of GERD. Similarly, the pathophysiology is uncertain and there are disagreements concerning diagnostic criteria. Consequently, it is challenging to provide evidence-based treatment recommendations. A significant number of patients are given a trial course with a proton pump inhibitor (PPI) for several months before symptoms are evaluated. In randomized controlled trials (RCTs) and meta-analyses of RCTs PPI treatment does not seem to be advantageous over placebo, and the evidence supporting that patients without verified GERD have any benefit of PPI treatment is negligible. There is a large increase in both over the counter and prescribed PPI use in several countries and a significant proportion of this use is without any symptomatic benefit for the patients. Whereas short-term treatment has few side effects, there is concern about side-effects after long-term use. Although empiric PPI treatment for suspected EE manifestations of GERD instead of prior esophageal 24-hour pH and impedance monitoring is included in several guidelines by various societies, this practice contributes to overtreatment with PPI. CONCLUSION: We argue that the current knowledge suggests that diagnostic testing with pH and impedance monitoring rather than empiric PPI treatment should be chosen in a higher proportion of patients presenting with symptoms possibly attributable to EE reflux.

Transcutaneous electrical acupoint stimulation for suspected laryngopharyngeal reflux disease.

PURPOSE: To determine the efficacy of transcutaneous electrical acupoint stimulation (TEAS) combined with proton pump inhibitor (PPI) therapy on symptoms and signs of patients with suspected laryngopharyngeal reflux disease (LPRD). METHODS: This was a prospective randomized controlled study. Seventy patients with reflux symptom index (RSI) > 13 and reflux finding score (RFS) > 7 were recruited and received PPI alone (control group) or TEAS combined with PPI (experimental group) for 12 weeks. Patients in the experimental group received TEAS at Tiantu (RN22), Renying (ST9), and Neiguan (PC6) once a day, five times a week. RSI, RFS, throat pain visual analog score (VAS), and LPR-health-related quality-of-life (LPR-HRQL) scores were evaluated at baseline and after 4 and 12 weeks. RESULTS: The decreases in total RSI and RFS, along with several subscores, were significantly higher in the experimental group than in the control group after 12 weeks (P < 0.05). The throat pain VAS and LPR-HRQL scores decreased significantly at 4 and 12 weeks after treatment in both groups, with significant differences between the groups (P < 0.001). No severe adverse events occurred, and the rates of adverse events were similar between the two groups. CONCLUSION: Compared with PPI alone, TEAS combined with PPI showed a significantly greater improvement in symptoms, signs, and quality of life in the treatment of LPRD without increasing the occurrence of adverse effects. Therefore, TEAS could serve as a useful and safe treatment method for LPRD. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2100046755.

Diagnosing Laryngopharyngeal Reflux: A Comparison between 24-hour pH-Impedance Testing and Pharyngeal Probe (Restech) Testing, with Introduction of the Sataloff Score.

OBJECTIVE: The purpose of this study was to compare the diagnostic utility of pH monitoring using 24-hour esophageal pH-Impedance (HEMII-pH) testing versus pharyngeal pH (Restech) testing (Respiratory Technology Corporation, Houston, Texas) for diagnosing laryngopharyngeal reflux (LPR). METHODS: Retrospectively, patients were reviewed who had completed a Reflux Symptom Index (RSI) survey and stroboscopy within 60 days before or after undergoing simultaneous esophageal pH-Impedance monitoring and Restech testing. Reflux Finding Score (RFS) was determined by 4 blinded observers. 80.45% of patients were on anti-reflux medications at the time of study and had incomplete response to treatment for reflux. Improvement on reflux treatment was determined by evaluating presenting pre-pH monitoring RFS, post treatment RFS, and improvement of symptoms. Pearson correlation coefficients were calculated to assess relationships among RSI, RFS, and test results from HEMII-pH and Restech tests. RESULTS: Eighty-seven patients were included in the analysis. The inter-rater reliability of the RFS determination was 74.57%, and the intra-rater reliability was 67.00%. Subjects who had a positive RYAN Score had a significant correlation with RFS (r of 0.222 and p-value of 0.0492). There was no correlation between RFS and number or percent time of reflux events, longest event, total number of events, or percent of time at alkaline pH for either HEMII-PH or Restech test. RSI correlated better with HEMII-pH test than with Restech for percent time spent in both upright (r of 0.226 and p-value of 0.029) and supine position (r of 0.261 and a p-value of 0.032). Restech correlated better with total patient symptom Scores including cough, heartburn, burping, and throat clearing, with a r of 0.242 and a p-value of 0.048. Restech detected more percent time in reflux for total reflux, supine reflux, and upright reflux (p-value less than 0.0001). Restech also detected longer event times than Impedance (p-value of less than 0.0001). When diagnosis of LPR is based on the definition of CRC, the Sataloff Score test had 70.45% sensitivity and 80.95% specificity. The RYAN Score had a sensitivity of 72%, and a specificity of 56.45%, and the Wu Score had a sensitivity of 62.16%, and specificity of 54.05%. When the Sataloff and Wu Score were used together, the sensitivity was 71.45%, specificity 100%, positive predictive value of 100%, and a negative predictive value of 59.46%. CONCLUSION: The amount of time of reflux events correlates with symptoms better than the number of events. The HEMII-pH test was able to detect more events of pH<4 than Restech, possibly because there might have been more acid events below than above the upper esophageal sphincter, while Restech detected more total events. Restech recorded longer event times than HEMII-pH test. Since length of time correlates with RFS (probably reflecting laryngeal inflammation), and since laryngeal clearance of acid is more similar to pharyngeal than esophageal clearance, this finding might prove valuable clinically. The Sataloff Score has a sensitivity of 70.45%, and a specificity of 80.95% and appears useful clinically to detect mild to moderate that is missed by the RYAN Score. A combination of Sataloff Score and Wu Score may be clinically valuable to identify LPR with an increased sensitivity of 71.45% and increased specificity of 100%. The Wu Score is not yet available for the general clinical use, but the Sataloff Score is.

Chronic Course, Weaning, and Awareness of Patients With Reflux Toward Proton Pump Inhibitor Therapy.

OBJECTIVES: To assess the feasibility of middle-term proton pump inhibitor (PPI) weaning in patients with laryngopharyngeal reflux (LPR) and evaluate patient awareness of PPI adverse events. METHODS: We conducted a cross-sectional study of 100 LPR patients treated with an association of diet, PPIs, and alginate. Patients were followed from September 2016 to May 2020. At the end of the initial 3-to-6 months therapeutic period, LPR patients were weaned from PPIs and instructed to respect diet and stress management over the long-term. The 3-year symptom recurrence rate, PPI use, and patient awareness of PPI adverse events were assessed. RESULTS: Sixty-seven patients completed the evaluation. Twenty-seven patients (40.3%) reported a chronic course of LPR-symptoms, requiring chronic or occasional PPI use. LPR symptom recurrence occurred 1-to-2 or 3-to-5 times yearly in 8.9% and 20.9% of patients, respectively. Recurrences were managed by short-term diet, alginate, or PPI intake. The remaining patients (29.9%) did not report middle-term LPR recurrence. The 3-year weaning rate of occasional or chronic use of PPIs was 64.2%. Among participants, 26.8% were aware of PPI-related adverse events, most frequently through physicians (33%), online sources (17%), and friends or family (17%). Nonresponder patients were significantly more aware of PPI adverse events than responders (P = 0.029). PPI-attributed adverse events occurred in 29.8% of patients. CONCLUSION: Sixty-four percent of LPR patients treated with PPIs were weaned at 3-year posttreatment time. Different forms of LPR may exist regarding symptom relief, recurrences, and chronic course.

Multidimentional assessment of voice quality in patients with laryngopharyngeal reflux disease.

<b><br>Introduction:</b> Gastroesophageal Reflux Disease (GERD) is a common disorder in world population. As a result of the regurgitation of acid content from the stomach to laryngopharynx and larynx, secondary damage of laryngeal mucosa occur, which is highly sensitive to hydrochloric acid, and morphological changes are observed. Symptomatology of laryngopharyngeal reflux is varied which makes differential diagnosis difficult.</br> <b><br>Aim:</b> The aim of the study was the assessment of voice quality, morphological changes in larynx as well as etiology of Laryngopharyngeal Reflux Disease.</br> <b><br>Material and method:</b> The severity of dysphonia was classified using perceptual and acoustic methods as well as RSI. Morphological control was performed using HSDI technique and RFS. Etiological factors were examined basing on barofunction of upper esophageal sphincter and 24-hour pH-metry of air exhaled expressed in Ryan score.</br> <b><br>Results:</b> In the majority of patients with Laryngopharyngeal Reflux, dysphonia was recognized, intensified especially in women (G3R2B0A0S3), which was confirmed in Yanagihara classification (type III) and parameters of acoustic analysis. Voice disorders were the most frequently the result of edema and congestion of interarytenoid area, aytenoids and vocal folds. Those symptoms were caused by the decrease of upper esophageal sphincter tension and acidity of exhaled air which was confirmed in 24-hour pHmetry.</br> <b><br>Conclusions:</b> It is important to educate physicians and patients about the possibilty of negative impact of reflux disease on the occurrence of voice quality disorders. Current diagnostic methods for dysphonia guarantee accurate recognition and therapeutic success improving the prognoses of patients with Laryngopharyngeal Reflux.</br>.

Treating and Managing Laryngopharyngeal Reflux Disease in the Over 65s: Evidence to Date.

Purpose: The clinical presentation and therapeutic outcomes of elderly patients may be different from those in younger populations, leading to additional diagnostic and therapeutic difficulties. The present study reviewed the findings on the epidemiology, and clinical, diagnostic, and therapeutic outcomes of elderly patients with laryngopharyngeal reflux (LPR). Methods: A PubMed, Cochrane Library, and Scopus literature search was conducted on the epidemiological, clinical, diagnostic, and therapeutic findings of elderly LPR patients. Findings: The prevalence of LPR in the elderly population remains unknown. From a clinical standpoint, older LPR patients report overall lower symptom scores and related quality-of-life outcomes at the time of the diagnosis. The required treatment time to obtain symptom relief appears to be longer in older compared with younger patients. Particular attention needs to be paid to prolonged medication use because the elderly population is characterized by polypharmacy and there is a higher risk of proton-pump inhibitor (PPI) interactions and adverse events. The plasma clearance of most PPIs is reduced with age, which must be considered by practitioners in the prescription of antireflux therapy. Conclusion: The clinical presentation and treatment efficacy of elderly LPR patients differ from those in younger patients. Practitioners need to carefully consider the risk of drug interactions and adverse events in elderly patients.

Observations of increased gastroesophageal reflux symptomology in an anhydrous ammonia exposed population.

OBJECTIVE: This case series describes a cohort of patients exposed to anhydrous ammonia vapors with clinical findings of laryngopharyngeal reflux (LPR). The study characterizes the identification of LPR as a consequence of vapor inhalation and the utility of PPI therapy in LPR secondary to inhalational ammonia exposure. METHODS: This is a case series of 15 patients exposed to anhydrous ammonia from a single chemical spill who experienced LPR several months after exposure. Symptoms of LPR were assessed at their initial consultation and by phone at least 30 days after treatment with low-dose PPI or diet modification. At this visit, patients underwent complete head and neck examination and flexible direct laryngoscopy. RESULTS: 15 patients were available for analysis before and after treatment. 93.3 % experienced at least three cardinal symptoms of LPR. 66 % of these patients had at least one LPR finding on flexible laryngoscopy. 73 % were treated with daily standard dose PPI, and 82 % of these patients experienced reduction of symptoms after 30 days of PPI treatment. Four of 15 patients were not taking the PPI as prescribed, and only one of these patients had resolution of LPR symptoms. CONCLUSION: We conclude that there is an association between anhydrous ammonia exposure and the development of LPR symptoms. In this study, treatment with PPIs was successful in reducing symptoms for most patients, and patients who did not receive PPIs experienced symptoms for a longer time.

Meta-analysis of Proton Pump Inhibitors in the Treatment of Pharyngeal Reflux Disease.

The present study aimed to examine the safety and healing effects of proton pump inhibitors (PPIs) in people with laryngopharyngeal reflux disease (LPRD). To find all relevant studies published before April 1, 2022, we searched the PubMed, Embase, Web of Science, Clinical Trials, Cochrane Library, CNKI, and Wanfang databases. For SLE, we looked for all randomized controlled clinical trials related to PPIs versus placebo-controlled treatment of LPRD. Overall efficiency, reflux symptom index (RSI), reflux finding score (RFS), improvement in cough and hoarseness, and adverse reactions were compared using the Review Manager 5.3. Using the reflux symptom index (RSI) as an outcome indicator for efficacy assessment, the PPI group showed significant improvement compared with the placebo group [MD = 3.35, 95% CI (1.34, 5.37, P < 0.05)]. In terms of overall efficacy, the PPI group showed effectiveness, but its efficacy was not statistically significantly dissimilar from that of the placebo group [OR = 1.62, 95% CI (0.89, 2.95), P > 0.05].

The effects of Helicobacter pylori eradication therapy on salivary pepsin concentration in patients with laryngopharyngeal reflux.

OBJECTIVE: To investigate the effect of Helicobacter pylori (HP) eradication therapy on salivary pepsin concentration in laryngopharyngeal reflux (LPR) patients with HP infection. MATERIALS AND METHODS: A total of 477 patients with suspected LPR were enrolled from June 2020 to September 2021. Reflux symptom index, reflux finding score, the positive rates and disintegrations per minute values of HP infection detected by 14C urea breath test and salivary pepsin concentrations analyzed using enzyme-linked immunosorbent assay were compared in LPR patients and non-LPR patients with or without HP infection. HP-positive patients were treated with HP eradication therapy while HP-negative patients with PPI therapy. RESULTS: The scores of nagging cough (0.88 vs. 0.50, P = 0.035), erythema or hyperemia (1.93 vs. 1.78, P = 0.035) and vocal fold edema (1.04 vs. 0.85, P = 0.025) were higher in the LPR (+) Hp (+) subgroup than in LPR (+) Hp (-) subgroup. The concentrations of salivary pepsin in the Hp (+) subgroup were higher than in the Hp (-) subgroup either in LPR patients (75.24 ng/ml vs. 61.39 ng/ml, P = 0.005) or the non-LPR patients (78.42 ng/ml vs. 48.96 ng/ml, P = 0.024). Compared to baseline (before treatment), scores of nagging cough (0.35 vs. 0.84, P = 0.019) and erythema or hyperemia (1.50 vs. 1.83, P = 0.039) and the concentrations of salivary pepsin (44.35 ng/ml vs. 74.15 ng/ml, P = 0.017) in LPR patients with HP infection decreased after HP treatment; yet, this was not observed for the LPR patients without HP infection treated with PPI only (P > 0.05). CONCLUSION: HP infection may aggravate the symptoms and signs of LPR patients, partly by increasing their salivary pepsin concentration.

Trial of transcutaneous electrical acupoint stimulation in laryngopharyngeal reflux disease: study protocol for a randomized controlled trial.

BACKGROUND: Patients with persistent globus sensation, throat clearing, chronic cough, hoarseness, and other throat symptoms account for a large proportion of patients in ears, nose, and throat clinics. Laryngopharyngeal reflux disease (LPRD) is increasingly valued by otolaryngologists. Transcutaneous electrical acupoint stimulation (TEAS) is possibly a new method for the treatment of LPRD. This trial aims to determine whether TEAS combined with proton pump inhibitor (PPI) is better than PPI alone in the treatment of LPRD. METHODS: This prospective randomized controlled trial will be implemented in a tertiary hospital in China. Seventy patients diagnosed with LPRD will be randomly assigned to the TEAS + PPI group (intervention group) or PPI group (control group), at a ratio of 1:1. In addition to using PPI, the intervention group will receive TEAS at four groups of acupoints, and each group will be treated for 15 min, once for 60 min, five times a week, for 12 weeks, 60 times. The main outcome will be changes in the Reflux Symptom Index scores at 4, 12, and 24 weeks after treatment. The secondary outcomes will include changes in the reflux finding score, Laryngopharyngeal Reflux-Health-related Quality of Life score, and throat pain visual analog scale score. DISCUSSION: This trial will explore the feasibility of TEAS combined with PPI for the treatment of LPRD and provide potential evidence for its effectiveness and safety. The results of this study will be published in a peer-reviewed journal. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100046755 . Registered on May 28, 2021.

'Persistent throat symptoms' versus 'laryngopharyngeal reflux': a cross-sectional study refining the clinical condition.

OBJECTIVE: Many patients are assessed for chronic symptoms including: dysphonia, 'globus', throat clearing, postnasal secretions and cough; commonly grouped together and attributed to 'laryngopharyngeal reflux'. This study aimed to explore a clinical trial's baseline dataset for patterns of presenting symptoms, which might provide a more rational basis for treatment. DESIGN: Baseline data were analysed for participants entering the Trial Of Proton-Pump Inhibitors in Throat Symptoms: age, body mass index, Reflux Symptom Index, Comprehensive Reflux Symptom Score, Laryngopharyngeal Reflux-Health-related Quality of Life questionnaire and Reflux Finding Score (RFS-endoscopic examination). The relationships between the questionnaires and demographic factors were assessed. Exploratory factor analysis (EFA) was conducted on individual symptom items in the combined questionnaires. The EFA factors were applied to a Cluster Analysis of participants, to explore the presence of identifiable patient. RESULTS: Throat clearing and globus were the highest ranked scores in the 344 participants. Increasing age was inversely associated with symptom severity (p<0.01). There was no relationship between the RFS and any of the three questionnaires. EFA resulted in a seven-factor model with clinically meaningful labels: voice, cough, gastrointestinal symptoms, airway symptoms and dysphagia, throat clearing, lump in throat, and life events. Cluster analysis failed to demonstrate any clinically meaningful clusters of patients. CONCLUSION: This study offers a framework for future research and demonstrates that individual symptoms cannot be used to group patients. The analysis supports the use of a broad 'umbrella' term such as persistent throat symptoms. TRIAL REGISTRATION NUMBER: ISRCTN38578686.

Alginates for Protection Against Pepsin-Acid Induced Aerodigestive Epithelial Barrier Disruption.

OBJECTIVE: Gastroesophageal reflux disease (GERD) and laryngopharyngeal reflux (LPR) are chronic conditions caused by backflow of gastric and duodenal contents into the esophagus and proximal aerodigestive tract, respectively. Mucosal barrier dysfunction resultant from the synergistic actions of chemical injury and the mucosal inflammatory response during reflux contributes to symptom perception. Alginates effectively treat symptoms of mild to moderate GERD and have recently shown benefit for LPR. In addition to forming a "raft" over gastric contents to reduce acidic reflux episodes, alginates have been found to bind the esophageal mucosa thereby preserving functional barrier integrity measured by transepithelial electrical resistance. The aim of this study was to further examine the topical protective capacity of alginate-based Gaviscon Advance (GA) and Double Action (GDA) against pepsin-acid mediated aerodigestive epithelial barrier dysfunction in vitro. STUDY DESIGN: Translational. METHODS: Immortalized human esophageal and vocal cord epithelial cells cultured in transwells were pretreated with liquid formula GA, GDA, matched viscous placebo solution, or saline (control), then treated for 1 h with saline, acid (pH 3-6) or pepsin (0.1-1 mg/ml) at pH 3-6. Endpoint measure was taken of horseradish peroxidase (HRP) allowed to diffuse across monolayers for 2 h. RESULTS: Pepsin (0.1-1 mg/ml) at pH 3-6 increased HRP flux through cultures pretreated with saline or placebo (p < 0.05); acid alone did not. GA and GDA prevented barrier dysfunction. CONCLUSIONS: GA and GDA preserved epithelial barrier function during pepsin-acid insult better than placebo suggesting that protection was due to alginate. These data support topical protection as a therapeutic approach to GERD and LPR. Laryngoscope, 132:2327-2334, 2022.

Acoustic measurements are useful therapeutic indicators of patients with dysphonia-related to reflux.

OBJECTIVES: The objective is to study the usefulness of acoustic measurements as therapeutic outcomes for patients with dysphonia related to laryngopharyngeal reflux (LPR). METHODS: From September 2019 to April 2021, 120 patients with LPR at the hypopharyngeal-esophageal multichannel intraluminal impedance pH-monitoring (HEMII-pH) were prospectively recruited from three University Hospitals. They were divided in two groups regarding the presence of dysphonia. The treatment consisted of a combination of diet, proton-pump inhibitors, magaldrate and alginate for 3-6 months. The following clinical and acoustic evaluations were studied regarding groups at baseline, 3- and 6-month posttreatment: reflux symptom score (RSS), reflux sign assessment (RSA), percent jitter, percent shimmer and noise-to-harmonic ratio (NHR). RESULTS: A total of 109 patients completed the evaluations, accounting for 49 dysphonic and 60 non-dysphonic individuals. HEMII-pH, gastrointestinal endoscopy, baseline clinical and acoustic features were comparable between groups. RSS and RSA significantly improved from pre- to 3-month posttreatment in both groups. Jitter, Shimmer and NHR significantly improved from pre- to 3-month posttreatment in dysphonic patients, without additional 3- to 6-month posttreatment changes. Acoustic parameters did not change throughout treatment in patients without dysphonia. CONCLUSION: Acoustic measurements may be an interesting indicator of treatment in LPR patients who reported dysphonia. In this group of individuals, the evolution of acoustic parameters was consistent with the evolution of symptoms and findings.