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.

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.

Variability and accuracy of multiple saliva pepsin measurements in laryngopharyngeal reflux patients.

OBJECTIVE: To study the variability and diagnostic value of multiple salivary pepsin measurements in the detection of laryngopharyngeal reflux (LPR). METHODS: Patients with LPR symptoms were consecutively recruited from December 2019 to Augustus 2022. Twenty-one asymptomatic individuals completed the study. The diagnostic was confirmed with hypopharyngeal-esophageal impedance-pH monitoring (HEMII-pH). Patients collected three saliva samples during the 24-h testing period. Symptoms and findings were studied with reflux symptom score-12 and reflux sign assessment. Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values of pepsin measurements were calculated considering morning, post-lunch and post-dinner samples. The consistency and relationship between HEMII-pH, pepsin measurements, and clinical features were investigated. RESULTS: Morning, post-lunch and post-dinner saliva pepsin concentrations were measured in 42 patients. Pepsin measurements were 64.9%, 59.5%, and 59.0% sensitive for morning, post-lunch and post-dinner collections at cutoff ≥ 16 ng/mL. Considering the highest concentration of the three pepsin saliva collections, the accuracy, sensitivity, specificity and PPV were 70.5%, 73.0%; 66.7% and 78.9%, respectively. Morning pepsin measurements reported higher consistency, sensitivity, and specificity than post-dinner and post-lunch pepsin measurements. CONCLUSION: The collection of several saliva pepsin samples improves the detection rate of LPR. In case of high clinical LPR suspicion and negative pepsin test, a HEMII-pH study could provide further diagnostic information.

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.

Atypical Clinical Presentation of Laryngopharyngeal Reflux: A 5-Year Case Series.

BACKGROUND: Laryngopharyngeal reflux (LPR) is a common disease in otolaryngology characterized by an inflammatory reaction of the mucosa of the upper aerodigestive tract caused by digestive refluxate enzymes. LPR has been identified as the etiological or favoring factor of laryngeal, oral, sinonasal, or otological diseases. In this case series, we reported the atypical clinical presentation of LPR in patients presenting in our clinic with reflux. METHODS: A retrospective medical chart review of 351 patients with LPR treated in the European Reflux Clinic in Brussels, Poitiers and Paris was performed. In order to be included, patients had to report an atypical clinical presentation of LPR, consisting of symptoms or findings that are not described in the reflux symptom score and reflux sign assessment. The LPR diagnosis was confirmed with a 24 h hypopharyngeal-esophageal impedance pH study, and patients were treated with a combination of diet, proton pump inhibitors, and alginates. The atypical symptoms or findings had to be resolved from pre- to posttreatment. RESULTS: From 2017 to 2021, 21 patients with atypical LPR were treated in our center. The clinical presentation consisted of recurrent aphthosis or burning mouth (N = 9), recurrent burps and abdominal disorders (N = 2), posterior nasal obstruction (N = 2), recurrent acute suppurative otitis media (N = 2), severe vocal fold dysplasia (N = 2), and recurrent acute rhinopharyngitis (N = 1), tearing (N = 1), aspirations (N = 1), or tracheobronchitis (N = 1). Abnormal upper aerodigestive tract reflux events were identified in all of these patients. Atypical clinical findings resolved and did not recur after an adequate antireflux treatment. CONCLUSION: LPR may present with various clinical presentations, including mouth, eye, tracheobronchial, nasal, or laryngeal findings, which may all regress with adequate treatment. Future studies are needed to better specify the relationship between LPR and these atypical findings through analyses identifying gastroduodenal enzymes in the inflamed tissue.

Saliva Pepsin Concentration of Laryngopharyngeal Reflux Patients Is Influenced by Meals Consumed Before the Samples.

OBJECTIVES/HYPOTHESIS: To assess the impact of diet on the saliva pepsin concentration of patients with laryngopharyngeal reflux (LPR). STUDY DESIGN: Non-controlled Prospective Study. METHODS: Patients with positive LPR regarding hypopharyngeal-esophageal impedance-pH monitoring (HEMII-pH) were enrolled from three European Hospitals. Patients collected three saliva samples, respectively, in the morning (fasting), and 1 to 2 hour after lunch and dinner. Patients carefully detailed foods and beverages consumed during meals and before the pepsin samples. The 3-month treatment was based on the association of diet, proton pump inhibitors, alginate, or magaldrate regarding the HEMII-pH characteristics. Reflux Symptom Score (RSS) and Reflux Sign Assessment (RSA) were used for assessing the pre- to posttreatment clinical evolution. The Refluxogenic Diet Score and the Refluxogenic Score of a Dish (RESDI) were used to assess the refluxogenic potential of foods and beverages. The relationship between saliva pepsin concentration, HEMII-pH, RESDI, RSS, and RSA was investigated through multiple linear regression. RESULTS: Forty-two patients were included. The saliva pepsin concentration of the 24-hour period of testing was significantly associated with foods and beverages consumed during the testing period and the evening dinner (rs = 0.973, P < .001). RSS and RSA significantly improved throughout treatment. The level of saliva pepsin in the morning was a negative predictive factor of the therapeutic response regarding RSA and RSS (P < .036). CONCLUSIONS: Foods and beverages may significantly impact the saliva pepsin concentration of patients with LPR. Patients with high-level saliva pepsin in the morning had lower therapeutic response compared with those with low-level saliva pepsin. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:350-359, 2021.

Hypopharyngeal-Esophageal Impedance-pH Monitoring Profiles of Laryngopharyngeal Reflux Patients.

OBJECTIVES/HYPOTHESIS: To investigate the profile of patients with laryngopharyngeal reflux (LPR) at hypopharyngeal-esophageal multichannel intraluminal impedance-pH (HEMII-pH) monitoring and the relationship between hypopharyngeal-proximal reflux episodes (HREs) and saliva pepsin concentration. STUDY DESIGN: Prospective non-controlled. METHODS: Patients were recruited from three European hospitals from January 2018 to October 2019. Patients benefited from HEMII-pH monitoring and saliva collections to measure saliva pepsin concentration in the same time. Saliva pepsin concentration was measured in the morning (fasting), after lunch, and after dinner. The LPR profile of patients was studied through a breakdown of the HEMII-pH findings over the 24 hours of testing. The relationship between the concentrations of saliva pepsin and 24-hour HREs was studied through linear multiple regression. RESULTS: One hundred twenty-six patients completed the study. The HEMII-pH analyses revealed that 73.99% of HREs occurred outside 1-hour postmeal times, whereas 20.49% and 5.52% of HREs occurred during the 1-hour postmeal and nighttime, respectively. Seventy-four patients (58.73%) did not have nighttime HREs. Patients with both daytime and nighttime HREs had more severe HEMII-pH parameters and reflux symptom score compared with patients with only daytime HREs. There were no significant associations between HREs and saliva pepsin concentration. CONCLUSIONS: Unlike gastroesophageal reflux disease, HREs occur less frequently after meals and nighttime. The analysis of the HEMII-pH profile of the LPR patients has to be considered to develop future personalized therapeutic strategies. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:268-276, 2021.

Does Pepsin Saliva Concentration (Peptest™) Predict the Therapeutic Response of Laryngopharyngeal Reflux Patients?

OBJECTIVE: To study the profile and the therapeutic response of patients with laryngopharyngeal reflux (LPR) at the hypopharyngeal-esophageal multichannel intraluminal impedance-pH monitoring (HEMII-pH) according to the initial pepsin saliva concentration. METHODS: From January 2018 to January 2020, patients with positive LPR diagnosis at the HEMII-pH were consecutively recruited from 3 European Hospitals. Saliva pepsin concentration (Peptest™) was measured during the HEMII-pH testing period and patients were classified into 2 groups: negative versus positive Peptest. The clinical outcomes, that is, gastrointestinal and HEMII-pH findings, reflux symptom score-12 (RSS-12), and 3-month therapeutic response, were compared between groups. RESULTS: A total of 124 patients completed the study. Among them, 30 patients had negative Peptest. Pharyngeal reflux events occurred outside 1-hour post-meal time in 74.0%, after the meals in 20.5% and nighttime in 5.5%. The pepsin saliva level was not significantly associated with the reflux events preceding the sample collection. Patients with positive Peptest had better improvement of RSS-12 digestive and respiratory subscores and oral, pharyngeal, and laryngeal findings compared with patients with negative Peptest. CONCLUSION: Patients with high saliva pepsin concentration had no stronger gastrointestinal, HEMII-pH, or clinical outcomes compared with those with low or undetectable saliva pepsin concentration.

Prevalence and Features of Laryngopharyngeal Reflux in Patients with Primary Burning Mouth Syndrome.

OBJECTIVES/HYPOTHESIS: To investigate the prevalence and features of laryngopharyngeal reflux (LPR) in patients with primary burning mouth syndrome (BMS). STUDY DESIGN: Prospective uncontrolled study. METHODS: Patients who visited our Departments of Otolaryngology-Head and Neck and Maxillofacial surgery with BMS were prospectively recruited from September 2018 to September 2020. Patients benefited from dental, maxillofacial, otolaryngological examinations, and hypopharyngeal-esophageal impedance pH-monitoring (HEMII-pH). Oral, pharyngeal, and laryngeal findings and symptoms were rated with Reflux Sign Assessment (RSA) and Reflux Symptom Score-12 (RSS-12). Patients were treated with a combination of diet, pantoprazole, and alginate. RESULTS: From the 81 included patients, 76 reported >1 pharyngeal reflux events (93.8%), accounting for 35 (46.1%), 24 (31.6%), and 17 (22.3%) acid, mixed, and nonacid LPR, respectively. Thirty-two patients had both LPR and gastroesophageal reflux disease (GERD). Thirty-eight patients benefited from pepsin saliva measurement, which was positive in 86.8% of cases. The mean scores of mouth/tongue burning, RSS-12, and RSA significantly improved from pre- to post-treatment (P < .004). At 3-month post-treatment, 62.5% of patients reported an improvement of mouth/tongue burning score. Patients with both GERD and LPR reported higher baseline RSS-12 and RSA scores. CONCLUSION: Acid, weakly acid, and nonacid LPR may be involved in the development of BMS. The use of an appropriate treatment considering the reflux features is associated with an improvement of symptoms and findings. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E2627-E2633, 2021.

Saliva pepsin level of laryngopharyngeal reflux patients is not correlated with reflux episodes.

OBJECTIVE: To investigate the relationship between the laryngopharyngeal reflux (LPR) episodes at the multichannel intraluminal impedance-pH monitoring (MII-pH) and the concentration of pepsin in the saliva of LPR patients. METHODS: Patients with LPR were enrolled from the polyclinic of Poitiers, France. Patients benefited from 24-hour MII-pH that allowed a correlation study between reflux episodes and symptoms. Patients reported the occurrence of the critical symptoms during the testing period through a recording device. Simultaneously, they collected a first saliva sample 30 minutes after the symptoms and a second saliva collection a few hours after the first collection. The patient symptoms were assessed with reflux symptom score (RSS). The relationship between pepsin concentration in the saliva, symptoms, and the reflux episode characteristics at the MII-pH was investigated through multiple linear regression. RESULTS: A total of 65 patients with LPR were recruited. The mean concentrations of the first and the second pepsin samples were 92.0 ± 108.1 and 101.8 ± 131.0, respectively. Peptest (RD Biomed, Milan, Italy) was positive in 51 LPR patients (78.5%). Concentrations of both pepsin samples were significantly correlated (P = 0.019). There was no significant association between pepsin concentrations in saliva samples, RSS, key symptoms during the test period, and MII-pH findings. CONCLUSION: The level of pepsin saliva concentration is not associated with the reflux episodes at the MII-pH. Future studies are needed to better understand the relationship between the extracellular pepsin concentration, mucosal inflammation, and related laryngopharyngeal symptoms. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:1278-1281, 2020.