Multichannel Intraluminal impedance-pH Monitoring Research Articles

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

To develop and validate the Reflux Sign Assessment-10 (RSA-10) for documenting the physical findings of laryngopharyngeal reflux disease (LPRD). 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. Fifty-five patients completed the pre- to posttreatment evaluations from January 2020 to December 2023. A total of 115 asymptomatic individuals completed the study. RSA-10 reported high internal consistency reliability (α = 0.822) and test-retest reliability (rs = 0.725). The RSA-10 scores of patients were significantly higher than those of controls (p = 0.001), suggesting high internal validity. RSA-10 was significantly correlated with the RFS (rs = 0.771). The interrater reliability was adequate for sub- and total RSA-10 scores (k = 0.708). RSA-10 significantly improved from baseline to 3-month posttreatment (p = 0.001). An RSA-10 > 13 may be suggestive of LPRD. Both RSA-10 > 13 and Reflux Symptom Score-12 > 11 were associated with a sensitivity of 92.7% and a specificity of 97.3%. The RSA-10 is a reliable and valid clinical instrument for documenting the most prevalent laryngeal and extra-laryngeal findings associated with LPRD. 3 Laryngoscope, 2024.

Inflammatory responses in esophageal mucosa before and after laparoscopic antireflux surgery.

Currently, the primary treatment for gastroesophageal reflux is acid suppression with proton pump inhibitors, but they are not a cure, and some patients don't respond well or refuse long-term use. Therefore, alternative therapies are needed to understand the disease and develop better treatments. Laparoscopic anti-reflux surgery (LARS) can resolve symptoms of these patients and plays a significant role in evaluating esophageal healing after preventing harmful effects. Successful LARS improves typical gastroesophageal reflux symptoms in most patients, mainly by reducing the exposure time to gastric contents in the esophagus. Amelioration of the inflammatory response and a recovery response in the esophageal epithelium is expected following the cessation of the noxious attack. To explore the role of inflammatory biomolecules in LARS and assess the time required for esophageal epithelial recovery. Of 22 patients with LARS (pre- and post/5.8 ± 3.8 months after LARS) and 25 healthy controls (HCs) were included. All subjects underwent 24-h multichannel intraluminal impedance-pH monitoring and upper gastrointestinal endoscopy, during which esophageal biopsy samples were collected using endoscopic techniques. Inflammatory molecules in esophageal biopsies were investigated by reverse transcription-polymerase chain reaction and multiplex-enzyme-linked immunosorbent assay. Post-LARS samples showed significant increases in proinflammatory cytokines [interleukin (IL)-1β, interferon-γ, C-X-C chemokine ligand 2 (CXCL2)], anti-inflammatory cytokines [CC chemokine ligand (CCL) 11, CCL13, CCL17, CCL26, CCL1, CCL7, CCL8, CCL24, IL-4, IL-10], and homeostatic cytokines (CCL27, CCL20, CCL19, CCL23, CCL25, CXCL12, migration inhibitory factor) compared to both HCs and pre-LARS samples. CCL17 and CCL21 levels were higher in pre-LARS than in HCs (P < 0.05). The mRNA expression levels of AKT1, fibroblast growth factor 2, HRAS, and mitogen-activated protein kinase 4 were significantly decreased post-LARS vs pre-LARS. CCL2 and epidermal growth factor gene levels were significantly increased in the pre-LARS compared to the HCs (P < 0.05). The presence of proinflammatory proteins post-LARS suggests ongoing inflammation in the epithelium. Elevated homeostatic cytokine levels indicate cell balance is maintained for about 6 months after LARS. The anti-inflammatory response post-LARS shows suppression of inflammatory damage and ongoing postoperative recovery.

ChatGPT-4 accuracy for patient education in laryngopharyngeal reflux.

Chatbot Generative Pre-trained Transformer (ChatGPT) is an artificial intelligence-powered language model chatbot able to help otolaryngologists in practice and research. The ability of ChatGPT in generating patient-centered information related to laryngopharyngeal reflux disease (LPRD) was evaluated. Twenty-five questions dedicated to definition, clinical presentation, diagnosis, and treatment of LPRD were developed from the Dubai definition and management of LPRD consensus and recent reviews. Questions about the four aforementioned categories were entered into ChatGPT-4. Four board-certified laryngologists evaluated the accuracy of ChatGPT-4 with a 5-point Likert scale. Interrater reliability was evaluated. The mean scores (SD) of ChatGPT-4 answers for definition, clinical presentation, additional examination, and treatments were 4.13 (0.52), 4.50 (0.72), 3.75 (0.61), and 4.18 (0.47), respectively. Experts reported high interrater reliability for sub-scores (ICC = 0.973). The lowest performances of ChatGPT-4 were on answers about the most prevalent LPR signs, the most reliable objective tool for the diagnosis (hypopharyngeal-esophageal multichannel intraluminal impedance-pH monitoring (HEMII-pH)), and the criteria for the diagnosis of LPR using HEMII-pH. ChatGPT-4 may provide adequate information on the definition of LPR, differences compared to GERD (gastroesophageal reflux disease), and clinical presentation. Information provided upon extra-laryngeal manifestations and HEMII-pH may need further optimization. Regarding the recent trends identifying increasing patient use of internet sources for self-education, the findings of the present study may help draw attention to ChatGPT-4's accuracy on the topic of LPR.

Development of a new endoscopy system to visualize bilirubin for the diagnosis of duodenogastroesophageal reflux.

Reflux hypersensitivity (RH) is a form of refractory gastroesophageal reflux disease in which duodenogastroesophageal reflux (DGER) plays a role. This study aimed to determine the usefulness of an endoscopy system equipped with image-enhanced technology for evaluating DGER and RH. The image enhancement mode for detecting bilirubin and calculated values were defined as the Bil mode and Bil value, respectively. First, the visibility of the Bil mode was validated for a bilirubin solution and bile concentrations ranging from 0.01% to 100% (0.002-20 mg/dL). Second, visibility scores of the Bil mode, when applied to the porcine esophagus sprayed with a bilirubin solution, were compared to those of the blue laser imaging (BLI) and white light imaging (WLI) modes. Third, a clinical study was conducted to determine the correlations between esophageal Bil values and the number of nonacid reflux events (NNRE) during multichannel intraluminal impedance-pH monitoring as well as the utility of esophageal Bil values for the differential diagnosis of RH. Bilirubin solution and bile concentrations higher than 1% were visualized in red using the Bil mode. The visibility score was significantly higher with the Bil mode than with the BLI and WLI modes for 1% to 6% bilirubin solutions (P < 0.05). The esophageal Bil value and NNRE were significantly positively correlated (P = 0.031). The area under the receiver operating characteristic curve for the differential diagnosis of RH was 0.817. The Bil mode can detect bilirubin with high accuracy and could be used to evaluate DGER in clinical practice.

A comparison between a gastroesophageal reflux disease questionnaire-based algorithm and multichannel intraluminal impedance-pH monitoring for the treatment of gastroesophageal reflux-induced chronic cough.

Empiric therapy with multichannel intraluminal impedance-pH monitoring (MII-pH) has been used for the initial treatment of gastroesophageal reflux-induced chronic cough (GERC). However, an algorithm based on the gastroesophageal reflux disease questionnaire (GerdQ) has the potential to achieve a simple, structured, and effective treatment approach for patients with GERC. This study compared the efficacy of anti-reflux therapy based on GerdQ (new structured pathway, NSP) with medical treatment after MII-pH examination (ordinary clinical pathway, OCP) in the management of GERC. For the NSP, we adapted the GerdQ score to establish the basis for a treatment algorithm. For the OCP, treatment was determined using the MII-pH examination results. The non-inferiority (NI) hypothesis was used to evaluate NSP versus OCP. Overall, the NSP and OCP-based therapeutic algorithms have similar efficacy for GERC [NI analysis: 95% confidence interval (CI), -4.97 to 17.73, p = 0.009; superiority analysis: p = 0.420]. Moreover, the cough symptom scores and cough threshold improved faster in the NSP group than in the OCP group at week 8 (p < 0.05). In the subgroup analyses using the GerdQ and GerdQ impact scale (GIS) scores, patients with low-likelihood GERC (GerdQ < 8) were more likely to benefit from OCP (NI analysis: 95% CI, -19.73 to 18.02, p = 0.213). On the other hand, in patients with high-likelihood and low-reflux impact GERC patients (GerdQ > 8 and GIS < 4), the NSP arm was not inferior to the standard treatment of OCP (NI analysis: 95% CI, -8.85 to 28.21%, p = 0.04; superiority analysis: p = 0.339), indicating that GerdQ- and GIS-guided diagnosis and management of patients with GERC could be an alternative to MII-pH management, especially in settings with reduced medical resources. The use of the GerdQ algorithm should be considered when handling patients with GERC in the primary care setting. This research was registered in the Chinese Clinical Trials Registry (ChiCTR-ODT-12001899).

Narrative review of relationship between chronic cough and laryngopharyngeal reflux.

Gastroesophageal reflux disease (GERD) as a possible cause of chronic cough is known for decades. However, more than 75% of patients with extraoesophageal symptoms do not suffer from typical symptoms of GERD like pyrosis and regurgitations and have negative upper gastrointestinal endoscopy. For such a condition term laryngopharyngeal reflux (LPR) was introduced and is used for more than two decades. Since the comprehensive information on relationship between chronic cough and LPR is missing the aim of this paper is to summarize current knowledge based on review of published information during last 13 years. Laryngopharyngeal reflux is found in 20% of patients with chronic cough. The main and recognized diagnostic method for LPR is 24-h multichannel intraluminal impedance-pH (MII-pH) monitoring, revealing reflux episodes irritating the upper and lower respiratory tract mucosa. The treatment of LPR should be initiated with dietary and lifestyle measures, followed by proton pump inhibitor (PPI) therapy and other measures. Despite progress, more research is needed for accurate diagnosis and targeted therapies. Key areas for exploration include biomarkers for diagnosis, the impact of non-acid reflux on symptom development, and the efficacy of new drugs. Further studies with a focused population, excluding other causes like asthma, and using new diagnostic criteria for LPR are essential. It's crucial to consider LPR as a potential cause of unexplained chronic cough and to approach diagnosis and treatment with a multidisciplinary perspective.

Post-reflux swallow-induced peristaltic wave index: a new parameter for the identification of non-acid gastroesophageal reflux-related chronic cough.

The current available diagnostic criteria for gastroesophageal reflux-related chronic cough (GERC) dominated by non-acid reflux is imperfect. The post-reflux swallow-induced peristaltic wave index (PSPWI) is a parameter reflecting esophageal clearance function. This study aims to investigate its diagnostic value for non-acid GERC. This study sought to compare the diagnostic value of PSPWI in different types of GERC, particularly non-acid GERC, and explore the clinical significance of PSPWI in the diagnosis of non-acid GERC through diagnostic experiments. A retrospective analysis was performed based on 223 patients with suspected GERC who underwent multichannel intraluminal impedance-pH monitoring (MII-pH) in the outpatient clinic of our department from August 2016 to June 2021. Their clinical information, laboratory test results, and treatment responses were assessed and the underlying etiologies of chronic cough were categorized. The predictive value of the PSPWI in diagnosing different types of GERC, especially non-acid GERC, was analyzed and compared. A total of 195 patients with chronic cough who met the inclusion criteria underwent MII-pH monitoring. 143 patients had a definitive diagnosis of GERC, including 98 with acid GERC and 45 with non-acid GERC. The diagnostic value of PSPWI alone was moderate for GERC with an area under the working curve (AUC) 0.760, but poor for non-acid GERC with an AUC of 0.569. However, PSPWI < 39.8% combining with acid exposure time (AET) ⩽ 6.2% demonstrated a moderate diagnostic value for non-acid GERC, with an AUC of 0.722. When PSPWI < 39.8% combined with a non-acid reflux ratio >68.75%, the diagnostic value for non-acid GERC was improved (AUCROC = 0.80 versus AUCROC = 0.722, p < 0.05), which was significantly superior to non-acid symptom index (AUCROC = 0.804 versus AUCROC = 0.550, p < 0.05) and non-acid symptom association probability (AUCROC = 0.804 versus AUCROC = 0.571, p < 0.05). PSPWI < 39.8% and AET ⩽ 6.2% have demonstrated good diagnostic value for non-acid GERC. The diagnostic value was further improved when combined with non-acid reflux ratio >68.75%.

Personalized Treatments Based on Laryngopharyngeal Reflux Patient Profiles: A Narrative Review.

To review the current findings of the literature on the existence of several profiles of laryngopharyngeal reflux (LPR) patients and to propose personalized diagnostic and therapeutic approaches. A state-of-the art review of the literature was conducted using the PubMED, Scopus, and Cochrane Library databases. The information related to epidemiology, demographics, clinical presentations, diagnostic approaches, and therapeutic responses were extracted to identify outcomes that may influence the clinical and therapeutic courses of LPR. The clinical presentation and therapeutic courses of LPR may be influenced by gender, age, weight, comorbidities, dietary habits and culture, anxiety, stress, and saliva enzyme profile. The clinical expression of reflux, including laryngopharyngeal, respiratory, nasal, and eye symptoms, and the hypopharyngeal-esophageal multichannel intraluminal impedance-pH monitoring profile of patients are important issues to improve in patient management. The use of more personalized therapeutic strategies appears to be associated with better symptom relief and cures over the long-term. The role of pepsin in LPR physiology is well-established but the lack of information about the role of other gastrointestinal enzymes in the development of LPR-related mucosa inflammation limits the development of future enzyme-based personalized diagnostic and therapeutic approaches. Laryngopharyngeal reflux is a challenging ear, nose, and throat condition associated with poor therapeutic responses and a long-term burden in Western countries. Artificial intelligence should be used for developing personalized therapeutic strategies based on patient features.

The Time-Point Distribution Characteristics of Laryngopharyngeal Reflux in Elderly Patients.

To identify the characteristics of the time-point distribution of the occurrence of hypopharyngeal-proximal reflux episodes (HREs) in elderly and younger patients with laryngopharyngeal reflux (LPR). Retrospective cohort study. Analysis of data from patients with LPR-related symptoms and 24-hour hypopharyngeal-esophageal multichannel intraluminal impedance-pH (24-hour HEMII-pH) monitoring from February 2017 to September 2022 at Sixth Medical Center of PLA General Hospital. Patients were divided into 2 age groups: the elderly group (>60 years) and the younger group (≤60 years). The time series of HREs and meals within 24hours were analyzed based on HEMII-pH. A total of 305 patients were included (126 elderly patients). In younger patients, except for nonacid-gas HREs, the incidence of the remaining types of HREs tended to increase within 2hours after meals, especially after dinner. The incidence of all types of HREs pre- and postmeal was not significantly different in the elderly group (χ2 = 0.080, P = .777). The incidence of nighttime HREs in elderly patients was statistically higher than in younger patients (6.23% vs3.96%, P = .030), particularly acid-/nonacid-liquid HREs. HREs tend to increase within 2hours after meals in younger LPR patients, except for nonacid-gas HREs. In elderly LPR patients, the incidence of all types of HREs pre- and postmeal were not significantly different, and nighttime fluid HREs was more prone to occur than in younger patients.

Higher obesity class is associated with more severe esophageal symptoms and reflux burden but not altered motor function or contractile reserve.

Patients with obesity often report esophageal symptoms, with abnormal reflux and esophageal motility suggested as potential mechanisms. However, prior studies showed varying results, often limited by study design/size and esophageal function/symptom measures utilized. We aimed to examine the relationship between obesity and objective esophageal function testing and patient-reported outcomes, utilizing prospective symptom, manometric and reflux monitoring data with impedance. Adults referred for high-resolution impedance-manometry (HRiM) and multichannel intraluminal impedance-pH monitoring (MII-pH) to evaluate esophageal symptoms were enrolled. Validated symptom and health-related quality of life (HR-QOL) instruments were prospectively collected: GERDQ, reflux symptoms index (RSI), dominant symptom intensity (DSI, multiplied 5-point Likert scales for symptom frequency/severity), global symptom severity (GSS, 100-point visual analog scale), and Short Form-12 (SF-12) for HR-QOL. Esophageal function testing measures were compared across body mass index (BMI) categories and correlated with patient-reported outcomes. Seven hundred and fifty four patients were included (Normal:281/Overweight:253/Class I obesity:137/Class II/III obesity:83). Reflux burden measures on MII-pH (acid exposure time, total reflux episodes, bolus exposure time), conclusive pathologic reflux (Lyon), and hiatal hernia were increased in higher obesity classes compared to normal BMI. Class II/III obesity was associated with more normal/hypercontractile swallows, less ineffective swallows, and better bolus transit on HRiM. BMI correlated positively with GERDQ/RSI/DSI/GSS, and negatively with physical component score (SF-12). Esophageal symptom severity and HR-QOL correlated strongly with MII-pH findings, but not HRiM measures. Obesity is associated with increased esophageal symptom burden and worse physical HR-QOL, which correlate with higher acid/bolus reflux burden but not altered esophageal motility/transit/contractile reserve.

Esophageal dysmotility detection in patients with gastroesophageal reflux-related cough and its influence on the efficacy of anti-reflux therapy

Objective: To investigate the characteristics of esophageal dysmotility in patients with an initial diagnosis of acid/non-acid gastroesophageal reflux-related cough (GERC), and its correlation with the therapeutic response to anti-reflux treatments to search for the useful indicators to screen patients with chronic cough suitable for anti-reflux therapy. Methods: A total of 173 patients with suspicious GERC who attended the Chronic Cough Specialist Clinic of Department of Pulmonary and Critical Care Medicine, Tongji Hospital, School of Medicine, Tongji University between June 2020 and December 2022 were retrospectively selected for the study. The age of the patients was (45.1±14.6) years old, including 87 males and 86 females. Their demographic characteristics, clinical manifestations, and the results of high-resolution manometry (HRM) and multichannel intraluminal impedance-pH monitoring (MII-pH) were collected. Information on the etiological identification process and final diagnosis was also recorded. The recruited cases were grouped according to therapeutic outcomes and divided into cases with a favourable response to conventional anti-reflux treatment, cases with a favourable response to intensified anti-reflux treatment, and cases with no response to anti-reflux treatment. Factors influencing the efficacy of anti-reflux treatment were investigated. Differences between groups were compared using the χ2 test, Student-Newman-Keuls test, and Kruskal-Wallis H(K) test, where applicable. Logistic regression analysis using forward stepwise regression based on maximum likelihood estimation was used to screen for influence factors. Results: The 175 patients with suspicious GERC included 45 (26.0%) patients who responded to conventional anti-reflux treatment, 54 (31.2%) who responded to intensified anti-reflux treatment and 74 (42.8%) who did not respond to anti-reflux therapies. Esophageal dysmotility was present in 52.0% of patients (90/173), but was less common in patients who responded to conventional anti-reflux treatment (χ2=8.09, P=0.018). Although the majority of reflux episodes were non-acid (136/173, 78.6%), the proportion of acid reflux (χ2=19.49, P<0.001) and acid exposure time (H=11.04, P=0.004) were significantly higher in patients who responded to conventional anti-reflux treatment. The patients with acid and non-acid GERC had comparable proportion of esophageal dysmotility (64.9% vs. 48.5%, χ2=3.11, P=0.078), with a shorter break [2.4 (0.7, 5.6) cm vs. 6.1 (1.4, 10.0) cm, Z=-2.39, P=0.017], longer upper esophageal sphincter [(4.1±0.9) cm vs. (3.7±1.3) cm, t=-2.09, P=0.038], higher percentage of normal esophageal contractions [60.0% (17.8%, 90.0%) vs. 30.0% (0, 80.0%), Z=-2.14, P=0.032], and lower percentage of large break [10.0% (0, 40.0%) vs. 50.0% (0, 100.0%), Z=-2.92, P=0.004] in the patients with non-acid GERC. The mean resting pressure of the lower esophageal sphincter was significantly lower (H=7.49, P=0.024), while the percentage of ineffective esophageal contractions was markedly higher (H=8.60, P=0.014) in the patients who responded to intensified anti-reflux treatment and in the patients who did not respond to the anti-reflux therapies. Multifactorial logistic regression analysis identified the percentage of ineffective contraction as an independent factor predicting the efficacy of conventional anti-reflux treatment, with a cut-off value of≤45% and a moderate predictive value (AUC=0.67, P=0.004). Conclusions: Esophageal dysmotility is common in GERC patients with different characteristics in acid and non-acid GERC. The percentage of ineffective esophageal contraction may be a useful indicator for selecting an anti-reflux strategy and predicting treatment outcomes.

A Study of the Diagnostic Value of the Sign and Symptom Questionnaires for Laryngopharyngeal Reflux Disease.

To investigate the diagnostic value of symptom questionnaires, sign questionnaires, and the combination of 2 questionnaires for laryngopharyngeal reflux disease (LPRD). Prospective, single-centered. Seventy-seven patients who were hospitalized in the Department of Otolaryngology-Head and Neck Surgery from October 2022 to April 2023 were included. Included patients completed the RSS, RSI, RSA, and RFS questionnaires and underwent 24-hour hypopharyngeal-esophageal multichannel intraluminal impedance-pH monitoring (HEMII-pH). The RSS, RSI, RSA, RFS, RSS+RSA, RSS+RFS, RSI+RSA, RSI+RFS, and RSI+RFS diagnostic value were compared using Cohen's k test and receiver operating characteristic analysis. Based on the 24 hours HEMII-pH results, 52 patients had LPRD, and 25 patients did not have LPRD. The Kappa values of RSS, RSI, RSA, RFS, RSS+RSA,2 RSS+RFS, RSI+RSA, and RSI+RFS with the 24 hours HEMII-pH monitoring results were 0.565, 0.442, 0.318, 0.431, 0.517, 0.631, 0.451, and 0.461, respectively. The RSS+RFS questionnaire had the highest AUC of 0.836 (95% confidence interval [CI] 0.762-0.909) and the RSA questionnaire had the lowest AUC (AUC = 0.665, 95% CI 0.560-0.790). The sensitivity of RSS was the highest (98%), the specificities of RSS+RFS and RSI+RFS were the highest (96%), and the specificity of RSS was the lowest (52%). RSS+RFS had a sensitivity of 75%, second only to RSS and RFS (76%). Among the 8 methods, the RSS combined with the RFS had the highest concordance with 24 hours HEMII-pH monitoring results and AUC values when screening for LPRD.

Relationship Between Laryngopharyngeal Reflux and Obstructive Sleep Apnea in Adult Males

To investigate the relationship between laryngopharyngeal reflux (LPR) and obstructive sleep apnea (OSA). Patients diagnosed with OSA who were hospitalized in the Department of Otolaryngology-Head and Neck Surgery from November 2021 to April 2022 were selected, and male patients with non-OSA during the same period were selected as the control group. Patients who participated in the study completed the Reflux Symptom Index (RSI), the Reflux Finding Sign (RFS), and 24-hour multichannel intraluminal impedance-pH (MII-pH) monitoring. RSI, RFS, and outcomes of 24hour-MII-pH monitoring were compared between the OSA group and the control group. A total of 86 patients were enrolled, of whom 49 were OSA patients and 37 were non-OSA patients. The positive rate of LPR (97.96% vs75.68%) and the median number of LPR episodes (9 vs5) were significantly higher in OSA patients than in non-OSA patients (P<0.01, P<0.05, respectively). A logistic regression model including body mass index, alcohol consumption, and the presence of OSA showed that having OSA was a risk factor for the occurrence of LPR (P<0.05,OR [odds ratio]=9.995, 95% CI [confidence interval] 1.084-92.181). There were correlations between Apnea-Hypopnea Index and the number of non-acid LPR episodes and the number of alkaline LPR episodes (r=0.243,P<0.05, r=0.274, P<0.05,respectively). Having OSA is a risk factor for LPR, and LPR episodes occur more frequently in patients with OSA compared to those without OSA. When OSA is comorbid with LPR, the occurrence of alkaline LPR, such as bile reflux, should be a concurrent concern.

Laryngopharyngeal Reflux and Benign Vocal Fold Lesions: A Systematic Review and Meta-analysis.

There is a link between laryngopharyngeal reflux (LPR) and the formation of benign vocal fold lesions (BVFLs). However, previous studies have mainly focused on LPR suggested by symptoms and signs, rather than objectively diagnosed LPR via pharyngeal pH monitoring. We, therefore, conducted a Meta-analysis to evaluate the association between pharyngeal pH monitoring diagnosed LPR and the odds of BVFLs. Relevant observational studies were identified by searching PubMed, Embase, Cochrane Library, and Web of Science. We evaluated between-study heterogeneity using the Cochrane Q test and estimated the I2 statistic. Random-effects models were used when significant heterogeneity was observed; otherwise, fixed-effects models were used. Thirteen datasets from 9 studies were included. Among them, 493 were diagnosed with LPR and 344 had BVFLs. LPR was related to a higher odds of BVFLs (odds ratio: 3.26, 95% confidence interval: 1.84-5.76, P < .001) with moderate heterogeneity (P for Cochrane Q test = .006, I2 = 57%). Subgroup analyses showed that the association was similar in studies with only pharyngeal pH monitoring (Restech), with double-probe or 3-site pH monitoring, and with 24-hour multichannel intraluminal impedance-pH monitoring (P for subgroup difference = .15). In addition, subgroup analysis showed consistent results in studies from Asia and Europe (P for subgroup analysis = .12), and the association seemed to be consistent for vocal Reinke's edema, nodules, and polyps (P for subgroup difference = .09). Pharyngeal pH monitoring diagnosed LPR is associated with the formation of BVFLs.

Can pepsin immunohistochemical staining of laryngeal lesions accurately diagnose non-acid laryngeal reflux?

Background Non-acid reflux is the most common form of laryngopharyngeal reflux (LPR). However, the damage caused by non-acid reflux to the laryngeal mucosa is weaker than that caused by acid reflux. Aims To evaluate whether pepsin immunohistochemical (IHC) staining of laryngeal lesions can accurately diagnose acidic and non-acidic LPR. Materials and Methods Hypopharyngeal-esophageal multichannel intraluminal impedance-pH monitoring was performed, and the patients were divided into acid reflux and non-acid reflux groups. Pathological sections of laryngeal lesions were examined using pepsin IHC staining, which was positive when pepsin was detected in the cytoplasm. Results The study included 136 patients, with 58 in the acid reflux group, 43 in the non-acid reflux group, and 35 in the without reflux group. There were no significant differences in the positive rate of pepsin IHC staining between the non-acid and acid reflux groups (p = .421). The sensitivity of pepsin IHC staining for the diagnosis of acid and non-acid reflux was 94.8% and 90.7%, respectively. Conclusions The sensitivity of pepsin IHC staining for laryngeal lesions in the diagnosis of non-acidic LPR is satisfactory. Significance Pepsin IHC staining is suitable for LPR screening of patients with laryngeal lesions as it is economical, non-invasive, and highly sensitive.

Distal Mean Nocturnal Baseline Impedance Predicts Pathological Reflux of Isolated Laryngopharyngeal Reflux Symptoms

Diagnosis of isolated laryngopharyngeal reflux symptoms (ILPRS), ie, without concomitant typical reflux symptoms (CTRS), remains difficult. Mean nocturnal baseline impedance (MNBI) reflects impaired mucosal integrity. We determined whether esophageal MNBI could predict pathological esophagopharyngeal reflux (pH+) in patients with ILPRS. In this cross-sectional study conducted in Taiwan, non-erosive or low-grade esophagitis patients with predominant laryngopharyngeal reflux symptoms underwent combined hypopharyngeal multichannel intraluminal impedance-pH monitoring when off acid suppressants. Participants were divided into the ILPRS (n = 94) and CTRS (n = 63) groups. Asymptomatic subjects without esophagitis (n = 25) served as healthy controls. The MNBI values at 3 cm and 5 cm above the lower esophageal sphincter (LES) and the proximal esophagus were measured. Distal but not proximal esophageal median MNBI values were significantly lower in patients with pH+ than in those with pH- (ILPRS in pH+ vs pH-: 1607 Ω vs 2709 Ω and 1885 Ω vs 2563 Ω at 3 cm and 5 cm above LES, respectively; CTRS in pH+ vs pH-: 1476 vs 2307 Ω and 1500 vs 2301 Ω at 3 cm and 5 cm above LES, respectively, P < 0.05 for all). No significant differences of any MNBI exist between any pH- subgroups and healthy controls. The areas under the receiver operating characteristic curve in the ILPRS group were 0.75 and 0.80, compared to the pH- subgroup and healthy controls (P < 0.001 for both), respectively. Interobserver reproducibility was good (Spearman correlation 0.93, P < 0.0001). Distal esophageal MNBI predicts pathological reflux in patients with ILPRS.

Study on the time-point distribution characteristics of the occurrence of laryngopharyngeal reflux

Objective: To investigate the characteristics of the time-point distribution of the occurrence of laryngopharyngeal reflux (LPR) by 24-hour multichannel intraluminal impedance-pH monitoring (24 h MII-pH) and to provide guidance for the development of individualized anti-reflux strategies for LPR patients. Methods: We conducted a retrospective analysis of 24 h MII-pH data from 408 patients [339 males and 69 females, aged 23-84 (55.08±11.08) years] attending the Department of Otorhinolaryngology Head and Neck Surgery at the Sixth Medical Center of the PLA General Hospital from January 2013 to March 2020. The number of gas acid/weak-acid reflux, mixed gas-liquid acid/weak-acid reflux, liquid acid/weak-acid reflux and alkaline reflux events at different time points were recorded and statistically analyzed through SPSS 26.0 software. Results: A total of 408 patients were included. Based on the 24 h MII-pH, the total positive rate of LPR was 77.45% (316/408). The type of positive gaseous weak-acid reflux was significantly higher than the remaining types of LPR (χ2=297.12,P<0.001). Except the gaseous weak-acid reflux, the occurrence of the remaining types of LPR showed a tendency to increase after meals, especially after dinner. Liquid acid reflux events occurred mainly between after dinner and the following morning, and 47.11% (57/121) of them occurred within 3 h after dinner. There was a significant positive association between Reflux Symptom Index scores and gaseous weak-acid reflux(r=0.127,P<0.01), liquid acid reflux(r=0.205,P<0.01) and liquid weak-acid reflux(r=0.103,P<0.05)events. Conclusions: With the exception of gaseous weak-acid reflux events, the occurrence of the remaining types of LPR events has a tendency to increase after meals, especially after dinner. Gaseous weak-acid reflux events accounts for the largest proportion of all types of LPR events, but the pathogenic mechanisms of gaseous weak-acid reflux are needed to further investigate.

Improved diagnostic yield of symptom association probability involving only cough for gastroesophageal reflux-induced chronic cough.

Use of symptom association probability (SAP) is recommended for identifying gastroesophageal reflux-induced chronic cough (GERC). This study aimed to compare the diagnostic yield of SAPs involving only cough (C-SAP) or total symptoms (T-SAP) for GERC identification. Patients with both chronic cough and other reflux-related symptoms underwent multichannel intraluminal impedance-pH monitoring (MII-pH) between January 2017 and May 2021. C-SAP and T-SAP were calculated based on the patient-reported symptoms. GERC was definitively diagnosed by the favorable response to anti-reflux therapy. The diagnostic yield of C-SAP in identifying GERC was evaluated by receiver operating characteristic curve analysis and compared with that of T-SAP. MII-pH was performed in 105 patients with chronic cough, and GERC was confirmed in 65 (61.9%), including 27 (41.5%) cases of acid GERC and 38 (58.5%) cases of non-acid GERC. The positive rates of C-SAP and T-SAP were comparable (34.3% vs. 23.8%, P>0.05), but C-SAP exhibited a higher sensitivity (53.85% vs. 33.85%, χ2=8.117, P=0.004) and similar high specificities (97.5% vs. 92.5%, P>0.05) compared with T-SAP for GERC identification. C-SAP was also more sensitive for recognition of acid GERC (51.85% vs. 33.33%, χ2=7.386, P=0.007) and non-acid GERC (65.79% vs. 39.47%, χ2=14.617, P<0.001). More GERC patients with positive C-SAP needed intensified anti-reflux therapy for cough resolution when compared with those with negative C-SAP (82.9% vs. 46.7%, χ2=9.449, P=0.002). C-SAP was superior to T-SAP for the identification of GERC and may improve the diagnostic yield of GERC.

Pediatric Laryngopharyngeal Reflux: An Evidence-Based Review

Pediatric laryngopharyngeal reflux (P-LPR) is associated with the development of common otolaryngological symptoms and findings. In the present study, the findings about epidemiology, clinical presentation, diagnostic and therapeutic outcomes of pediatric population were reviewed. A PubMed, Cochrane Library, and Scopus literature search was conducted about evidence-based findings in epidemiology, clinical presentation, diagnostic and therapeutic outcomes of P-LPR. The prevalence of LPR remains unknown in infant and child populations. The clinical presentation depends on age. Infants with LPR symptoms commonly have both gastroesophageal reflux disease (GERD) and laryngopharyngeal reflux and related digestive, respiratory and ear, nose and throat symptoms. The GERD prevalence appears to decrease over the growth, and the clinical picture is increasingly associated with LPR symptoms and findings without GERD. The prevalence of LPR and proximal acid and nonacid esophageal reflux events may be high in some prevalent otolaryngological conditions (chronic otitis media, laryngolomalacia and apnea). However, the lack of use of hypopharyngeal-esophageal multichannel intraluminal impedance pH monitoring (HEMII-pH) limits the establishment of etiological associations. Proton pump inhibitors are less effective in P-LPR patients compared to GERD populations, which may be related to the high prevalence of weakly or nonacid reflux events. Many gray areas persist in P-LPR and should be not resolved without the establishment of diagnostic criteria (guidelines) based on HEMII-pH. The unavailability of HEMII-pH and the poor acid-suppressive therapeutic response are all issues requiring future investigations. Future controlled studies using HEMII-pH and enzyme measurements in ear, nose or throat fluids may clarify the epidemiology of P-LPR according to age and its association with many otolaryngological conditions.

Mean Nocturnal Baseline Impedance (MNBI) Provides Evidence for Standardized Management Algorithms of Nonacid Gastroesophageal Reflux-Induced Chronic Cough.

The clinical management of nonacid gastroesophageal reflux-induced chronic cough (GERC) is challenging, and patient response to standard antireflux therapy (omeprazole 20 mg twice daily plus mosapride 10 mg thrice daily) is suboptimal. This study aimed to identify predictors of standard antireflux therapy efficacy and provide evidence for standardized management algorithms of nonacid GERC. A total of 115 nonacid GERC patients who underwent multichannel intraluminal impedance-pH monitoring (MII-pH) were enrolled between March 2017 and March 2021. Retrospective analysis of general information and MII-pH indications were used to establish a regression analysis model for multiple factors affecting standard antireflux therapy efficacy. 90 patients met the inclusion criteria, and the overall response rate to standard antireflux therapy was 55.5% (50/90). The mean nocturnal baseline impedance (MNBI) (1817.75 ± 259.26 vs. 2369.93 ± 326.35, P = 0.030) and proximal MNBI (1833.39 ± 92.16 vs. 2742.57 ± 204.64, P ≤ 0.001) of responders were lower than those of nonresponders. Weakly acid reflux (56.00 (31.70, 86.00) vs. 14.00 (14.00, 44.20), P = 0.022), nonacid reflux (61.35 (15.90.86.50) vs. 21.60 (0.00, 52.50), P = 0.008), and proximal extent (19.00 (5.04, 24.00) vs. 5.50 (2.56, 11.13), P = 0.011) were markedly higher in responders than nonresponders. Proximal MNBI (OR = 0.997, P = 0.042, and optimal cutoff = 2140 Ω) and weakly acid reflux (OR = 1.051, P = 0.029, and optimal cutoff = 45) were independent predictors of standard antireflux therapy efficacy. The combination predictive value did not show better results than either individual predictor. Proximal MNBI < 2140 Ω may be used to screen patients with nonacid GERC suitable for standard antireflux therapy and in standardized management algorithms for nonacid GERC. In the absence of MNBI, weakly acid reflux > 45 can be used as an auxiliary indicator.