Laryngopharyngeal Reflux Patients Research Articles

Correlation of Dry Eye Disease and Laryngopharyngeal Reflux Based on Improved Symptoms With Combined Therapy

ObjectiveTo investigate the correlation between dry eye disease (DED) and laryngopharyngeal reflux (LPR) from the perspective of treatment response. Study DesignCross-sectional studies. SettingSetting: Analysis of data from patients with DED-related symptoms and LPR-related symptoms from May 2022 to January 2023 at AIER EYE HOSPITAL (HAINAN) Hospital. MethodsThe Ocular Surface Symptom Index (OSDI) scales and The Reflux Symptom Score (RSS)were investigated in patients attending China Aier Eye Hospital (Hainan) from May 2022 to January 2023, and OSDI scores >12 were categorized as dry eye disease (DED), and RSS scores >13 were categorized as suspected laryngopharyngeal reflux (suspected LPR). Patients with DED and suspected LPR were randomly divided into three groups (Group A: 0.3% sodium vitreous acid drops and 1% cyclosporine A drops only; Group B: 0.3% sodium vitreous acid drops, 1% cyclosporine A drops, and Gastroflex tablets containing magnesium alginate and cimicifugal oil and esomeprazole; and Group C: Gastroflex tablets and esomeprazole only orally), and were reviewed after three months for the RSS and DED-related examinations. Result219 patients were enrolled. 191 DED-positive and 28 DED-negative patients, 84 suspected LPR-positive and 135 LPR-negative patients, and the OSDI scores of LPR patients were significantly higher than those of LPR-negative patients (P<0.001). Parameters related to DED and LPR were significantly lower in patients in Group B than in Groups A and C after treatment (P<0.001). ConclusionLPR and DED are closely related. For patients with both LPR and DED, treating LPR and DED at the same time may be a better option.

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

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

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

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

Types of Epiglottic Collapse in Breathing Sleep Disorder and Their Impact in Clinical Practice.

Introduction Obstructive sleep apnea (OSA) is a severe form of sleep-disordered breathing (SDB) that is strongly correlated with comorbidities, in which epiglottic collapse (EC) and other contributing factors are involved. Objectives To evaluate the occurrence of EC in OSA patients through drug-induced sleep endoscopy (DISE) and to determine the factors contributing to EC. Methods A retrospective study of 37 adult patients using medical history. Patients were assessed for laryngopharyngeal reflux (LPR) and lingual tonsil hypertrophy (LTH) using reflux symptom index and reflux finding score (RFS); for OSA using polysomnography, and for airway collapse through DISE. An independent t -test was performed to evaluate risk factors, including the involvement of three other airway structures. Results Most EC patients exhibited trap door epiglottic collapse (TDEC) (56.8%) or pushed epiglottic collapse (PEC) (29.7%). Lingual tonsil hypertrophy, RFS, and respiratory effort-related arousal (RERA) were associated with epiglottic subtypes. Laryngopharyngeal reflux patients confirmed by RFS (t(25) = -1.32, p = 0.197) tended to suffer PEC; LTH was significantly associated (X2(1) = 2.5, p = 0.012) with PEC (odds ratio [OR] value = 44) in grades II and III LTH patients; 11 of 16 TDEC patients had grade I LTH. Pushed epiglottic collapse was more prevalent among multilevel airway obstruction patients. A single additional collapse site was found only in TDEC patients. Conclusion Laryngopharyngeal reflux causes repetitive acid stress toward lingual tonsils causing LTH, resulting in PEC with grade II or III LTH. Trap door epiglottic collapse requires one additional structural collapse, while at least two additional collapse sites were necessary to develop PEC. Respiratory effort-related arousal values may indicate EC.

Analysis of bile acid in saliva of patients with laryngopharyngeal reflux and non-laryngopharyngeal reflux

ABSTRACT — Background: Laryngopharyngeal reflux (LPR) is the backflow of gastric and or duodenal fluid into the larynx, pharynx, trachea, and bronchi. The prevalence of LPR is difficult to determine due to the limited gold standard and the large variety of LPR symptoms. Damage can occur due to the decrease in pH value and also because of exposure to harmful enzymes in reflux, including bile acid. Purpose : This study was conducted to analyze bile acid levels in the saliva of LPR patient and non LPR subject. Methods: This study is an observational study with a case-control design. The study was conducted in the ORL-HNS Department of Dr. M. Djamil Hospital, Padang, West Sumatra, Indonesia. The total sample size was 44 people. We enrolled 22 healthy subjects as the control group and 22 patients suspected of having LPR. Result: LPR patients are more common in women than in men, with 12 women and 10 men. Bile acid in the LPR group means of is 25.08±7.67µM, meanwhile, in the healthy group, the mean was 18.99±8.26 µM. There is a statistically significant in the incidence of LPR with the bile acids (p = 0.015) based on t- independent test. Conclusion: Our study confirmed that bile acids in saliva play a major role in diagnosing LPR.

Relationship between burning mouth disorder and gastroesophageal reflux disease: A scoping review

AbstractObjectiveThis study aims to provide a scoping review and attempts to uncover the possible association between burning mouth disorder and gastroesophageal reflux disease.MethodsPubMed, EMBASE, Web of Science, the Cochrane Library, Ovid, Scopus, and a search platform (EBSCOhost) were searched from their inception to August 22, 2023.ResultsAfter screening 2795 records, 18 articles were included in the final review, comprising cross‐sectional studies (n = 9), case–control studies (n = 5), case reports (n = 2), case series (n = 1), and experimental study (n = 1). The prevalence of gastroesophageal reflux disease and its extraesophageal manifestations of laryngopharyngeal reflux in burning mouth patients was reported 3.39%–23.4% and 50%–93.8%, respectively, while oral burning was reported in 9%–45% of patients with gastroesophageal reflux disease. In case–control studies, gastroesophageal reflux disease was more prevalent in patients with burning mouth disorder compared with controls. Burning mouth would be resolved after antireflux therapy in laryngopharyngeal reflux patients in case series. PH value and saliva alternation might be the possible mechanisms.ConclusionThe possibility of the correlation between burning mouth disorder and gastroesophageal reflux disease still needs to be clearly demonstrated through better‐conducted studies. The link between them is worth to be explored in future research.

Usefulness of pepsin saliva measurement for the detection of primary burning mouth syndrome related to reflux.

To study the diagnostic value of salivary pepsin tests for detecting laryngopharyngeal reflux (LPR) in patients with primary burning mouth syndrome (BMS). Patients with BMS and asymptomatic individuals were consecutively recruited from September 2018 to June 2023. Patients underwent hypopharyngeal-esophageal impedance pH-monitoring (HEMII-pH) and saliva collections to measure pepsin. Stomatology evaluation was carried out to exclude other causes of BMS. Oral, pharyngeal and laryngeal signs and symptoms were evaluated with Reflux Sign Assessment (RSA) and Reflux Symptom Score (RSS). Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values of pepsin test were calculated considering the highest values of pepsin tests at ≥ 16, ≥ 36, and ≥ 100ng/mL cutoffs. Receiver operating characteristic curve (ROC) was evaluated. Forty-nine patients with both BMS and LPR at the HEMII-pH and 21 asymptomatic individuals were recruited. Pepsin test was 83.7%, 79.6%, and 71.4% sensitive at cutoffs ≥ 16, ≥ 36, and ≥ 100ng/mL, respectively. The ROC analysis reported that a threshold of ≥ 21.5ng/mL was associated with sensitivity, specificity, PPV and NPV of 81.6%, 81.0%, 90.1% and 65.4%, respectively. The severity score of burning mouth symptom was significantly associated with the saliva pepsin concentration (rs = 0.263; p = 0.029) and the oral RSA (rs = 0.474; p = 0.007). Pepsin test is a valuable diagnostic approach for detecting LPR in patients with BMS. Patients with high level of saliva pepsin reported more severe burning mouth symptoms. Future studies are needed to confirm the role of LPR in the primary BMS.

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.

Characteristics of Laryngopharyngeal Reflux in Patients with Chronic Cough Induced by Gastroesophageal Reflux Disease.

Objective: To summarize the characteristics of laryngopharyngeal reflux in patients with chronic cough induced by gastroesophageal reflux disease (GERD). Materials and Methods: The clinical data of patients with chronic cough induced by GERD treated at our hospital were retrospectively analyzed, including their reflux symptom index (RSI), reflux finding scores (RFS), and results of oropharyngeal pH monitoring. Results: There were 44 patients in total, including 21 males and 23 females. The average history of chronic cough was 29.60 (29.60 ± 37.60) months. In addition to coughing, all patients had at least 2 symptoms of laryngopharyngeal reflux disease (LPRD), and their RSI averaged 15.66 (15.66 ± 6.33). The most frequent symptoms were cough, throat clearing, excessive phlegm, or postnasal drip. All patients had LPRD signs, with an average RFS of 10.89 (10.89 ± 2.81). The most frequent signs were erythema or hyperemia/vocal cord edema, posterior commissure hypertrophy, and diffuse laryngeal edema. There were 42 patients (42/44, 95.45%) whose RSI and/or RFS were abnormal. Oropharyngeal pH monitoring identified 10 patients (10/44, 22.72%) with abnormal Ryan scores. Conclusions: All patients with chronic cough induced by GERD had symptoms and signs of LPRD, and most of them had an abnormal RSI and/or RFS and could be diagnosed with suspect LPRD. A part of the patients had LPR episodes according to Dx-pH monitoring, most of which occurred in the upright position. These results indicated that most patients with chronic cough induced by GERD may have suspected LPRD simultaneously and that cough was one of their LPRD symptoms.

Laryngopharyngeal Reflux Patient Changes during the COVID-19 Quarantine.

Background and Objective: To examine the effects of the lockdown on diet adherence and stress levels in patients with laryngopharyngeal reflux (LPR). Materials and Methods: Patients with a positive LPR diagnosis at the hypopharyngeal-esophageal impedance-pH monitoring were treated from a pre- to lockdown period with a 3-month high-protein, low-fat, alkaline, plant-based diet, with behavioral changes, and an association of pantoprazole (20 MG/d) and alginate (Gaviscon 3/d). The following patient-reported outcomes questionnaire and findings instrument were used: Reflux Symptom Score-12 (RSS-12) and Reflux Sign Assessment (RSA). At the posttreatment time, patients were invited to evaluate the impact of lockdown on diet adherence and stress management with a predefined grid of foods and beverages and the perceived stress scale (PSS), respectively. Results: Thirty-two patients completed the evaluations. RSS-12 and RSA significantly improved from baseline to 3-month posttreatment. Most patients experienced mild-to-severe stress levels at the end of the lockdown. The level of stress substantially increased in 11 patients (34%) due to the lockdown, while it did not change in 11 patients (44%). In 11 cases (34%), patients reported that the adherence to the anti-reflux diet was better than initially presumed thanks to the lockdown period, while 44% (N = 14) reported that the lockdown did not impact the adherence to a diet. PSS and RSS-12 were significantly correlated at the end of the pandemic (rs = 0.681; p < 0.001). The increase in stress level was positively associated with the lack of adherence to diet (rs = 0.367; p = 0.039). Conclusions: During the lockdown, the diet habits of LPR patients were improved in one-third and unchanged in 44% of cases. The stress level was increased in one-third of patients, which was associated with an increase in symptom scores.

Effect of positive airway pressure compliance on laryngopharyngeal reflux in obstructive sleep apnea patients

ObjectivesTo determine the effect of continuous positive airway pressure (CPAP) compliance on symptoms and signs of laryngopharyngeal reflux (LPR) in patients with obstructive sleep apnea (OSA).ResultsThirty patients were included. The participants were divided into good compliance (n = 21) and poor compliance (n = 9) groups. After 6-month CPAP treatment, the reflux symptom index score significantly decreased in both the good compliance group (20 (17,24) vs. 14 (10,18), p < 0.001) and the poor compliance group (21 (18,25) vs. 10 (5,16), p < 0.05). Reflux finding score was significantly reduced in both the good compliance group (8 (6,9) vs. 4 (3,5), p < 0.001) and the poor compliance group (6 (4,8) vs. 3 (2,4), p < 0.05). However, there were no statistically significant differences between the groups. CPAP treatment reduces the symptoms and signs of LPR. However, CPAP compliance does not correlate with improvement in LPR in patients with OSA.

A preliminary study on salivary microbiota of patients with laryngopharyngeal reflux

Objective: To investigate the characteristics of salivary microbiota in patients with laryngopharyngeal reflux (LPR). Methods: A case-control study was applied to enroll 60 patients and healthy subjects who were outpatients of the Department of Otorhinolaryngology Head and Neck Surgery of the Eighth Medical Center of the PLA General Hospital from December 2020 to March 2021, including 35 males and 25 females, aged from 21 to 80 (33.75±11.10) years. Thirty patients with suspected laryngopharyngeal reflux were selected as study group and thirty healthy volunteers without pharyngeal symptoms were selected as control group. Their salivary samples were collected, and the salivary microbiota was detected and analyzed by 16S rDNA sequencing. SPSS 18.0 software was used for statistical analysis. Results: There was no significant difference in the diversity of salivary microbiota between the two groups. At the phylum classification level, the relative abundance of Bacteroidetes in the study group was higher than that in the control group[37.86(31.15, 41.54)% vs 30.24(25.51, 34.18)%,Z=-3.46,P<0.01]. And the relative abundance of Proteobacteria in the study group was lower than that in the control group [15.76(11.81, 20.17)% vs 20.63(13.98, 28.82)%, Z=-1.98,P<0.05]. At the genus level, the relative abundance of Prevotella, Lactobacillus, Parascardovia and Sphingobium in the study group was higher than that in the control group(Z values were-2.92, -2.69, -2.05, -2.31, respectively, P<0.05).And the relative abundance of Streptococcus, Cardiobacterium, Klebsiella and Uruburuella of study group was lower than that of control group(Z values were -2.43, -2.32, -2.17, -2.32, respectively, P<0.05). LEfSe difference analysis showed that there were 39 bacteria with significant differences between the two groups, including Bacteroidetes, Prevotellaceae and Prevotella, which were enriched in the study group, and Streptococcaceae, Streptococcus and other taxa, which were enriched in the control group(P<0.05). Conclusion: The changes of the microflora in the saliva between LPR patients and healthy people suggest that the dysbacteriosis might exist in LPR patients, which may play an important role in the pathogenesis and development of LPR.

Inflammation and Dry Eye-like Symptoms as Concomitant Manifestations of Laryngo-Pharyngeal Reflux

Purpose Laryngopharyngeal reflux (LPR) is a common worldwide disease. LPR symptoms may involve distant organs and tissues including the ocular surface with manifestations of a Dry Eye-like disease. We evaluated the concomitant involvement of the ocular surface in patients with LPR. We also defined the clinical signs and the roles of chemical and neuro-inflammatory mediators in the tears of LPR patients. Methods Seventy-seven patients with LPR (mean age 65.8 ± 16.8 SD) and 25 healthy controls (mean age 56.5 ± 16.3 SD) were recruited from the otorhinolaryngology unit. Each subject was evaluated for the presence of concomitant ocular surface disease through clinical examination, including the measurement of tear break-up time (TBUT) and the Ocular Surface Disease Index (OSDI) questionnaire. Tears and conjunctival imprints were collected. The presence of pepsin in tears was detected by ELISA. HLA-DR in conjunctival imprints were imaged by immunofluorescence microscopy. RT-PCR quantified conjunctival mRNA transcripts of HLA-DR, IL-8, MUC5AC, NADPH, VIP, and NPY. Results Patients with LPR had significantly increased OSDI and reduced TBUT scores compared to control subjects (p < 0.05 each). Pepsin was detected in 51% of patient tears while it was not measurable in the controls (p < 0.01). Immunoreactivity for HLA-DR in the conjunctival impressions was greater than for the controls with an increased mRNA expression (p < 0.05). mRNA transcripts for IL-8, NADPH, and VIP were significantly increased in LPR patients (p < 0.05 each), but neither MUC5AC nor NPY was different from controls. Conclusions LPR can adversely affect the ocular surface, leading to moderate signs and symptoms of dry eye. This study provides evidence that the presence of pepsin, HLA-DR immunoreactivity, and increased mRNA expression of neuro-inflammatory markers in the tears and conjunctival imprints of LPR patients suggests a potential link between LPR inflammation and ocular surface disease.

Saliva pepsin measurements in the detection of gastroesophageal reflux disease in laryngopharyngeal reflux patients: a cohort study.

To study the diagnostic value of salivary pepsin measurement (Peptest) for detecting gastroesophageal reflux disease (GERD) in laryngopharyngeal reflux (LPR) patients. Patients with reflux symptoms were consecutively recruited from January 2020 to November 2022. Patients benefited from hypopharyngeal-esophageal impedance-pH monitoring (HEMII-pH), fasting and bedtime saliva collections to measure pepsin. Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values were evaluated for GERD and LPR patients considering the highest values of pepsin tests at ≥ 16, ≥ 75, and ≥ 216ng/mL cutoffs. The relationship between HEMII-pH, endoscopic and clinical findings, and pepsin measurements was studied. Saliva was collected in 109 LPR patients and 30 individuals with both LPR and GERD. The total number of pharyngeal reflux events was significantly higher in GERD-LPR patients compared with LPR patients (p = 0.008). The mean fasting and bedtime pepsin saliva concentrations were similar between groups. The sensitivity of Peptest in LPR patients was 30.5%, 70.2%, and 84.0% at cutoffs ≥ 16, ≥ 75 and ≥ 216ng/mL. In GERD-LPR group, Peptest was 80.0%, 70.0%, and 30.0% sensitive. At cutoff 16ng/mL, Peptest reported PPV of 20.7% and 94.8% in LPR-GERD and LPR groups, respectively. NPV were 73.9% and 8.7% in GERD-LPR and LPR groups, respectively. The consistency analysis between Peptest and HEMII-pH was not significant. Peptest was significantly associated with the number of acid pharyngeal reflux events (rs = 0.182; p = 0.032). Pepsin saliva measurements appear to be not a reliable diagnostic tool for the detection of GERD in LPR patients. Future studies are needed to determine the place of Peptest in laryngopharyngeal reflux and gastroesophageal reflux diseases.

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.

Increased Sensitivity of Cough Reflex is Not the Mechanism of Cough Attributed to Laryngopharyngeal Reflux

In laryngopharyngeal reflux (LPR) patients acid reaches laryngopharyngeal area and stimulates/sensitizes respiratory nerve terminals mediating cough. We addressed several hypothesis: if stimulation of respiratory nerves is responsible for coughing then acidic LPR should correlate with coughing and proton pump inhibitor (PPI) treatment should reduce both LPR and coughing. If sensitization of respiratory nerves is responsible for coughing then cough sensitivity should correlate with coughing and PPI should reduce both coughing and cough sensitivity. In this prospective single center study, patients with positive reflux symptom index (RSI > 13) and/or reflux finding score (RFS > 7) and ≥1 LPR episode/24 hours were enrolled. We evaluated LPR by dual channel 24-hour pH/impedance. We determined number of LPR events with pH drop at levels 6.0, 5.5, 5.0, 4.5, and 4.0. Cough reflex sensitivity was determined as lowest capsaicin concentration causing at least 2/5 coughs (C2/C5) by single breath capsaicin inhalation challenge. For statistical analysis C2/C5 values were -log transformed. Troublesome coughing was evaluated on the scale 0-5. We enrolled 27 LPR patients. The number of LPR events with pH 6.0, 5.5, 5.0, 4.5, and 4.0 was 14[8-23],4[2-6],1[1-3],1[0-2] and 0[0-1], respectively. There was no correlation between number of LPR episodes at any pH level and coughing (Pearson range -0.34 to 0.21, P = NS). There was no correlation between cough reflex sensitivity C2/C5 and coughing (R = -0.29 to 0.34, P = NS). Of patients that completed PPI treatment, 11 had RSI normalized (18.36 ± 2.75 vs. 7 ± 1.35, P < 0.01). There was no change in cough reflex sensitivity in PPI-responders. C2 threshold was 1.41 ± 0.19 vs. 1.2 ± 0.19 (P = 0.11) before and after PPI. No correlation between cough sensitivity and coughing and no change in cough sensitivity despite improvement of coughing by PPI argue that an increased cough reflex sensitivity is not mechanism of cough in LPR. We identified no simple relationship between LPR and coughing suggesting that this relationship is more complex.

To Determine the Prevalence of Laryngopharyngeal Reflux in Patients of Various Throat Disorders and to Evaluate the Efficacy of Anti-reflux Therapy.

To study the prevalence of Laryngopharyngeal reflux in individuals having throat complaints by applying the Reflux Symptom Index and Reflux finding score as a prognostic tool after anti reflux therapy. Materials and Methods: A Cross-sectional study of 75 patients of age 18years and above with clinical diagnosis of Laryngopharyngeal reflux was conducted in ENT. Cases were examined with detailed history and thorough examination with indirect laryngoscopy and Hopkins 70 degree endoscope. Symptoms and findings of patients were assessed by Belafsky Reflux Symptom Index and Reflux Finding Score. Patients presenting Belafsky Reflux Symptom Index > 13 and also Reflux Finding Score > 7 were classified as having Laryngopharyngeal reflux. After 6weeks of treatment, patients were reassessed and Reflux Symptom Index and Reflux finding score were calculated. Results: The mean age of the study subjects was 37.12 ± 12.39years. Most common symptom reported based on RSI questionnaire was excessive throat mucus (81.33%) followed by clearing of throat (75%) and coughing on lying down and heartburn. Based on the Laryngoscopy, about 57.33% had thick endolarygeal mucus, 56% had diffuse erythema, 45.33% had granulations and 29.33% had subglottic edema. Based on the reflux symptom scores, we found 53.33% and 80% of patients based on reflux findings score to have Laryngopharyngeal Reflux. The mean Reflux Symptom Index scores were 16.25 ± 5.53 and 10.73 ± 4.40 and also the mean Reflux Finding scores were 13.81 ± 2.42 and 6.61 ± 2.16 respectively before and after the treatment which was statistically significant.

Variability and accuracy of multiple saliva pepsin measurements in laryngopharyngeal reflux patients

ObjectiveTo study the variability and diagnostic value of multiple salivary pepsin measurements in the detection of laryngopharyngeal reflux (LPR).MethodsPatients with LPR symptoms were consecutively recruited from December 2019 to Augustus 2022. Twenty-one asymptomatic individuals completed the study. The diagnostic was confirmed with hypopharyngeal–esophageal impedance-pH monitoring (HEMII-pH). Patients collected three saliva samples during the 24-h testing period. Symptoms and findings were studied with reflux symptom score-12 and reflux sign assessment. Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values of pepsin measurements were calculated considering morning, post-lunch and post-dinner samples. The consistency and relationship between HEMII-pH, pepsin measurements, and clinical features were investigated.ResultsMorning, post-lunch and post-dinner saliva pepsin concentrations were measured in 42 patients. Pepsin measurements were 64.9%, 59.5%, and 59.0% sensitive for morning, post-lunch and post-dinner collections at cutoff ≥ 16 ng/mL. Considering the highest concentration of the three pepsin saliva collections, the accuracy, sensitivity, specificity and PPV were 70.5%, 73.0%; 66.7% and 78.9%, respectively. Morning pepsin measurements reported higher consistency, sensitivity, and specificity than post-dinner and post-lunch pepsin measurements.ConclusionThe collection of several saliva pepsin samples improves the detection rate of LPR. In case of high clinical LPR suspicion and negative pepsin test, a HEMII-pH study could provide further diagnostic information.

The key timing of pharyngeal reflux in patients with laryngopharyngeal reflux

ObjectiveTo analyze the incidence of pharyngeal reflux in laryngopharyngeal reflux patients over a 24-hour period and find out the key timing of pharyngeal reflux. MethodsWe reviewed 69 patients who visited our clinic with LPR-related symptoms and were proven to have pharyngeal reflux via 24‐hour multichannel intraluminal impedance‐pH (24hr MII‐pH) monitoring. Quantitative analysis was conducted for the LPR profiles, such as the acidity of reflux, nighttime reflux, and positional reflux. The time series of pharyngeal reflux episodes and mealtimes were analyzed over a 24-hour period. Also, we recruited 26 normal controls. We compared the timing of pharyngeal reflux between LPR patients and asymptomatic controls. ResultsThe quantitative analysis revealed that pharyngeal reflux occurred 4.88 ± 4.59 times over 24 hours. Weakly acidic pharyngeal reflux was more abundant than acidic or weakly alkaline reflux. Pharyngeal reflux occurred mainly during daytime in the upright position. The most frequent timing of pharyngeal reflux episodes was within 2 hours after meals. Additionally, there was no significant difference of the timing of post-prandial reflux between LPR patients and asymptomatic controls. ConclusionThe key timing of pharyngeal reflux in patients with LPR was post-prandial 2 hours.