Incidental Laryngeal Findings in Routine Laryngopharyngeal Reflux Diagnosis.

BACKGROUND: Laryngopharyngeal reflux (LPR) refers to the backflow of acidic stomach content into the larynx, pharynx, and upper aerodigestive tract. The diagnosis of LPR is based on the patient's history and findings of the laryngoscopy associated with LPR. Other possible manifestations consistent with LPR symptoms include laryngeal cancer, vocal fold granulomas, Reinke's space edema, and vocal polyps. In this study, we compared the characteristics of patients with LPR symptoms and incidental laryngeal findings (ILF) in the laryngoscopic evaluation to those without ILF (WILF). OBJECTIVES: Determine the characteristics of LPR-symptomatic patients with ILF versus WILF. METHODS: In this retrospective study, we examined 160 medical charts from patients referred to the otolaryngology clinic at Galilee Medical Center for LPR evaluation 2016-2018. The reflux symptoms index (RSI), reflux finding score (RFS), and demographics of the patient were collected. All patients with a positive RSI score for LPR (RSI > 9) were included, and the profiles of patients with versus without ILF on laryngoscopy examination were compared. RESULTS: Of the 160 patients, 20 (12.5%) had ILF during laryngoscopy. Most had vocal cord findings such as leukoplakia (20%), polyps (15%), and nodules (20%). Hoarseness, throat clearing, swallowing difficulty, breathing difficulties, and total RSI score were significantly higher in patients with ILF. CONCLUSIONS: Evaluation of LPR symptoms may provide otolaryngologists with a tool to identify patients with other findings on fiberoptic laryngoscopy. A laryngoscopic examination should be part of the examination of every patient with LPR to enable diagnosis of incidental findings.

Usefulness of pepsin saliva measurement for the detection of primary burning mouth syndrome related to reflux.

OBJECTIVES: To study the diagnostic value of salivary pepsin tests for detecting laryngopharyngeal reflux (LPR) in patients with primary burning mouth syndrome (BMS). METHODS: Patients with BMS and asymptomatic individuals were consecutively recruited from September 2018 to June 2023. Patients underwent hypopharyngeal-esophageal impedance pH-monitoring (HEMII-pH) and saliva collections to measure pepsin. Stomatology evaluation was carried out to exclude other causes of BMS. Oral, pharyngeal and laryngeal signs and symptoms were evaluated with Reflux Sign Assessment (RSA) and Reflux Symptom Score (RSS). Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values of pepsin test were calculated considering the highest values of pepsin tests at ≥ 16, ≥ 36, and ≥ 100 ng/mL cutoffs. Receiver operating characteristic curve (ROC) was evaluated. RESULTS: Forty-nine patients with both BMS and LPR at the HEMII-pH and 21 asymptomatic individuals were recruited. Pepsin test was 83.7%, 79.6%, and 71.4% sensitive at cutoffs ≥ 16, ≥ 36, and ≥ 100 ng/mL, respectively. The ROC analysis reported that a threshold of ≥ 21.5 ng/mL was associated with sensitivity, specificity, PPV and NPV of 81.6%, 81.0%, 90.1% and 65.4%, respectively. The severity score of burning mouth symptom was significantly associated with the saliva pepsin concentration (rs = 0.263; p = 0.029) and the oral RSA (rs = 0.474; p = 0.007). CONCLUSION: Pepsin test is a valuable diagnostic approach for detecting LPR in patients with BMS. Patients with high level of saliva pepsin reported more severe burning mouth symptoms. Future studies are needed to confirm the role of LPR in the primary BMS.

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.

Association between oropharyngeal ph-monitoring, pepsin saliva concentration and degree of apnea-hypopnea index of obstructive sleep apnea.

OBJECTIVE: To investigate the association between obstructive sleep apnea (OSA) and laryngopharyngeal reflux (LPR) through oropharyngeal pH-monitoring and pepsin saliva measurements. DESIGN: Prospective uncontrolled study. METHODS: Patients with sleep disturbances and reflux symptoms underwent polysomnography, 24-h oropharyngeal pH-monitoring and saliva pepsin collections. The prevalence of LPR was investigated in OSA patients according to oropharyngeal pH-monitoring and pepsin measurements. A correlation analysis was performed between pH-monitoring findings, pepsin saliva levels, reflux symptom score-12 (RSS-12), reflux sign assessment (RSA), Apnea-Hypopnea Index (AHI), Epworth Sleepiness Scale, Pichot and arousal findings. RESULTS: Thirty-seven patients completed the evaluations. LPR was detected in 34/37 (92%) and 29/34 (85%) patients at the oropharyngeal-pH monitoring and pepsin test, respectively. OSA was detected in 30 patients (81%). Among them, LPR was detected in 28/30 (93%) cases. Pharyngeal reflux events mainly occurred nighttime/supine in OSA patients. Both Ryan score and supine reflux time at pH < 6.5 were significantly associated with BMI and the RSA sub- and total scores (p < 0.02). Tongue-base hypertrophy score was positively associated with the number of micro-arousals (p = 0.027); the supine percent of pH < 6.5 (p = 0.030); morning (p = 0.030) and bedtime pepsin saliva measurements (p = 0.037). The bedtime pepsin saliva level was significantly associated with Ryan Score (p = 0.047); AHI (p = 0.017) and the sleep saturation < 90% time (p = 0.040). The saliva level of the morning pepsin was associated with a shortest paradoxical sleep phase (p = 0.013). CONCLUSION: OSA patients may have high prevalence of pharyngeal reflux events at the oropharyngeal pH-monitoring and high pepsin saliva measurements. Oropharyngeal pH-monitoring should be useful for the correlation between reflux and sleep findings in OSA patients. Future large cohort controlled studies are needed to determine the prevalence of LPR in OSA and healthy individuals.

Self-reported symptoms of laryngopharyngeal reflux using the reflux symptom score in patients with obstructive sleep apnea syndrome.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with many chronic diseases among which is laryngopharyngeal reflux disease (LPRD). OBJECTIVE: To investigate the prevalence of laryngopharyngeal reflux (LPR)-related symptoms in patients with OSA using the Reflux Symptoms Score (RSS) and Reflux Symptom Index (RSI). METHODS: The medical records and video-recordings of patients with OSA who presented to a tertiary referral center were reviewed. The diagnosis of OSA was made using the STOP-BANG questionnaire and/or polysomnography. The prevalence of LPR-related symptoms was assessed using both the RSS and RSI questionnaires. RESULTS: Thirty-nine patients were included in this study. Twenty-seven patients (69.2%) had a positive RSS in comparison to only 7 (17.9%) using the RSI (p = .052). Subgroup analysis of those who had polysomnography (n = 24) showed that 18 patients (75%) had a positive RSS in comparison to only 5 patients (20.8%) using the RSI. Patients in the high-risk category for OSA were also found to have a higher prevalence of LPR-related symptoms using both the RSS and RSI questionnaires in comparison to those in the lower risk categories. CONCLUSION: The results of this investigation indicate that the prevalence of LPR-related symptoms is higher using the RSS in comparison to the RSI.

Effect of positive airway pressure compliance on laryngopharyngeal reflux in obstructive sleep apnea patients.

OBJECTIVES: To determine the effect of continuous positive airway pressure (CPAP) compliance on symptoms and signs of laryngopharyngeal reflux (LPR) in patients with obstructive sleep apnea (OSA). RESULTS: Thirty patients were included. The participants were divided into good compliance (n = 21) and poor compliance (n = 9) groups. After 6-month CPAP treatment, the reflux symptom index score significantly decreased in both the good compliance group (20 (17,24) vs. 14 (10,18), p < 0.001) and the poor compliance group (21 (18,25) vs. 10 (5,16), p < 0.05). Reflux finding score was significantly reduced in both the good compliance group (8 (6,9) vs. 4 (3,5), p < 0.001) and the poor compliance group (6 (4,8) vs. 3 (2,4), p < 0.05). However, there were no statistically significant differences between the groups. CPAP treatment reduces the symptoms and signs of LPR. However, CPAP compliance does not correlate with improvement in LPR in patients with OSA.

[Risk factors of recurrence and canceration for premalignant vocal fold lesions after surgery].

Objective:To analyze the risk factors of recurrence and canceration for premalignant vocal fold lesions after surgery, and to provide a reasonable basis for preoperative evaluation and postoperative follow-up. Methods:This study retrospective analyzed the relationship between clinicopathological factors and clinical outcome（recurrence, canceration, recurrence-free survival, and canceration-free survival） in 148 patients undergoing surgical treatment in Chongqing General Hospital from 2014 to 2017. Results:The five-year overall recurrence rate was 14.86% and the overall recurrence rate was 8.78%. Univariate analysis showed that smoking index, laryngopharyngeal reflux and lesion range were significantly associated with recurrence（P<0.05）, and smoking index and lesion range were significantly associated with canceration（P<0.05）. Multivariate logistic regression analysis showed that smoking index ≥600 and laryngopharyngeal reflux were independent risk factors for recurrence（P<0.05）, and smoking index ≥600 and lesion range ≥1/2 vocal cord were independent risk factors for canceration（P<0.05）. The mean carcinogenesis interval for the postoperative smoking cessation group was significantly longer（P<0.05）. Conclusion:Excessive smoking, laryngopharyngeal reflux and a wide range of lesions may be related to postoperative recurrence or malignant progression of precancerous lesions in the vocal cord, and further large-scale multi-center prospective randomized controlled studies are needed to clarify the effects of the above factors on recurrence and malignant changes in the future.

Saliva pepsin measurements in the detection of gastroesophageal reflux disease in laryngopharyngeal reflux patients: a cohort study.

OBJECTIVE: To study the diagnostic value of salivary pepsin measurement (Peptest) for detecting gastroesophageal reflux disease (GERD) in laryngopharyngeal reflux (LPR) patients. METHODS: Patients with reflux symptoms were consecutively recruited from January 2020 to November 2022. Patients benefited from hypopharyngeal-esophageal impedance-pH monitoring (HEMII-pH), fasting and bedtime saliva collections to measure pepsin. Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values were evaluated for GERD and LPR patients considering the highest values of pepsin tests at ≥ 16, ≥ 75, and ≥ 216 ng/mL cutoffs. The relationship between HEMII-pH, endoscopic and clinical findings, and pepsin measurements was studied. RESULTS: Saliva was collected in 109 LPR patients and 30 individuals with both LPR and GERD. The total number of pharyngeal reflux events was significantly higher in GERD-LPR patients compared with LPR patients (p = 0.008). The mean fasting and bedtime pepsin saliva concentrations were similar between groups. The sensitivity of Peptest in LPR patients was 30.5%, 70.2%, and 84.0% at cutoffs ≥ 16, ≥ 75 and ≥ 216 ng/mL. In GERD-LPR group, Peptest was 80.0%, 70.0%, and 30.0% sensitive. At cutoff 16 ng/mL, Peptest reported PPV of 20.7% and 94.8% in LPR-GERD and LPR groups, respectively. NPV were 73.9% and 8.7% in GERD-LPR and LPR groups, respectively. The consistency analysis between Peptest and HEMII-pH was not significant. Peptest was significantly associated with the number of acid pharyngeal reflux events (rs = 0.182; p = 0.032). CONCLUSION: Pepsin saliva measurements appear to be not a reliable diagnostic tool for the detection of GERD in LPR patients. Future studies are needed to determine the place of Peptest in laryngopharyngeal reflux and gastroesophageal reflux diseases.

Association between laryngopharyngeal reflux, gastroesophageal reflux and recalcitrant chronic rhinosinusitis: A systematic review.

OBJECTIVE: To investigate the association between laryngopharyngeal reflux (LPR), gastroesophageal reflux disease (GERD) and recalcitrant chronic rhinosinusitis (CRS). DATA SOURCES: PubMed, Cochrane Library and Scopus. REVIEW METHODS: Three investigators searched the specified databases for studies investigating the relationship between LPR, GERD and recalcitrant CRS with or without polyposis. The following outcomes were investigated with PRISMA criteria: age; gender; reflux and CRS diagnosis; association outcomes and potential treatment outcomes. The authors performed a bias analysis of papers and provided recommendations for future studies. RESULTS: A total of 17 studies investigated the association between reflux and recalcitrant CRS. According to pharyngeal pH monitoring, 54% of patients with recalcitrant CRS reported hypo or nasopharyngeal acid reflux events. The number of hypo- and nasopharyngeal acid reflux events was significantly higher in patients compared to healthy individuals in 4 and 2 studies, respectively. Only one study did not report intergroup differences. The proportion of GERD was significantly higher in CRS patients compared to controls, with a prevalence ranging from 32% to 91% of cases. No author considered nonacid reflux events. There was significant heterogeneity in the inclusion criteria; definition of reflux and association outcomes, limiting the ability to draw clear conclusions. Pepsin was found in sinonasal secretions more frequently in CRS patients than controls. CONCLUSION: Laryngopharyngeal reflux and GERD may be contributing factors of CRS therapeutic resistance, but future studies are needed to confirm the association considering nonacid reflux events.

SPECIFIC FEATURES OF THE ORAL MICROBIOME IN YOUNG CHILDREN WITH ARYNGOPHARYNGEAL REFLUX AND ITS ROLE THE DEVELOPMENT OF RECURRENT RESPIRATORY DISEASES.

OBJECTIVE: The aim: To examine the composition of the oral microbiome in young children with laryngopharyngeal reflux (LPR) and its role the development of recurrent respiratory diseases. PATIENTS AND METHODS: Materials and methods: There were examined 38 children with physiological gastroesophageal reflux (GER), 18 children with LPR who had a medical history of recurrent bronchitis and 17 healthy children (control group). The study included the collection of anamnesis, objective examination. The qualitative and quantitative microbial composition of the upper respiratory tract was performed obtained by oropharyngeal deep swab. Salivary pepsin level and IL-8 were determined by enzyme-linked immunosorbent assay. RESULTS: Results: This research showed significant alterations in the oral microbiome of patients with GER and LPR as compared to healthy control. We found that gram-negative microbiota such as Klebsiella pneumoniae, Escherichia coli, Proteus vulgaris, Proteus spp. and Candida albicans were identified in children with GER and LPR compared to the healthy control. At the same time, the amount of such a representative of the normal microbiome as Streptococcus viridans in children with LPR was sharply reduced. There were established a much higher mean salivary pepsin level of the patients with LPR than in the GER and control group. We found the association between high pepsin levels, saliva IL-8 levels and frequency of respiratory pathology in children with LPR. CONCLUSION: Conclusions: Our study confirms that increased levels of pepsin in saliva are a risk factor for recurrent respiratory diseases in children with LPR.

Development of a New Self-Assessment Tool for Laryngopharyngeal Reflux Screening in Singers (SVHI-12-LPR).

INTRODUCTION: The present study aimed to develop a new tool for the evaluation of singers with self-reported symptoms suggestive of laryngopharyngeal reflux (LPR) (the SVHI-12-LPR), by correlating RSI with SVHI in a population sample of 163 subjects (both professional and amateur singers), evaluated also by videolaryngostroboscopy. This study was a cross-sectional, double-observational study. METHODS: RSI and SVHI were administered to 159 singers (amateurs, singing students, and professional singers). All subjects underwent videolaryngostroboscopy to objectively identify four subgroups: normal subjects (41.5%), subjects with organic lesions occupying the glottic space (17.6%), subjects with functional dysphonia (18.2%), and subjects presenting solely signs suggestive of LPR (22.6%). Using the validated RSI threshold, 33.9% of participants presented an RSI total score >13, suggestive of LPR. RESULTS: Subjects with a suspected diagnosis of LPR at videolaryngostroboscopy presented a mean RSI significantly higher than other subgroups (p < 0.001). Moreover, the SVHI-36 score did not statistically differ between pathological subgroups. A significant positive relationship was observed between RSI and SVHI total score (Spearman's rank correlation coefficient [ρ] = 0.474, p < 0.001). 12 SVHI items (items 1, 2, 4, 5, 6, 7, 12, 20, 24, 25, 26, 30) showed a significant association with RSI pathology classification. Statistical analysis demonstrated for the 12 selected items (SVHI-12-LPR) acceptable specificity (0.691) and sensibility (0.833) for the suspected diagnosis of LPR with a cut-off of 15. CONCLUSIONS: From the SVHI-36, 12 items were extracted that correlated with the specific impact that LPR has on the singer's voice (SVHI-12-LPR), as evaluated by RSI and videolaryngostroboscopy. Such questionnaire represents a new tool that could be applied to singers with symptoms suggestive of LPR to select which patients would benefit from a further phoniatric and videolaryngostroboscopic evaluation.

Voice Hoarseness with Reflux as a Suspected Etiology: Incidence, Evaluation, Treatment, and Symptom Outcomes.

PURPOSE: To describe the clinical evaluation course, treatments, and outcomes of patients with a primary complaint of hoarseness due to suspected laryngopharyngeal reflux (LPR). METHODS: A retrospective chart review was conducted of patients with a primary complaint of hoarseness with acid reflux as the suspected cause at a single institution between October 2011 and March 2020 who underwent clinical evaluation, treatment, and follow-up. Data collected included diagnostic procedures and treatments received, subjective symptom outcomes, and final diagnosis as determined by the treating physician. RESULTS: A total of 134 patients met the inclusion criteria. Videostroboscopy was the most performed procedure (n = 59, 44%) followed by endoscopy (n = 38, 28%) and pH monitoring (n = 28, 21%). Three patients were removed for statistical analysis of treatment differences and outcomes due to variant treatment plans. Most patients received sole medical management (n = 86, 66%), 7 patients received only voice therapy (5%), and 10 patients underwent surgical management (8%). Several patients received combined medical management and voice therapy (n = 21, 16%). Final diagnoses included gastroesophageal reflux disease (GERD) (25%), followed by multifactorial causes (17%) and dysphonia with unclear etiology (13%). Among all patients, 82 (61%) reported symptom improvement. Twenty-eight patients were diagnosed with LPR or LPR with GERD (21%), and 22 reported symptom improvement (79%). There was a statistically significant relationship between a final diagnosis with a reflux component and symptom improvement (p = .038). There was no statistically significant difference between treatment types and symptom outcomes both within the total patient population (p = .051) and patients diagnosed with a reflux condition (p = .572). CONCLUSION: LPR remains a difficult diagnosis to establish and represents a minority of patients with voice complaints. Despite varying evaluation and treatment modalities, most patients with LPR improved during their treatment and evaluation period without a clear association with any specific type of treatment. Further studies should explore diagnostic criteria for LPR, the necessary and efficient clinical evaluation to establish a diagnosis, and possible beneficial treatments.

A Prospective Controlled Study Investigating Odor Identification in Laryngopharyngeal Reflux.

OBJECTIVE: To psychophysically evaluate olfaction in patients with laryngopharyngeal reflux (LPR). STUDY DESIGN: Prospective controlled study. SETTING: Tertiary medical center. METHODS: From January 2021 to January 2022, patients with LPR diagnosed with hypopharyngeal-esophageal multichannel intraluminal impedance-pH monitoring underwent psychophysical evaluation of the sense of smell. Reflux symptoms and findings were assessed with the Reflux Symptom Score (RSS) and Reflux Sign Assessment (RSA). Nasal symptoms were assessed through the Sino-Nasal Outcome Test 22 (SNOT-22). From pre- to posttreatment, patients underwent identification Sniffin' Sticks test and olfactory cleft examination. Clinical outcomes were compared between LPR patients and healthy individuals. RESULTS: In total, 107 patients and 76 healthy individuals completed the evaluations. LPR patients reported significant higher RSS, RSA, and SNOT-22 scores. Psychophysical olfactory evaluations were significantly lower in reflux patients compared with controls, while there were no significant differences in olfactory cleft score. RSS and RSA significantly improved from baseline to 3 months posttreatment. SNOT-22, olfactory cleft endoscopy scale, and psychophysical olfactory evaluations did not change throughout treatment. Patients with higher number of acid pharyngeal reflux events reported lower psychophysical olfactory scores (P = .025). CONCLUSION: LPR disease was associated with low odor identification results in patients without olfactory cleft abnormalities. The sense of smell did not improve after 3-month therapy. Future controlled studies using threshold, discrimination, and identification testing are needed.

Usefulness, acceptation and feasibility of electronic medical history tool in reflux disease.

OBJECTIVES: To investigate usefulness, feasibility, and patient satisfaction of an electronic pre-consultation medical history tool (EPMH) in laryngopharyngeal reflux (LPR) work-up. METHODS: Seventy-five patients with LPR were invited to complete electronic medical history assessment prior to laryngology consultation. EPMH collected the following parameters: demographic and epidemiological data, medication, medical and surgical histories, diet habits, stress and symptom findings. Stress and symptoms were assessed with perceived stress scale and reflux symptom score. Duration of consultation, acceptance, and satisfaction of patients (feasibility, usefulness, effectiveness, understanding of questions) were evaluated through a 9-item patient-reported outcome questionnaire. RESULTS: Seventy patients completed the evaluation (93% participation rate). The mean age of cohort was 51.2 ± 15.6 years old. There were 35 females and 35 males. Patients who refused to participate (N = 5) were > 65 years old. The consultation duration was significantly lower in patients who used the EPMH (11.3 ± 2.7 min) compared with a control group (18.1 ± 5.1 min; p = 0.001). Ninety percent of patients were satisfied about EPMH easiness and usefulness, while 97.1% thought that EPMH may improve the disease management. Patients would recommend similar approach for otolaryngological or other specialty consultations in 98.6% and 92.8% of cases, respectively. CONCLUSION: The use of EPMH is associated with adequate usefulness, feasibility, and satisfaction outcomes in patients with LPR. This software is a preliminary step in the development of an AI-based diagnostic decision support tool to help laryngologists in their daily practice. Future randomized controlled studies are needed to investigate the gain of similar approaches on the traditional consultation format.

Laryngopharyngeal Reflux: Effect of Race and Insurance Status on Symptomology.

OBJECTIVES: Laryngopharyngeal reflux (LPR) is an extraesophageal variant of gastroesophageal reflux disease associated with intermittent dysphonia, throat-clearing, and chronic cough. This study aims to evaluate the impact of race and insurance status on symptoms often attributable to LPR. METHODS: Retrospective review of all patients with suspected LPR from 2017 to 2019 was performed at a tertiary care center. The diagnostic criteria comprised evaluation by a fellowship trained laryngologist and Reflux Symptom Index (RSI) scores. Demographics, patient history, and insurance status were recorded. Descriptive statistics were calculated for each parameter using SPSS version 22. RESULTS: A total of 170 patients (96 White, 44 Black, 26 Latinx, 4 Asian) were included in this study. About 57.1% had private insurance, 30.6% had Medicare, and 11.8% had Medicaid. Black and Latinx patients demonstrated higher RSI scores (26.67 ± 8.61, P = .017) when compared to their White and Asian counterparts. RSI scores between all 3 insurance types also varied significantly (P = .035). Medicaid patients reported higher RSI scores (28.65 ± 10.09, P = .028), while private insurance patients reported significantly lower scores (23.75 ± 7.88, P = .03). Controlling for insurance type eliminates the statistically significant association between RSI scores and Black and Latinx patients. Particularly, within the Medicaid group, Black, Latinx, and White patients did not have statistically different RSI scores. CONCLUSIONS: Black and Latinx patients presented with higher RSI scores than White and Asian patients. Similarly, Medicaid patients reported higher RSI scores than the Non-Medicaid cohort. These findings suggest that access to appropriate healthcare, due to varied insurance coverage and socioeconomic, may potentially influence symptoms attributed to LPR.