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.

Impedance-pH monitoring profile of patients with reflux and obstructive sleep apnea syndrome: A controlled study.

OBJECTIVE: To study the profile of patients with obstructive sleep apnoea syndrome (OSAS) and laryngopharyngeal reflux (LPR) at the hypopharyngeal-oesophageal multichannel intraluminal impedance-pH monitoring (HEMII-pH) and to compare their reflux findings with LPR patients without OSAS. DESIGN: Prospective controlled study. METHODS: Patients with LPR and OSAS were prospectively recruited from August 2019 to June 2020. The profile of hypopharyngeal reflux events (HREs) of patients was studied through a breakdown of the HEMII-pH findings over the 24 hours of testing. Reflux symptom score (RSS), and gastrointestinal and HEMII-pH outcomes were compared between LPR patients and patients with LPR and OSAS. Multivariate analysis was used to study the relationship between reflux data and the following sleep outcomes: Apnea Hypopnea Index, Epworth Sleepiness Scale (ESS) and paradoxical sleep data. RESULTS: A total of 89 patients completed the study. There were 45 patients with LPR and 44 subjects with both OSAS and LPR. The numbers of upright and daytime HREs and the otolaryngological RSS were significantly higher in patients with LPR compared with those with OSAS and LPR. There was a significant positive association between RSS quality-of-life score and ESS (P = .001). The occurrence of HREs in the evening was associated with higher ESS (P = .015). Patients with OSAS, LPR and GERD had higher number of nocturnal HREs compared with those without GERD (P = .001). CONCLUSION: The presence of OSAS in LPR patients is associated with less severe HEMII-pH and ear, nose and throat symptoms. There may have different OSAS patient profiles according to the occurrence of GERD.

The efficacy of a personalised treatment depending on the characteristics of reflux at multichannel intraluminal impedance-pH monitoring in patients with acid, non-acid and mixed laryngopharyngeal reflux.

OBJECTIVE: To assess the evolution of symptoms and findings of laryngopharyngeal reflux (LPR) patients according to the type of reflux (acid, non-acid, mixed and gastro-oesophageal (GERD)). DESIGN: Prospective uncontrolled multicentre study. METHODS: One hundred and six patients with LPR have been recruited from 3 European Hospitals. According to the reflux characteristics at the impedance-pH monitoring (acid, non-acid, mixed, GERD), patients received a personalised treatment based on the association of diet, pantoprazole, alginate or magaldrate for 3 months. Reflux Symptom Score (RSS) was assessed at baseline, 6 and 12 weeks post-treatment. Reflux Sign Assessment (RSA) has been used to rate laryngeal and extra-laryngeal findings at baseline and 12 weeks post-treatment. Overall success rate and the evolution of symptoms and findings were evaluated according to the LPR types. RESULTS: One hundred and two LPR patients (42 acid, 33 non-acid, 27 mixed, including 49 with LPR and GERD) completed the study. RSS and RSA total scores significantly improved from baseline to post-treatment time in acid, mixed and non-acid groups. The presence of GERD in addition to LPR did not impact the clinical improvement. The 3-month success rates of treatment ranged from 62% to 64%, and there were no significant differences between groups. The success rate of patients with non-acid LPR was similar to those of patients with mixed and acid LPR. CONCLUSION: MII-pH is useful to specify the type of LPR and the related most adequate therapeutic regimen. Non-acid or mixed LPR similarly respond to treatment than acid LPR but require a treatment based on alginate or magaldrate covering the non-acid proximal reflux events.

Patients with acid, high-fat and low-protein diet have higher laryngopharyngeal reflux episodes at the impedance-pH monitoring.

OBJECTIVE: To assess the impact of diet on the occurrence of proximal reflux episodes at the multichannel intraluminal impedance-pH monitoring (MII-pH) in patients with laryngopharyngeal reflux (LPR). METHODS: Patients with LPR symptoms and findings were recruited from three European hospitals. The LPR diagnostic was confirmed through MII-pH and patients were benefited from gastrointestinal (GI) endoscopy. Regarding the types of reflux at the MII-pH (acid, nonacid, mixed), patients received a 3 month-therapy based on the association of alkaline, low-fat and high-protein diet, proton pump inhibitors, alginate or magaldrate. Reflux symptom score (RSS) and reflux sign assessment (RSA) were used to evaluate laryngeal and extra-laryngeal symptoms and findings from pretreatment to posttreatment. The Global Refluxogenic Score (GRES) was used to assess the refluxogenic potential of the diet of the patients at baseline and posttreatment. The relationship between GRES severity; the MII-pH findings; GI endoscopy; and the therapeutic response was explored through multiple linear regression. RESULTS: Eighty-five LPR patients were included. The mean GRES significantly improved from pretreatment (50.7 ± 23.8) to posttreatment (27.3 ± 23.2; P = 0.001). Similarly, RSS and RSA significantly improved from baseline to posttreatment. The baseline GRES was significantly associated with the occurrence of proximal reflux episodes at the MII-pH (P = 0.001). Trends were found regarding the association between GRES and the occurrence of esophagitis (P = 0.06) and between hiatal hernia and DeMeester score (P = 0.06). There was a significant and strong association between the concomitant respect of diet and medication and the improvement of RSS (P = 0.001). CONCLUSION: The consumption of high-fat, low-protein, high-sugar, acid foods, and beverages is associated with a higher number of proximal reflux episodes at the MII-pH, according to the global refluxogenic score of LPR patients.

Development of scores assessing the refluxogenic potential of diet of patients with laryngopharyngeal reflux.

OBJECTIVE: To develop clinical tools assessing the refluxogenic potential of foods and beverages (F&B) consumed by patients with laryngopharyngeal reflux (LPR). METHODS: European experts of the LPR Study group of the Young-Otolaryngologists of the International Federation of Oto-rhino-laryngological societies were invited to identify the components of Western European F&B that would be associated with the development of LPR. Based on the list generated by experts, four authors conducted a systematic review to identify the F&B involved in the development of esophageal sphincter and motility dysfunctions, both mechanisms involved in the development of gastroesophageal reflux disease and LPR. Regarding the F&B components and the characteristics identified as important in the development of reflux, experts developed three rational scores for the assessment of the refluxogenic potential of F&B, a dish, or the overall diet of the patient. RESULTS: Twenty-six European experts participated to the study and identified the following components of F&B as important in the development of LPR: pH; lipid, carbohydrate, protein composition; fiber composition of vegetables; alcohol degree; caffeine/theine composition; and high osmolality of beverage. A total of 72 relevant studies have contributed to identifying the Western European F&B that are highly susceptible to be involved in the development of reflux. The F&B characteristics were considered for developing a Refluxogenic Diet Score (REDS), allowing a categorization of F&B into five categories ranging from 1 (low refluxogenic F&B) to 5 (high refluxogenic F&B). From REDS, experts developed the Refluxogenic Score of a Dish (RESDI) and the Global Refluxogenic Diet Score (GRES), which allow the assessment of the refluxogenic potential of dish and the overall diet of the LPR patient, respectively. CONCLUSION: REDS, RESDI and GRES are proposed as objective scores for assessing the refluxogenic potential of F&B composing a dish or the overall diet of LPR patients. Future studies are needed to study the correlation between these scores and the development of LPR according to impedance-pH study.

Diagnostic Value of Fasting and Bedtime Saliva Pepsin Measurements in Laryngopharyngeal Reflux.

BACKGROUND: The pepsin test is an emerging non-invasive diagnostic approach for laryngopharyngeal reflux (LPR). The aim of this study was to investigate the diagnostic value of multiple salivary pepsin tests for detecting LPR. METHODS: Patients with suspected LPR and asymptomatic individuals were consecutively recruited from January 2020 to November 2022. Patients benefited from hypopharyngeal-esophageal impedance-pH monitoring (HEMII-pH) and fasting and bedtime saliva collections to measure oral pepsin. The sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values were calculated considering fasting, bedtime, and the highest values of the pepsin tests at ≥16, ≥36, ≥45, and ≥100 ng/mL cutoffs. RESULTS: The pepsin test was adequately performed in 147 LPR patients and 32 controls. The pepsin tests were 81.6%, 74.8%, and 61.5% sensitive at cutoffs of ≥16, ≥45, and ≥100 ng/mL, respectively. The PPVs were 93.0%, 94.0%, and 94.8%, respectively. The highest specificity (81.8%) was found for the fasting pepsin test at a cutoff of 100 ng/mL. The highest sensitivity (81.6%) was found by considering the highest measured pepsin test at the ≥16 ng/mL threshold. The measurement of fasting saliva pepsin was associated with the highest sensitivity and specificity value. At ≥16 ng/mL, 27 patients had negative findings, indicating that 18.4% (27/147) of the true positive cases were missed by considering the highest pepsin test. The receiver operating characteristic curve reported that a cutoff of 21.5 was 76.9% sensitive and 62.5% specific, while the PPV and NPV were 91.1% and 38.2%, respectively. CONCLUSIONS: The consideration of the highest concentration of the fasting and bedtime saliva pepsin collections at a cutoff of 21.5 was associated with the best detection rate and sensitivity of the pepsin tests.

The Dubai Definition and Diagnostic Criteria of Laryngopharyngeal Reflux: The IFOS Consensus.

OBJECTIVE: The objective of this work was to gather an international consensus group to propose a global definition and diagnostic approach of laryngopharyngeal reflux (LPR) to guide primary care and specialist physicians in the management of LPR. METHODS: Forty-eight international experts (otolaryngologists, gastroenterologists, surgeons, and physiologists) were included in a modified Delphi process to revise 48 statements about definition, clinical presentation, and diagnostic approaches to LPR. Three voting rounds determined a consensus statement to be acceptable when 80% of experts agreed with a rating of at least 8/10. Votes were anonymous and the analyses of voting rounds were performed by an independent statistician. RESULTS: After the third round, 79.2% of statements (N = 38/48) were approved. LPR was defined as a disease of the upper aerodigestive tract resulting from the direct and/or indirect effects of gastroduodenal content reflux, inducing morphological and/or neurological changes in the upper aerodigestive tract. LPR is associated with recognized non-specific laryngeal and extra-laryngeal symptoms and signs that can be evaluated with validated patient-reported outcome questionnaires and clinical instruments. The hypopharyngeal-esophageal multichannel intraluminal impedance-pH testing can suggest the diagnosis of LPR when there is >1 acid, weakly acid or nonacid hypopharyngeal reflux event in 24 h. CONCLUSION: A global consensus definition for LPR is presented to improve detection and diagnosis of the disease for otolaryngologists, pulmonologists, gastroenterologists, surgeons, and primary care practitioners. The approved statements are offered to improve collaborative research by adopting common and validated diagnostic approaches to LPR. LEVEL OF EVIDENCE: 5 Laryngoscope, 134:1614-1624, 2024.

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.

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.

Safety and Feasibility of Hypnosis-Induced Sleep Endoscopy in Obstructive Sleep Apnea Patients.

BACKGROUND: Hypnosis was never used in sleep endoscopy assessment of obstructive sleep apnea syndrome (OSAS). The aim of the study was to assess the feasibility, safety, and patient satisfaction of hypnosis-induced sleep endoscopy (HISE). METHODS: From January to July 2021, 24 adults with moderate-to-severe OSAS at the polysomnography were included in the HISE protocol. The following outcomes were evaluated by the otolaryngologist and the hypnotherapist: safety, feasibility, and performance. The patient outcomes were assessed through a patient-reported outcome questionnaire assessing hypnosis acceptance, stress, anxiety, nasofibroscopy examination pain, and discomfort. RESULTS: Twenty-three patients completed the evaluations (16 males). The mean age of patients was 50.8 years. The nasofibroscopy was well-tolerated with low levels of stress during the HISE. Otolaryngologist adequately completed the VOTE scoring in 22 patients (95.7%). Hypnosis was ineffective in one patient because he felt pain during the nasofibroscopy procedure due to an important septal deviation. The hypnotherapist reported adequate satisfaction outcomes, with better results for trance compliance compared to other steps. There were no adverse effects or complications. The percentage of snoring was negatively associated with the level of consciousness during hypnosis (p = 0.012). The easiness of nasofibroscopy was positively associated with the levels of muscle relaxation (p = 0.036) and consciousness (P = 0.002). CONCLUSION: HISE is an effective alternative approach for the work-up of OSAS. Future controlled studies are needed to compare HISE with drug-induced sleep endoscopy and assess the cost-effective outcomes of both approaches.

The role of pH-impedance monitoring in swallowing disorders.

PURPOSE OF REVIEW: To review the current evidence about the usefulness and the place of pH study in the management of patients with swallowing disorders. RECENT FINDINGS: Gastroesophageal reflux disease (GERD) and laryngopharyngeal reflux (LPR) are found in approximately 30% of patients with esophageal or oropharyngeal dysphagia. Patients with suspected GERD may benefit from gastrointestinal endoscopy and proton pump inhibitors according to guidelines. The diagnosis of LPR in patients with oropharyngeal dysphagia is more controversial because there are no gold standard and diagnostic guidelines. The clinical diagnosis based on empirical therapeutic trial is a reasonable first-line strategy, but many dysphagic patients should not respond to treatment. These patients require hypopharyngeal-esophageal multichannel intraluminal impedance-pH monitoring (HEMII-pH), which is the most effective examination providing important information on GERD and LPR features. At the HEMII-pH, GERD patients often report upright (daytime) and supine (nighttime) liquid acid esophageal events with significant esophageal distal acid exposure time. LPR patients have more frequently upright (daytime) gaseous weakly acid or nonacid pharyngeal reflux events without distal esophageal acid exposure abnormalities in many times. The features of reflux at the HEMII-pH may indicate a personalized treatment for dysphagic patients combining proton pump inhibitors, alginate/magaldrate or gastroprokinetic in cases of esophageal dysmotility. SUMMARY: GERD and LPR are prevalent causes of dysphagia. The large number of reflux patients who do not respond to empirical treatment makes important the awareness of otolaryngologists about pH-impedance monitoring indication, features, and interpretation.

Influence of Age and Sex on Clinical and Therapeutic Features of Laryngopharyngeal Reflux.

OBJECTIVE: To explore the influence of age and sex on the clinical presentation and therapeutic response of patients with laryngopharyngeal reflux (LPR). STUDY DESIGN: Prospective study. SETTING: Prospective multicenter study of 271 patients with a diagnosis of LPR confirmed by impedance-pH monitoring. METHODS: Patients were prescribed 6 months of diet changes and a combination of pantoprazole and/or alginate depending on the results of their impedance-pH results. The Reflux Symptom Score (RSS) and Reflux Sign Assessment (RSA) were collected at baseline and at 3 and 6 months posttreatment. Data were explored according to sex and age. RESULTS: A total of 237 patients completed the evaluations (138 females). On the RSS, patients of the oldest group (>60 years) had lower symptom scores (throat pain, ear pain, odynophagia, chest pain, tongue burning, nausea, halitosis, and indigestion) and lower quality-of-life scores than younger individuals. RSS and RSA outcomes significantly improved from pretreatment to 3 months posttreatment in all groups. Scores on the RSS and RSA continued to improve from 3 to 6 months posttreatment in the elderly group. Females with LPR had a higher score on the RSS at baseline as compared with males. On the RSS, scores significantly improved after 3 months in males and females; however, they continued to improve from 3 to 6 months in the female group. CONCLUSION: Age and sex may influence the clinical presentation and pre- to posttreatment evolution of symptoms and findings. Age and sex differences could be considered in future therapeutic approaches to guide more effective personalized treatment plans for patients with LPR.

Normative Ambulatory Reflux Monitoring Metrics for Laryngopharyngeal Reflux: A Systematic Review of 720 Healthy Individuals.

OBJECTIVES: To review the normative data for acid, weakly acid, and nonacid proximal esophageal (PRE) and hypopharyngeal reflux (HRE) events in diagnosing laryngopharyngeal reflux (LPR) using ambulatory reflux monitoring. DATA SOURCES: PubMed, Cochrane Library, and Scopus. REVIEW METHODS: A literature search was conducted about the normative data for PRE and HRE on multichannel intraluminal impedance-pH monitoring (MII-pH), hypopharyngeal-esophageal MII-pH (HEMII-pH), or oropharyngeal pH monitoring using PICOTS (population, intervention, comparison, outcome, timing, and setting) and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statements. Outcomes reviewed included device characteristics, impedance/pH sensor placements, study duration, number/average and percentiles of PRE or HRE occurrence, and the event characteristics (pH, composition, and position). RESULTS: Of 154 identified studies, 18 met criteria for analysis, including 720 healthy individuals. HEMII-pH, MII-pH, and oropharyngeal pH monitoring were used in 7, 6, and 5 studies, respectively. The definition and inclusion/exclusion criteria of healthy individuals varied substantially across studies, with 6 studies considering only digestive symptoms to exclude potential LPR patients. Substantial heterogeneity across studies was noted, including impedance/pH sensor placements/configurations and definitions of composition (liquid, gas, mixed) and type (acid, weakly acid, nonacid) of PRE/HRE. The 95th percentile thresholds were 10 to 73 events for PRE, 0 to 10 events for HRE on HEMII-pH, and 40 to 128 for events with pH <6.0 on oropharyngeal pH monitoring. Most HREs were nonacid and occurred upright. The mean HRE among healthy individuals was 1. CONCLUSION: The low number of studies and the heterogeneity in inclusion criteria, definitions, and characterization of PRE and HRE limit the establishment of consensual normative criteria for LPR on ambulatory reflux monitoring. Future large multicenter studies are needed.

Laryngopharyngeal Reflux Disease is More Severe in Obese Patients: A Prospective Multicenter Study.

OBJECTIVES/HYPOTHESIS: To investigate whether there is an impact of obesity and overweight on the clinical findings and therapeutic responses of patients with laryngopharyngeal reflux (LPR). STUDY DESIGN: Prospective uncontrolled. METHODS: Patients with LPR-related symptoms and positive LPR diagnosis at the hypopharyngeal-esophageal multichannel intraluminal impedance pH-monitoring (HEMII-pH) were recruited from December 2017 to December 2020. Patients were treated with a combination of diet, proton pump inhibitors, and alginate for 3 to 6 months. The following outcomes were studied according to the weight of patients: HEMII-pH, gastrointestinal endoscopy features, symptoms, findings, and therapeutic response. RESULTS: A total of 262 patients completed the study, accounting for 134, 85, and 43 patients with normal weight (body mass index [BMI] <25), overweight (BMI = 25-29.99), and obesity (BMI >30). Obese patients reported significant higher prevalence of gastroesophageal reflux disease (GERD), acid LPR, and a more severe LPR disease regarding the number of pharyngeal reflux events, reflux symptom score (RSS), and reflux sign assessment (RSA). RSS and RSA scores significantly improved from baseline to 3-month posttreatment irrespective of the patient weight group. Symptoms and signs continued to improve from 3 to 6-month posttreatment only in patients with a normal weight. CONCLUSION: Obesity is associated with a more severe LPR disease and a higher proportion of GERD and acid LPR. Obese LPR patients may require more frequently PPI-therapy regarding the higher prevalence of GERD. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:E2742-E2748, 2021.

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.

Changes of Laryngeal and Extralaryngeal Symptoms and Findings in Laryngopharyngeal Reflux Patients.

OBJECTIVES/HYPOTHESIS: To assess the evolution of laryngeal and extralaryngeal symptoms and findings of laryngopharyngeal reflux (LPR) throughout a 3-month to 9-month treatment. STUDY DESIGN: Prospective Controlled Study. METHODS: One hundred twenty-seven LPR patients and 123 healthy individuals were enrolled from four European hospitals. Patients were managed with a 3-month personalized treatment considering the LPR characteristics at the impedance-pH monitoring. Regarding the clinical therapeutic response, treatment was adapted for 3 to 6 additional months. Symptoms and findings were assessed throughout the therapeutic course with the Reflux Symptom Score (RSS) and the short version of the Reflux Sign Assessment (sRSA). The relationship between patient and reflux characteristics, symptoms, and findings was assessed. RESULTS: One hundred twenty-one LPR patients completed the study. LPR patients exhibited more laryngeal and extralaryngeal symptoms and findings than healthy individuals. RSS significantly improved from baseline to 6 weeks posttreatment and continued to improve from 3 months to 6 months posttreatment. sRSA significantly improved from baseline to 3 months posttreatment. No further improvement was noted at 6 months posttreatment for pharyngeal and oral findings. Laryngeal findings continued to improve from 3 months to 6 months posttreatment. There was a significant association between patient stress level and RSS (P = .045). At 3 months posttreatment, 28.1% of patients had high or complete response, whereas 47.1% required 6 months or 9 months of treatment. Overall, 24.8% of patients had an LPR chronic course. CONCLUSIONS: Laryngeal and extralaryngeal symptoms and findings significantly improved throughout treatment in LPR patients. The improvement of laryngeal findings was slower. Regarding the low prevalence of some digestive or otolaryngological symptoms, a short version of the RSS could be developed. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:1332-1342, 2021.