Perspectives in Laryngopharyngeal Reflux: An International Survey

Objectives Although data exists to support the relationship between laryngopharyngeal reflux (LPR) and laryngitis, there is variability among otolaryngologists regarding the methods and criteria used to make the diagnosis. This study was undertaken to discern the current attitudes and practices of a select cohort of otolaryngologists in regards to LPR. Methods Four hundred fifteen surveys were mailed to members of the American Broncho‐Esophagological Association. Survey recipients were asked to rate patient symptomatology and physical examination findings in terms of their relationship to LPR and their preferred laryngeal visualization procedure in terms of clinical use and diagnostic accuracy. The role and validity of adjunctive diagnostic tests were also surveyed. Results Survey response rate was 38%. Symptoms felt to be most related to reflux were: throat clearing (98.3%), persistent cough (96.6%), heartburn/dyspepsia (95.7%), globus sensation (94.9%), and voice quality change (94.9%). The physical examination findings felt to be most related to reflux included: arytenoid erythema (97.5%), vocal cord erythema (95.7%) and edema (95.7%), posterior commissure hypertrophy (94.9%), and arytenoid edema (94.0%). Fiberoptic laryngoscopy was the most commonly performed diagnostic visualization procedure (75.7%) and was also considered to be most sensitive and specific (45.0%). The most commonly ordered adjunctive test was a double pH probe (37.2%), which was also felt to be the most sensitive and specific adjunctive test (75.9%). Conclusion A polling of a select group of otolaryngologists demonstrated agreement in the criteria used to diagnose reflux laryngitis, although some variability exists. The development of objective guidelines for the diagnosis of LPR is a critical initial step toward evaluating the manifestations and therapeutic interventions for this disease process.     

Direct nasopharyngeal reflux of gastric acid is a contributing factor in refractory chronic rhinosinusitis

OBJECTIVES/HYPOTHESIS: To determine whether there is a difference in the prevalence of reflux in patients with refractory chronic rhinosinusitis (CRS) compared with control patients, including whether direct nasopharyngeal reflux (NPR) occurs in CRS patients. It is hypothesized that refractory CRS patients have a greater incidence of laryngopharyngeal reflux and NPR events and that NPR is a significant etiologic factor for CRS in these patients. STUDY DESIGN: Prospective study. METHODS: The study group consisted of 38 patients with a history of at least one endoscopic sinus surgery (ESS) with continued CRS symptoms and mucosal inflammation on endoscopy. The first control group consisted of 10 patients who had at least one ESS procedure and had no symptoms of CRS or mucosal inflammation a minimum of 1 year postoperatively. The second control group consisted of 20 subjects with no history of CRS or sinus surgery. All patients completed reflux symptom scales, a 20 item sinonasal outcome test, and a sinusitis symptom scale and underwent nasal endoscopy to grade the nasal mucosal findings. Patients underwent a 24 hour pH study with a specially designed probe with sensors located in the nasopharynx, 1 cm above the upper esophageal sphincter (UES), and the distal esophagus. The pH recordings were evaluated for NPR events less than pH 4 and 5. Reflux at the UES probe was considered pathologic if there were more than 6.9 episodes for the entire study or the reflux area index (RAI) exceeded 6.3. Esophageal reflux was defined as abnormal if greater than 4% of the study time was spent at pH less than 4. Statistical analysis was performed with Fisher's exact test to compare the reflux parameters and with analysis of variance and Tukey's post hoc analysis for the symptom and examination scores. RESULTS: No statistical difference was found between the two control groups for any parameters at any sites. When a single outlier was dropped from the nonCRS control group, less NPR was found in the nonCRS group compared with the successful ESS control group (P = .03). Because these groups were statistically homogenous, they were collapsed into a single control group. Compared with the control group, the study group had significantly more patients with NPR events pH less than 4 (39% vs. 7%, P = .004) and an even greater difference in the number of patients with NPR events pH less than 5 (76% vs. 24%, P = .00003). At the UES, 74% of the study group had greater than 6.9 reflux episodes, compared with 38% of control patients (P = .006). The UES RAI was abnormal for 58% of the study group compared with 21% of the control group (P = .007). The study group also had more gastroesophageal reflux (66% vs. 31%, P = .007). For nasopharynx and UES reflux parameters, the differences between study and control groups increased when the patients with isolated frontal recess disease were removed from the dataset. The study group also had higher scores on all symptom and examination scores (P = .001 for each scale). CONCLUSIONS: Patients with persistent CRS after ESS have more reflux at the nasopharynx, UES, and distal esophagus than controls. The greatest difference is in NPR, especially pH less than 5. This is the first study to document NPR in CRS patients, and it is likely to represent an important causative factor of refractory CRS in adults.     

Nissen fundoplication surgery for extraesophageal manifestations of gastroesophageal reflux (EER)

OBJECTIVE: To determine the outcome of Nissen fundoplication surgery for the treatment of patients with chronic extraesophageal manifestations of reflux (EER). METHODS: A retrospective medical record analysis was performed. Patient demographics, extraesophageal disease secondary to gastroesophageal reflux (GER), methods of GER diagnosis, acid suppression therapy before antireflux surgery, and response to surgical intervention were evaluated. RESULTS: The charts of 29 patients who underwent Nissen fundoplication surgery for EER were included in the study. Hoarseness was present in 17 patients; laryngopharyngeal reflux (LPR) was the most common diagnosis (n = 20). Barium esophagram was done in all patients and revealed abnormalities indicative of GER in 26 patients. Twenty-four-hour ambulatory pH study was done in 27 patients and pharyngeal reflux was present in 19. Preoperative esophageal endoscopy was performed in 22 patients. This study revealed evidence of gastroesophageal reflux disease (GERD) in 14 patients with 8 having evidence of Barrett's esophagus. Sixteen of the 29 patients had symptoms or findings of GERD. Twenty-eight patients had laparoscopic Nissen fundoplication (LNF) and 1 had an open procedure. Twenty-five of the 29 patients (follow-up ranging from 6-108 mo) had excellent results with near-total freedom from symptoms and are taking no acid-suppressive medications. CONCLUSIONS: GER has an important role in the cause of many otolaryngologic and pulmonary disorders. Nissen fundoplication is an effective modality to treat EER in selected cases.     

Pachydermia is not diagnostic of active laryngopharyngeal reflux disease

OBJECTIVE: To determine the change in pachydermia/posterior commissure hypertrophy in patients with laryngopharyngeal reflux disease (LPR) on long-term acid-suppressive therapy. STUDY DESIGN: Retrospective chart review. METHODS: Seventeen patients with LPR who were compliant with long-term acid-suppressive treatment and had good control of their symptoms for at least 20 months were examined. Pre- and posttreatment still laryngeal images from these patients were analyzed by five otolaryngologists blinded to patient information and were scored for pachydermia/posterior commissure hypertrophy according to the Reflux Finding Score (RFS) subset. Test-retest intraobserver reliability, intergrader correlations, as well as a paired t test for means of the data sets were then calculated. RESULTS: There was no significant difference in the grading scores between the pre- and posttreatment group for degree of pachydermia/posterior commissure hypertrophy despite a prolonged treatment interval (mean = 32 months) (P = .25). CONCLUSIONS: There is no statistically significant difference in the degree of pachydermia/posterior commissure hypertrophy found at diagnosis and after long-term acid suppressive therapy in patients with LPR. Therefore, it appears that pachydermia, as an isolated finding, is unreliable in determining the presence of active LPR.     

中国喉科医师应用反流体征评分量表的信度研究

目的评估中国喉科医师应用反流体征评分量表(reflux finding score,RFS)的信度。方法 2009-02-10～2009-04-30收集了在美国加州大学戴维斯分校医学中心耳鼻咽喉头颈外科嗓音和吞咽障碍诊疗中心就诊的喉疾病患者的喉镜图片50张。由中国医师李进让(作者本人)和RFS的设计者、美国喉科医师Peter C Belafsky分别分两次(间隔48h以上)对50张喉镜图片进行RFS双盲评分。之后应用统计学处理,进行组间和组内信度评估。结果中国喉科医师初次和第2次RFS评分的平均值分别为8.28±2.78和8.10±2.75,美国喉科医师的分别分8.20±2.77和7.84±3.13。中国喉科医师和美国喉科医师各次RFS评分的均值无统计学差异(P>0.05)。中国喉科医师和美国喉科医师2次RFS评分的相关系数分别为0.929和0.874。中国喉科医师和美国喉科医师第1次RFS评分的相关系数为0.703。我们把RFS≥7判定为异常,中国喉科医师和美国喉科医师的组内一致性分别为94%(κ=0.861,P<0.0001)和94%(κ=0.855,P<0.0001),组间一致性为88%(κ=0.663,P<0.0001)。结论中国喉科医师应用RFS对喉镜图片进行评分组内和组间有很好的一致性和重复性,说明中国喉科医师可以准确的应用RFS来进行咽喉反流性疾病患者的初筛。     

Reflux symptom index and reflux finding score in 91 asymptomatic volunteers

Background: The primary goal of this study was to investigating the symptoms, in addition to the reflux-related laryngopharynx inflammation performance of asymptomatic, volunteers, and verified the ‘normal point’.

Methods: A total of 91 asymptomatic subjects were recruited for this cross-sectional study between March 2016 and September 2016. Participants completed the reflux symptom index (RSI) assessment and underwent laryngostroboscopic examination using a rigid endoscope. Their RFS were graded according to the laryngeal findings. The distribution and the relationship of the RSI and the RFS were analyzed.

Results: The mean RSI of individuals was 2.24?±?2.34 [95% confidence interval (CI)?=?1.75, 2.72], and the mean RFS of individuals was 5.78?±?1.74 (95% CI?=?5.42, 6.15). The Pearson product–moment correlation coefficient of the RSI and RFS scores was –0.084 (n?=?91, p?=?.428).

Conclusions: Asymptomatic people could present relatively high RFS scores, and no linear relationship existed between RSI and RFS.     

Esophageal dysmotility as an important co-factor in extraesophageal manifestations of gastroesophageal reflux

OBJECTIVE: Esophageal motility problems have been demonstrated in patients with noninflammatory typical gastroesophageal reflux (GER) and esophagitis, but the frequency of motility disorders in patients with extraesophageal manifestations of GER has not been studied. The primary aim of this study was to assess the frequency of esophageal motility disorders in patients with atypical GER. METHODS: A prospective study of 112 consecutive patients with laryngopharyngeal reflux (LPR) symptoms and demonstrated physical findings consistent with LPR were studied. Patients were divided into one of the following diagnostic categories: hoarseness; chronic cough; dysphagia or globus pharyngeus; and paroxysmal laryngospasm. Of the 112 patients, 81 (72%) underwent esophageal manometry and ambulatory 24-hour pH monitoring (pH-metry), 19 (17%) had motility studies only, and 12 (11%) had pH-metry studies only. Only patients who had motility studies were included in the analysis. Therefore the study population was 100 patients. Associations between diagnostic category, motility disorder, and abnormal reflux were evaluated with contingency-table analyses. RESULTS: Of the 100 patients, 29 (29%) presented normal motility function, 48 (48%) had ineffective esophageal motility, 10 (10%) had hypertensive lower esophageal sphincter (LES), and 9 (9%) and 4 (4%) had nutcracker esophagus and achalasia, respectively. There was a significant association between esophageal dysmotility and extraesophageal manifestations of GER However, there was no statistically significant association between esophageal motility disorders and abnormal acid reflux in our patients with atypical GER. CONCLUSIONS: In the present study, the frequency of esophageal motility problems in patients with extraesophageal or atypical manifestations of GER was 73% and suggested that these problems exist as an accompanying condition or pathogenic co-factor in some patients with atypical GER.     

Laryngopharyngeal reflux symptoms improve before changes in physical findings

BACKGROUND: Patients with laryngopharyngeal reflux (LPR) undergoing treatment appear to have improvement in symptoms before the complete resolution of the laryngeal findings. OBJECTIVE: To determine whether patients with LPR experience an improvement in symptoms before the complete resolution of the laryngeal findings. METHODOLOGY: Forty consecutive patients with LPR documented by double-probe pH monitoring were evaluated prospectively. Symptom response to therapy with proton pump inhibitors was assessed at 2, 4, and 6 months of treatment with a self-administered reflux symptom index (RSI). In addition, transnasal fiberoptic laryngoscopy (TFL) was performed and a reflux finding score (RFS) was determined for each patient at each visit. RESULTS: The mean RSI at entry was 19.3 (+/- 8.9 standard deviation) and it improved to 13.9 (+/- 8.8) at 2 months of treatment (P <.05). No further significant improvement was noted at 4 months (13.1 +/- 9.8) or 6 months (12.2 +/- 8.1) of treatment. The RFS at entry was 11.5 (+/- 5.2), and it improved to 9.4 (+/- 4.7) at 2 months, 7.3 (+/- 5.5) at 4 months, and 6.1 (+/- 5.2) after 6 months of treatment (P <.05 with trend). CONCLUSIONS: Symptoms of LPR improve over 2 months of therapy. No significant improvement in symptoms occurs after 2 months. This preliminary report demonstrates that the physical findings of LPR resolve more slowly than the symptoms and this continues throughout at least 6 months of treatment. These data imply that the physical findings of LPR are not always associated with patient symptoms, and that treatment should continue for a minimum of 6 months or until complete resolution of the physical findings.     

Expression of claudin-3 in the esophagus and larynx of rat reflux model

Objective

The aim of this study was to investigate the association between laryngeal expression of claudin-3 and laryngopharyngeal reflux (LPR) in a rat reflux model.

Methods

Eight Wistar rats were divided into two groups. Four rats underwent total esophageal myectomy to induce reflux, and the remainder underwent a sham operation as a control. All animals were sacrificed 12 weeks after surgery to perform tissue histology and Western blot analysis.

Results

Lymphocyte infiltration increased significantly in the study group in both esophageal and laryngeal samples (P = 0.001, 0.002, respectively). Both esophageal and laryngeal expressions of claudin-3 were significantly lower in the study group when compared with that in the control group (P = 0.045, 0.037, respectively).

Conclusion

The results of this study suggest that a decrease in claudin-3 could be a sensitive indicator of reflux laryngitis in rats.     

Empiric esomeprazole in the treatment of laryngopharyngeal reflux

OBJECTIVE: Objectives were to determine the efficacy of empiric treatment with esomeprazole for patients diagnosed with laryngopharyngeal reflux and to determine a treatment paradigm for this patient population. STUDY DESIGN: Prospective study. METHODS: Patients were treated with a once-daily dose of 40 mg esomeprazole for 8 weeks. All patients completed a subjective symptom scale (rating laryngeal symptoms and esophageal symptoms) and scoring of flexible fiberoptic examination before treatment and at 4 and 8 weeks of treatment. Nonresponders (<50% reduction in symptom score) were recommended to undergo 24-hour dual-probe pH study while on a regimen of 40 mg esomeprazole once a day, to evaluate for the adequacy of acid suppression. RESULTS: Thirty patients completed the course of therapy. After 4 weeks of treatment, only 8 of 30 patients had significant improvement of their overall symptoms (8 of 30 improved on laryngeal score, and 11 of 18 improved on esophageal score). At 8 weeks of treatment, 19 of 30 patients had significant improvement on their overall symptoms (18 of 30 on laryngeal score, and 13 of 18 on their esophageal score). Five of seven nonresponders who agreed to be tested had positive findings on pH studies (on medication regimen) at 1 cm above the upper esophageal sphincter. Four of 10 nonresponders improved further after increasing their dosage to 40 mg twice a day. Laryngeal examination scores were statistically improved in responders after 8 weeks of treatment. CONCLUSIONS: Laryngopharyngeal reflux symptoms require at least 8 weeks of treatment for significant improvement in the majority of patients. Esophageal symptoms improve sooner. Nonresponders at a daily dose of 40 mg should be treated with a dosage of 40 mg twice daily, and pH study on medication reserved for nonresponders at this higher dose. Laryngeal examination scores showed mild but statistically significant improvement at 8 weeks of therapy in responders.     

Laryngopharyngeal reflux finding scores correlate with gastroesophageal reflux disease and Helicobacter pylori expression

Conclusion. The expression of Helicobacter pylori (HP) positivity and degree of gastroesophageal reflux disease (GERD) correlate with laryngopharyngeal reflux (LPR). HP positivity and degree of GERD were more adverse in patients with a reflux finding score (RFS) of 7 or more. Objective. We aimed to investigate the relationship between RFS and inflammation of the lower part of the esophagus as well as RFS and HP infection. Patients and methods. Forty-five consecutive patients were analyzed prospectively. The degree of LPR was evaluated using the RFS method. The degree of GERD, lower esophageal mucosal inflammation, and antral HP positivity were evaluated using endoscopic surveys. Results. The mean RFS of the whole population was 11.5±4.4. The mean RFS of patients who had lower esophageal mucosal inflammation was 7±0.1, 8.1±1.3, 13.9±3.7, and 16.6±3.5, for grades A, B, C and D, respectively. The RFS of patients according to HP expression was as follows: 7.2±0.4, 9.3±3.07, 12.7±3.16, and 17.8±2.1, for normal (score 0), score I, score II, and score III, respectively.     

Prevalence of laryngopharyngeal reflux in a population with gastroesophageal reflux

OBJECTIVE: Laryngopharyngeal reflux (LPR) is a syndrome associated with a constellation of symptoms usually treated by ENT surgeons. It is believed to be caused by the retrograde flow of stomach contents into the laryngopharynx, this being a supra-esophageal manifestation of gastroesophageal reflux disease (GERD). It has been cited that LPR and GERD can be considered separate entities. Our hypothesis was that LPR is a supra-esophageal manifestation of GERD and therefore that patients with GERD should have a degree of symptoms suggestive of LPR because of the reflux of the gastric contents. We examined a population of patients with both upper gastrointestinal endoscopy and symptom-proven GERD and, using a questionnaire, looked at their existing symptoms to help assess the prevalence of LPR. We also looked at whether, with more severe GERD (suggestive of increased gastric content reflux), the degree of symptoms suggestive of LPR would be increased, as would be expected. METHODS: A population of patients with endoscopically proven GERD were recruited and divided into groups depending on the severity of their reflux disease. A questionnaire was then administered that examined both LPR and GERD scoring criteria. The relationship between GERD and LPR was then analyzed. RESULTS: We recruited 1,383 subjects with GERD; those with severe GERD had significantly higher LPR scores compared with those with mild (P < .01), moderate (P < .05), or inactive disease (P < .001). CONCLUSIONS: The condition of LPR is likely to represent a supra-esophageal manifestation of GERD. This study examined a large number of patients with endoscopically proven GERD and has demonstrated a correlation between the severity of GERD and the prevalence of LPR. LPR and GERD are common and interlinked conditions. The subsequent prevalence of LPR in the population with GERD is therefore likely to be dramatically underestimated.     

The value of a liquid alginate suspension (Gaviscon Advance) in the management of laryngopharyngeal reflux

Laryngopharyngeal reflux (LPR) refers to the backflow of stomach contents into the laryngopharynx. Increasing evidence has demonstrated that LPR is a contributing factor in some cases of hoarseness, vocal fatigue, voice breaks, cough and globus and chronic throat clearing. However, several randomised placebo-controlled trials of proton pump inhibitors in the treatment of LPR have been reported with the majority showing no significant benefit in patient symptom scores over placebo. The aim of this pilot clinical study was to investigate whether any improvement in LPR-related symptoms, using the Reflux Symptom Index (RSI), and clinical findings, using the Reflux Finding Score (RFS), could be achieved with treatment with a liquid alginate suspension compared to control (no treatment). Patients presenting with the symptoms of LPR to the Otorhinolaryngology Outpatient Department at the Queen’s Medical Centre, Nottingham, UK were considered eligible if they had an RSI of greater than 10 and an RFS greater than 5 based on a fibreoptic examination of the larynx. A total of 49 patients were randomised into the open, parallel group study; 24 patients were randomised to receive 10 ml liquid alginate suspension (Gaviscon^® Advance) four times daily after meals and at bedtime, and 25 patients into the control group (no treatment). Patients were assessed pre-treatment and at 2, 4 and 6 months post treatment. Mean (SD) RSI and RFS pre-treatment scores were 23.9 (7.0) and 10.4 (3.6) for the treatment group and 24.6 (7.4) and 10.3 (3.3) for the control group, respectively. Significant differences between treatment and control were observed for RSI at the 2-month (11.2 (7.0) vs. 16.8 (6.4), P = 0.005) and 6-month (11.2 (8.1) vs. 18.3 (9.4), P = 0.008) assessments and for RFS at the 6-month (7.1 (2.8) vs. 9.5 (3.4), P = 0.005) assessment. Significant improvement in symptom scores and clinical findings were achieved with liquid alginate suspension (Gaviscon^® Advance) compared to control and further evaluation for the management of patients presenting with LPR is warranted.     

双探头24小时pH监测对咽喉反流的诊断价值及特点

目的对咽喉反流患者用食道测压定位法行双探头24小时pH监测,探讨其诊断价值及特点。方法对53例疑咽喉反流患者用食道测压定位法行双探头24小时pH监测同时用反流症状指数量表(reflux symptom index,RSI)、反流检查计分量表(reflux finding score,RFS)2个量表评估。结果 53例患者中31例咽喉反流阳性,与吸烟有相关性。RSI中以声嘶、咽异物感、持续清嗓为主要症状,RFS中以后连合增生、假声带沟、喉内黏液附着为主要体征。咽喉部酸反流主要发生在直立位,其中9例患者只有咽喉反流性疾病,10例只有胃食管反流性疾病;酸反流次数、酸暴露时间(即pH<4.0的总时间)与2个量表的评估有显著性差异。咽喉部pH监测结果与2个量表评估结果程度一致。结论咽喉反流性疾病可不伴发胃食管反流性疾病,减少酸反流次数及减少酸在咽喉部停留时间在治疗疾病中较为重要,RSI和RFS 2个量表可作为咽喉反流性疾病诊断的初筛。     

Ambulatory 24‐Hour Double‐Probe pH Monitoring: The Importance of Manometry

Objective Historically, manometry has been used for sphincter localization before ambulatory 24‐hour double‐probe pH monitoring to ensure accurate placement of the probes. Recently, direct‐vision placement (DVP), using transnasal fiberoptic laryngoscopy (TFL), has been offered as an alternative technique. Presumably, DVP might be used to precisely place the proximal (pharyngeal) pH probe; however, using DVP, there appears to be no way to accurately position the distal (esophageal) probe. The purpose of this study was to evaluate the accuracy of DVP for pH probe placement using manometric measurement as the gold standard. Methods Thirty patients undergoing pH monitoring participated in this prospective study. Each subject underwent manometric examination of the esophagus to determine the precise location of the upper and lower esophageal sphincters (UES and LES). In addition, external anatomic landmarks were used to estimate interprobe distances. A physician blinded to the manometry results then placed a pH catheter using DVP so that the proximal probe was located just above the UES. The results were recorded and compared with those obtained by manometry. Results Accurate DVP of the proximal pH probe was achieved in 70% (23 of 30) of the subjects. The use of external anatomic landmarks to estimate interprobe distance resulted in accurate positioning of the distal probe in only 40% (12 of 30) of the subjects. Using fixed interprobe distances of 15 cm and 20 cm, distal probe position accuracy was 3% (1 of 30) and 40% (12 of 30), respectively. Therefore, using DVP, the distal esophageal probe was in an incorrect position in 60% to 97% of subjects. Conclusion For double‐probe pH monitoring, the proximal probe can be accurately positioned by DVP; however, there is no precise way to determine the interprobe distance required to correctly position the distal pH probe. Failure to accurately position the distal probe results in grossly inaccurate esophageal acid‐exposure times. Thus, manometry is needed to ensure valid double‐probe pH monitoring data.