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Objective: Patients with Laryngopharyngeal Reflux（LPR） have chronic inflammation of the laryngeal mucosa leading to a high response state in the larynx, which may make the vocal fold movement too fast. This paper discusses the characteristics of vocal fold movement and voice onset by analyzing laryngeal high-speed videoendoscopy in patients with LPR. Methods: Forty patients with LPR were enrolled as LPR group. The diagnostic criteria of LPR included positive reflux symptom index（RSI） and reflux syndrome score（RFS） to identify suspected LPR, objective oropharyngeal DX pH monitoring was carried out, and positive Ryan index indicated reflux. According to age and sex matching, 40 healthy volunteers were selected as the normal group. Laryngeal high-speed videoendoscopy, and the vocal fold motion and vibration parameters, including vocal fold adduction time, vocal fold abduction time, vocal fold vibration onset mode（vocal onset time and mode） and the opening quotient of vocal fold vibration cycle. Statistical analysis was performed using SPSS 25.0. Results: The time of vocal fold adduction in LPR group（mean 225.81ms） was less than that in normal group（mean 277.01 ms）, and the difference was statistically significant（ P <0.05）. There was no significant difference in adduction time between LPR group and normal group（ P >0.05）. The vocal onset time in LPR group was significantly longer than that in normal group（ P <0.05）. High speed video endoscope showed that there were 17 patients with hard onset in LPR group and 8 patients with hard onset in normal group, the difference was statistically significant（ P <0.05）. There was no significant difference in the open quotient of vocal fold vibration between LPR group and normal group（ P >0.05）. The vocal fold abduction time in LPR group（mean 372.92 ms） was less than that in normal group（mean 426.98ms）, but the difference was not statistically significant（ P >0.05）. The time difference of bilateral abduction of vocal fold in LPR group was significantly higher than that in normal group（ P <0.05）. Conclusion: The larynx of LPR patients is in a high response state, the vocal fold moves faster, and it is more likely to have a hard vocal onset. These may result in voice dysfunction., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Objectives: To evaluate the different characteristics of oropharyngeal pH changes in patients with different laryngeal diseases., Methods: A retrospective analysis was performed. The clinical data of 262 patients were summarized. The patients were divided into 4 groups. Group 1 included 123 patients with suspected laryngopharyngeal reflux disease (LPRD). Group 2 included 45 patients with vocal cord polyps. Group 3 included 40 patients with vocal cord leukoplakia. Group 4 included 54 patients with laryngeal carcinoma. Their reflux symptom indexes (RSIs), reflux finding scores (RFSs), and Dx-pH monitoring results were compared., Results: In total, 235 patients had abnormal RSI/RFS, 90 patients had abnormal Ryan scores. The rate of abnormal RSI/RFS of Group 1 was significantly higher than that of Group 4 (P = .001). Significant differences of the rates of abnormal Ryan scores existed between Groups 2 and 4 (P = .021) and Groups 3 and 4 (P = .027). There were obvious differences in upright Ryan scores between Groups 1 and 2 (P = .013), Groups 1 and 3 (P = .002), Groups 2 and 4 (P = .046), and Groups 3 and 4 (P = .009). There were significant differences in time percentage of oropharyngeal pH of upright 5.5∼6.5 and supine 5.0∼6.5 between Groups 1 and 3 as well as Groups 1 and 4 (upright: Groups 1 and 3: P = .017; Groups 1 and 4: P = .019. Supine: Groups 1 and 3: P = .018; Groups 1 and 4: P = .023)., Conclusions: There were different oropharyngeal pH characteristics in patients with different laryngeal diseases, which indicated laryngopharyngeal reflux may play different roles in different diseases through various patterns. Patients with vocal cord polyps, vocal cord leukoplakia, and laryngeal carcinoma had more and different patterns of oropharyngeal pH change than patients with LPRD. Patients with vocal cord polyps and vocal cord leukoplakia had more severe acid oropharyngeal pH change episodes than patients with laryngeal carcinoma., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To evaluate the efficacy of distal esophageal mean nocturnal baseline impedance (MNBI), a general marker of esophageal mucosal barrier integrity, in predicting laryngopharyngeal reflux (LPR) and symptomatic response to acid reflux therapy., Methods: This retrospective study analyzed 173 patients who presented with symptoms of laryngopharyngeal reflux and underwent 24-h multichannel intraluminal impedance-pH (MII-pH) testing. Mean nocturnal baseline impedance values were calculated and assessed for their association and ability to predict LPR symptoms, MII-pH results, treatment response, and other markers of LPR., Results: Notably, 153 of the 173 patients were tested off acid suppression medication and included in statistical analysis. Based on the MII-pH probe data, 108 (71%) patients had LPR, 8 (5%) had gastroesophageal reflux disease (GERD), and 37 (24%) were without pathologic reflux. Distal esophageal MNBI of LPR patients was significantly lower in LPR patients than patients with negative studies (1332 ± 94.8 vs. 2158 ± 173.5, p = 0.001). Among 118 patients who trialed antireflux therapy, a distal esophageal MNBI cutoff value of <1580 Ω was an independent predictor of treatment response (OR = 4.148 [1.877-9.189]). This value better predicted improvement with antireflux therapy for LPR than other objective MII-pH probe data, which were not independent predictors of treatment response., Conclusion: Distal esophageal MNBI values may have value in the diagnosis of LPR and potentially predict medication responsiveness in LPR patients., Level of Evidence: 3 Laryngoscope, 134:4071-4077, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: Laryngopharyngeal reflux (LPR) causes laryngopharyngeal hypersensitivity and laryngeal muscle hyperfunction, which may result in hard voice onset in patients with LPR. The purpose of this study is to examine the incidence of hard voice onset in patients with LPR and the effects of hard voice onset on objective voice function in patients with LPR., Methods: Forty patients with confirmed LPR were enrolled in the LPR group, and 40 healthy subjects were enrolled in the non-LPR group. Subjects underwent laryngeal high-speed videoendoscopy, and the presence or absence of hard voice onset in each subject was determined by two experienced laryngologists based on whether glottal closure was complete or incomplete before vocal fold vibration. Based on the results, the subjects with LPR were divided into a hard voice onset group and a non-hard voice onset group. The voice onset time (VOT) was measured and compared between the hard and non-hard voice onset groups within the LPR group. Laryngeal aerodynamic assessment was also carried out on the LPR group, and subglottal pressure, phonation threshold pressure (PTP), glottal resistance, and mean flow rate were measured. The voice acoustic signals of subjects were additionally analyzed in the LPR group, and the fundamental frequency, jitter, shimmer, and noise-harmony ratio were determined. The kappa statistic, chi-square test and independent-samples t test in SPSS were used for statistical analysis., Results: The two laryngologists had substantial inter-rater consistency on the evaluation of hard voice onset and non-hard voice onset, with a kappa statistic of 0.71. In the LPR group, 42.5% of patients had hard voice onset (17/40), significantly more than in the non-LPR group (8/40, 20%) (P < 0.05). The VOT in the LPR group was significantly longer than in the non-LPR group (P < 0.05). Within the LPR group, the VOT, PTP and shimmer were significantly greater in the hard voice onset group than in the non-hard voice onset group (all P < 0.05). The other laryngeal aerodynamic parameters and acoustic parameters were not significantly different between the hard voice onset group and the non-hard voice onset group (P > 0.05)., Conclusion: Changes in vocal production may occur in LPR patients, causing them to be more susceptible to hard voice onset. The patients with hard voice onset require longer VOT and greater PTP to initiate phonation., Competing Interests: Conflict of interest The authors had no conflict of interest to declare., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Patients with suspected laryngopharyngeal reflux (LPR) present with a variety of symptoms, such as cough, hoarseness, and globus sensation, and often do not have the classic features associated with gastroesophageal reflux disease., Study Design: To achieve greater clarity in the symptom presentation, response to treatment, and the impact on vocal function among patients presenting with signs and symptoms consistent with LPR, we prospectively evaluated initial assessments and outcomes after medication or surgical management., Methods: A sample of 109 patients completed self-report measures of reflux symptoms, voice handicap, and underwent diagnostic workup by both laryngologist and foregut surgeon to include laryngoscopy, esophagogastroduodenoscopy, manometry and pH monitoring. Patients were then followed for at least 3 months, and outcomes of therapy were recorded., Results: The most common indicators on initial workup were reflux symptom inventory score ≥ 13 and at least one abnormality on manometry. Male patients were significantly more likely to demonstrate esophagitis on biopsy, abnormal upper esophageal sphincter mean pressure, and acid (vs nonacid) reflux. Older patients were more likely to have normal esophageal distal contractile integral activity. Significantly higher voice handicap ratings were observed among patients with a positive reflux indicator score in addition to abnormal upper esophageal sphincter mean basal pressure and contractile front velocity. Patients with acid versus nonacid reflux were equally as likely to report non-responsivity to antisecretory medications. Among a subset of patients with 3-month follow-up data (N = 39), reflux scores were significantly lower irrespective of treatment modality (surgical vs pharmacological intervention)., Conclusion: Extensive comprehensive workup did not reveal a single predictive indicator for LPR. Voice assessments may be more sensitive to upper esophageal symptomatology or dysfunction compared to reflux assessments, which may be better indicators of inflammation. Our collaborative data confirms the value of assessing vocal quality and impairment, especially in the presence of equivocal reflux indicators, as together these measures may achieve greater sensitivity to reflux issues and may aid in surgical decision making., (Copyright © 2022 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

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 (r s  = 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 (r s  = 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, 134:3981-3988, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Rumination syndrome (RS) is an underdiagnosed behavioral disorder of recurrent regurgitation. Regurgitation occurs in RS due to increased gastric pressure achieved by subconscious contraction of the abdominal musculature wall, reversing the pressure gradient between the esophagus and the stomach. RS is mainly diagnosed clinically by the Rome Criteria with symptoms of regurgitation without retching of recently ingested food into the mouth and subsequent spitting or re-mastication. When the diagnosis is unable to be made clinically, supportive testing including fed impedance manometry can be considered. RS occurs worldwide, affecting patients of all ages, races, and genders with a prevalence of 3.1-5.8%. There is significant overlap with RS and disorders of a gut-brain interaction and upright gastroesophageal reflux driven by aerophagia and supragastric belching. There is also an association with mood disorder, fibromyalgia, and eating disorders. RS may be misdiagnosed as a variety of other syndromes including gastroesophageal reflux disease, gastroparesis, achalasia, and bulimia nervosa. Once RS is diagnosed, the mainstay of treatment is diaphragmatic breathing to lower the intragastric pressure and increase the lower esophageal pressure. Diaphragmatic breathing can be supported with biofeedback and cognitive behavioral therapy as well as medication options for more refractory cases. Response to therapy overtime and changes in symptoms overtime can now be tracked with a validated questionnaire., (© The Author(s) 2024. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose of Review: Symptoms/complications related to extraesophageal reflux (EER) are increasingly prevalent presentations and pose significant challenges for clinicians. We summarize and discuss clinical advances and developments in pathophysiology, testing and treatment algorithms of upper/lower airway manifestations of EER., Recent Findings: Growing evidence supports likely multifactorial causes of laryngeal symptoms, including EER, oropharyngeal pathologies, allergic conditions, and cognitive-affective processes (brain-larynx interaction). Diagnostic paradigm for laryngopharyngeal reflux (LPR) is shifting towards a personalized approach with noninvasive strategies/prediction tools to risk-stratify patients for upfront reflux testing over empiric acid suppression trials. Management should be multipronged to include antireflux therapies and treatments targeting other causes. Lower airway complications of EER may result in lung dysfunction and poor transplant outcomes. Esophageal symptoms are often absent and routine esophageal/reflux testing to guide timely antireflux therapies may lead to improved outcomes. Modalities that leverage impedance technology may be important, given the potential role of nonacidic reflux. Novel impedance-based metrics such as mean nocturnal baseline impedance and postreflux swallow-induced peristaltic wave index may provide adjunctive diagnostic values., Summary: Standardized approach to diagnosis/management of EER should include multidisciplinary care teams and consider different phenotypes, nonreflux contributors, and the complex gut-airway relationships. Prompt antireflux therapies after careful candidate selection may improve outcomes of these airway complications., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: To evaluate the effect of proton pump inhibitor (PPI) after laryngeal microsurgery (LMS) in patients with benign vocal fold (VF) mucosal disease and in patients with overt reflux symptom according to subjective and objective voice assessment., Methods: The improvement of voice handicap index-10 (VHI-10) score, reflux symptom index (RSI) score, grade, roughness, breathiness, asthenia, and strain (GRBAS) score, Jitter, Shimmer, noise to harmonics ratio (NHR), maximum phonation time of acoustic voice analysis RESULTS: A total of 47 patients (PPI group [n = 24] and non-PPI group [n = 23]) completed the study. The scores for VHI-10, RSI, GRBAS, and acoustic parameters significantly improved in both groups after surgery. In the subgroup analysis of patients with overt reflux symptoms (RSI ≥ 13; non-PPI group [n = 12], PPI group [n = 15]), significant between-group differences were observed in terms of the improvement in NHR and the strain factor., Conclusion: Postoperative PPI administration in patients with VF benign mucosal disease with reflux symptoms might improve subjective and objective voice outcomes after LMS., Competing Interests: Conflict of interest No potential conflict of interest relevant to this article was reported., (Copyright © 2022 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Research Question: Laryngopharyngeal reflux (LPR) may cause inflammation of the laryngeal and pharyngeal mucosa. Gastroesophageal reflux disease (GERD) involves retrograde flow of gastric content into the esophagus below the upper esophageal sphincter (UES). The goal of this study was to investigate the esophageal anatomical and manometric variations of the esophagus in patients with LPR and/or GERD., Methods: Adult voice center patients who underwent diagnostic workup for reflux complaints with 24-hour multichannel intraluminal pH-impedance testing and esophageal manometry were included in this retrospective study. Subjects were classified as having LPR (>10 proximal reflux events), LPR + GERD (>10 proximal reflux events plus >73 distal reflux events) or were assigned to a control group (≤10 proximal events and ≤73 distal reflux events) based on pH study results. Anatomic and manometric parameters were evaluated between groups., Results: There were 169 cases (65 male, 104 female) included in this study. The average age was 50.50 ± 17.29. Subjects in the LPR group had significantly higher UES relaxation pressures and greater UES length compared with the control group. Lower esophageal sphincter relaxation pressure was significantly higher in the control group compared with the LPR group or the GERD + LPR group. Subjects in the GERD + LPR group had a significantly shorter intra-abdominal portion of the lower esophageal sphincter compared with the LPR only group and the control group. Intrabolus pressure was significantly lower in both the LPR group and the LPR + GERD group compared with the control group. Distal wave amplitude was significantly lower in the LPR + GERD group compared to both the LPR group and the control group. The percentage of swallows with incomplete clearance was significantly greater in the LPR + GERD group than both the control group and the LPR group. The LPR group had significantly fewer swallows with incomplete clearance than the control group., Conclusions: Anatomic and manometric abnormalities are present in subjects with LPR with or without GERD and may contribute to the pathogenesis of reflux disease. Further research is needed to confirm or refute these findings., (Copyright © 2021 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: The current study aimed to translate, culturally adapt, and validate the Reflux Symptomatic Index in the Hindi language. Secondly, we aimed to compare its outcomes between normal individuals and people suffering from laryngopharyngeal reflux., Study Design: Cross-sectional study design., Material and Methods: The original Reflux Symptom Index was translated into Hindi language using the forward-backward translation method. A total of 192 participants were included in the study. Among 192 participants, 57 were healthy controls, and 135 were individuals with laryngopharyngeal reflux. Internal consistency, test-retest reliability, and clinical validity were measured., Results: The majority of the population reported the presence of globus sensation. Results revealed that the Hindi version of the Reflux Symptom Index exhibited an excellent internal consistency (ie, 0.829). A significant difference was found between the mean scores of both groups, and the excellent test-retest reliability score (ie, 0.94 & 0.96) was obtained., Conclusion: We can conclude that the Hindi version of the Reflux Symptom Index exhibited a similar psychometric functional property as the Original version of the Reflux Symptom Index. So, the developed tool is a quick, reliable, and valid tool to assess laryngopharyngeal reflux., (Copyright © 2021 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Laryngopharyngeal reflux disease (LPRD) is an inflammatory condition in the laryngopharynx and upper aerodigestive tract mucosa caused by reflux of stomach contents beyond the esophagus. LPRD commonly presents with sym-ptoms such as hoarseness, cough, sore throat, a feeling of throat obstruction, excessive throat mucus. This complex condition is thought to involve both reflux and reflex mechanisms, but a clear understanding of its molecular mechanisms is still lacking. Currently, there is no standardized diagnosis or treatment protocol. Therapeutic strategies for LPRD mainly include lifestyle modifications, proton pump inhibitors and endoscopic surgery. This paper seeks to provide a comprehensive overview of the existing literature regarding the mechanisms, patho-physiology and treatment of LPRD. We also provide an in-depth exploration of the association between LPRD and gastroesophageal reflux disease., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest to declare., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Laryngopharyngeal reflux symptom is a troublesome upper esophageal problem, and reflux symptom index (RSI) is commonly applied for the assessment of clinical severity. We investigated the relationship between the upper esophageal sphincter impedance integral (UESII) and RSI scores in this study. Totally 158 subjects with high-resolution esophageal impedance manometry (HRIM) with RSI questionnaire assessment were recruited. There are 57 (36.08%), 74 (46.84%), 21 (13.29%), and 6 (3.79%) patients were categorized as normal, ineffective esophageal motility disorder, absent contractility, and achalasia by HRIM examination, respectively. Subjects with RSI > 13 were noted to have lower UESII than others with RSI ≦ 13 (7363.14 ± 1085.58 vs. 11,833.75 ± 918.77 Ω s cm; P < 0.005). The ROC analysis yielded a UESII cutoff of < 2900 Ω s cm for the best prediction of subjects with RSI > 13 (P = 0.002). Both female gender and UESII cutoff of < 2900 Ω s cm were significant predictors of RSI > 13 in logistic regression analysis (OR = 3.84 and 2.83; P = 0.001 and 0.01; respectively). Lower UESII on HRIM study, indicating poor bolus transit of UES during saline swallows, is significantly associated with prominent laryngopharyngeal reflux symptoms scored by RSI score., (© 2021. The Author(s).)

Hypopharyngeal multichannel intraluminal impedance (HMII) that can measure laryngopharyngeal reflux (LPR) events has supported the causal relationship between chronic cough (CC) and LPR containing liquid. However the role of "gas" LPR associated with CC has been poorly understood. We present two cases of patients with CC who had negative LPR containing liquid but had multiple episodes of "gas" LPR on HMII. The majority of "gas" LPR events had a minor pH drop at hypopharynx. Since any etiology of CC was excluded and medical therapy failed, both patients underwent laparoscopic antireflux surgery (LARS). Both of the patients had complete resolution of cough postoperatively. The present cases demonstrated successful outcome of LARS to treat the patients with CC who had documented "gas" LPR on HMII, thus suggesting the causal relationship between CC and "gas" LPR. The number of "gas" LPR events may need to be considered as an important diagnostic parameter., Competing Interests: Declaration of Competing Interest Drs. Takeshi Suzuki, Yosuke Seki, Tomoaki Matsumura, Jun Ikari, Makoto Arai, Toyoyuki Hanazawa, Yoshitaka Okamoto, Haruhiko Suzuki, Yoshimoti Kurokawa, Akiko Umezawa, Kazunori Kasama and Toshitaka Hoppo have no conflicts of interest., (Copyright © 2020. Published by Elsevier B.V.)

Objectives: The pathophysiology of laryngopharyngeal reflux (LPR) remains incompletely understood. Proximal esophageal motor dysfunction may impair bolus clearance, increasing the risk of pharyngeal refluxate exposure. We aimed to evaluate the association of proximal esophageal contractility with objective reflux metrics., Methods: We evaluated adults with LPR symptoms undergoing high-resolution manometry (HRM) and combined hypopharyngeal-esophageal multichannel intraluminal impedance-pH testing at a tertiary center between March 2018 and August 2019. Routine parameters per Chicago classification were obtained on HRM. Proximal esophageal contractility was evaluated using proximal contractile integral (PCI), which quantifies contractile pressure >20 mm Hg for the region spanning the distal margin of the upper esophageal sphincter and transition zone. Univariate (Kendall correlation and Student t test) and multivariable (general linear regression and logistic regression) analyses were performed., Results: We enrolled 138 patients (66.7% women, mean age 57.1 years) in this study. Lower PCI was associated with an elevated risk of increased pharyngeal reflux (adjusted odds ratio 0.83 per 100 mm Hg-s-cm change in PCI, 95% confidence interval: 0.69-0.98), with a trend toward increased bolus exposure time and total reflux events, after multivariable adjustment. The relationship between PCI and pharyngeal reflux was strongest among participants without a primary motility disorder on HRM (adjusted odds ratio 0.63, 95% confidence interval: 0.42-0.85, P interaction = 0.04). Among continuously expressed reflux parameters, lower PCI was significantly associated with more distal acid reflux events (β = -0.0094, P = 0.03) and total reflux events (β = -0.0172, P = 0.05), after adjusting for confounders., Discussion: Reduced proximal esophageal contractility as assessed by decreased PCI on HRM independently predicted increased pharyngeal reflux in patients with LPR symptoms, particularly among those without a coexisting motility disorder., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Objective: The aim of this study was to investigate the relationship of chronic REM-sleep deprivation with laryngopharyngeal reflux (LPR) and its mechanism., Methods: Forty healthy male SD rats (body weight 250-280 g) were randomly divided into four groups. The first three ones were test group, which underwent REM-sleep deprivation with different duration of time by modified multiplatform water surface method. The last group was the control one having normal sleep. All the animals were performed Dx-pH monitoring when finishing sleep deprivation, and sacrificed to study the gastric residual rate (GRR) and small intestine peristalsis (SPR) rate by charcoal meal method., Results: At prone position, the reflux incidence in the test groups fairly increased with the duration of sleep deprivation (p<0.05). The total number of reflux episodes at prone position in the test group rats with 3 months duration of sleep deprivation was significantly increased compared with that in the control ones (p<0.05). GRR in rats experiencing sleep deficiency for different duration all reduced significantly when compared to the control group (p<0.05). GRR and SPR presented continuous decline tendency with the duration of sleep deprivation (p>0.05)., Conclusions: It is suggested that chronic sleep deficiency could cause LPR in rats, which might result from the uncoordinated digestive tract motility caused by dysfunction of central nervous system after chronic REM-sleep deprivation. Our results implied that chronic REM-sleep deprivation might be one of the causes of LPR. Addressing sleep problems might help to decrease the prevalence of LPR and enhance its treatment efficacy., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2020. Published by Elsevier B.V.)

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., (© 2021 John Wiley & Sons Ltd.)

Background: Rumination is defined as the repetitive, effortless regurgitation of recently ingested food into the mouth. These episodes are preceded by a rise in intragastric pressure (IGP) and mainly occur postprandially. IGP peaks >30 mmHg have been proposed as a cutoff to differentiate rumination from reflux events. In clinical practice, we observed that this cutoff, which does not consider esophagogastric junction (EGJ) resistance, is not always reached., Methods: We studied 27 patients with rumination syndrome [age: 43.6, 59% female] and 28 gastro-esophageal reflux disease patients [age: 45.9, 54% female]. For each rumination episode, reflux event, transient lower esophageal sphincter relaxation (TLESR), or straining without regurgitation, the following parameters were registered: maximal IGP, IGP, and EGJ pressure preceding the respective episodes. We also quantified the gastro-sphincteric pressure gradient (GSPG) prior to the respective episodes., Key Results: Five reflux episodes were characterized by a maximal IGP >30 mmHg. In 28% of the rumination episodes, the IGP peak did not exceed 30 mmHg. Median GSPG was positive for rumination episodes and significantly higher compared with TLESRs, reflux episodes, and straining without regurgitation (7 [3-13] vs. 0 [-1-0] vs. 0 [-1-0] vs. -9 [-13--2]; p < 0.0001)., Conclusions & Interferences: Applying the proposed cutoff of 30 mmHg, 28% of the rumination episodes were missed. We found that the GSPG differentiates between rumination (positive GSPG), TLESRs and reflux events (GSPG around 0), and straining without regurgitation (negative GSPG). We propose a GSPG value ≥2 mmHg to distinguish rumination from reflux episodes, TLESRs, and straining without regurgitation., (© 2020 John Wiley & Sons Ltd.)

Objective: To analyze the Reflux Symptom Index (RSI) and the Voice-Related Quality of Life (V-RQOL) scores based on the perceptual and analytical parameters in primary MTD patients with no reflux., Study Design: Cross-sectional study., Methods: One hundred and eighteen participants, that is, sixty patients with normal voices and fifty-eight patients with primary MTD were recruited in this study. The diagnosis of primary MTD was made by perceptual voice analysis, neck palpation, video-laryngoscopic examination, and exclusion of other etiologies. Acoustic analysis and the GRBAS (Grade, Roughness, Breathiness, Asthenia, and Strain) scale were evaluated for all participants. The V-RQOL and RSI questionnaires were then given to all participants., Results: This study included 118 participants of 29 males (48.3%) and 31 females (51.7%) in the normal group. MTD group also included 27 males (46.6%) and 31 (53.4%) female patients. Mean (SD) RSI and V-RQOL scores were 12.35 (3.84) and 11.09 (2.20) for the normal group, and 22.87 (6.97) and 22.89 (7.94) for the MTD group (P = .000). In the MTD group, V-RQOL had a positive correlation with jitter for /i/ and /u/, Noise to Harmonic Ratio (NHR) for /i/, /a/, and /u/, and Grade, Roughness, and Strain of GRBAS scale (P < .05). In addition, RSI had a positive correlation with Strain in the MTD group (P < .05)., Conclusion: MTD patients in the absence of laryngopharyngeal reflux findings may have high RSI scores. Hence, patients with high RSI scores and disproportionate acoustic and perceptual analysis would require a thorough evaluation of MTD., Level of Evidence: 4 Laryngoscope, 131:E1573-E1579, 2021., (© 2020 American Laryngological, Rhinological and Otological Society Inc, "The Triological Society" and American Laryngological Association (ALA).)

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., (© 2020 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Pseudoachalasia manifests high-resolution manometry (HRM) findings of achalasia but results from a secondary process. We analyzed clinical and HRM characteristics of pseudoachalasia, including malignant and non-malignant subtypes., Methods: High-resolution manometry was retrospectively reviewed in patients with confirmed pseudoachalasia, and corroborated with endoscopic and radiographic studies. A control cohort of idiopathic achalasia patients was identified. Clinical characteristics, Eckardt score, and HRM metrics were extracted from institutional records. Grouped data and medians (interquartile range) were compared between pseudoachalasia and idiopathic achalasia, and between malignant and non-malignant pseudoachalasia, using parametric and non-parametric statistical tests., Key Results: Of 28 pseudoachalasia patients (62.2 ± 2.5 years, 60.7% female), 18 (64.3%) had malignancy, and 10 (35.7%) had non-malignant obstruction. Although Eckardt score did not differentiate pseudoachalasia from 58 achalasia patients (55.9 ± 2.5 years, 53.4% female), weight loss was greater (median 9.1 [5.0-18.5] vs 3.6 [0-9.1] kg, P < .02) with shorter duration of symptoms (median 12.9 [8.0-38.6] vs 36.0 [25.7-45.0] weeks, P < .001] in pseudoachalasia. Esophagogastric junction (EGJ) metrics demonstrated lower mean IRP values and lower EGJ contractile integral in pseudoachalasia (P < .04 for each comparison with idiopathic achalasia). Type 1 pattern was more frequent in pseudoachalasia (39.3% vs 13.8%, P < .008). Pseudoachalasia demonstrated incomplete HRM patterns, with lower rates of lack of peristalsis (79.6%, vs 93.1% in achalasia, P < .05). Despite higher Eckardt scores in malignant vs non-malignant pseudoachalasia (median 8.0 [7.0-9.0] vs 6.0 [3.5-7.8], P < .03], no significant HRM differences were noted., Conclusions and Inferences: Pseudoachalasia manifests with a shorter history, greater weight loss, and incomplete HRM achalasia patterns compared to achalasia., (© 2020 John Wiley & Sons Ltd.)

Objective: To determine whether an anatomical difference in esophageal hiatus (EH) size exists between brachycephalic and nonbrachycephalic dogs., Study Design: Retrospective clinical study., Animals: Client-owned dogs (n = 87)., Methods: Clinical records and images of dogs that underwent computed tomography between June 2015 and September 2018 were reviewed. For the first part of the study, EH and aortic (Ao) cross-sectional surface areas were measured in brachycephalic (group 1) and nonbrachycephalic dogs of similar body size (<15 kg) without respiratory or gastroesophageal (GE) signs (group 2) by using multiplanar reconstruction. Esophageal hiatus:aortic ratio was calculated. In the second part of the study, absolute EH measurements were also compared in weight-matched (WM) dogs (8-10 kg) from groups 1 and 2., Results: Mean (±SD) of EH:Ao values for group 1 (8.1 ± 2.8) were higher (P < .0001) than those for group 2 (3.7 ± 1.1). In addition, EH measurements of 20 WM dogs in group 1 were higher than those of 20 dogs in group 2 (P < .05)., Conclusion: Esophageal hiatus cross-sectional surface area (directly and indirectly measured) in brachycephalic dogs was considerably larger than that in nonbrachycephalic dogs of generally similar body size., Clinical Significance: Results of this study provide evidence to support the existence of a specific anatomical factor that could likely correlate to functional GE alterations (eg, regurgitation, gastroesophageal reflux, and sliding hiatal hernia) commonly seen in brachycephalic dogs., (© 2020 American College of Veterinary Surgeons.)

Purpose of Review: Gastroesophageal and extraesophageal reflux are prevalent and costly diseases. Recognition of the pathogenicity of nonacid reflux has stimulated interest in alternatives to acid-targeting diagnostics and therapeutics. Pepsin is the most deleterious enzyme in refluxate, eliciting inflammatory and carcinogenic effects irrespective of acid. Its presence in all refluxate and detection in saliva have situated pepsin as the most widely researched biomarker for reflux today. This review summarizes emerging findings regarding pepsin-mediated damage during reflux and developments in pepsin-targeting diagnostics., Recent Findings: New evidence supports a role for pepsin in epithelial--mesenchymal transition, an important process in carcinogenesis and fibrosis. The first global transcriptomic analysis of pepsin-exposed laryngeal cells was described, yielding evidence of a putative airway pepsin receptor. Evaluation of pepsin diagnostics highlighted the need for rigorous validation in which pepsin concentrations are corroborated by a secondary quantitative assay, and reflux is confirmed or excluded by multichannel intraluminal impedance pH testing. Standards for sample collection and storage, and normative and pathological values are lacking., Summary: Progress continues to be made in our understanding of pepsin-mediated damage with implications for novel therapeutic strategies. Salivary pepsin diagnostics continue to garner interest; however, further work appears necessary to improve their accuracy and reproducibility.

Purpose: The objective of this study was to determine the correlation of reported symptom improvement in laryngopharyngeal reflux (LPR) with physical findings on laryngoscopic examination following medical therapy., Materials and Methods: This IRB-approved, retrospective, single-institution study included all patients who were diagnosed and medically treated for LPR from Jan. 1, 2015-October 21st, 2019. Only patients who received at least six weeks of treatment with a proton pump inhibitor and those with pre- and post-treatment Reflux Symptom Index; RSI (n = 91) and Reflux Finding Score; RFS (n = 33) were included in the study., Results: A total of 91 patients were included in the analysis (61.54% female). There was a 19.99% improvement in total RSI (p = 0.0034) and a 25.20% improvement in total RFS (p = 0.0011) following at least six weeks of treatment (average = 253 ± 213 SD days). RSI symptoms were significantly decreased between pre- and post-treatment for hoarseness (p = 0.0005), clearing of the throat (p = 0.0066), excess throat mucus or postnasal drip (p = 0.0004), troublesome cough (p = 0.0231), and heartburn/chest pain (p = 0.0053). RFS demonstrated a statistically significant decrease in only subglottic edema (p < 0.0001) and ventricular obliteration (p = 0.0295). Pearson's correlation test did not demonstrate a relationship between RSI and RFS in the pre- and post-treatment analyses alone, but did demonstrate a statistically significant relationship when analyzed across all captured pre and post data (r = 0.265, p = 0.006)., Conclusions: RSI and RFS are complimentary to one another when assessing for treatment response, but improvement in RSI does not correlate with that in RFS., (Copyright © 2020. Published by Elsevier Inc.)

Background/aims: Jackhammer esophagus (JE) is a hypercontractile esophageal motor disorder defined by at least two swallows with a distal contractile integral (DCI) >8000 mm Hg.s.cm during high-resolution manometry (HRM). The relationship between symptoms and hypercontractility and the response to therapies have been poorly evaluated. The aim of this study was to determine the clinical presentation, manometric diagnosis, and therapeutic results in a large cohort of JE patients., Methods: Patients with JE diagnosed among the HRM tests performed in nine academic French centers from 01/01/2010 to 08/31/2016 were included. Patient charts were reviewed to collect clinical and therapeutic data., Results: Among the 16 264 HRM tests performed during this period, 227 patients (60.8 ± 13.8 years, 151 male) had JE (1.7%). Dysphagia was the most frequent symptom (74.6%), followed by regurgitation (37.1%) and chest pain (36.6%); 4.7% of the patients were asymptomatic. The diagnostic workup was heterogeneous, and only a minority of patients had esophageal biopsies. None of the individual symptoms were significantly associated with any of the manometric parameters defined, except for dysphagia, which was significantly associated with the mean of all DCIs >8000 mm Hg.s.cm (P = .04). Additionally, the number of symptoms was not associated with any manometric parameter. Medical treatment and endoscopic treatments had poor efficacy and a high relapse rate., Conclusion: Jackhammer esophagus is a rare motility disorder. Diagnostic workup is heterogeneous and should be standardized. Symptoms are poorly associated with manometric parameters. The medical treatments and endoscopic therapies currently used are inefficient., (© 2020 John Wiley & Sons Ltd.)

Background: Jackhammer esophagus (JE) is a newly described esophageal motility disorder. However, there are limited data on JE and this entity remains misunderstood., Methods: We performed a systematic review of clinical series on JE through MEDLINE, EMBASE, and Web of Science. Data from included studies were then extracted, and random-effects meta-analyses were performed., Results: Thirty-eight studies met inclusion criteria. The pooled prevalence of JE was 1.97% [95% CI: 1.39%-2.78%] among patients referred for high-resolution manometry (HRM). The mean age at diagnosis was 60.8 years [95% CI: 57.1-64.4] and 65% [95% CI: 58%-72%] of patients were female. JE was significantly more prevalent in postlung transplant patients and morbidly obese patients undergoing HRM (23.99% [95% CI: 9.00%-38.97%] and 5.18% [95% CI: 1.76%-14.3%] respectively). Dysphagia was the most common presentation of JE (64% [95% CI: 52%-77%]) followed by gastroesophageal reflux disease (46% [95% CI: 26%-67%]). The pooled mean distal contractile integral (DCI) of all standard HRM swallows was 9249 mm Hg·s·cm [95% CI: 7834-10 663], and the pooled mean integrated relaxation pressure (IRP) was 13.9 mm Hg [95% CI: 8.2-19.7]. Overall, 73.6% [95% CI: 64.0%-83.1%] of JE patients who underwent treatment achieved clinical symptom improvement (79% [95% CI: 74%-85%] for endoscopic treatment and 63% [95% CI: 47%-79%] for medical treatment). The pooled clinical success rate of peroral endoscopic myotomy (POEM) specifically was 82% [95% CI: 75%-90%]., Conclusions: JE is a new motility disorder most commonly presenting with dysphagia. High clinical suspicion is important because the diagnosis can only be made through HRM., (© 2020 John Wiley & Sons Ltd.)

Objectives: To investigate the psychometric properties of the reflux symptom index (RSI) as short screening approach for the diagnostic of laryngopharyngeal reflux (LPR) in patients with confirmed diagnosed regarding the 24-hour multichannel intraluminal impedance-pH monitoring (MII-pH)., Methods: From January 2017 to December 2018, 56 patients with LPR symptoms and 71 healthy individuals (control group) were prospectively enrolled. The LPR diagnosis was confirmed through MII-pH results. All subjects (n = 127) fulfilled RSI and the Reflux Finding Score (RFS) was performed through flexible fiberoptic endoscopy. The sensitivity and the specificity of RSI was assessed by ROC (Receiver Operating Characteristic) analysis., Results: A total of 15 LPR patients (26.8%) of the clinical group met MII-pH diagnostic criteria. Among subjects classified as positive for MII- pH diagnoses, RSI and RFS mean scores were respectively 20 (SD ± 10.5) and 7.1 (SD ± 2.5), values not significantly different compared to the negative MII-pH group. The metric analysis of the items led to the realization of a binary recoding of the score. Both versions had similar psychometric properties, α was 0.840 for RSI original version and 0.836 for RSI binary version. High and comparable area under curve (AUC) values indicate a good ability of both scales to discriminate between individuals with and without LPR pathology diagnosis. Based on balanced sensitivity and specificity, the optimal cut-off scores for LPR pathology were ≥ 5 for RSI binary version and ≥ 15 for RSI original version. Both version overestimated LPR prevalence. The original version had more sensitivity and the RSI Binary version had more specificity., Conclusions: It would be necessary to think about modifying the original RSI in order to improve its sensitivity and specificity (RSI binary version, adding or changing some items), or to introduce new scores in order to better frame the probably affected of LPR patient.

Studies have demonstrated that comorbidities, especially cardiovascular and endocrine diseases, correlated with poorer clinical outcomes. However, the impact of digestive system diseases has not been issued. The aim of this study is to determine the impact of laryngopharyngeal reflux disease (LPRD) on hospitalized patients with coronavirus disease 2019 (COVID-19). We extracted clinical data regarding 95 patients in Wuhan Jinyintan Hospital, Wuhan, China, between 26 January and 21 February 2020. The Reflux Symptom Index (RSI) was used to assess the presence and severity of LPRD. An RSI  greater than  13 is considered to be abnormal. A total of 95 patients with COVID-19 were enrolled, with 61.1% (58/95), 32.6% (31/95), and 6.3% (6/95) being moderately ill, severely ill, and critically ill, respectively. In this study, 38.9% (37/95) of the patient had an RSI score over 13, which was indicative of LPRD. In univariable analysis, the age and RSI scores of severely or critically ill patients were statistically significantly higher than patients with moderate disease (P  =  .026 and P = .005, respectively). After controlling for age difference in a multivariable model, the RSI greater than 13, compared to RSI equal to  0, was associated with significantly higher risk of severe infection (P < .001; odds ratio [OR] = 11.411; 95% confidence interval [CI], 2.95-42.09) and critical infection (P = .028; OR= 19.61; 95% CI, 1.38-277.99). Among hospitalized patients with COVID-19, RSI scores greater than 13, indicative of LPRD, correlated with poorer clinical outcomes. The prevalence of LPRD may be higher than the general population, which indicated that COVID-19 can impair the upper esophageal sphincter and aggravate reflux., (© 2020 Wiley Periodicals LLC.)

Objective: Few studies have investigated pharyngeal intraluminal baseline impedance (BI) levels in patients with laryngopharyngeal reflux (LPR). The aim of this study was to compare intraluminal BI levels between patients with LPR and healthy controls., Study Design: Retrospective case series., Setting: Tertiary care medical center., Subjects and Methods: We conducted a retrospective analysis of 24-hour multichannel intraluminal impedance (MII)-pH monitoring results from patients with suspected LPR complaining of reflux symptoms. Patients with suspected LPR were divided into 2 groups according to the 24-hour MII-pH monitoring (LPR group: patients with symptoms with reflux events ≥1, symptom but no reflux [SNR] group: patients with symptoms but no reflux event). Healthy controls were recruited and also underwent 24-hour MII-pH monitoring. We compared the esophageal and pharyngeal BI levels and ratios between 3 groups., Results: Pharyngeal BI levels in the LPR group were significantly higher than in the healthy controls. In addition, the pharyngeal BI levels in the SNR group were significantly higher than in the healthy controls. All ratios of pharyngeal to distal esophageal BI levels in the LPR and SNR group were significantly higher than in the healthy controls. However, there were no significant differences in esophageal BI levels and ratios between the 3 groups., Conclusion: We found that the pharyngeal BI levels were higher in patients with LPR than in healthy controls. In addition, the pharyngeal BI levels measured by 24-hour MII-pH monitoring in patients with LPR symptoms, but without a reflux episode, were higher than in the healthy controls.

Background and Aim: Laryngopharyngeal reflux (LPR) is caused by the reflux of gastric contents beyond the esophagus into the larynx and pharynx. However, upper esophageal sphincter (UES) motility and proximal esophagus reflux parameters are poorly studied. This study aims to explore the characteristics of UES motility and reflux parameter among LPR patients., Methods: Patients with laryngopharyngeal symptoms only (L), patients with laryngopharyngeal symptoms and typical esophageal symptoms (L + E), patients with typical esophageal symptoms only (E), and healthy controls (H) were retrospectively included. Physiological profiles were studied and compared among groups using both high-resolution manometry and pH-impedance monitoring, including UES basal pressure, residual pressure, relaxation duration time, recovery time, the time to nadir pressure, UES length, proximal contractile integral, and proximal mean nocturnal baseline impedance (MNBI). Patients' symptom outcomes were also analyzed., Results: A total of 242 patients were included. Proximal MNBI was significantly lower in patients with both laryngopharyngeal and esophageal symptoms (17 cm above low esophageal sphincter [LES]: L vs L + E vs E vs H = 3689.7 vs 2500.0 vs 3073.0 vs 3996.0; 15 cm above LES: L vs L + E vs E vs H = 3155.9 vs 2553.4 vs 3198.9 vs 2985.2; P < 0.001). Patients responded to proton pump inhibitor treatment also had lower proximal MNBI than those who did not (17 cm above LES: 1834.0 vs 3500.0; 15 cm above LES: 1946.5 vs 3432.6; P < 0.001)., Conclusion: Decreased proximal MNBI can not only identify LPR patients but also predict patients' symptom outcomes., (© 2020 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Objective: To evaluate the patient-reported reflux symptom index (RSI) and the doctors-reported Reflux finding score (RFS) as potential predictors for proton pump inhibitor (PPI) response in patients with suspected lower pharyngeal reflux, presenting with globus pharyngeus as their primary complaint., Methods: The research project was performed at the ENT department of Isala hospital Zwolle, the Netherlands. A before and after design was used for this single institution prospective exploratory study. 101 participants with globus pharyngeus symptoms as a primary complaint were included. All participants were assessed by an otorhinolaryngologist at enrollment and after eight weeks of esomeprazole use. Fiberoptic laryngoscopy was performed to document the RFS, and RSI questionnaires were self-administered by the participants. Our main outcome measurement was the patient- reported therapeutic response evaluation, that differentiated three categories: responders, partial responders and non-responders. For evaluation of the assessment tools, RFS > 7 and RSI > 13 were considered deviant., Results: Among the 101 participants, 43 (42.6%) were responders, 28 (27.7%) partial responders and 30 (29.7%) non-responders. Both baseline RSI > 13 and RFS > 7 were statistically significant associated with treatment response. Also, combined into RSI/RFS baseline categories, a significant overall association between baseline scores and patient-reported treatment response was found. Patients reported success rates for deviant RSI and RFS baseline scores were 76.6% and 96%, respectively. 95.5% of patients with both deviant RSI and RFS baseline scores, reported (partial) treatment response., Conclusion: Both together, as well individually, pre-treatment RSI and RFS ratings can help predict treatment response of empirical PPI treatment in patients experiencing globus pharyngeus symptoms., (Copyright © 2020. Published by Elsevier B.V.)

Objectives: Describe acoustic and laryngeal findings in pediatric patients with subjective dysphonia attributed to laryngopharyngeal reflux (LPR). Determine the impact of LPR on perceived voice quality using the pediatric Voice Handicap Index (pVHI). Compare these findings with age-matched normative values as well as data on pediatric patients with dysphonia due to other etiologies., Methods: Retrospective case series of pediatric patients (age 2-17 years) evaluated at a specialty pediatric voice clinic at a tertiary care children's hospital from January 1 2007 to December 31 2017 in whom LPR in whom LPR was deemed to be the most significant contributing factor for dysphonia based on physical examination and history. Patients with structural laryngeal abnormalities unrelated to LPR, such as raised lesions, stenosis, papillomatosis, or vocal fold immobility were excluded., Results: 163 out of 1195 evaluable patients met inclusion criteria. Of these, 87% had pVHI and 83% had acoustic data available from their first appointment for analysis. Mean total pVHI score was 24 (range: 0-81). Perturbation measures were elevated in both females (jitter 1.38%, shimmer 4.16%) and males (jitter 2.01%, shimmer 5.62%). Laryngologic assessment revealed: vocal fold changes including erythema and/or pre-nodules in 72% of patients. Cobblestoning of any portion of the pharynx was present in 67% with hypopharyngeal cobblestoning the most common, present in 64% of patients., Conclusion: Pediatric patients with clinically diagnosed LPR have pVHI, jitter, and shimmer scores that are comparable to previously reported patients with raised lesions, scar and immobility, and values that are significantly higher than published normative data. Dysphonic children should be assessed for LPR and treated when indicated., Level of Evidence: 4., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objectives: Laryngopharyngeal reflux (LPR) is a common upper airway disease. Salivary pepsin is a proposed marker for LPR; however, the optimal time for collection of specimens for pepsin detection and pepsin's presence in the oral and nasal secretions relative to concurrent multichannel intraluminal impedance-pH (MII-pH) monitoring are unknown., Study Design: Prospective case-control study with an experimental design., Methods: Patients undergoing MII-pH testing for evaluation of LPR and asymptomatic control subjects were selected. Nasal lavage and saliva samples were collected in the clinic prior to MII-pH probe placement. Additional saliva samples were obtained an hour after each meal and upon waking the following morning. Nasal lavage and salivary pepsin were measured by ELISA., Results: Twenty-six patients undergoing MII-pH testing and 13 reflux-free control patients were enrolled. Salivary pepsin was detected in 11 of 26 patients with suspected LPR and 0 of 13 controls. Pepsin was most frequently detected in the specimen provided upon waking at an average concentration of 186.9 ng/mL. A significant correlation was observed between salivary pepsin in waking samples to MII-pH measurements, including reflux bolus duration, and proximal and distal recumbent reflux episodes (P < 0.05). A significant correlation was also observed between salivary pepsin upon waking or sinus lavage and reflux symptom index (P < 0.05)., Conclusion: Pepsin in salivary and nasal lavage samples demonstrated an association with MII-pH-documented LPR. Pepsin detection was most frequent in morning samples, supporting use of morning salivary pepsin levels as a potential noninvasive technique for LPR diagnosis., Level of Evidence: 2 Laryngoscope, 130:961-966, 2020., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Smoking is known to increase laryngeal inflammation and laryngopharyngeal reflux (LPR), which cause laryngeal irritation. Thus, the aim of this study is to evaluate the changes in the symptoms and the findings of laryngeal irritation in smokers after a smoking cessation period. The reflux symptom index (RSI) and the reflux finding score (RFS) were used for evaluating the symptoms and findings of laryngeal irritation in smokers. Endoscopic examination of the laryngeal structures for RFS and symptom inquiry for RSI were performed at the beginning of the study and after a 2 months of cigarette cessation period. This study was carried out in 24 volunteers (14 female and 10 male), between the ages of 24 and 62 years. When we compared the results of RSI and RFS that were performed before and after the cigarette cession period, we found that there was a significant improvement both in RSI and in RFS ( P < .001 and P < .001, respectively). Also, there was significant correlation between the cigarette smoking period and RFS score that was determined at the beginning of the study ( P = .006, r = .54). A significant improvement was found both in RSI and in RFS after smoking cessation period, which might be the evidence of improvement in laryngeal irritation possibly caused by inflammation due to smoking and LPR. A significant positive correlation was found between smoking period and RFS, especially with vocal fold edema and posterior commissure hypertrophy.

Purpose: To study the usefulness of voice quality as therapeutic outcome in laryngopharyngeal reflux disease., Material and Methods: A total of 80 patients with reflux finding score (RFS) > 7 and reflux symptom index (RSI) > 13 were treated with pantoprazole, diet, and lifestyle recommendations for 3 months. The therapeutic effectiveness was assessed with RSI; RFS; Voice Handicap Index; blinded Grade, Roughness, Breathiness, Asthenia, Strain, and Instability (GRBASI); aerodynamic and a panel of acoustic measurements before and after treatment. A correlation analysis between symptoms, videolaryngostroboscopic signs, and acoustic measurements was conducted., Results: Compared to baseline, means of RSI, RFS, Voice Handicap Index, perceptual dysphonia, and roughness significantly decreased. Significant improvements of phonatory quotient, percent jitter, percent shimmer, Relative Average Perturbation, Pitch Perturbation Quotient, Phonatory F0 Range, Amplitude Perturbation Quotient, smooth Amplitude Perturbation Quotient, and Peak-to-Peak Amplitude Variation were found at the end of treatment. Studies of correlation did not identify relevant correlation between videolaryngostroboscopic signs, especially vocal folds edema, and objective voice quality evaluations., Conclusion: Voice quality assessments can help to better understand voice disorders and can be used as indicators of the treatment effectiveness in patients with laryngopharyngeal reflux-related symptoms., (Copyright © 2018 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study aimed to examine the validity of the modified Reflux Symptom Questionnaire-electronic Diary (mRESQ-eD) through patient input and psychometric testing of the questionnaire to support use in clinical trials in patients with persistent gastroesophageal reflux disease (GERD) and in accordance with Food and Drug Administration guidance on patient-reported outcome instruments., Methods: Cognitive interviews were conducted with patients (n = 30) to evaluate the interpretability and content validity of draft mRESQ-eD items. Patient data from a phase 2b clinical study (ClinicalTrials.gov identifier: NCT02637557) on persistent GERD served to aid in the construction of weekly scores for heartburn severity, regurgitation severity, and total GERD severity. These scores' psychometric properties were also evaluated., Results: Minor modifications were made to the draft mRESQ-eD based on patient feedback to improve interpretability and clarity of the instrument. Psychometric analysis suggested that an 8-item version of the mRESQ-eD was best suited to the clinical data. The internal consistency was found to be high (Coefficient ω = 0.95). Retest reliability and convergent validity were strong for a heartburn weekly severity score, regurgitation weekly severity score, and total GERD severity score., Discussion: The final 8-item mRESQ-eD is a reliable and valid instrument with good psychometric properties for use in clinical trials in patients with persistent GERD. The mRESQ-eD may be considered for inclusion in clinical trials for persistent GERD and potentially positioned, in consultation with Food and Drug Administration, as endpoints to characterize treatment benefit.

Background: The pathophysiological mechanism(s) of gastroesophageal reflux disease (GERD)-related chronic cough (CC) is unclear. We aimed to determine the mechanism of reflux-induced cough by synchronous monitoring of reflux episodes, esophageal motility, and cough., Methods: Patients with GERD were prospectively enrolled and classified into GERD with CC (GERD-CC) and without CC (GERD) groups. Twenty-four-hour ambulatory pH-impedance-pressure monitoring was performed; the reflux patterns, esophageal motility during prolonged exposure to acid and characteristics of reflux episodes that induced coughing paroxysms were analyzed., Key Results: Thirty-one patients with GERD-CC and 47 with GERD were enrolled; all of whose monitoring results fulfilled the criteria for diagnosis of GERD. Patients with GERD-CC had higher reflux symptom scores, longer exposure to acid, higher DeMeester scores, and more frequent reflux episodes, proximal extent reflux detected by impedance, and higher percentage of strongly acidic reflux than patients in the GERD group (all P < .05). Of 63 reflux-cough episodes identified in the GERD-CC group, 74.6% of distal reflux and 67.0% of proximal reflux episodes were acidic. More patients had low pan-esophageal pressure in primary peristalsis (48.5% vs 11.8%, P = .000) and synchronous contraction in secondary peristalsis during prolonged exposure to acid in the GERD-CC than in the GERD group (63.9% vs 9.1%, P = .000)., Conclusions & Inferences: Proximal acidic reflux and distal reflux-reflex are jointly associated with reflux-induced cough in patients with GERD. Low pan-esophageal pressure in primary peristalsis and synchronous contraction in secondary peristalsis may play important roles in GERD-associated chronic cough., (© 2019 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

The findings of functional endoscopy (upper esophageal sphincter insufficiency, cardia insufficiency, esophagitis, gastric heterotopia, axial sliding hernia, and visible aerosols) can be traced back to pharyngeal acid exposure by oropharyngeal pH measurement. Significantly increased pharyngeal acid loads are seen in gastric heterotopy and axial sliding hernia. For all measured statistics, the pharyngeal acid load is in the pathological or even very pathological range. The value of functional endoscopy in the context of laryngopharyngeal reflux diagnosis is clearly documented. The findings "heterotopic gastric mucosa" and "axial sliding hernia" may cause marked airway symptoms and a pathogenetic relationship with otorhinolaryngologic reflux-associated symptoms must be postulated for these entities.

Objective: To investigate the usefulness of voice quality assessment as a treatment outcome in responder and nonresponder patients with laryngopharyngeal reflux (LPR)., Material and Methods: Eighty clinically diagnosed LPR patients with reflux finding score (RFS) > 7 and reflux symptom index (RSI) > 13 were treated with pantoprazole, lifestyle changes, and diet recommendations for three months. RSI; RFS; Voice Handicap Index; blinded Grade, Roughness, Breathiness, Asthenia, Strain, and Instability; aerodynamic and acoustic measurements were assessed at baseline and after treatment. These data were analyzed and compared with regard to the clinical evolution of patients (responder versus nonresponder). Patients who significantly improved RSI ≤ 13 and RFS ≤ 7 after treatment were considered as responder. Nonresponders were defined as patients with RSI > 13 and/or RFS > 7 at the end of treatment. Studies of correlation between the adherence to the diet regimen and the evolution of both signs and symptoms and between videolaryngostroboscopic signs; blinded Grade, Roughness, Breathiness, Asthenia, Strain, and Instability; and acoustic measurements were conducted., Results: Significant improvements in RSI, RFS, Voice Handicap Index, perceptual voice quality (dysphonia and roughness), and some fundamental frequency and intensity perturbation cues (phonatory fundamental frequency range, percent jitter, pitch perturbation quotient, relative average perturbation, percent shimmer, smoothed amplitude perturbation quotient, amplitude perturbation quotient, and peak-to-peak amplitude variation) were mainly identified after treatment in responder patients. The clinical and voice quality improvements of nonresponder patients were lower; highlighting a similar evolution of symptoms, signs, and voice quality. The correlation analysis revealed significant relationships between the adherence to lifestyle changes and diet recommendations and the improvement of symptoms and substantial correlations between breathiness and fundamental frequency perturbation parameters., Conclusion: Voice quality assessments can be used as indicators of the treatment effectiveness in patients with LPR. Voice quality improvement seems to be consistently associated with clinical improvement., (Copyright © 2018 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Study Objectives: The aim of the current study was to test the hypothesis that there is a temporal correlation between reflux episodes and respiratory events in patients with laryngopharyngeal reflux and obstructive sleep apnea., Methods: Adults with clinically diagnosed laryngopharyngeal reflux confirmed by two validated instruments (reflux symptom index ≥ 13 and reflux finding score ≥ 7) and obstructive sleep apnea (OSA) underwent full polysomnography with concomitant and synchronized multichannel intraluminal impedance-pH esophageal monitoring. The apnea-hypopnea and arousal indexes that occurred 15, 30, and 45 minutes before and after each reflux episode were recorded and compared to full-night apnea and hypopnea and arousal index., Results: We studied 27 patients (14 males, age 51.7 ± 9.1 years, body mass index 32.4 ± 4.2 kg/m²) with laryngopharyngeal reflux (reflux symptom index 16 ± 2 and reflux finding score 12 ± 3) and OSA (apnea-hypopnea index = 32.3 ± 28.4 events/h). We evaluated 102 reflux episodes. Almost half of the reflux episodes occurred while awake (43.1%) and only five reflux episodes (4.9%) occurred during an obstructive respiratory event. The apnea and hypopnea and arousal indexes 15, 30, and 45 minutes before and after reflux episodes were lower than full-night apnea and hypopnea and arousal indexes, respectively., Conclusions: Among patients with well-established laryngopharyngeal reflux and OSA, there is no temporal association between reflux and obstructive respiratory events. Even though the data comprised a small sample size, it seems that a more complex mechanism is involved with these two highly prevalent diseases., (© 2019 American Academy of Sleep Medicine.)

Background and Aim: Laryngopharyngeal reflux (LPR) defined as reflux of gastric content reaching above the upper esophageal sphincter is frequently found in patients with gastroesophageal reflux disease (GERD). This study aimed to investigate clinical and psychological differences between GERD patients with or without LPR symptoms., Methods: This study enrolled 303 consecutive patients with proton pump inhibitor treatment-naïve scheduled for upper endoscopy because of troublesome reflux symptoms and recognized as GERD by non-dyspepsia reflux disease questionnaire score. Included GERD patients were further categorized into two study groups: with or without LPR by reflux symptoms index score. All participants were also evaluated with questionnaires for depression, anxiety, and sleep disturbances., Results: There were 132 (43.6%) GERD patients with LPR symptoms and 171 (56.4%) GERD patients without LPR symptoms. GERD patients with LPR symptoms had more depression (P < 0.001), sleep disturbance (P = 0.002), irritable bowel syndrome (P = 0.008), functional dyspepsia (P = 0.005), and reflux symptoms burden (P < 0.001) than those without LPR symptoms. Erosive esophagitis was more in patients without LPR symptoms (P = 0.03). GERD patients with LPR symptoms (28.8%) had more complex psychological distress than those without LPR symptoms (28.8% vs 14%, P < 0.001). Reflux symptoms burden, sleep disturbance, and erosive esophagitis were independently associated with GERD overlapping with LPR symptoms., Conclusions: Gastroesophageal reflux disease patients with LPR symptoms appear to have more reflux symptoms, psychological distress, and functional gastrointestinal disturbance but less erosive esophagitis. This work suggests that therapeutic strategy with tailored multidimensional approach is promising for GERD patients overlapping with LPR symptoms., (© 2019 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Laryngopharyngeal reflux (LPR) is commonly treated with empiric acid suppression. More evidence points to pepsin in the pathophysiology of LPR. Previous studies have evaluated esophageal impedance in patients who had previously failed high dose proton pump inhibitor (PPI) using older catheters without proximal esophageal (just under the upper esophageal sphincter) and pharyngeal impedance sensors. The aim of this study was to compare what traditional diagnostic tools, used for esophageal reflux, would detect and diagnose compared with what a combined hypopharyngeal-esophageal MII catheter with dual pH (HEMII-pH) can detect in the esophagus and pharynx in patients with suspected LPR., Methods: Forty-two subjects with presumed LPR were referred for HEMII-pH testing. The number of distal and proximal esophageal impedance events, number of pharyngeal impedance events, symptom correlation, and event acidity were recorded. Previous normative values (>1 pharyngeal impedance events every 24 hours) were used to designate what was pathological LPR on HEMII-pH., Results: Forty-two total subjects had pharyngeal impedance sensor data recorded. Twelve (28.6%) of the subjects were tested while taking high-dose PPI therapy. The mean number of proximal esophageal events was 23.3. The mean number of pharyngeal impedance events was 10. Thirty-four subjects (81%) tested positive for pharyngeal reflux. All patients who tested positive using traditional proximal impedance criteria also tested positive using pharyngeal criteria. Of patients who tested negative using traditional criteria, 72% were positive based on pharyngeal criteria., Conclusions: HEMII-pH catheters should be considered in patients with LPR symptoms. Traditional criteria used for diagnosing esophageal reflux may not translate into LPR., (Copyright © 2018 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Face mask ventilation (FMV) during induction of anaesthesia is associated with risk of gastric insufflation that may lead to gastric regurgitation and pulmonary aspiration. A continuous positive airway pressure (CPAP) has been shown to reduce gastric regurgitation. We therefore hypothesised that CPAP followed by FMV with positive end-expiratory pressure (PEEP) during induction of anaesthesia would reduce the risk of gastric insufflation., Objective: The primary aim was to compare the incidence of gastric insufflation during FMV with a fixed PEEP level or zero PEEP (ZEEP) after anaesthesia induction. A secondary aim was to investigate the effects of FMV with or without PEEP on upper oesophageal sphincter (UES), oesophageal body and lower oesophageal sphincter (LES) pressures., Design: A randomised controlled trial., Setting: Single centre, Department of Anaesthesia and Intensive Care, Örebro University Hospital, Sweden., Participants: Thirty healthy volunteers., Interventions: Pre-oxygenation without or with CPAP 10 cmH2O, followed by pressure-controlled FMV with either ZEEP or PEEP 10 cmH2O after anaesthesia induction., Main Outcome Measures: A combined impedance/manometry catheter was used to detect the presence of gas and to measure oesophageal pressures. The primary outcome measure was the cumulative incidence of gastric insufflation, defined as a sudden anterograde increase in impedance of more than 1 kΩ over the LES. Secondary outcome measures were UES, oesophageal body and LES pressures., Results: The cumulative incidence of gastric insufflation related to peak inspiratory pressure (PIP), was significantly higher in the PEEP group compared with the ZEEP group (log-rank test P < 0.01). When PIP reached 30 cmH2O, 13 out of 15 in the PEEP group compared with five out of 15 had shown gastric insufflation. There was a significant reduction of oesophageal sphincter pressures within groups comparing pre-oxygenation to after anaesthesia induction, but there were no significant differences in oesophageal sphincter pressures related to the level of PEEP., Conclusion: Contrary to the primary hypothesis, with increasing PIP the tested PEEP level did not protect against but facilitated gastric insufflation during FMV. This result suggests that PEEP should be used with caution after anaesthesia induction during FMV, whereas CPAP during pre-oxygenation seems to be safe., Trial Registration: ClinicalTrials.gov, identifier: NCT02238691.

Objective: To evaluate the feasibility of pepsin strip test in the diagnosis of laryngopharyngeal reflux. Methods: From August 2017 to September 2018,80 patients in Department of Otorhniolaryngology Head and Neck Surgery,Chinese People's Liberation Army General Hospital-Six Medical Centre, underwent pepsin strip test and 24-hour multichannel intraluminal impedance(MII)-pH monitoring. The results of the two methods were analyzed for consistency,and 24-hour MII-pH monitoring was used as a statistical reference for the sensitivity and specificity of pepsin strip test in the diagnosis of laryngopharyngeal reflux. Data were analyzed by SPSS 19.0 software. Results: There were 57 patients with positive pepsin test strip and 23 patients with negative pepsin test strip. The score of reflux symptoms and signs, and the positive rate of laryngopharyngeal reflux events in patients with positive pepsin strip test were significantly higher than those in patients with negative pepsin test strip. If there was one or more throat reflux events (including acid reflux,weak acid reflux and alkali reflux) as the positive results of 24-hour MII-pH monitoring,the consistency between the results of pepsin strip and 24-hour MII-pH was moderate ( Kappa =0.614). The sensitivity and specificity of pepsin strip were 86.9% (53/61) and 78.9% (15/19) respectively. Conclusions: Pepsin strip detection has the advantages of non-invasive,cheap and easy to operate.As an objective method for early diagnosis of laryngopharyngeal reflux, pepsin strip detectionis feasible,but can not be the final diagnosis for laryngopharyngeal reflux disease.

Laryngopharyngeal reflux (LPR) is an inflammatory condition suspected to be associated with dysphonia. In this study, we investigated multidimensional perceptual, aerodynamic, and acoustic voice changes in patients with clinically diagnosed LPR compared to healthy participants. We prospectively included 80 outpatients with Reflux Finding Score (RFS) >7 and Reflux Symptom Index (RSI) >13 from September 2013 to April 2016 and we compared clinical and voice quality assessments of these patients with 80 healthy participants. Statistically significant differences were found between groups with regard to Voice Handicap Index, perceptual voice quality (grades of dysphonia, roughness, strain, breathiness, asthenia, and instability), phonatory quotient, percentage jitter, percentage shimmer, peak-to-peak amplitude variation, standard deviation of fundamental frequency, and noise to harmonic ratio. Granulation score of RFS was found to affect the highest number of acoustic parameters. We did not identify significant correlation between vocal fold edema and objective voice quality measurements. This study supports that patients with LPR have significant deterioration of both subjective and objective voice quality compared to healthy participants.