The Consistency Between Symptom Scales and Multi-time Point Salivary Pepsin Test for Diagnosing Laryngopharyngeal Reflux Disease.

OBJECTIVE: To investigate the screening diagnostic value of reflux symptom index (RSI) and reflux symptom score (RSS) for laryngopharyngeal reflux disease (LPRD). METHODS: Fifty-two patients hospitalized in the Department of Otolaryngology-Head and Neck Surgery at The Sixth Medical Center of PLA General Hospital between October 2022 and April 2023 were enrolled in the study. These patients completed the RSS, RSI scales, as well as underwent the multi-time point salivary pepsin test (MTPSPT). Cohen's kappa test and receiver operating characteristic analysis were utilized to assess and compare the diagnostic values of the RSI and RSS. RESULTS: A total of 52 patients, comprising 37 males and 15 females, with a mean age of 44 ± 12 years, were enrolled in the study. The Kappa values between RSS, RSI, and MTPSPT were found to be 0.403 (P < 0.05) and 0.192 (P < 0.05), respectively. When considering MTPSPT as the diagnostic criterion, the sensitivity and specificity of RSS were determined to be 76.70% and 76.90%, respectively, while those of RSI were 41.10% and 42.30%. Additionally, the negative predictive values for RSS and RSI stood at 77.70% and 64.70%, respectively, and their positive predictive values were 94.20% and 57.10%. Furthermore, the area under the curves (AUC) for RSS and RSI were calculated to be 0.677 (95% confidence interval [CI]: 0.464-0.742) and 0.609 (95% CI: 0.533-0.800), respectively. CONCLUSIONS: RSS had a better concordance with multi-time point salivary pepsin test results and AUC values when screening for LPRD.

Applying Lyon consensus criteria in the work-up of patients with extra-oesophageal symptoms - A multicentre retrospective study.

BACKGROUND: The diagnosis of gastro-oesophageal reflux disease (GERD) based on otolaryngologist's assessment of laryngoscopic findings remains contentious in terms of sensitivity and specificity. AIMS: To evaluate GERD prevalence, applying Lyon 2.0 Consensus criteria, in patients with extra-oesophageal symptoms undergoing laryngoscopic examination and impedance-pH monitoring. METHODS: In this retrospective assessment, we included 470 patients with extra-oesophageal symptoms, either isolated or combined with typical symptoms, who had been referred to six tertiary Italian Gastroenterology Units between January and December 2020. Of these, 274 underwent 24-h impedance-pH monitoring and laryngoscopy off PPI therapy. GERD diagnosis followed Lyon Consensus 2.0 criteria, incorporating mean nocturnal baseline impedance when pH-impedance monitoring was inconclusive. RESULTS: Laryngoscopic examination revealed pathological findings (predominantly posterior laryngitis) in 71.2% (195/274). GERD was diagnosed in 29.2% (80/274) via impedance-pH monitoring. The prevalence of GERD in patients with positive or negative laryngoscopy was similar (32.3% vs. 21.5%, p = 0.075). No significant difference in proximal reflux occurrences was noted between positive and negative laryngoscopy groups (33.3% vs. 24.1%, p = 0.133). Laryngoscopy demonstrated sensitivity and specificity of 78.8% and 32.0%, respectively, with a positive predictive value (PPV) of 32.3% and negative predictive value (NPV) of 28.4%. In contrast, a threshold of four concurrent laryngoscopic signs, identified in only eight patients, demonstrated a PPV of 93.8% and a NPV of 73.6% (sensitivity 25.4%, specificity 99.2%). CONCLUSION: This study underscores the limited diagnostic accuracy of laryngoscopy, emphasising the necessity of impedance-pH monitoring for confirming GERD diagnoses using Lyon 2.0 criteria in patients with suspected extra-oesophageal symptoms.

A Novel Laryngopharyngeal Reflux Disease Model for Bama Pigs.

OBJECTIVE: To develop a novel Laryngopharyngeal Reflux Disease (LPRD) model in Bama pigs through endoscopic cricopharyngeal myotomy. METHODS: A total of eight 8-month-old Bama pigs were randomly assigned to either the control or surgery group. Prior to intervention, upper esophageal sphincter (UES) manometry and laryngopharyngeal Dx-pH monitoring were conducted to establish baseline physiological parameters for each pig. Subsequently, the surgery group underwent endoscopic cricopharyngeal myotomy, while the control group did not. Two weeks postintervention, these procedures were repeated to evaluate changes in UES contractility and the occurrence of reflux events. At week eight postsurgery, mucosal tissues from both groups were harvested for histological analysis. Hematoxylin and eosin (H&E) staining was used to assess inflammation, while transmission electron microscopy (TEM) examined alterations in intercellular spaces and desmosomes. RESULTS: The mean UES pressures in the control and surgery groups were 59 ± 9 mmHg and 68 ± 12 mmHg, respectively. In the surgery group, there was a significant decrease in UES pressure 2weeks after the operation compared to preoperative values (P = 0.005), whereas no significant change was observed in the control group (P = 0.488). Laryngopharyngeal reflux (LPR) was successfully induced in the surgery group as evidenced by reflux events with pH <5.0, which were not detected in the control group. HE staining revealed marked inflammatory cell infiltration and submucosal gland expansion in throat tissues of the surgery group Bama pigs. TEM further showed enlarged intercellular spaces and reduced desmosome numbers in the laryngopharyngeal epithelium compared to controls. CONCLUSION: Given analogous throat epithelial structures to humans, Bama pigs are an appropriate species for an LPRD animal model. Endoscopic cricopharyngeal myotomy effectively induces LPR and observable pathological changes in Bama pigs, providing a valuable platform for further research into LPRD pathophysiology.

A Study of the Diagnostic Value of the Sign and Symptom Questionnaires for Laryngopharyngeal Reflux Disease.

OBJECTIVE: To investigate the diagnostic value of symptom questionnaires, sign questionnaires, and the combination of 2 questionnaires for laryngopharyngeal reflux disease (LPRD). STUDY DESIGN: Prospective, single-centered. SETTING: Seventy-seven patients who were hospitalized in the Department of Otolaryngology-Head and Neck Surgery from October 2022 to April 2023 were included. METHODS: Included patients completed the RSS, RSI, RSA, and RFS questionnaires and underwent 24-hour hypopharyngeal-esophageal multichannel intraluminal impedance-pH monitoring (HEMII-pH). The RSS, RSI, RSA, RFS, RSS+RSA, RSS+RFS, RSI+RSA, RSI+RFS, and RSI+RFS diagnostic value were compared using Cohen's k test and receiver operating characteristic analysis. RESULTS: Based on the 24 hours HEMII-pH results, 52 patients had LPRD, and 25 patients did not have LPRD. The Kappa values of RSS, RSI, RSA, RFS, RSS+RSA,2 RSS+RFS, RSI+RSA, and RSI+RFS with the 24 hours HEMII-pH monitoring results were 0.565, 0.442, 0.318, 0.431, 0.517, 0.631, 0.451, and 0.461, respectively. The RSS+RFS questionnaire had the highest AUC of 0.836 (95% confidence interval [CI] 0.762-0.909) and the RSA questionnaire had the lowest AUC (AUC = 0.665, 95% CI 0.560-0.790). The sensitivity of RSS was the highest (98%), the specificities of RSS+RFS and RSI+RFS were the highest (96%), and the specificity of RSS was the lowest (52%). RSS+RFS had a sensitivity of 75%, second only to RSS and RFS (76%). CONCLUSION: Among the 8 methods, the RSS combined with the RFS had the highest concordance with 24 hours HEMII-pH monitoring results and AUC values when screening for LPRD.

Prevalence of Laryngopharyngeal Reflux Disease in Indian Population.

Laryngopharyngeal Reflux Disease (LPRD) is form of extra-oesophageal reflux due to the backflow of gastric contents into the upper aero digestive tract leading to throat symptoms. World over, the prevalence rate of LPRD, ranges from 5 to 30%. The aim of this study was to find the prevalence rate of LPRD in Indian population. This was an observational study whereby the RSI questionnaire was circulated amongst the population and records collected. All subjects who had RSI score more than 13 were considered to be suffering from LPRD. 2300 responses were collected from almost all strata of population. Out of 2300 people who responded 253 had RSI score > 13, and were considered as suffering from LPRD. Thus the prevalence rate of LPRD in population was 11%. The prevalence rate of LPRD in females was 11.2% and in males was 10.6%. The difference in prevalence among both the genders was not significant.The most common symptom of LPR reported by subjects was heartburn followed by clearing of throat and excess throat mucous. The prevalence of LPRD in Indian population as assessed by RSI score > 13 was 11%. The prevalence is same in males and females.

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.

Reflux Symptom Index (RSI) and Singing Voice Handicap Index (SVHI) in Singing Students: A Pilot Study.

OBJECTIVE: To correlate, RSI with SVHI, in a group of singing students, by means of a specific anamnestic questionnaire which analyzes the physical, social, emotional, and economic impacts of voice problems on their lives. This study is a cross-sectional single-center observational study. METHODS: Forty-two modern singing students (26F/16M; average age: 24.9 ± 5.7; range: 16-46 years old) were recruited. A self-assessment of the singing-voice (SVHI) and of reflux symptom (RSI) was performed. RESULTS: Using the validated RSI threshold, 31% of participants were classified as RSI greater than 13 as an indication of suspected LPR. Classifying the SVHI score as proposed in the recent literature (cutoff of 20.35) our sample was a voice disorders prevalence of 71.4%. There was no significant positive or negative relationship between RSI and SVHI total score (rho = 0.238, P = 0.13). Instead, by considering the relationship between the individual items of the two questionnaires, it is highlighted that the item 1 of SVHI was significantly correlated with most of the RSI items (P = 0.0001-0.006). In the same vein, the item 5 of SVHI was correlated to hoarseness and coughing (P = 0.005-0.006). The item 20 of SVHI was significantly correlated with hoarseness, excess mucus in the throat or postnasal drip and with the pharyngeal Globus sensation (P = 0.001-0.005). By aggregating the SVHI item response as a positive response (2-4) versus a negative response (0 or 1) between "RSI pathology classification," a significant association was observed for SVHI item 1 (P < 0.021), item 5 (P < 0.006), item 20 (P < 0.042), item 24 (P < 0.044) item 25 (P < 0.047). These associations were confirmed by univariate binary logistic. Multivariate binary logistic regression confirms that SVHI Item 1, Item 5 were more associated with RSI positive. Based on results, we propose a questionnaire that combines the most relevant SVHI items correlated to LPRD (SVHI-10-LPRD questionnaire). Cronbach's alpha coefficient for the 10 items selected was 0.87; item-total correlation coefficients for each item were in the range of 0.461 to 0.670. CONCLUSIONS: This pilot study shows that, in case of significant RSI for LPR, it is possible to observe a significant association with some symptoms described in SVHI. These results underline that the association of the RSI and SVHI questionnaires administered to singers and singing students, can represent a simple screening to reveal possible alterations of the singing voice correlate to LPR. Moreover, we propose a Singing Voice Handicap Index correlated to LPR (SVHI-10-LPRD). It will be necessary to increase the sample of subjects in the study to confirm these preliminary data.

Voice Component Relationships with High Reflux Symptom Index Scores in Muscle Tension Dysphonia.

OBJECTIVE: To analyze the Reflux Symptom Index (RSI) and the Voice-Related Quality of Life (V-RQOL) scores based on the perceptual and analytical parameters in primary MTD patients with no reflux. STUDY DESIGN: Cross-sectional study. METHODS: One hundred and eighteen participants, that is, sixty patients with normal voices and fifty-eight patients with primary MTD were recruited in this study. The diagnosis of primary MTD was made by perceptual voice analysis, neck palpation, video-laryngoscopic examination, and exclusion of other etiologies. Acoustic analysis and the GRBAS (Grade, Roughness, Breathiness, Asthenia, and Strain) scale were evaluated for all participants. The V-RQOL and RSI questionnaires were then given to all participants. RESULTS: This study included 118 participants of 29 males (48.3%) and 31 females (51.7%) in the normal group. MTD group also included 27 males (46.6%) and 31 (53.4%) female patients. Mean (SD) RSI and V-RQOL scores were 12.35 (3.84) and 11.09 (2.20) for the normal group, and 22.87 (6.97) and 22.89 (7.94) for the MTD group (P = .000). In the MTD group, V-RQOL had a positive correlation with jitter for /i/ and /u/, Noise to Harmonic Ratio (NHR) for /i/, /a/, and /u/, and Grade, Roughness, and Strain of GRBAS scale (P < .05). In addition, RSI had a positive correlation with Strain in the MTD group (P < .05). CONCLUSION: MTD patients in the absence of laryngopharyngeal reflux findings may have high RSI scores. Hence, patients with high RSI scores and disproportionate acoustic and perceptual analysis would require a thorough evaluation of MTD. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E1573-E1579, 2021.

Screening Test for LPRD: History Versus Video Laryngoscopy.

OBJECTIVE: To find a better screening test by correlating between history and video-laryngoscopy in patients with laryngopharyngeal reflux disease. To compare the Reflux Symptom Index (RSI) and the Reflux Finding Score (RFS). METHOD: Patients with the signs and symptoms of LPRD were scored based on RSI. Those with RSI above 13 were included in study and evaluated further by videolaryngoscopy examination and rated according to RFS. The correlation between RSI and RFS was analysed. RESULT: Out of the 107 patients included in study 55% were females. Among these patients positive RFS score (i.e. > 7) was seen in 58.3%. The average RSI was 18.22, and average RFS was 7.45. According to RSI the most common symptom was heartburn/indigestion (44.5%) and from RFS the most common finding was posterior commissure hypertrophy (95%). Correlation between RSI and total RFS was found to be 0.184 with a p value of 0.159 which was not significant. CONCLUSION: LPRD is more common in females and in the middle age group. A correlation of RSI and RFS was not found to be significant suggesting that both should be used for diagnosis of LPRD instead of relying on only one. RFS and RSI are easy, quick and out patient based screening tools and when used together can be more reliable for LPRD diagnosis.

Role of Proton Pump Inhibitors in Laryngopharyngeal Reflux: Clinical Evaluation in a North Indian Population.

There has been an escalation of patients presenting with symptoms of Laryngopharyngeal reflux disease (LPRD) in the otorhinolaryngology clinics due to life style and dietary changes. This study was undertaken to evaluate the effect of various proton pump inhibitors in the treatment of LPRD using Reflux symptom index (RSI) and Reflux finding score (RFS). This was a prospective study conducted from June 2016 to February 2017 with a total of 240 patients with symptoms and signs of LPR. The patients were divided into 5 groups. Each group was subjected to particular proton pump inhibitor. There were 124 males 116 females with a mean age 34.3 and rural to urban ratio being 11. After 3 months, RFS and RSI score within each group, improved significantly with Proton pump inhibitor therapy. In our study patients who were treated with omeprazole 20 mg twice daily had the highest improvement in laryngeal symptoms and laryngeal findings. We conclude emphasizing the effectiveness of proton pump inhibitors with incorporation of lifestyle modification in the successful management of LPRD.

Different cutoffs of the reflux finding score for diagnosing laryngopharyngeal reflux disease should be used for different genders.

OBJECTIVES: To assess the differences in Reflux Finding Score (RFS) between the genders and determine the suitable RFS threshold for diagnosing laryngopharyngeal reflux disease (LPRD) in each gender. METHODS: Asymptomatic volunteers and patients with LPRD, confirmed with an oropharyngeal Dx-pH monitoring system, were included. All study subjects underwent transnasal flexible fiber-optic video laryngoscopy. Reliability was assessed with intra-class correlation coefficients (ICCs) and Bland-Altman plots. The RFS cutoffs for determining the presence and absence of LPRD between the two genders were examined by receiver operating characteristic (ROC) analysis. RESULTS: One hundred seven asymptomatic volunteers and fifty-five LPRD patients were recruited. The mean RFS for LPRD subjects (9.4 ± 3.2) was significantly higher than that for control subjects (7.1 ± 2.6; p < 0.001). The mean RFS for asymptomatic females (6.1 ± 2.7) was significantly lower than that for males (7.7 ± 2.5; p < 0.001). The mean RFS for female subjects with LPRD (7.8 ± 2.6) was lower than that for males (11.0 ± 2.8; p < 0.001). According to ROC analysis, the best cutoffs were 9.0 for males and 6.0 for females. CONCLUSIONS: There was a significant difference in the RFS cutoff between the genders. For male subjects, we recommend a cutoff of 9.0 for diagnosing LPRD, and for female subjects, we recommend a cutoff of 6.0.

Dental and oropharyngeal lesions in rats with chronic acid reflux esophagitis.

OBJECTIVE: In this study, we evaluated pathological changes in the tooth and pharynx of GERD rats to elucidate the association between gastric acid reflux and oral and pharyngeal diseases. METHODS: An experimental rat model of chronic acid reflux esophagitis was surgically created. The oral cavities were observed histologically every 2 weeks until 20 weeks after surgery. RESULTS: At 10 weeks after surgery, molar crown heights in GERD rats were shorter than that in control rats, and inflammatory cell infiltration by gastric acid reflux was found in the periodontal mucosa of GERD rats. Furthermore, dental erosion progressed in GERD rats at 20 weeks after surgery, and enamel erosion and dentin exposure were observed. During the same period, inflammatory cell infiltration was observed in the mucosa of the posterior part of the tongue. These findings suggest that gastric acid reflux may be one of the exacerbating factors of dental erosion, periodontitis and glossitis. CONCLUSION: We investigated oral changes in an experimental rat model of GERD and observed development of dental erosion, periodontitis and glossitis. Our findings suggested chronic gastric acid reflux may be involved in the pathogenesis of oral disease.

Weaning of proton pump inhibitors in patients with suspected laryngopharyngeal reflux disease.

OBJECTIVE: To evaluate the feasibility of a proton pump inhibitor (PPI) weaning protocol in a cohort of patients following successful empiric treatment for suspected laryngopharyngeal reflux disease (LPRD). STUDY DESIGN: Retrospective chart review. METHODS: LPRD patients were weaned from PPIs using a standardized weaning protocol. Symptom recurrence rate following PPI wean and present PPI use were determined. All numeric data were analyzed. The setting was a tertiary laryngology practice. The subjects were patients who had a positive response to empiric treatment for LPRD and subsequently were weaned from PPI therapy. RESULTS: Thirty-five patients with suspected LPRD were instructed to wean from PPI after successful empiric treatment of their LPRD symptoms from July 2013 to September 2015. Twenty-three patients (66%) remained symptom-free post-wean. Twelve patients (34%) had symptom recurrence post-wean; of those, 11 of them (92%) needed to go back on a PPI. Median durations of follow-up for the unsuccessful wean group and the successful wean group were 13 (range 6-29) months and 18 (range 6-38) months, respectively. Pre-wean and post-wean reflux symptom index (RSI) scores in the unsuccessful wean group were 7.7 ± 5.6 and 12.9 ± 6 (P = .11). Pre-wean and post-wean RSI scores in the successful wean group were 8.1 ± 6.5 and 8.1 ± 9.0 (P < .99). Body mass index (BMI) was found to be a significant predictor of failure to wean (odds ratio = 0.72, 95% confidence interval = 0.55-0.95) after controlling for age, sex, PPI treatment duration, and PPI regime. None of the other covariates were found to be significant predictors of failure of PPI wean. CONCLUSION: Approximately 66% of patients who were on PPIs for LPRD were successfully weaned. High BMI was significantly predictive of failure to wean. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:133-137, 2018.

Laryngeal granuloma in experimental rats with gastroesophageal reflux disease and mechanically injured vocal cord mucosa.

OBJECTIVE: This study was undertaken to elucidate the mechanisms underlying laryngeal granuloma formation in a rat model of gastroesophageal reflux disease (GERD) with mechanically injured vocal cord mucosa. METHODS: The rat model of GERD was surgically created by tying the pyloric sphincter and ligating the transitional region between the forestomach and the glandular portion (limiting ridge). The control rats received only a midline incision. In all the animals, a plastic bar was inserted into the trachea, and moved vertically thrice in 3 seconds to cause mechanical injury of the vocal cord mucosa. The rats were sacrificed 2 weeks postsurgically, and their pharynx and larynx were observed histologically. RESULTS: Granulomas were observed in the vocal cord mucosa of the GERD group (3 of 5 animals); they presented a similar pathological structure to that of human laryngeal granulomas. In contrast, only abrasions and blisters were observed on the vocal cord mucosa in the control group (all 5 animals). CONCLUSIONS: The development of laryngeal granuloma may involve both mechanical injury and gastric acid reflux.