Dilated intercellular space in the larynx and esophagus of a rabbit reflux model

Objective

In this study, we investigated histological and electron microscopic changes of the laryngeal and esophageal epithelium in an animal model of reflux to demonstrate: (1) the association between laryngopharyngeal reflux (LPR) and gastroesophageal reflux disease (GERD) and (2) the value of dilated intercellular space (DIS) as a marker of LPR.

Methods

Eight New Zealand albino rabbits were utilized. Four rabbits underwent total cardiomyectomy to induce reflux. The remains underwent a sham operation as controls. The animals were sacrificed 12 weeks after surgery to obtain histological and electron microscopic results.

Results

There were significant differences in the histological results between the study group and the control group in both the esophagus and the larynx (P = 0.041 and 0.014). Significant changes in the intercellular space (IS) were observed between the study group and the control group in the esophageal and laryngeal samples (P < 0.001).

Conclusion

The results of this study suggest that LPR and GERD have a common mechanism and DIS is a morphologic marker of LPR in rabbits.     

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。     

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.     

管腔内pH监测在反流性疾病中的应用

反流性疾病包括为食管反流病(GERD)和咽喉反流性疾病(LPRD),两者虽在发病机制及表现上有所不同,但均指胃内容物向上反流导致的疾病。GERD尤其是LPRD/胃食管气道反流性疾病其临床症状缺乏特异性,且体征往往不完全与疾病严重程度相符,临床实践中做出正确诊断并不容易。pH监测可以客观直接监测食管或咽喉部酸碱度变化,克服了通过主观症状诊断的非特异性,其在反流性疾病诊断中的意义不言而喻,论文对管腔内pH监测的发展历程和其特点进行综述。     

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.     

Association of reflux symptom index scores with gastroesophageal flap valve status

Objective

Gastroesophageal reflux disease is a chronic symptom of mucosal damage caused by gastric acid reflux. Impaired gastroesophageal flap valve (GEFV) is one of the common etiologic factors of gastroesophageal reflux. The aim of this study was to investigate the association between GEFV, RSI, and GER in patients who underwent gastroesophageal endoscopy.

Methods

Two hundred and fifty seven consecutive patients with reflux symptoms (151 men and 106 women, mean age was 50.22 years) who underwent routine upper gastrointestinal endoscopy were enrolled to our study. GEFV was graded as I through IV according to the Hill's classification. Symptoms of laryngopharyngeal and upper gastrointestinal disease and endoscopic severity of esophageal injury were correlated with GEFV status. The GEFV was classified into two groups: normal GEFV group (grade I) and the abnormal GEFV group (grades II–III and IV). The reflux symptom index (RSI) was used as a diagnostic tool for LPR.

Results

Age, male gender, and body mass index were significantly related to an abnormal GEFV. The rate of abnormal grades of GEFV (Grade II + III + IV) was 31%. Age of normal and abnormal grades of GEFV (49.0/50.8 vs 52.9) and values of BMI (26.2/26.7 vs 26.5) were similar. RSI scores were correlated with gastroesophageal flap valve grades but RSI scores were not correlated with Los Angeles gastroesophageal reflux (GER) Classification. Moreover, gastroesophageal reflux grade of Los Angeles Classification was positively correlated with gastroesophageal flap valve grades.

Conclusion

Endoscopic grading of GEFV is a simple and useful technique which may provide an accurate diagnosis of laryngopharyngeal and gastroesophageal reflux. Also, reflux symptom index (RSI) is a simple, economic and noninvasive diagnostic tool for gastroesophageal reflux. However, in this research, we did not find any correlation between reflux symptom index and degree of esophageal mucosal injury which was classified according to LA classification.     

艾司奥美拉唑与奥美拉唑治疗胃食管反流病的临床疗效及应用价值比较研究

目的探析胃食管反流病采取艾司奥美拉唑和奥美拉唑诊疗的临床效果。方法选取2019年4月~2020年5月在我院就诊56例胃食管反流病患者,以双色球法分为对照组和治疗组,每组28例,对照组予奥美拉唑,治疗组予艾司奥美拉唑,比较两组效果。结果治疗组有效率相比于对照组明显提升(P<0.05);治疗组复发率、各症状积分较对照组显著下降(P<0.05)。结论较奥美拉唑,胃食管反流病采取艾司奥美拉唑效果更为理想,可有效改善症状,减小复发风险。     

Pathophysiological mechanisms of extraesophageal reflux in otolaryngeal disorders

As more than 40% of adults experience symptoms of the gastroesophageal reflux (GER) and 26% are affected by the extraesophageal reflux (EER), the aim of this article was to review the literature concerning pathophysiological mechanisms contributing to these common diseases. Reflux symptoms are ascribable for nearly one-third of otolaryngeal disorders. In contrast to patients solely affected by GERD, patients with otolaryngeal disorders attributable to extraesophageal reflux have a relatively good esophageal acid clearance but for unknown reasons increased amounts of laryngeal reflux. Transient upper esophageal sphincter relaxations are discussed as the pathophysiological mechanism, as the resting tone of the upper esophageal sphincter is not affected. When exposed to gastroduodenal contents, the ciliated epithelium of otolaryngeal structures is more susceptible to damage, and thereby even a few reflux episodes are suggested to cause extraesophageal reflux disease (EERD). Particularly active pepsin contributes to laryngeal lesions and eustachian tube dysfunction. Despite the importance of EER in laryngeal diseases, the causative role in other otolaryngeal disorders like sinusitis and otitis media with effusion remains unresolved.     

E-cadherin but not β-catenin expression is decreased in laryngeal biopsies from patients with laryngopharyngeal reflux

Abnormal exposure of acid refluxate on the esophageal mucosa has been shown to decrease the epithelial barrier function through an alteration in the intercellular junctional complex. However, only few studies have examined the molecular effects caused by abnormal exposure of gastric refluxate on the laryngeal epithelium. E-cadherin and β-catenin are cell membrane-associated proteins playing a major role in the maintenance of cell–cell adhesion in epithelial tissues. In this study we tried to analyse the molecular effect of laryngopharyngeal reflux (LPR) on the cellular expression of these proteins. Therefore, we compared the expression of E-caherin and β-catenin in laryngeal biopsies from patients with and without pH-documented laryngopharyngeal reflux. Paraffin-embedded archival laryngeal biopsies taken from 21 patients, who had undergone rigid laryngoscopy under general anaesthesia and postoperative 24-h pH monitoring, were evaluated immunohistochemically with antibodies to E-cadherin and β-catenin. The membrane expression of the two proteins was categorized in no expression, mild, moderate and strong (grade 0–3). In LPR patients (n = 14) the mean grade of E-cadherin and β-catenin expression was 1.57 and 1.21, while in specimens of patients without pH-documented LPR it was 2.57 and 1.29. The difference in E-cadherin expression was statistically significant (P = 0.011). From our findings we conclude that LPR can cause a decrease in the laryngeal expression of E-cadherin but not of β-catenin. The reduction of E-cadherin-mediated adhesion could contribute to the development of laryngeal neoplasms. E-cadherin immunostaining of laryngeal biopsies could be a further diagnostic tool to confirm the diagnosis in patients with suspected LPR.     

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.     

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.     

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.     

康复新液治疗反流性咽喉炎的疗效观察

目的观察康复新液对反流性咽喉炎( laryngopharyngeal reflux disease,LPRD)所致慢性咽炎的疗效。方法对440例慢性咽炎患者行胃镜检查,符合胃食管反流病(gastroesophagal refax disease,GERD),并确诊LPRD,且幽门螺旋杆菌阴性者156例,随机分为两组,对照组：应用质子泵抑制剂,胃肠动力药。观察组：在前述方案基础上应用康复新液含潄后咽下早晚各一次。以三周为一疗程,疗程结束后复查喉镜,并就症状,体征,及内镜检查进行评价,评价两组总有效率。结果观察组显效（75）例,有效（16）例,总有效率（92.86%）,对照组显效（26）例,有效（19）例,总有效率（77.59%）。两组比较,差异有统计学意义(P<0.05)。结论康复新液、质子泵抑制剂、胃肠动力药治疗LPRD的疗效优于常规组。     

反流性咽喉炎与胃食管反流病的关系研究

目的 :探讨反流性咽喉炎与胃食管反流病 (GRED)发生的关系。方法 :对 130例顽固的慢性咽喉炎患者行胃镜检查或 2 4h食管 pH监测 ,将检测的GRED随机分为两组 ,治疗组 :应用抑胃酸药、促动力药和清热解毒治疗 ;对照组 :单用清热解毒的咽喉炎药 ,对两组咽喉部症状缓解及内镜下病理改善情况进行统计学比较。结果 :检出GRED 45例 (34 .6 % ) ,反流性咽喉炎的体征多样化 ,治疗组 2 3例 ,有效率 91.3% (2 1例 ) ,对照组 2 2例 ,有效率 13.6 % (3例 ) ,P <0 .0 1。结论 :GRED是导致反流性咽喉炎的重要病因 ,抑酸剂与促动力药、清热解毒药合用 ,可缓解或改善反流性咽喉炎的症状和病理。     

Utility of 24-hour pharyngeal pH monitoring and clinical feature in laryngopharyngeal reflux disease

Background: pH monitoring can reflect the changes in H⁺ in the airway.

Objectives: To explore the utility of pharyngeal pH monitoring in the diagnosis of laryngopharyngeal reflux disease (LPRD).

Material and methods: Clinical data from 956 suspected LPRD patients from February 2016 to March 2018 were analyzed retrospectively.

Results: One hundred forty-one patients had positive Ryan score. The positive rates of reflux symptom index (RSI), reflux finding score (RFS), RSI and RFS and RSI or RFS were 14.7%, 32.5%, 21.9%, 7.8% and 46.5%, respectively. The RFS in the positive Ryan score group was higher than that in the negative Ryan score group [(6?±?3.5) vs. (4.8?±?2.9)], while the RSI was not significantly different from that in the negative Ryan score group [(10.9?±?8) vs. (11.3?±?7.1)]. Regarding Ryan score as the gold standard in the diagnosis of LPRD, the sensitivity, specificity, positive and negative predictive value of identifying LPRD by RSI/RFS were 15.9%, 86.3%, 50.4% and 54%, respectively.

Conclusions: Ryan score, RSI and RFS have poor correlation in detecting LPRD. Some patients may be missed with the Ryan score as a diagnostic criterion.

Significance: Pharyngeal pH monitoring is useful and more appropriate index is expected.     

Incidence and treatment results of laryngopharyngeal reflux in chronic obstructive pulmonary disease

Laryngopharyngeal reflux (LPR) is defined as the movement of gastric content towards the larynx and the pharynx and it may cause respiratory symptoms or difficulty in their control. We aimed to find the frequency of LPR in chronic obstructive pulmonary disease (COPD) patients and to investigate its effect on COPD symptoms and the results of its treatment. At baseline 30 (20 male, 10 female, mean age: 65 ± 10 years) COPD patients completed LPR and COPD symptom questionnaires and 13 (44%) were diagnosed with LPR based on laryngeal examination. Patients with LPR were given 2 months of PPI treatment, after which LPR and COPD symptom questionnaires, laryngeal examinations and pulmonary function tests were repeated. Following the treatment, significant improvements in COPD symptom index, LPR symptom index and laryngeal examination findings were observed in patients with LPR (P < 0.01, P < 0.01, P < 0.0001, respectively). Treatment of LPR resulted in a significant improvement in the symptoms of COPD.     

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.     

南京市居民咽喉返流疾病的流行病学调查分析

目的了解南京市居民的咽喉返流疾病（ Laryngopharyngeal reflux disease, LPR ）的现状,为临床工作提供诊疗依据。方法采取多阶段随机抽样法抽取2500例南京市居民,对其LPR的患病情况进行调查,返流指数量表（Therefluxsymptomindex,RSI）按咽喉返流问卷的评分定义,总积分大于13分为阳性,并对相关因素进行分析。结果有效问卷1950例,阳性75例,患病率为3．86％（75／1950）;其中男性的患病率为3．77％（43／1140）,女性的患病率为3．95％（32／810）,两组患病率比较差异无统计学意义（P〉0．05）。声嘶或发音障碍（症状1）和持续清嗓（症状2）与LPR相关性最大。51—70岁年龄组返流指数量表（RSI）阳性率显著高于其他年龄组。结论南京市LPR的发病率为3．86％,症状1和症状2是LPR的主要相关因素,51～70岁年龄组患者应特别警惕LPR可能性。     

Gastroesophageal reflux and eustachian tube dysfunction in an animal model

OBJECTIVE: To explore the possible relationship between gastroesophageal reflux and eustachian tube dysfunction in an animal model. STUDY DESIGN: Randomized trial. METHODS: Twenty Sprague-Dawley rats were randomly assigned into two groups, the control (phosphate-buffered saline, n = 10) and experimental (hydrochloric acid [HCl]/pepsin, n = 10) groups. All rats underwent an operation to implant a polyethylene tube into the posterior nasopharynx, through which phosphate-buffered solution or simulated gastric juice (0.5 mg/mL pepsin in 0.01 HCl) was infused at a rate of 0.1 mL/h for 2 0 minutes three times a day for 7 days. Passive opening pressure (POP), passive closing pressure (PCP), active clearance of positive pressure (ACPP) and active clearance of negative pressure (ACNP) were measured before catheter implantation, on postoperative day 5, and after days 1, 3, 5, and 7 of infusion. Mucociliary clearance time (MCCT) was measured after day 7 of infusion. Statistical analysis used a two-way analysis of variance (POP, PCP, ACPP, and ACNP) and Mann-Whitney rank sum test (MCCT). RESULTS: Significant increases in POP (P = .004), PCP (P <.001), ACPP (P <.001), ACNP (P <.001), and MCCT (P <.001) were demonstrated in the HCl/pepsin group compared with the control group. No significant difference was seen between preoperative and postoperative values. CONCLUSIONS: Nasopharyngeal exposure to simulated gastric juice causes eustachian tube dysfunction in rats. Specifically, middle ear pressure regulation and mucociliary clearance of middle ear contents were disabled. These results support recent reports in the literature linking nasopharyngeal reflux to eustachian tube dysfunction and secondary development of otitis media.