Validity and Reliability of the Reflux Sign Assessment-10 (RSA-10).

OBJECTIVE: To develop and validate the Reflux Sign Assessment-10 (RSA-10) for documenting the physical findings of laryngopharyngeal reflux disease (LPRD). METHODS: Patients with LPRD at the hypopharyngeal-esophageal multichannel intraluminal impedance-pH monitoring and asymptomatic individuals were consecutively recruited from two European hospitals. Three experienced otolaryngologists rated RSA-10 in patients and controls for assessing internal validity. RSA-10 was rated within a 7-day period to assess test-retest reliability. Internal consistency was measured using Cronbach's α in patients and controls. Convergent validity was evaluated through a correlation analysis between RSA-10 and Reflux Finding Score (RFS). Interrater reliability was evaluated by comparing the RSA-10 evaluations of the three otolaryngologists through Fleiss kappa. Pre- to posttreatment change of RSA-10 was evaluated to assess responsiveness to change. The RSA-10 thresholds were examined by receiver operating characteristic analysis. RESULTS: Fifty-five patients completed the pre- to posttreatment evaluations from January 2020 to December 2023. A total of 115 asymptomatic individuals completed the study. RSA-10 reported high internal consistency reliability (α = 0.822) and test-retest reliability (rs = 0.725). The RSA-10 scores of patients were significantly higher than those of controls (p = 0.001), suggesting high internal validity. RSA-10 was significantly correlated with the RFS (rs = 0.771). The interrater reliability was adequate for sub- and total RSA-10 scores (k = 0.708). RSA-10 significantly improved from baseline to 3-month posttreatment (p = 0.001). An RSA-10 > 13 may be suggestive of LPRD. Both RSA-10 > 13 and Reflux Symptom Score-12 > 11 were associated with a sensitivity of 92.7% and a specificity of 97.3%. CONCLUSION: The RSA-10 is a reliable and valid clinical instrument for documenting the most prevalent laryngeal and extra-laryngeal findings associated with LPRD. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

Digestive Biomarkers of Laryngopharyngeal Reflux: A Preliminary Prospective Controlled Study.

OBJECTIVE: To investigate the digestive enzymes and biomarkers in the saliva of patients with laryngopharyngeal reflux (LPR) and asymptomatic individuals. STUDY DESIGN: Prospective controlled study. SETTING: Multicenter study. METHODS: Patients with LPR at the hypopharyngeal-esophageal impedance-pH monitoring (HEMII-pH) and asymptomatic individuals were consecutively recruited from January 2020 to April 2023 from 2 University Hospitals. The saliva of patients (off PPIs) and asymptomatic individuals was collected to measure pH, elastase, bile salts, cholesterol, gastric, and pancreatic lipases. Anxiety, symptoms, and findings were studied through perceived stress scale (PSS), reflux symptom score (RSS), and reflux sign assessment (RSA). RESULTS: Sixty-seven LPR patients and 57 asymptomatic individuals completed the evaluations. LPR patients reported higher PSS, RSS, and RSA than asymptomatic individuals. The mean saliva pH was more alkaline in LPR patients (7.23: 95% confidence interval [CI]: 7.08, 7.38) compared to controls (6.13; 95% CI: 5.95, 6.31; P = .001). The mean concentration of elastase was higher in patients (51.65 µg/mL; 95% CI: 44.47, 58.83 µg/mL) versus asymptomatic individuals (25.18 µg/mL; 95% CI: 21.64, 28.72 µg/mL; P = .001). The saliva cholesterol reported higher concentration in healthy individuals (3.43 mg/dL; 95% CI: 3.21, 3.65 mg/dL) compared to patients (1.16 mg/dL; 95% CI: 1.05, 1.27 mg/dL; P = .001). The saliva pH, and elastase concentration were significantly associated with the baseline RSS, while saliva cholesterol was negatively associated with the severity of RSS and RSA. CONCLUSION: Cholesterol, bile salts, and elastase are biomarkers of LPR and should be considered to develop future non-invasive saliva device for the detection of LPR.

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.

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.

Proof-of-concept of a new FFP2 mask adapted to Otolaryngological practice in pandemic: a prospective study.

OBJECTIVE: The objective of this study was to appreciate the tolerance and convenience of a new FFP2 mask allowed the realization of nasal examination in period of pandemic. METHODS: Fifty-one patients were prospectively recruited from two European hospitals to test the FFP2 mask prototype. The following outcomes were evaluated in patients after the clinical examination: fear about coronavirus disease 2019 (COVID-19) infection; easiness of mask placement; tolerability; reassurance; and overall satisfaction about the use of this kind of mask in a pandemic context. Seven otolaryngologists evaluated the mask acceptance and usefulness in patients through a standardized physician-reported outcome questionnaire. RESULTS: Fifty patients completed the evaluation. There were 25 males and 25 females. The mean age of patients was 41 years. Ninety percent of patients considered that the use of the mask reduced the risk to be infected during the examination. Seventy percent of patients reported high or very high satisfaction and should recommend mask to other patients in pandemic period. The realization of nasal examination was easier with optic compared with flexible trans-nasal examination (p = 0.001), which significantly impacted the satisfaction level of physician (p = 0.001). The physician difficulty to perform the examination significantly impacted the satisfactory of patient (p = 0.033). CONCLUSION: The new bioserenity FFP2 mask allows the realization of the trans-nasal endoscopic examination during a pandemic. The use of this mask requires little training period of physician. The use of this mask prototype is well received by patients who reported better perception of self-protection against the virus.

Laryngopharyngeal Reflux: Evolution and Predictive Value of Symptoms and pH-Impedance Features on Clinical Evolution.

OBJECTIVES: To investigate the features of patients with laryngopharyngeal reflux (LPR) who did not respond to medical treatment. STUDY DESIGN: Prospective uncontrolled study. SETTING: Multicenter study. METHODS: Patients with LPR at 24-hour HEMII-pH monitoring (hypopharyngeal-esophageal multichannel intraluminal impedance-pH) were prospectively recruited from 3 European university centers. Patients were treated with 3- to 6-month medication (proton pump inhibitor and alginate) and categorized as mild to moderate responders, high responders, or nonresponders according to Reflux Symptom Score (RSS) changes at 6 months posttreatment. The predictive value of the following outcomes was studied: epidemiologic data, HEMII-pH, gastrointestinal endoscopy findings, baseline RSS and Reflux Sign Assessment, and early therapeutic response (6-week RSS). RESULTS: A total of 148 patients completed the evaluations, accounting for 40 mild to moderate responders (20%-60% RSS changes), 76 high responders (>60% RSS changes), and 32 nonresponders. Nonresponders presented more often with hiatal hernia and lower esophageal sphincter insufficiency when compared with mild to moderate and high responders (P = .032). Baseline otolaryngologic, digestive, and respiratory RSS and the number of pharyngeal reflux events at the HEMII-pH were predictive of the 6-month therapeutic response (P < .05). The early therapeutic response (6 weeks posttreatment) was predictive of the 6-month treatment response. CONCLUSION: Hiatal hernia and baseline and 6-week RSS were the most predictive indicators of therapeutic effectiveness in patients with LPR.

Is Diet Sufficient as Laryngopharyngeal Reflux Treatment? A Cross-Over Observational Study.

OBJECTIVES/HYPOTHESIS: To investigate the efficacy of low-fat, low-quick-release sugar, high-protein, alkaline, and plant-based diet as single treatment for patients with laryngopharyngeal reflux (LPR). STUDY DESIGN: Cross-over observational study. METHODS: Patients with LPR diagnosis at the hypopharyngeal-esophageal multichannel intraluminal impedance-pH-monitoring were prospectively recruited from the reflux clinic of three University Hospitals. Patients were instructed to follow low-fat, low-quick-release sugar, high-protein, alkaline, and plant-based diet for 6 to 12 weeks. Pre- to post-treatment symptom and finding changes were evaluated with reflux symptom score (RSS) and reflux sign assessment. Findings were compared to those of a control period where patients did not receive any treatment or diet. Diet was evaluated with refluxogenic diet score (REDS). RESULTS: Fifty patients completed the study (19 males). Otolaryngological, digestive, and total RSS scores significantly improved from baseline to 6-week post-diet, while there were no significant changes during the control period. At 6-week post-diet, 37 (74%) patients reported significant symptom improvement or relief. Among them, symptoms continued to improve from 6 to 12 weeks in 27 cases, corresponding to a diet success rate of 54%. The REDS was predictive of the baseline RSS (P = .031). CONCLUSION: Low-fat, low-quick-release sugar, high-protein, alkaline, and plant-based diet is an alternative cost-effective therapeutic approach for patients with LPR. Patients with higher REDS reported higher baseline symptom score. LEVEL OF EVIDENCE: 3 Laryngoscope, 132:1916-1923, 2022.

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.

Surgical Treatment for Laryngopharyngeal Reflux Disease: A Systematic Review.

Importance: Laryngopharyngeal reflux (LPR) is a prevalent disease that is usually treated with diet, lifestyle modifications, and proton pump inhibitor therapy. However, nearly 10% to 30% of patients do not achieve adequate acid suppression even with high doses of proton pump inhibitors. For these patients with resistant disease, fundoplication may be recommended but the success rate of fundoplication surgery on laryngopharyngeal symptoms and findings remains uncertain. Objective: To determine whether fundoplication is associated with control of signs and symptoms in patients with LPR. Evidence Review: A literature search was conducted on PubMed, Cochrane Library, and Scopus according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline to identify studies published between 1990 and 2018 about the efficacy of fundoplication on clinical outcomes of LPR. Three investigators screened publications for eligibility and exclusion based on predetermined criteria. Study design, patient characteristics, diagnostic method, exclusion criteria, treatment characteristics, follow-up, and quality of the outcome assessment were evaluated. Findings: Of the 266 studies identified, 34 met the inclusion criteria, accounting for 2190 patients with LPR (1270 women and 920 men; mean [SD] age at the time of surgery, 49.3 [6.3] years). A weighted mean of 83.0% of patients (95% CI, 79.7%-86.3%) experienced improvement and a weighted mean of 67.0% of patients (95% CI, 64.1%-69.9%) experienced a disappearance of symptoms, but there is a high level of methodological heterogeneity among studies according to diagnostic method, exclusion criteria, and outcomes used to assess the efficacy of fundoplication. A pH study without impedance study was used in most studies but with various inclusion criteria. According to results of an a priori assessment, the clinical outcomes used were overall poor, excluding many symptoms and findings associated with LPR. Conclusion and Relevance: The reported studies of fundoplication in LPR disease have important heterogeneity in method of diagnosis, exclusion criteria, symptoms, and signs assessed as therapeutic outcomes; therefore, this systematic review was nonconclusive regarding whether surgery for LPR disease is associated with effective control of sight and symptoms. Otolaryngologists, gastroenterologists, and surgeons must establish a diagnostic criterion standard, clear indications for surgery, and future clinical outcomes to precisely assess the effectiveness of treatment.

Clinical outcomes of laryngopharyngeal reflux treatment: A systematic review and meta-analysis.

OBJECTIVES: To investigate the therapeutic benefit of proton pump inhibitors (PPIs) over placebo in patients with laryngopharyngeal reflux (LPR) and to analyze the epidemiological factors of heterogeneity in the literature. METHODS: An electronic literature search was conducted to identify articles published between 1990 and 2018 about clinical trials describing the efficiency of medical treatment(s) on LPR. First, a meta-analysis of placebo randomized controlled trials (RCTs) comparing PPIs versus placebo was conducted according to diet. The heterogeneity, response to PPIs, and evolution of clinical scores were analyzed for aggregate results. Second, a systematic review of diagnosis methods, clinical outcome of treatment, and therapeutic regimens was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. RESULTS: The search identified 1,140 relevant publications, of which 72 studies met the inclusion criteria for a total of 5,781 patients. Ten RCTs were included in the meta-analysis. The combined relative risk was 1.31 in favor of PPIs and increased to 1.42 when patients did not receive diet recommendations. Randomized controlled trials were characterized by a significant heterogeneity due to discrepancies in clinical therapeutic outcomes, diagnosis methods (lack of gold standard diagnostic tools), and therapeutic scheme. The epidemiological analysis of all articles supports the existence of these discrepancies in the entire literature. In particular, many symptoms and signs commonly encountered in LPR are not assessed in the treatment effectiveness. The lack of diagnosis precision and variability of inclusion criteria particularly create bias in all reported and included articles. CONCLUSION: This meta-analysis supports a mild superiority of PPIs over placebo and the importance of diet as additional treatment but demonstrates the heterogeneity between studies, limiting the elaboration of clear conclusions. International recommendations are proposed for the development of future trials. Laryngoscope, 129:1174-1187, 2019.

Instruments evaluating the clinical findings of laryngopharyngeal reflux: A systematic review.

OBJECTIVES: To identify the instruments for evaluating the clinical findings (ICFs) of laryngopharyngeal reflux (LPR) designed for use with regard to diagnosis and treatment effectiveness. METHODS: The PubMed, Scopus, and Cochrane databases were used to search for subject headings following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. Three investigators retrieved relevant studies published between 1990 and 2018 describing the evolution of laryngopharyngeal findings throughout LPR treatment. Issues of clinical relevance, that is, LPR diagnosis, treatments, and signs assessed for diagnosis or as therapeutic outcomes, were assessed. The investigators also evaluated the psychometric properties (conceptual model, content validity, consistency, reliability, concordance, convergent validity, known-groups validity, responsiveness to change, and interpretability) of the ICF. The risk of bias was assessed with the tool of the Clarity Group and Evidence Partners. RESULTS: The search identified 1,227 publications with a total of 4,735 LPR patients; of these studies, 53 met the inclusion criteria. Of these 53 studies, we identified 10 unvalidated and six validated ICFs. None of the validated ICFs included all the psychometric properties. The main identified deficiencies related to ICF psychometric validation included variable construct validity, disparate and uncertain reliabilities, and a lack of interpretability. The lack of consideration of certain LPR laryngeal and extralaryngeal signs is the main weakness of ICFs, biasing content, and construct validities. CONCLUSION: The low specificity of LPR signs, the lack of consideration of many findings, and the absence of a gold standard for diagnosis constitute barriers to the further validation of these ICFs. Additional studies are needed to develop complete and reliable ICFs. Laryngoscope, 129:720-736, 2019.

Contact allergy to benzalkonium chloride in patients using a steroid nasal spray: A report of 3 cases.

Benzalkonium chloride (BAC) is a bactericidal preservative excipient commonly found in steroid nasal sprays used to treat allergic rhinitis and nasal polyposis. In rare cases, BAC can be responsible for type I and type IV hypersensitivity reactions that can manifest as rhinorrhea, which a clinician might misinterpret as a lack of response to nasal spray therapy rather than a complication of it. We report 3 cases of type IV hypersensitivity reactions in patients who were being treated with mometasone nasal spray. We describe the epidemiology, clinical features, diagnosis, and treatment of these reactions.

Unusual presentation of an adult pedunculated hemangioma of the oropharynx.

Hemangioma is a benign tumor rarely found in adult, especially in oropharynx. This study describes the first case of mixed hemangioma occurring as an oropharyngeal asymptomatic pedunculated mass. Biopsy is excluded given the risk of hemorrhage. Diagnosis and treatment are based on the surgical resection and the histopathologic examination.