Hoarseness and laryngopharyngeal reflux: a cause and effect relationship or coincidence?

The role of laryngopharyngeal reflux (LPR) on hoarseness is widely assumed and accepted. Few articles present objective information on the subject. One of the main problems in establishing a relationship is our lack of knowledge of what is normal. We compared patients with chronic hoarseness and healthy controls to establish three goals: (1) to demonstrate the presence of additional symptoms and signs of LPR in patients with hoarseness; (2) to find the prevalence of LPR by utilizing 24 h double-probe in patients with hoarseness and compare it with that of the control group; (3) to contribute data to establish prevalence of LPR in healthy population. Forty-three patients with hoarseness and 20 healthy volunteers were enrolled in the study. All the patients in the study group had hoarseness of more than 3 months duration. The subjects recieved videolaryngoscopic evaluation and 24 h double-probe pH monitoring, and the results were compared. In the study group, 27 patients (62.8%) out of 43 had LPR episodes, compared to 6 (30%) of 20 healthy volunteers. Mean number of LPR episodes recorded by the pharyngeal probe was 7.0 [standard deviation (SD): 8.8] in 24 h, and this was significantly higher than that of the healthy controls [0.9/24 h (SD: 1.9)] (P = 0.003). Mean number of LPR episodes of the study group in upright position was 5.8 (SD: 7,0) and in supine position was 1.2 (SD: 3.3). These numbers were also significantly higher from the controls (P = 0.005 and P = 0.014 respectively). The results of this study show that: (1) most common additional symptoms were heartburn and chronic throat clearing and most common finding is pachydermia; (2) LPR incidence in patients with chronic hoarseness is significantly higher than the LPR incidence in healthy controls; (3) LPR is present in healthy people. However, the severity of LPR seems to be the causative factor rather than its presence.     

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.     

食管动力和反流事件在声带息肉发病机制中的意义

目的 探讨咽喉反流和胃食管反流与声带息肉发病的关系.方法 2011年10月至2012年5月期间就诊于南方医院的声带息肉患者32例,采用36通道ManoScan360TM固态高分辨率食管测压系统(high-resolution esophageal manometry)和Zephr多通道腔内阻抗-pH监测(multichannel intralumminal impedance combined with pH-metry,MII-pH)便携系统进行监测,观察食管上、下括约肌压力、食管动力分段特点及咽喉反流、胃食管反流事件及反流物性质,并与16例健康成人对照组比较.结果 声带息肉组较对照组平均食管上括约肌松弛持续时间、松弛恢复时间、食管下括约肌长度均缩短,食团内压最大平均值增加,差异均有统计学意义(t值分别为2.244、2.624、2.310和-2.397,P值均＜0.05).声带息肉组咽喉反流发生率为40.6％ (13/32),胃食管反流发生率为50.0％(16/32).声带息肉组与对照组咽喉酸反流次数中位数(M[P25;P75])分别为0.5[0.0;3.5]和0.0[0.0;0.0]次,酸反流时间分别为0.1[0.0;1.7]和0.0[0.0;0.0]min,酸清除时间分别为3.5[0.0;53.5]和0.0[0.0;0.0]s,DeMeester评分分别为14.8[1.6;31.3]和1.8[1.1;4.1]分,总计液体反流次数分别为46.5[25.3;69.0]和32.5[20.0;36.3]次.声带息肉组咽喉酸反流次数、酸反流时间、酸清除时间、DeMeester评分及总液体反流次数均较对照组增加,差异均有统计学意义(z值分别为2.481、2.767、2.767,2.344及1.980,P值均＜0.05).结论 声带息肉部分患者存在食管上、下括约结构与功能障碍,存在咽喉反流和胃食管反流,反流事件以立位酸反流为主.     

Monitoring of gastric acid suppression in patients with extraesophageal reflux disease

OBJECTIVE: Response to acid suppressive therapy varies in patients with extraesophageal esophageal reflux disease (EERD). Inadequate suppression of gastric acid may contribute to the observed differences in the response to the treatment. The aim of this study was to evaluate suppression of gastric acid in EERD patients being treated with acid suppressive therapy. METHODS: Charts of patients with EERD who underwent dual channel 24h esophageal pH monitoring while receiving acid suppressive therapy between January 2002 and June 2004 were reviewed. Suppression of gastric acid was determined based on the number of acid reflux episodes, esophageal acid exposure, and acid clearance time. RESULTS: Twenty patients (12 male, 8 female, age range: 2-19 years) were identified. Esophageal pH monitoring was within normal limits, documenting complete acid suppression in nine patients (45%). Increased numbers of acid reflux episodes were observed in seven patients. In four patients, the number of acid reflux episodes was normal in spite of incomplete acid suppression. However, other abnormal pH monitoring parameters included delayed acid clearance in three patients and increased acid exposure time in three. The majority of patients also showed alkaline reflux. CONCLUSION: Esophageal pH monitoring documented incomplete acid suppression in this group of infants, children, adolescents and teens with EERD. Monitoring of gastric acid suppression can be useful in guiding the follow-up of EERD patients who receive acid suppressive therapy.     

唾液胃蛋白酶检测在反流性咽喉炎诊断中的价值

目的 评估口腔中唾液胃蛋白酶检测对反流性咽喉炎(LPR)患者的诊断价值。 方法 选取25例LPR患者,反流症状指数量表(RSI)>13分,反流体征指数量表(RFS)>7分,治疗前采用蛋白印迹法检测患者唾液胃蛋白酶,之后口服埃索美拉唑肠溶片+2.5%碳酸氢钠雾化吸入治疗2个月,治疗完成后再次行RSI及RFS量表评分并行唾液中胃蛋白酶检测。 结果 治疗前唾液胃蛋白酶检测结果阳性12例,阴性13例。治疗后PPI实验结果阳性10例,阴性15例。唾液胃蛋白酶检测结果与PPI实验结果同为阳性9例,同为阴性12例;PPI实验结果阳性而唾液胃蛋白酶结果阴性1例,PPI实验结果阴性而唾液胃蛋白酶结果阳性3例。以PPI实验阳性作为本研究的诊断标准,胃蛋白酶检测结果诊断LPR的敏感度为90.00%,特异度为80.00%。25例患者均能完成所有检查和治疗,症状得到改善19例,症状未见明显改善6例。治疗前后RSI量表症状评分分别为(19.84±3.96)、(7.00±2.84)分,治疗前后RSI量表症状评分差异有统计学意义(P<0.001)。25例患者体征均得到明显改善,治疗前后RFS量表体征评分分别为(14.08±3.51)、(5.44±3.07)分,治疗前后的RFS量表体征评分差异有统计学意义(P<0.001)。 结论 唾液中胃蛋白酶的检测可用于辅助诊断LPR。     

Association of gastroesophageal reflux disease and laryngeal cancer

ObjectiveStudies examining the association of reflux disease with the risk of developing laryngeal cancer have both proven and disproven the null hypothesis.MethodsThis retrospective case–control study examines the association of reflux in two populations exposed to similar risk factors, including tobacco, to the extent that end-organ malignant transformation has occurred. After IRB approval was obtained, a search of our hospital's cancer center's database was performed from 2000 to 2013. A retrospective chart review was then performed and the prevalence of gastroesophageal reflux disease among patients with laryngeal cancer (n = 290) was determined. It was then compared to the prevalence of gastroesophageal reflux disease among patients presenting with lung cancer (n = 2440) during the same time period. A multivariate logistic regression was performed to determine the association of reflux with laryngeal cancer.ResultsTaking into consideration tobacco use, there was a strong association between male gender and occurrence of laryngeal cancer as opposed to lung cancer (OR = 3.30; 95% CI 2.53–4.36, P < 0.001). There was a modest association between reflux and laryngeal cancer (OR = 1.65; 95% CI 1.19–2.25, P = 0.003). However, there was no association between reflux and the propensity for carcinoma in specific laryngeal subsites (P = 0.47).ConclusionsIn this study examining a heterogeneous population with end-organ malignancy there was a modest association between reflux and laryngeal cancer. Further research is necessary to determine the biologic relevance of this finding.     

咽喉反流的中医认识及辨证治疗

正咽喉痛、异物感、恶心、干呕、咽干、吭咯、咯痰,咽喉部灼烧感等都是耳鼻喉科门诊的常见主诉,目前医生和患者常在咽喉部追究其病因,然而绝大多数(约95%~98%)针对上述症状的喉内镜描述中,除了"咽部黏膜充血、淋巴滤泡增生、会厌囊肿"等外,与临床症状并不相符。从解剖上来说,颈部除了咽部外,还有喉部、颈段气管、颈段食管、甲状腺等器     

Evaluation of laryngopharyngeal reflux in patients with suspected laryngopharyngeal reflux, chronic otitis media and laryngeal disorders

We investigated the prevalence of laryngopharyngeal reflux in patients with signs and symptoms of reflux, chronic otitis media and benign and malignant vocal cord lesions. Three groups of patients in Ankara Ataturk Education and Research Hospital ENT–Head and Neck Surgery Clinics were compared between 2005 and 2006. The first group had patients with signs and symptoms of reflux, the second group consisted of patients with chronic otitis media, and in the third group had patients with laryngeal pathology, i.e. vocal cord lesions. The results of pH monitoring of all the three groups of patients were analyzed for laryngopharyngeal reflux. In the evaluation, two different criteria, based on reflux number and time spent in reflux, were used. It was investigated whether there was a difference in terms of reflux among these three groups. Also, the effects of reflux in etiopathogenesis of chronic otitis media and vocal cord lesions are discussed. A total of 84 patients were studied, with 22 patients with signs and symptoms of reflux in Group 1, 42 patients with chronic otitis media in Group 2, and 20 patients with vocal cord lesions in Group 3. No statistical difference could be detected among the groups in terms of the two criteria mentioned above. The frequency of laryngopharyngeal reflux in patients with chronic otitis media and vocal cord lesions was found to be as high as than in the patients with signs and symptoms of reflux. During the treatment of chronic otitis media and laryngeal disorders, we advise reflux work-up, and in case if there is reflux, we recommend reflux treatment in addition to treatment of primary disease.     

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.     

Laryngeal pseudosulcus as a predictor of laryngopharyngeal reflux.

OBJECTIVES/HYPOTHESIS: Laryngeal pseudosulcus is an accurate prognostic indicator of laryngopharyngeal reflux (LPR) disease. STUDY DESIGN: Prospective study of 20 consecutive patients with laryngeal pseudosulcus. Pseudosulcus is infraglottic laryngeal edema that is thought to be secondary to LPR. All patients were evaluated with dual-channel pH probe 24-hour monitoring to evaluate for the presence of laryngopharyngeal reflux. METHODS: Twenty patients identified with laryngeal pseudosulcus on routine physical examination were included in the study. Each patient underwent a 24-hour dual-channel pH probe. The data were analyzed and compared with previously published normative data. The data included the total number of reflux episodes and the percentage of time the pH dropped below 4 at the proximal probe. RESULTS: Eighteen of the 20 patients with laryngeal pseudosulcus were found to have LPR. The mean number of reflux episodes at the proximal probe was 29.4 (range, 3-82). The mean percentage of time the pH dropped below 4 was 1.15%. In the upright position the mean value was 1.59% and in the supine position it was 0.19%. This gives pseudosulcus a positive predictive value for LPR of 90%. CONCLUSION: This study shows laryngeal pseudosulcus to be an accurate predictor of laryngopharyngeal reflux disease.     

咽喉反流与变应性鼻炎的相关性研究

目的 咽喉反流（LPR）与变应性鼻炎（AR）临床表现常类似,本研究的目的是探讨这两种疾病的相关性。方法 纳入2019年6月—2020年6月就诊的72例疑似LPR患者,根据24hDx-pH监测结果将患者分为LPR阳性组和LPR阴性组,用AR表评分（SFAR）（SFAR≥7分）诊断AR,探讨Dx-pH与SFAR评分的相关性及进行LPR阳性与LPR阴性组中AR患病率的比较。结果 72例疑似LPR患者有40例AR患者,LPR阳性组（32例）中有22例AR患者,LPR阴性组（40例）中有18例AR患者,LPR阳性组的SFAR评分显著高于LPR阴性组（P<0.05）,LPR阳性组中AR患病率更高（P<0.05）。结论 LPR阳性组患者SFAR评分更高,LPR与AR可能具有相关性。     

口咽、食管同步Dx-pH检测研究咽喉反流性疾病

采用口咽、食管同步Dx-pH检测探讨咽喉反流性疾病（LPRD）与胃食管反流病（GERD）的关系。     

Change of acoustic parameters before and after treatment in laryngopharyngeal reflux patients

OBJECTIVES: To evaluate the usefulness of acoustic parameters as an indicator of laryngopharyngeal reflux (LPR) treatment efficacy. STUDY DESIGN: A prospective case series analysis. MATERIALS AND METHODS: From January to September 2005, we prospectively analyzed 40 patients who were diagnosed with laryngopharyngeal reflux by 24-hour ambulatory double-probe pH monitoring. Laryngopharyngeal reflux patients were treated medically and voice analysis was conducted three times: before treatment, 1 to 2 months after treatment, and 3 to 4 months after treatment. Jitter, shimmer, and harmonic-to-noise ratio (HNR) were analyzed as the acoustic parameters. Pre- and posttreatment reflux symptom index and reflux finding score were documented. RESULTS: Jitter, shimmer, and HNR had improved significantly at 1 to 2 months after treatment and were maintained at 3 to 4 months after treatment. Jitter was significantly correlated with reflux symptom index. CONCLUSION: Acoustic parameters can be used as indicators of treatment efficacy for laryngopharyngeal reflux disease.     

Is laryngopharyngeal reflux an important risk factor in the development of laryngeal carcinoma?

Laryngopharyngeal reflux (LPR) as a causative irritating factor in the development of laryngeal carcinoma has been suggested. However, the association between LPR and laryngeal carcinoma remains unclear. The aim of this study was to compare the prevalence and severity of reflux between patients with laryngeal carcinoma and clinical LPR. The intention was to find out if a correlation exists between the laryngeal findings and the level of acid reflux. The study population consisted of 29 patients with laryngeal cancer (group I), 33 LPR patients with normal laryngeal findings (group II) and 70 LPR patients with related laryngeal pathology (group III). The results of 24-h, double-channel ambulatory esophageal pH monitoring were analyzed comparing the three groups. The occurrence and severity of abnormal acid reflux at the upper and lower esophageal segments were evaluated. The incidence of LPR or gastroesophageal reflux (GER) did not vary in any of the three groups (LPR was present in 62, 42 and 56% of the patients, while GER was present in 45, 24 and 37% of the patients, respectively). Patients with LPR or GER from the three groups did not differ significantly in terms of the number of acid reflux episodes and percentage of times when the pH was <4. Our data do not support the hypothesis that LPR can be an independent risk factor in the development of larynx cancers. However, the data also do not thoroughly exclude the possibility. The reason why LPR leads to variable pathologies in the larynx may be uncovered by studies probing the differences between patients via detailed examinations of the local anti-reflux barriers such as epithelial morphology and functions.     

Association of laryngopharyngeal manifestations and gatroesophageal reflux

The aim of this study was to investigate the prevalence of gastroesophageal reflux disease (GERD) in patients with laryngopharyngeal symptoms, the relationship between laryngopharyngeal reflux (LPR) and Helicobacter Pylori infection and treatment response to proton pump inhibitors. Forty-five patients with suspected gastroesophageal reflux diseases related symptoms (sore throat, throat burning, throat clearing, globus sensation, cough, halitozis, dysphonia, dysphagia, postnasal dripping, vocal fatigue, and sputum) were included in this study. For pre-therapeutic and post-therapeutic comparison, symptoms and laryngological findings were graded on a 4-point scale. The patients underwent upper gastrointestinal system endoscopy. During endoscopy, antral biopsies from the stomach were obtained to detect H. Pylori. Antireflux medication with proton pump inhibitors (PPI) and H. Pylori eradication therapy if present were prescribed to the patients. The improvement in symptoms and laryngological findings were evaluated after treatment. By means of esophagogastroduodenoscopy (EGD), reflux was detected in only 11% of patients. But there can be reflux patients other than the detected ones. Although, H. Pylori was present in 62% of patients, no correlation was found between H. Pylori positivity and symptoms. All patients responded well to antireflux treatment and H. Pylori eradication therapy. Laryngopharyngeal symptoms and findings can be predictors of gastroesophageal diseases when response to reflux treatment is taken into account.     

Pepsin and carbonic anhydrase isoenzyme III as diagnostic markers for laryngopharyngeal reflux disease

OBJECTIVES/HYPOTHESIS: The objective was to investigate the potential use of pepsin and carbonic anhydrase isoenzyme III (CA-III) as diagnostic markers for laryngopharyngeal reflux disease. STUDY DESIGN: Prospective cell biological investigation was conducted of laryngeal biopsy specimens taken from 9 patients with laryngopharyngeal reflux disease and 12 normal control subjects using antibodies specific for human pepsin (produced in the authors' laboratory within the Department of Otolaryngology at Wake Forest University Health Sciences, Winston-Salem, NC) and CA-III. METHODS: Laryngeal biopsy specimens were frozen in liquid nitrogen for Western blot analysis and fixed in formalin for pepsin immunohistochemical study. Specimens between two groups (patients with laryngopharyngeal reflux disease and control subjects) were compared for the presence of pepsin. Further analyses investigated the correlation between pepsin, CA-III depletion, and pH testing data. RESULTS: Analysis revealed that the level of pepsin was significantly different between the two groups (P < .001). Secondary analyses demonstrated that presence of pepsin correlated with CA-III depletion in the laryngeal vocal fold and ventricle (P < .001) and with pH testing data in individuals with laryngopharyngeal reflux disease. CONCLUSION: Pepsin was detected in 8 of 9 patients with laryngopharyngeal reflux disease, but not in normal control subjects (0 of 12). The presence of pepsin was associated with CA-III depletion in the laryngeal vocal fold and ventricle. Given the correlation between laryngopharyngeal reflux disease and CA-III depletion, it is highly plausible that CA-III depletion, as a result of pepsin exposure during laryngopharyngeal reflux, predisposes laryngeal mucosa to reflux-related inflammatory damage.