Chronic Laryngeal Symptoms Research Articles

Validated Clinical Score to Predict Gastroesophageal Reflux in Patients With Chronic Laryngeal Symptoms: COuGH RefluX

Background & AimsDiscerning whether laryngeal symptoms result from gastroesophageal reflux is clinically challenging and a reliable tool to stratify patients is needed. We aimed to develop and validate a model to predict likelihood of gastroesophageal reflux disease (GERD) among patients with chronic laryngeal symptoms. MethodsThis multicenter international study collected data from adults with chronic laryngeal symptoms that underwent objective testing (upper GI endoscopy and/or ambulatory reflux monitoring) between 3/2018-5/2023. The training phase identified a model with optimal receiver operating characteristic curves, and beta coefficients informed a weighted model. The validation phase assessed performance characteristics of the weighted model. Results856 adults, 304 in training cohort and 552 in the validation cohort, were included. In the training phase the optimal predictive model [AUC 0.68 (95% CI 0.62, 0.74)] - the COuGH RefluX score - consisted of Cough, Overweight/obesity, Globus, Hiatal Hernia, Regurgitation, and male seX with a lower threshold of 2.5 and upper threshold of 5.0 to predict proven GERD. In the validation phase, the COuGH RefluX score had an AUC of 0.67 (0.62, 0.71) with 79% sensitivity and 81% specificity for proven GERD. ConclusionsThe externally validated COuGH RefluX score is a clinically practical model to predict likelihood of proven GERD. The score classifies most patients with chronic laryngeal symptoms as low/high likelihood of proven GERD, with only 38% remaining as indeterminate. Thus, the COuGH RefluX score can guide diagnostic strategies and reduce inappropriate proton pump inhibitor use or testing for patients referred for evaluation of chronic laryngeal symptoms.

Validation of the Laryngeal Cognitive-Affective Tool

Background and AimsCognitive-affective processes, including hypervigilance and symptom-specific anxiety, may contribute to chronic laryngeal symptoms and are potentially modifiable; however, a validated instrument to assess these constructs is lacking. The aims of this study were to develop and validate the Laryngeal Cognitive-Affective Tool (LCAT) instrument. MethodsThis two-phase single-center prospective study enrolled participants from 11/2021 to 6/2023. In the initial phase 1:1 patient cognitive interviews and multidisciplinary team consensus were conducted to develop the LCAT. In the second phase asymptomatic and symptomatic participants completed a series of questionnaires to examine psychometric properties of the LCAT. Results268 participants were included: 8 in the initial phase and 260 in the validation phase (56 asymptomatic; 204 symptomatic). A 15-item LCAT was developed. In the validation phase, mean total LCAT and hypervigilance/anxiety sub-scores were significantly higher in symptomatic vs asymptomatic participants (p<0.01). The LCAT had excellent internal consistency (α=0.942) and split-half reliability (Guttman=0.853). Using a median split, a score of 33 or greater was defined as elevated. ConclusionsThe 15-item LCAT evaluates laryngeal hypervigilance and symptom-specific anxiety among patients with laryngeal symptoms. It has excellent reliability and construct validity. The LCAT highlights burdensome cognitive-affective processes which can accordingly help tailor treatments.

High Diagnostic Yield of Abnormal Endoscopic Findings in the Evaluation of Laryngopharyngeal Reflux

Esophagogastroduodenoscopy (EGD) is recommended in patients with typical gastroesophageal reflux disease (GERD) symptoms (heartburn, regurgitation, chest pain) in the setting of proton pump inhibitor (PPI) nonresponse. EGD evaluates for erosive disease, assesses antireflux barrier integrity, excludes non-GERD conditions, and, in the absence of erosive findings, is followed by reflux testing.1,2 The diagnostic utility of EGD is less clear in the evaluation for laryngopharyngeal reflux (LPR), and the current reference standard is ambulatory reflux monitoring.1,3,4 This study of patients referred for evaluation of chronic laryngeal symptoms had the following aims: (1) to characterize endoscopic findings, (2) to discern whether findings differed between patients with or without concomitant esophageal reflux symptoms, and (3) to measure the association between endoscopic findings and objective GERD on ambulatory reflux monitoring.

Review article: Diagnosis and management of laryngopharyngeal reflux.

Laryngopharyngeal reflux has classically referred to gastroesophageal reflux leading to chronic laryngeal symptoms such as throat clearing, dysphonia, cough, globus sensation, sore throat or mucus in the throat. Current lack of clear diagnostic criteria significantly impairs practitioners' ability to identify and manage laryngopharyngeal reflux. To discuss current evidence-based diagnostic and management strategies in patients with laryngopharyngeal reflux. We selected studies primarily based on current guidelines for gastroesophageal reflux disease and laryngopharyngeal reflux, and through PubMed searches. We assess the current diagnostic modalities that can be used to determine if laryngopharyngeal reflux is the cause of a patient's laryngeal symptoms, as well as review some of the common treatments that have been used for these patients. In addition, we note that the lack of a clear diagnostic gold-standard, as well as specific diagnostic criteria, significantly limit clinicians' ability to determine adequate therapies for these patients. Finally, we identify areas of future research that are needed to better manage these patients. Patients with chronic laryngeal symptoms are complex due to the heterogenous nature of symptom pathology, inconsistent definitions and variable response to therapies. Further outcomes data are critically needed to help elucidate ideal diagnostic workup and therapeutic management for these challenging patients.

Distinct Clinical Physiologic Phenotypes of Patients with Laryngeal Symptoms Referred for Reflux Evaluation

One third of adults experience laryngeal symptoms such as throat clearing and chronic cough and 50-80% of adults seeking care of these symptoms are told that laryngopharyngeal reflux (LPR) is the etiology. LPR results from retrograde flow of gastroduodenal contents to the larynx and pharynx; however, treatment of presumed LPR remains challenging with limited evidence-based guidance. This article summarizes the @GIJournal Twitter discussion of Yadlapati et al, “Distinct Clinical Physiologic Phenotypes of Patients with Laryngeal Symptoms Referred for Reflux Evaluation,” originally published in Clinical Gastroenterology and Hepatology. In this study of 302 patients with chronic laryngeal symptoms referred for reflux evaluation, five distinct phenotypic groups were described, and reflux was only present in two of the proposed phenotypes. LPR and GERD with hiatal hernia (group A); mild LPR/GERD (group B); no LPR/no GERD (group C); reflex cough (group D); and mixed/possible obstructive esophagogastric junction (EGJ) (group E). Phenotypic differences can inform targeted clinical trials design and improve outcomes.

Distinct Clinical Physiologic Phenotypes of Patients With Laryngeal Symptoms Referred for Reflux Evaluation

Heterogeneous presentations and disease mechanisms among patients with laryngeal symptoms account for misdiagnosis of laryngopharyngeal reflux (LPR), variations in testing, and suboptimal outcomes. We aimed to derive phenotypes of patients with laryngeal symptoms based on clinical and physiologic data and to compare characteristics across phenotypes. A total of 302 adult patients with chronic laryngeal symptoms were prospectively enrolled at 3 centers between January 2018 to October 2020 (age 57.2 ± 15.2 years; 30% male; body mass index 27.2 ± 6.0 kg/m2). Discriminant analysis of principal components (DAPC) was applied to 12 clinical and 11 physiologic variables collected in stable condition to derive phenotypic groups. DAPC identified 5 groups, with significant differences across symptoms, hiatal hernia size, and number of reflux events (P < .01). Group A had the greatest hiatal hernia size (3.1 ± 1.0 cm; P < .001) and reflux events (37.5 ± 51; P < .001), with frequent cough, laryngeal symptoms, heartburn, and regurgitation. Group B had the highest body mass index (28.2 ± 4.6 kg/m2; P < .001) and salivary pepsin (150 ± 157 ng/mL; P= .03), with frequent cough, laryngeal symptoms, globus, heartburn, and regurgitation. Group C frequently reported laryngeal symptoms (93%; P < .001), and had fewest esophageal symptoms (9.6%; P < .001) and reflux events (10.7 ± 11.0; P < .001). Group D commonly reported cough (88%; P < .001) and heartburn. Group E (18%) was oldest (62.9 ± 14.3 years; P < .001) and distinguished by highest integrated relaxation pressure. DAPC identified distinct clinicophysiologic phenotypes of patients with laryngeal symptoms referred for reflux evaluation: group A, LPR and gastroesophageal reflux disease (GERD) with hiatal hernia; group B, mild LPR/GERD; group C, no LPR/No GERD; group D, reflex cough; and group E, mixed/possible obstructive esophagogastric junction. Phenotypic differences may inform targeted clinical trials design and improve outcomes.

Usefulness of Pep-Test for Laryngo-Pharyngeal Reflux: A Pilot Study in Primary Care.

BackgroundGastroesophageal reflux disease is a digestive disorder characterized by nausea, regurgitation, and heartburn. Gastroesophageal reflux is the primary cause of laryngeal symptoms, especially chronic posterior laryngitis. The best diagnostic test for this disease is esophageal impedance-pH monitoring; however, it is poorly employed owing to its high cost and invasiveness. Salivary pepsin measured using a lateral flow device (Pep-test) has been suggested as an indirect marker of laryngopharyngeal reflux (LPR). The present study tested the reliability of Pep-test in diagnosing LPR in uninvestigated primary care attenders presenting with chronic laryngeal symptoms, and evaluated the raw pepsin concentration in patients with LPR.MethodsA multicenter, non-interventional pilot study was conducted on 86 suspected patients with LPR and 59 asymptomatic subjects as controls in three Italian primary care settings. A reflux symptom index questionnaire was used to differentiate patients with LPR (score >13) from controls (score <5). Two saliva samples were collected, and comparisons between the groups were performed using two-sided statistical tests, according to variable distributions.ResultsThere was no statistical difference in the salivary pepsin positivity between LPR patients and controls, whereas the pepsin intensity value was higher in controls than in LPR patients.ConclusionA high prevalence of pepsin positivity was observed in asymptomatic controls. Pepsin measurement should not be considered as a diagnostic test for LPR in primary care patients.

The Upper Esophageal Sphincter Assist Device Is Associated With Symptom Response in Reflux-Associated Laryngeal Symptoms

Reflux-associated laryngeal symptoms (RALS) is the process in which chronic laryngeal symptoms are related to gastroesophagopharyngeal reflux.1 Impairment of upper esophageal sphincter (UES) reflexes may predispose to esophagopharyngeal reflux.1 The novel noninvasive nonpharmacologic UES assist device (UESAD) applies external cricoid pressure to augment intraluminal UES pressure by 20 to 30 mm Hg and reduce esophagopharyngeal reflux events.2 This study aimed to assess the therapeutic efficacy of the UESAD in a pragmatic clinical setting, and to identify factors associated with symptom response among patients with suspected RALS.

Editorial: Reflux and Laryngeal Symptoms: A Sea of Confusion.

Chronic laryngeal symptoms are often attributed to gastroesophageal reflux disease based on nonspecific testing by laryngoscopy resulting in overdiagnosis of this condition. Identifying optimal means by which we can diagnose reflux in patients with chronic laryngeal symptoms is an unmet clinical area. One such technique might be measurement of oropharyngeal acid exposure employing a novel pH monitoring device. We outline the strengths and limitations of this new technology relative to the observational cohort study by Yadlapti et al. published in this issue of the Journal.

A study with pharyngeal and esophageal 24-hour pH-impedance monitoring in patients with laryngopharyngeal symptoms refractory to proton pump inhibitors.

The role of gastroesophageal reflux in chronic laryngeal symptoms is difficult to establish. The aim of this study was to characterize pharyngeal and esophageal pH-impedance reflux patterns in a group of patients with suspected laryngopharyngeal reflux and to determine predictive factors of response to proton pump inhibitors. Patients with chronic pharyngolaryngeal symptoms were evaluated with a symptom score questionnaire, laryngoscopy, and 24-hour pharyngeal and esophageal pH-impedance monitoring at baseline and after 8-week treatment with esomeprazole 40mg b.i.d. Response to treatment was defined by a diminution of more than 50% of the score for the primary symptom. Reflux patterns and baseline impedance values were compared to those obtained in 46 healthy subjects. Twenty-four patients were included (17 women, median age 54years), all previously refractory to antisecretory therapy. Symptom scores were 46 (32-62) and 40 (27-76) off and on therapy, respectively (P=.1). There was no significant difference between patients and controls for pH-impedance reflux parameters and baseline values off and on therapy in distal and proximal esophagus and in the pharynx. Median numbers of pharyngeal reflux were 0 and 0 off and on therapy, respectively. Only two patients were responders to treatment, both with excessive distal reflux but no pharyngeal reflux. Only one patient had abnormal pharyngeal reflux but did not respond to proton pump inhibitors. Patients with suspected laryngopharyngeal reflux refractory to therapy do not exhibit abnormal pharyngeal or esophageal pH-impedance reflux. In these patients, laryngopharyngeal reflux is unlikely.

Utility of Allergy Testing in Patients with Chronic Laryngopharyngeal Symptoms

To determine the utility of allergy evaluation in patients with chronic refractory laryngeal symptoms. Case series with chart review. Tertiary academic medical center. All patients who underwent in vitro allergy testing at a single institution from 2006 to 2010, for a total of 998 patients. Charts of patients who underwent in vitro allergy testing were identified. The charts were reviewed for the primary indication for allergy testing, as categorized into rhinitis complaints, chronic sinusitis, otitis media, and refractory laryngeal symptoms (globus, cough, throat clearing, increased secretions, and hoarseness). Results of allergy tests and comorbid conditions were analyzed and compared among groups. The positive yield of allergy testing in patients with primary laryngeal indications was 51.8%, 63.3% for rhinitis, 60.9% for sinusitis, and 33.3% for otitis media. The odds ratio of having a positive test was not statistically different for patients with laryngeal symptoms, rhinitis, or sinusitis. Patients with chronic laryngeal symptoms and positive allergy testing were most often sensitized to dust mites (63%) and least often sensitized to molds (1.3%). Allergy testing in patients with chronic laryngeal symptoms yields positive results in equivalent proportion to patients with other common presenting symptoms. Dust mites sensitization is the most common sensitization in patients with allergic laryngitis.

Responder Definition of a Patient-Reported Outcome Instrument for Laryngopharyngeal Reflux Based on the US FDA Guidance

BackgroundDifferent end-point measures may contribute to inconsistent therapeutic responses in relief of laryngopharyngeal reflux (LPR) symptoms. ObjectivesWe aimed to determine an a priori responder definition for a patient-reported outcome instrument, the Reflux Symptom Index (RSI), using an anchor-based method, to interpret individual treatment benefit in patients with LPR, on the basis of the US Food and Drug Administration guidance. MethodsPatients with chronic laryngeal symptoms suggestive of LPR underwent twice-daily 40 mg esomeprazole treatment for 12 weeks. We used a 50% or more reduction in the primary laryngeal symptom at week 12, an empirical criterion, as an anchor to dichotomize the participants into two groups, and to establish a responder definition of the RSI score change. The optimal cutoff point of the RSI score change was determined on the basis of the maximal Youden index of the receiver operating characteristic analysis. ResultsThe mean reduction in the RSI score was significantly greater in subjects with a 50% or more reduction in the primary laryngeal symptom than in those without (−11.0 ± 7.8 vs. −3.1 ± 8.3, P < 0.0001). A reduction of six points or more in the RSI score at week 12 was considered to be the responder definition with a sensitivity of 0.79 and a specificity of 0.70. ConclusionsWe propose an a priori responder definition derived from an empirical criterion according to the Food and Drug Administration guidance: a reduction of six points or more in the RSI score at week 12. This preliminary estimate provides a clinically meaningful change at an individual level, although additional studies and validations across various languages are required.

A Cross-sectional Analysis of the Prevalence of Barrett Esophagus in Otolaryngology Patients With Laryngeal Symptoms

Populations at risk for esophageal adenocarcinoma remain poorly defined. Laryngeal symptoms can be secondary to laryngopharyngeal reflux (LPR) and can occur without associated gastroesophageal reflux symptoms such as heartburn and regurgitation. We sought to determine the prevalence of Barrett esophagus (BE) in otolaryngology patients with laryngeal symptoms±typical gastroesophageal reflux disease (GERD) symptoms. We performed a cross-sectional study of otolaryngology clinic patients who reported laryngeal symptoms. Symptoms, medications, and exposure histories were obtained. Unsedated transnasal endoscopy was performed. Suspected BE was biopsied and confirmed histologically. Risk factors and prevalence of BE were assessed. Two hundred ninety-five patients were enrolled [73% male, median age 60 y (interquartile range 51 to 68 y)]. The overall prevalence of BE was 11.8% (n=33). Antisecretory medication use was present in 56% (n=156) of patients at enrollment. Compared with patients without BE, patients with BE were more likely to be male (P=0.01) and to report occupational lung injury (P=0.001). Duration, but not severity of laryngeal symptoms, significantly increased the odds of BE (odds ratio, 5.64; 95% confidence interval, 1.28-24.83; for a duration of symptoms >5 y). Of patients with BE, 58% (n=19) had coexisting LPR and GERD symptoms and 30% (n=10) had only LPR symptoms. Presence and size of hiatal hernia and length of columnar-lined esophagus were significant risk factors for BE. Long-standing laryngeal symptoms are associated with the presence of BE in otolaryngology patients. Patients with chronic laryngeal symptoms and no identifiable ear, nose, or throat etiology for those symptoms may benefit from endoscopic screening regardless of whether typical GERD symptoms are present.

Oropharyngeal pH Monitoring for Laryngopharyngeal Reflux: Is It a Reliable Test Before Therapy?

Current methods of measuring pharyngeal pH are problematic. The aim of the study was to assess the ability of the oropharyngeal pH monitoring (Restech) in predicting the response to proton pump inhibitor (PPI) therapy in patients with gastroesophageal reflux disease-related laryngopharyngeal symptoms. The study design is prospective and uncontrolled. Twenty-two consecutive naive patients with chronic laryngeal symptoms were enrolled. Reflux symptom index, fibrolaryngoscopy, and 24-hour oropharyngeal pH monitoring were performed. Both patients and laryngoscopist were blinded by the results of Restech. All the patients were given a 3-month therapy with pantoprazole of 40mg twice a day and then repeated both the reflux symptom index and fibrolaryngoscopic evaluation. Patients were considered as responders if a five-point decrease in symptom score was recorded. Thirteen of the 22 patients (59.1%) responded to therapy. Laryngoscopic findings did not correlate with the clinical improvement after the 3 months of PPI. Nine patients (40.9%) had a pathologic Restech study, and all resulted responsive to PPI; nine patients (40.9%) with a negative Restech were nonresponsive to PPI, and four patients (18.2%) despite a negative Restech resulted responsive to therapy. Responsive patients showed both a higher oropharyngeal acid exposure in orthostatic position and a higher Ryan score, compared with nonresponders (49.74±58.11 vs 2.12±0.0, P=0.002). Considering responsiveness to medical therapy as the gold standard of laryngopharyngeal reflux (LPR) for the diagnosis of LPR, Restech showed a sensitivity of 69% and a specificity of 100%. The high specificity and reasonable sensitivity of this technique make the Restech an interesting tool before therapy of patients with pharyngoesophageal reflux.

Role of Rhinitis in Laryngitis: Another Dimension of the Unified Airway

We evaluated the prevalence of dysphonia and secondary laryngeal symptoms among patients with allergic rhinitis (AR), nonallergic rhinitis (NAR), and no rhinitis symptoms (controls). Patients with rhinitis symptoms with positive and negative allergy tests were recruited from allergy clinics, and patients without rhinitis symptoms were recruited from an orthopedic clinic. All groups completed the Voice-Related Quality of Life survey (VRQOL),the mini-Rhinoconjunctivitis Quality of Life Questionnaire (mini-RQLQ), and the Reflux Symptom Index (RSI). Completing the study were 134 patients with AR, 54 patients with NAR, and 62 controls. Both AR and NAR patients had an increased prevalence of dysphonia compared to controls (32.8% and 26.9% versus 8.1%, respectively; p = 0.001). When we controlled for confounding variables such as asthma, inhaled steroid use, and gastroesophageal reflux, patients with either AR or NAR had higher odds of dysphonia (odds ratio, 4.22; 95% confidence interval, 1.03 to 17.32). Patients with worse mini-RQLQ scores had lower VRQOL scores and higher RSI scores (Spearman correlation of -0.47 and p < 0.001 and Spearman correlation of 0.6 and p <0.001, respectively). Patients with rhinitis (AR or NAR) had a higher prevalence of dysphonia than did controls. Patients with worse rhinitis symptoms had worse voice-related quality of life and more severe chronic laryngeal symptoms.

Chronic Laryngeal Symptoms in Patients with GERD

Epidemiological studies consistently show a strong association between laryngeal symptoms and gastroesophageal reflux disease. Studies of proton-pump

Patients with Throat Symptoms on Acid Suppressive Therapy: Do They Have Reflux?

The aim of this study was to characterize the reflux events in patients with laryngeal symptoms unresponsive to proton pump inhibitor (PPI) therapy. Gastroesophageal reflux disease (GERD) is commonly implicated as the cause of laryngeal symptoms. We retrospectively reviewed the pH/impedance records of 21 patients evaluated for persistent throat symptoms despite PPI therapy. They were compared to 30 others with typical reflux symptoms despite medication. Five of 21 (24%) patients in the "throat group" had normal reflux values, 13 (62%) continued to have abnormal acid reflux, and three (14%) had abnormal nonacid reflux but normal acid reflux while on medication. These results did not differ from those with typical symptoms unresponsive to medication. In patients with chronic laryngeal symptoms despite PPI therapy, a substantial minority have no reflux at all, but the majority have abnormal amounts of acid reflux despite their taking PPI medication.

Poor Correlation Between Reflux Esophagitis and Laryngeal Lesions

Proton-pump inhibitors were not beneficial for patients with chronic laryngeal symptoms in two placebo-controlled randomized trials published last year (Journal Watch Sep 28 2006). This new study raises additional questions about the diagnosis of reflux laryngitis. Swiss researchers videotaped the laryngopharyngeal …

Effect of PPI Therapy on Symptom Association Using Four-Day Bravo pH Recordings Combining 48 Hour Periods Off and on PPI

Purpose: Controversy exists as to whether pH studies are best done off or on PPI therapy. Off therapy testing maximizes the yield of symptom association while on therapy testing evaluates the efficacy of therapy in normalizing esophageal acid exposure. The aim of this study was to determine the effect of PPI on symptom association using 4-day pH recordings that encompassed 2 day periods before and during PPI therapy. Methods: 15 patients underwent 4-day Bravo pH recordings (2 day off; 2 day on) using 2 separate receivers calibrated to a single Bravo capsule. Indications for pH testing were refractory heartburn, chest pain, and chronic laryngeal symptoms. Patients were off PPI therapy for days 1 and 2. Omeprazole/Na bicarbonate 40 mg PO BID was administered on days 3 and 4. Symptom association was measured by both the symptom index (SI) and Symptom Association Probability (SAP). Results: Off therapy, 7 patients (58%) had esophageal acid exposure values exceeding 5.3%. 6 patients had abnormal pH exposure only on day 1 and 1 patient only on Day 2. 3 patients were excluded from the study due to premature detachment or malfunction. On therapy, all patients showed significant and progressive reductions is esophageal acid exposure (Figure, p < 0.01). By day 4, all patients had normal esophgeal acid exposure values. 5 patients had complete symptom resolution by day 4; the remaining 6 patients continued to experience symptoms while on PPI therapy. Both the SI and SAP significantly decreased during the on therapy compared with off therapy recording period (p < 0.05).Figure 1Conclusions: (1) Prolonged 96 hour esophageal pH recordings using the Bravo system are feasible and allow for combined testing both off and on therapeutic trial of PPI. (2) Yield of symptom association indices are significantly diminished with PPI therapy. (3) 96 hour pH studies allow for acquisition of information useful in the evalulation of refractory and atypical reflux symptoms. [figure 1]