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.

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.

Effect of 5-Hydroxytryptophan on Fatigue in Quiescent Inflammatory Bowel Disease: A Randomized Controlled Trial.

BACKGROUND & AIMS: Fatigue is highly prevalent among patients with inflammatory bowel disease (IBD), and only limited treatment options are available. Based on the hypothetical link between low serum tryptophan concentrations and fatigue, we determined the effect of 5-hydroxytryptophan supplementation on fatigue in patients with inactive IBD. METHODS: A multicenter randomized controlled trial was performed at 13 Belgian hospitals, including 166 patients with IBD in remission but experiencing fatigue, defined by a fatigue visual analog scale (fVAS) score of ≥5. Patients were treated in a crossover manner with 100 mg oral 5-hydroxytryptophan or placebo twice daily for 2 consecutive periods of 8 weeks. The primary end point was the proportion of patients reaching a ≥20% reduction in fVAS after 8 weeks of intervention. Secondary outcomes included changes in serum tryptophan metabolites, Functional Assessment of Chronic Illness Therapy Fatigue scale, and scores for depression, anxiety, and stress. The effect of the intervention on the outcomes was evaluated by linear mixed modeling. RESULTS: During 5-hydroxytryptophan treatment, a significant increase in serum 5-hydroxytryptophan (estimated mean difference, 52.66 ng/mL; 95% confidence interval [CI], 39.34-65.98 ng/mL; P < .001) and serotonin (3.0 ng/mL; 95 CI, 1.97-4.03 ng/mL; P < .001) levels was observed compared with placebo. The proportion of patients reaching ≥20% reduction in fVAS was similar in placebo- (37.6%) and 5-hydroxytryptophan (35.6%)-treated patients (P = .830). The fVAS reduction (-0.18; 95% CI, -0.81 to 0.46; P = .581) and Functional Assessment of Chronic Illness Therapy Fatigue scale increase (0.68; 95% CI, -2.37 to 3.73; P = .660) were both comparable between 5-hydroxytryptophan and placebo treatment as well as changes in depression, anxiety, and stress scores. CONCLUSIONS: Despite a significant increase in serum 5-hydroxytryptophan and serotonin levels, oral 5-hydroxytryptophan did not modulate IBD-related fatigue better than placebo. (Trial Registration: Belgian Federal Agency for Medication and Health Products, EudraCT number: 2017-005059-10 and ClinicalTrials.gov: NCT03574948, https://clinicaltrials.gov/ct2/show/NCT03574948.).

New-onset Graves' disease following SARS-CoV-2 vaccination: a case report.

A 22-year-old male with a history of ulcerative colitis and nephrotic syndrome treated with immunomodulatory agents including vedolizumab and mycophenolic acid developed hyperthyroidism 2 weeks following the first administration of BNT162b2 vaccine (Pfizer-BioNTech COVID-19 vaccine). Graves' disease (GD) was diagnosed based on the elevated thyrotropin-receptor antibody, thyroid scintigraphy and ultrasound. To this day, four cases of new-onset GD following SARS-CoV-2 vaccine were reported in patients with no previous history of thyroid disease. Two cases of recurrence of GD following SARS-CoV-2 vaccine were also reported. Although the underlying mechanisms of vaccine-induced autoimmunity remain to be clarified, there is a rationale for the association between SARS-CoV-2 vaccination and the development of Th1-mediated diseases, at least in predisposed individuals. The BNT162b2 vaccine could be a trigger for GD in some patients. However, the benefit/risk ratio remains by far in favour of SARS-CoV-2 vaccination considering the potentially higher risk of severe infection in these patients.

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.

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.

ImmunoStart: preparing patients for immunosuppression.

OBJECTIVES: Patients with immune-mediated inflammatory disease (IMID) present an increased risk of infection. Here, we present the concept of a preventive consultation called ImmunoStart and the first results of its implementation in the care pathway of patients with IMID. METHODS: Relevant information about vaccination history, tuberculosis exposure and other infectious risks were collected through blood sampling, complete anamnesis, chest X-ray and Mantoux test. During the ImmunoStart consultation, vaccination schedules, specific treatments and risk considerations were discussed. RESULTS: Between October 2016 and February 2020, 437 patients were seen at an ImmunoStart consultation, mainly referred by rheumatologists (56%), dermatologists (25%) and gastroenterologists (18%). A total of 421 (96%) patients needed at least one vaccine (a mean of 3.3 vaccines per patient). Live attenuated vaccine was indicated for 45 patients (10%), requiring them to reduce or interrupt their immunosuppressive drug(s). Ninety-two patients (21%) were treated for latent tuberculosis infection. CONCLUSION: This preventive consultation provides a centralized and systematic setting for the direct management of patients with IMID in need of vaccination, treatment of latent disease and specific advice regarding their immunomodulating treatments.

Primary antibiotic resistance of Helicobacter pylori isolates is twofold more frequent in HIV-positive than HIV-negative individuals: A descriptive observational study.

The antimicrobial susceptibility of Helicobacter pylori strains isolated from HIV-positive individuals is not well characterized. This study aimed to measure the prevalence and long-term trends associated with primary H. pylori antibiotic resistance, evaluate correlations with antibiotic consumption, and compare predictors for H. pylori antibiotic resistance between HIV-positive and HIV-negative individuals. In this longitudinal registry study, we evaluated consecutive adults with and without HIV infection, naïve to H. pylori treatment, who underwent upper gastrointestinal endoscopy and had a positive H. pylori culture, with susceptibility testing available, between 2004 and 2015. Outpatient antibiotic consumption data were based on nationwide aggregated numbers. H. pylori was isolated from gastric biopsies of 3008/8321 patients, 181/477 (37.9%) were HIV-positive and 2827/7844 (36.0%) HIV-negative. Overall cohort mean prevalence of H. pylori primary antibiotic resistance was 11.1% for clarithromycin, 17.8% levofloxacin, and 39.4% metronidazole. The prevalence of H. pylori primary resistance was significantly higher for these three drugs in HIV-positive individuals across the study period. Linear regression showed that the prevalence of clarithromycin and levofloxacin resistance correlated with the country aggregate daily dose consumption of macrolides and quinolones, respectively. Multivariable regression analysis showed that HIV infection is a strong independent risk factor for multiple H. pylori antibiotic resistance. In summary, HIV infection is a risk factor for carrying multi-resistant H. pylori strains and this is correlated with antibiotic consumption. Empirical therapies should be avoided in HIV-positive individuals. These data highlight the need to implement ongoing monitoring of H. pylori antimicrobial susceptibility among HIV-positive individuals. The study is registered at ISRCTN registry, number 13466428: https://www.isrctn.com/ISRCTN13466428.

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.

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.

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.

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.

A 10-Year Follow-Up of a Randomized Prospective Study of 2 Treatments for Chronic Rhinosinusitis Without Nasal Polyps and Investigation of the Impact of Gastroeosophageal Reflux Disease in the Resistance to Treatment.

OBJECTIVES: To compare the 2 long-term medical strategies in chronic rhinosinusitis without nasal polyps (CRSnNP) and to identify the role of gastroesophageal reflux disease (GERD) and Helicobacter pylori as factors of treatment failure. MATERIAL AND METHODS: Fifty-seven patients with CRSnNP were randomized into 2 therapeutic groups. The first group was treated with 4 weeks of amoxicillin/clavulanate and a short course of oral steroids. The second group received 8 weeks of clarithromycin. Sinonasal Outcome Test-20 (SNOT-20) and Lund and Mackay scores were assessed at baseline and after treatment, and GERD Health-Related Quality of Life (GERD-HRQL) questionnaire was evaluated in all patients. Patients with a GERD-HRQL score >8 received esogastroscopy and H pylori detection. Patients were followed during a 10-year period for clinical course and GERD evolution. The 10-year evolution of patients was described in terms of recurrence, medical, and surgical treatments. RESULTS: Thirty-seven patients completed the study; SNOT-20 and Lund and Mackay scores similarly improved in both groups. Amoxicillin/clavulanate group had significantly more adverse reactions than the clarithromycin group (P = .03). After the therapeutic course, 35% (amoxicillin/clavulanate) and 41% (clarithromycin) of patients needed functional endoscopic sinus surgery (FESS). During the long-term follow-up, 54% (amoxicillin/clavulanate) and 40% (clarithromycin) of patients had late CRSnNP recurrence; FESS was performed in less than 15% of cases of recurrence. Gastroesophageal reflux disease complaint's severity was associated with late recurrence of CRSnNP. CONCLUSION: Amoxicillin/clavulanate and clarithromycin would be competitive treatments for CRSnNP. Gastroesophageal reflux disease seems to be a negative factor for treatment response and recurrence.

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.

Development and Validation of the Short Version of the Reflux Symptom Score: Reflux Symptom Score-12.

OBJECTIVE: To develop and validate a short version of the Reflux Symptom Score-the 12-question Reflux Symptom Score-12 (RSS-12)-for patients with laryngopharyngeal reflux disease (LPR). STUDY DESIGN: Prospective study. SETTING: Multicenter academic hospitals. METHODS: Patients with LPR diagnosed via multichannel intraluminal impedance pH monitoring were enrolled from 3 European hospitals. Healthy individuals completed the study. Individuals completed the Reflux Symptom Score, Reflux Symptom Index (RSI), and Voice Handicap Index (VHI) at baseline and 3 months posttreatment. The Reflux Symptom Score was completed twice within a 7-day period to assess test-retest reliability. Cronbach's α was used for assessing internal consistency. The RSS-12 was developed and validity assessed through a comparison of the RSS-12, RSI, and VHI. Responsiveness to change was evaluated through the pre- to posttreatment evolution of the RSS-12 total score. Receiver operating characteristic analysis was used to determine the RSS-12 threshold that is suggestive of LPR. RESULTS: The RSS-12 was characterized by high test-retest reliability (rs = 0.956) and adequate internal consistency reliability (α = 0.739). The RSS-12 was significantly correlated with the RSI (rs = 0.845), suggesting high external validity. The RSS-12 total and item scores were significantly higher in patients with LPR as compared with healthy individuals (P = .001), supporting high internal validity. RSS-12, VHI, and RSI significantly improved throughout treatment. Regarding the receiver operating characteristic curve, an RSS-12 score >11 is suggestive of LPR, exhibiting a sensitivity of 94.5% and a specificity of 86.2%. CONCLUSION: The RSS-12 is a shorter, reliable, and valid self-administered patient-reported outcome measure questionnaire that can be used in the outpatient setting to suggest and monitor LPR.

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.