The clinical characteristics of gastroesophageal reflux disease in patients with laryngeal symptoms who are referred to gastroenterology

The prevalence of gastroesophageal reflux disease (GERD) has increased recently in Asia‐Pacific countries. However, little is known about its prevalence and clinical characteristics in GERD patients with atypical symptoms in Asia. The aim of this study was to investigate the clinical characteristics of GERD in patients who had laryngeal symptoms in Korea. Data were gathered retrospectively from patients who presented with atypical symptoms, such as throat discomfort, globus pharyngeus, hoarseness, and chronic cough. They underwent a 24‐hour ambulatory intraesophageal pH monitoring and filled in a validated reflux questionnaire. Overall, 128 patients (36 men and 92 women) with laryngeal symptoms were included. Of these 128, 43 patients (34%) had erosive esophagitis or pathological reflux from 24‐hour ambulatory pH monitoring, and 24 (19%) had a positive Bernstein test or positive symptom index from 24‐hour pH monitoring. Sixty‐one patients (48%) had no evidence of reflux esophagitis on upper endoscopy and pathological acid reflux on 24‐hour pH monitoring. Fifty‐six patients (44%) had weekly heartburn or regurgitation. Typical symptoms and dyspepsia were significantly more common in patients with GERD who had laryngeal symptoms than non‐GERD. Fifty‐two percent of patients had laryngeal symptoms that were associated with GERD. The presence of typical reflux symptoms and dyspepsia are risk factors for GERD in patients who present with laryngeal symptoms.     

Hypopharyngeal pH monitoring artifact in detection of laryngopharyngeal reflux

Hypopharyngeal pH artifacts have been a concern in the detection of laryngopharyngeal reflux. Our purpose was to analyze and quantify artifacts from dual-sensor hypopharyngeal pH monitoring. In all, 42 hypopharyngeal and 58 esophageal pH studies were reviewed. Type 1 (out of range), type 2 (pH drift), and type 3 (isolated pH drop) artifacts were identified. The proportion of proximal-sensor pH drop to <4 that was artifactual was determined. The median number (range) of artifacts was 1 (0–17) and 2 (0–28) for hypopharyngeal and esophageal pH studies, respectively (P = NS). The median proportion of artifactual pH drop to <4 was 1% (0–84%) and 2% (0–74%) for hypopharyngeal and esophageal pH studies, respectively (P = NS). The diagnosis did not change in any patient after excluding pH artifacts. In all, 19% of the combined 2432 hypopharyngeal pH drops of <4 were artifacts. In conclusion, hypopharyngeal pH artifacts per study were uncommon but can be prominent in a few patients. One can identify these artifacts and exclude them from analysis.     

Laryngeal examination is superior to endoscopy in the diagnosis of the laryngopharyngeal form of gastroesophageal reflux disease

Objective. The laryngopharyngeal form of gastroesophageal reflux disease (LF GERD) is a frequent manifestation of supraesophageal GERD. Diagnosis of LF GERD is difficult: most of the common diagnostic methods of GERD have insufficient accuracy in establishing LF GERD. The purpose of this study was to evaluate the role of endoscopic and laryngologic examination in the diagnosis of LF GERD and to create a laryngoscopic reflux index (LRI). Material and methods. A total of 108 LF GERD patients and 90 controls were investigated. The criteria for LF GERD were: complaints, reflux-laryngitis, and esophagitis (endoscopically or histologically proven). Lesions in four laryngeal regions were evaluated: arytenoids (A), intraarytenoid notch (IAN), vestibular folds (VF), and vocal cords (VC). Three types of mucosal lesions were evaluated on a points basis: alterations of the epithelium, erythema, and edema. Total LRI was calculated by summing-up the indices in the separate laryngeal areas. Results. The LRI mean value (11.48±3.78 points) of LF GERD patients was statistically significantly greater than that (1.64±1.93 points) of the controls. The most significant laryngoscopic changes of LF GERD were: mucosal lesions of IAN, mucosal lesions of VC, and edema of VC. A combination of these three findings reliably distinguishes the LF GERD patients from controls in 95.9% of cases. The mucosal lesions of IAN have the greatest importance in diagnosing LF GERD: the odds ratio to LF GERD – 21.32, p<0.001. Endoscopic esophagitis was established in 36 (33.3%) cases. The severity of esophagitis did not correlate with the severity of the laryngeal findings. Conclusions. Laryngoscopy is superior to endoscopy in diagnosing LF GERD. Endoscopy has limited value in the diagnosis of LF GERD. Establishing the LRI could be helpful in the differential diagnosis of the disease in the everyday clinical practice.     

Comparison of patients of chronic laryngitis with and without troublesome reflux symptoms

Background and Aim: Little is known about the difference between patients of chronic laryngitis with and without troublesome reflux symptoms. The aim of this study was to compare the clinical characteristics and response to acid suppression between patients of chronic laryngitis with and without troublesome reflux symptoms. Methods: Consecutive patients with chronic laryngitis were enrolled. The frequency and severity of reflux and laryngeal symptoms were scored. All the patients underwent laryngoscopy, esophagogastroduodenoscopy and 24‐h multichannel intraluminal impedance and pH monitoring before receiving rabeprazole 10 mg b.i.d. for 3 months. Mild typical reflux symptoms (heartburn or regurgitation) occurring ≥ 2 days/week or moderate/severe symptoms occurring ≥ 1 day/week were defined as troublesome reflux symptoms. Results: Compared to patients without troublesome reflux symptoms, those with troublesome reflux symptoms were older and had more episodes of acid and liquid gastroesophageal reflux (GER) and acid and weakly acidic laryngopharyngeal reflux (LPR). They also had higher percentages of both bolus exposure time and acid exposure time of GER and LPR. Patients with troublesome reflux symptoms responded to acid suppression more often at 12 weeks (67.3% vs 20.9%, P < 0.001) and more rapidly (40.8% vs 14.0%, 3 weeks after the start of acid suppression; P = 0.004) compared to those without. Conclusion: Difference in reflux profile of GER and LPR between patients with and without troublesome reflux symptoms could partly explain the discrepancy of response to acid suppression among patients with chronic laryngitis. Acid suppression therapy may provide limited therapeutic benefits to patients of chronic laryngitis without troublesome reflux symptoms.     

Extraesophageal gastroesophageal reflux disease (GERD) symptoms are not more frequently associated with proximal esophageal reflux than typical GERD symptoms

Extraesophageal (EE) symptoms such as cough and throat clearing are common in patients referred for reflux testing, but are less commonly associated with gastroesophageal reflux disease (GERD). Patients with reflux associated EE symptoms often lack typical GERD symptoms of heartburn and regurgitation. Our aim was to compare the frequency of proximal esophageal reflux between esophageal (typical) symptoms and EE (atypical) symptoms. Combined multichannel intraluminal impedance‐pH (MII‐pH) tracings were blinded by an investigator so that symptom markers were relabeled with a number without disclosure of symptom type. We selected 40 patients with at least five reflux‐related symptom events for one of four symptoms (heartburn, regurgitation, cough, or throat clearing). A blinded investigator analyzed all 200 reflux episodes, reporting the proximal esophageal extent of the reflux for all symptoms. The percentage of symptom‐related reflux extending proximally to 17 cm above the LES was similar among all four symptom types. At least 50% of all symptoms were associated with proximal esophageal reflux to 17 cm, with regurgitation having the highest frequency at 60%. Our data indicate that EE symptoms are not more frequently associated with proximal esophageal reflux than typical esophageal symptoms.     

Tolerance to H2 receptor antagonist correlates well with the decline in efficacy against gastroesophageal reflux in patients with gastroesophageal reflux disease

BACKGROUND AND AIM: The attenuated antisecretory activity of H2 receptor antagonists (H2RA) during continuous administration is known as the tolerance phenomenon. The authors recently clarified that presence or absence of Helicobacter pylori infection influences the occurrence of the tolerance phenomenon. The aim of this study was to clarify whether tolerance to H2RA is correlated with attenuation of the inhibitory effect against gastroesophageal acid reflux in patients with gastroesophageal reflux disease (GERD). METHODS: Ten male patients with GERD symptoms and abnormal gastroesophageal reflux were investigated by pH monitoring on days 1 and 15 of continuous oral famotidine administration at 20 mg twice daily, and H. pylori infection was examined using the urea breath test. RESULTS: Intragastric and intraesophageal acidity were significantly decreased on the first day of famotidine administration, but then increased during the 15-day administration period in seven patients who were negative for H. pylori. In contrast, the efficacy of famotidine against gastric acid secretion and gastroesophageal acid reflux was not attenuated in three H. pylori-positive patients. The changes in GERD symptoms were correlated with the change in the degree of gastroesophageal reflux. CONCLUSION: The presence or absence of tolerance to H2RA during 15-day administration is correlated with the efficacy for inhibition of gastroesophageal acid reflux.     

十二指肠胃食管反流在胃食管反流病中的作用

目的　研究十二指肠胃食管反流 (DGER)在胃食管反流病发病机制中的作用及其对非糜烂性反流病 (NERD)的诊断价值。方法　 95例患者根据内镜检查的结果分为反流性食管炎和NERD组 ,对其均进行 2 4h食管 pH和胆汁联合监测。 结果　反流性食管炎患者DGER的各项指标 :吸光度值 >0 14时间百分比 (% )、总反流次数和反流 >5min的次数分别为 19 0 5± 2 3 4 4、30 5 6±34 0 4和 5 90± 6 37,均显著高于NERD组相应的 7 2 6± 11 0 8、15 6 8± 2 0 92和 2 5 9± 3 5 7(P <0 0 5 ) ,而酸反流差异无显著性 ,随着反流性食管炎的程度加重DGER发生率增高 ;18 2 %的NERD患者存在单纯DGER ,联合胆汁监测可使NERD诊断阳性率由 6 5 9%升高到 84 1%。结论　DGER可以单独发生 ,在引起反流性食管黏膜损伤或症状方面都有作用 ,2 4h食管 pH和胆汁联合监测有助于NERD的诊断。     

Role of duodenogastroesophageal reflux in the pathogenesis of esophageal mucosal injury and gastroesophageal reflux symptoms.

BACKGROUND AND AIM: Patients with gastroesophageal reflux disease (GERD) usually suffer from acid reflux and duodenogastroesophageal reflux (DGER) simultaneously. The question of whether DGER has an important effect on the development of GERD remains controversial. The aim of the present study was to investigate the role of DGER in the pathogenesis of GERD and its value for the diagnosis of nonerosive reflux disease (NERD). METHODS: GERD was initially diagnosed using the reflux disease questionnaire. For further diagnosis, results of the upper gastrointestinal endoscopy (excluding a diagnosis of Barrett's esophagus) were considered in conjunction with simultaneous 24 h esophageal pH and bilirubin monitoring. RESULTS: According to endoscopic findings, 95 patients (43 men, 50+/-10 years of age) were divided into two groups: the reflux esophagitis (RE) group (n=51) and the NERD group (n=44). Three DGER parameters, the percentage of time with absorbance greater than 0.14, the total number of reflux episodes and the number of bile reflux episodes lasting longer than 5 min, were evaluated in the study. For the RE group, the values of the DGER parameters (19.05%+/-23.44%, 30.56+/-34.04 and 5.90+/-6.37, respectively) were significantly higher than those of the NERD group (7.26%+/-11.08%, 15.68+/-20.92 and 2.59+/-3.57, respectively, P<0.05 for all) but no significant difference was found in acid reflux. Of NERD patients, 18.5% were diagnosed with simple DGER. The positive diagnosis rate of NERD could be significantly elevated from 65.9% to 84.1% (P<0.05), if bilirubin monitoring was employed in diagnosis. CONCLUSIONS: DGER may occur independently but plays an important role in the development of RE and GERD symptoms. Simultaneous 24 h esophageal pH and bilirubin monitoring is superior to simple pH monitoring in helping identify patients at risk for NERD.     

胃食管反流病中非酸反流的比例及其与烧心的关系

目的 应用食管联合阻抗-pH监测技术探讨胃食管反流病中非酸反流的比例及其与烧心的相关程度.方法 选取消化专科门诊以烧心为主诉的连续病例,通过上消化道内镜将上述患者分为糜烂性食管炎(EE)组和非糜烂性反流病(NERD)组,并进一步通过24 h食管多通道腔内阻抗-pH监测及雷贝拉唑试验性治疗予以确诊.比较两组的联合阻抗-pH监测指标.结果 EE组36例,NERD组62例.两组患者酸反流次数、酸反流时间百分比差异有统计学意义(P值分别=0.001和0.002).EE组和NERD组中非酸反流次数的百分比分别为37.3%(663/1777)和44.3%(1220/2754),差异有统计学意义(x=21.723,P=0.000).EE组酸反流烧心症状指数阳性、非酸反流烧心症状指数阳性及总反流烧心症状指数阳性的百分比分别为36.1%(13/36)、19.4%(7/36)和55.6%(20/36),NERD组则为27.4%(17/62)、6.4%(4/62)和33.8%(21/62).结论 EE组和NERD组患者中非酸反流次数的比例分别为37.3%及44.3%,非酸反流与烧心关系密切.     

Ambulatory intraesophageal bilirubin monitoring in Japanese patients with gastroesophageal reflux

Background: The role of reflux of duodenal contents in gastroesophageal reflux in Japanese patients, which may be different from that in Western patients, was studied. Methods: Intraesophageal pH and the bilirubin concentration were monitored, using the Bilitec 2000, in 43 patients with reflux symptoms and 10 normal volunteers. The percentage of the time that spectrophotometric absorbence was 0.15 or more and pH was less than 4.0 was defined as the holding times (HTs) of bilirubin and acid, respectively. Severity of esophagitis was classified using the Savary-Miller (S-M) classification. Results: Esophagitis was present in 37 patients; 5, 10, 13, and 9 patients had S-M grades 1, 2, 3, and 4, respectively. Both HTs in the volunteers were less than 5%. Bilirubin HT was more than 5% in 3 of the 6 patients without esophagitis, but the acid HT was less than 5% in these 6 patients. Acid HT was less than 5% in 4, 2, 2, and 2 patients with S-M grades 1, 2, 3, and 4, respectively. Bilirubin HT was less than 5% in 1 patient with S-M grade 2 esophagitis. Bilirubin HT in patients with S-M grades 3 and 4 esophagitis (50.9 ± 5.8%) was higher than that in grades 1 and 2 (14.9 ± 2.9%) (P < 0.0001), but this was not so for acid HT. In 32 patients, bilirubin HT exceeded acid HT. Bilirubin HT did not correlate with acid HT. Conclusions: Duodenogastroesophageal reflux occurred independently of and exceeded acid reflux. The amount of duodenogastroesophageal reflux correlated with the severity of esophagitis. Received: October 22, 2001 / Accepted: January 25, 2002 Reprint requests to: H. Osugi     

胃食管反流病维持治疗方式的影响因素分析

目的评估胃食管反流病(GERD)维持治疗方式的影响因素.方法调查1999-09～2001-12北京协和医院门诊156例GERD病人,根据治疗后的症状及生活质量改善情况,分为按需治疗组和连续治疗组.探讨两种维持治疗方式与病程、症状积分、食管动力功能、24 h食管pH监测结果及内镜下炎症程度之间的关系.并对同期接受内镜、食管动力以及24 h食管pH监测的86例患者,进行影响因素的Logistic分析.结果 (1)96.7%GERD患者对药物治疗有效,其中按需治疗组92例,连续治疗组59例.(2)按需治疗组病程(年)和反流症状积分明显低于连续治疗组(P<0.05),(3)按需治疗组的LESP和食管远端蠕动收缩波幅显著低于连续治疗组(P<0.05);(4)按需治疗组中Ⅱ～Ⅲ级RE占10.9%,明显低于连续治疗组52.5%(P<0.05),同时按需治疗组(19.6%)合并食管裂孔疝的百分比也较连续治疗组(39.0%)低(P<0.01);(5)按需治疗组和连续治疗组的24 h食管pH监测均以卧位型酸反流为主.与按需治疗组比较,连续治疗组24 h总的酸反流的时间百分比和卧位酸反流的时间百分比明显增加(P<0.05);(6)对于同期接受内镜、24 h食管pH监测和食管动力检查的86例患者进行多因素Logistic分析显示,食管炎程度、食管远端收缩波幅和卧位酸反流程度对于采用维持治疗方式具有明显的影响作用.结论病程、内镜下的炎症程度、食管的动力功能以及卧位酸反流的程度是决定是否需连续治疗方式的关键因素.     

Comparison of gastroesophageal reflux in 100 patients with or without prior gastroesophageal surgery

Background and purpose  The role of duodenogastroesophageal reflux (DGER) in gastroesophageal reflux disease (GERD) remains controversial. Few studies of reflux have compared patients with an intact stomach to those without intact stomach after gastroesophageal surgery. This study aimed to investigate differences of the refluxate between patients with and without prior gastroesophageal surgery and to assess the role of DGER in GERD. Methods  One hundred patients (34% with reflux symptoms) were divided into four groups: 23 with an intact stomach, and 27, 42, and 8 with esophagectomy followed by gastric tube reconstruction, distal gastrectomy, and total gastrectomy, respectively. Reflux symptoms were evaluated, and endoscopy and simultaneous 24-h monitoring of esophageal pH and bilirubin were performed. Results  Of 44 patients with increased DGER but without increased acid reflux, three had severe reflux esophagitis and seven had Barrett’s esophagus. DGER was most frequent under weakly acidic conditions in the intact stomach, esophagectomy, and distal gastrectomy groups. Pure acid reflux and DGER at any pH were elevated in GERD patients with an intact stomach, while weakly acidic and alkaline DGER were elevated in GERD patients after gastrectomy. Esophagectomy patients had reflux with the combined characteristics of those in the intact stomach and gastrectomy groups. Weakly acidic or alkaline DGER was correlated with symptoms and esophageal mucosal changes in gastrectomy patients. Conclusion  The refluxate causing GERD differed between patients with and without prior gastroesophageal surgery. Weakly acidic or alkaline DGER may cause both symptoms and esophageal mucosal damage.     

Effect of gluten-free diet on preventing recurrence of gastroesophageal reflux disease-related symptoms in adult celiac patients with nonerosive reflux disease

Background and Aim:  In Celiac Disease (CD) the role of a gluten-free diet (GFD) on gastroesophageal reflux disease–related symptoms (GERD-rs) is unclear. The aim of this study was to establish the recurrence of GERD-rs, in CD patients with nonerosive reflux disease (NERD).
Methods:  From a total of 105 adult CD patients observed, 29 who presented with the NERD form were enrolled in the study. Thirty non-CD patients with NERD were studied as controls. Recurrence of GERD-rs was clinically assessed at 6, 12, 18, and 24 months follow-up (FU) after withdrawal of initial proton-pump inhibitor (PPI) treatment for 8 weeks.
Results:  GERD-rs were resolved in 25 (86.2%) CD patients and in 20 (66.7%) controls after 8 weeks of PPI treatment. In the CD group, recurrence of GERD-rs was found in five cases (20%) at 6 months but in none at 12, 18, and 24 months while in the control group recurrence was found in six of 20 controls (30%), in another six (12/20, 60%), in another three (15/20, 75%), and in another two (17/20, 85%) at 6, 12, 18, and 24 months FU respectively.
Conclusions:  The present study is the first to have evaluated the effect of a GFD in the nonerosive form of GERD in CD patients, by means of clinical long-term follow-up, suggesting that GFD could be a useful approach in reducing GERD symptoms and in the prevention of recurrence.     

Laboratory based investigations for diagnosing gastroesophageal reflux disease

Gastroesophageal reflux disease (GERD) still remains the most common out- GI-related condition in the out-patient setting. While primary care physicians often use empiric trials with proton pump inhibitors (PPI trial) to diagnose GERD, often specialised tests are required to confirm or exclude gastroesophageal reflux causing esophageal or extraesophageal symptoms. The most commonly used procedures to diagnose GERD include: conventional (catheter based) pH monitoring, wireless esophageal pH monitoring (Bravo), bilirubin monitoring (Bilitec), and combined multichannel intraluminal impedance-pH monitoring (MII-pH). Each technique has strengths and limitations of which clinicians and investigators should be aware when deciding which one to choose.     

Small volume acid reflux in gastroesophageal reflux disease patients with hiatal hernia is only detectable by pH‐metry but not by multichannel intraluminal impedance

Until now, it is uncertain if the so‐called pH‐only reflux episodes that consist of a pH drop without evidence of retrograde bolus movement in multichannel intraluminal impedance (MII) represent reflux episodes or artifacts. Hiatal hernia (HH) may allow reflux of small volumes to occur that can be detected by pH‐metry but not by MII. The aim was to search for a mechanism that can explain pH‐only reflux, 20 patients (12 females and 8 males, median age 52 years, interquartile range [IQR]: 40.5–60.75 years) were investigated with MII–pH off PPI. Impedance and pH‐metry data were analyzed separately. The differences in detection rate of acid reflux between pH‐metry and MII were correlated with the presence of HH. In an in vitro experiment, MII–pH probes were flushed with citric acid in plastic tubes of different size with capillary diameter and diameters of 2.5 mm and 4.5 mm, while recording pH values and impedance. HH was present in six patients and absent in 14 patients. In patients with HH in comparison with patients with absent HH, the difference of acid reflux detection between pH‐metry and MII is significantly higher (70%, IQR: 15–88% and 3.6%, IQR: 0–31%, respectively). In vitro all simulated reflux lead to a fall in pH whereas a corresponding decrease in impedance was only recognizable in the 4.5‐mm plastic tubes. Acid reflux episodes in patients with HH are more frequently detected by pH‐metry than by MII. Small volume reflux that does not lead to a decrease in impedance is the likely explanation for this phenomenon.     

Correlation of 24-hr esophageal pH patterns with clinical features and endoscopy in gastroesophageal reflux disease

We performed 24-hr ambulatory esophageal pH monitoring in north Indian patients with gastroesophageal reflux disease (GERD) and correlated it with symptom severity and endoscopic abnormalities. Thirty-six consecutive patients with symptomatic GERD and 16 healthy volunteers underwent objective grading of clinical symptoms and endoscopic findings. Total, supine, and upright reflux periods as well as frequency and duration of reflux episodes were determined from the 24-hr pH-metry record using standard software. This was abnormal in 32 patients, who could be categorized into upright refluxers (31.2%), supine refluxers (34.4%), and combined refluxers (34.4%). Supine reflux and upright reflux were distinct entities that did not correlate with each other (r=0.22,P=NS). In upright refluxers, symptoms (P<0.02) and=" endoscopic=" abnormalities=">P<0.005) were=" milder=" than=" in=" combined=" refluxers.=" total=" duration=" of=" acid=" exposure=" correlated=" significantly=" with=" severity=" of=" symptoms=">P<0.001) and=" endoscopic=" esophagitis=">P<0.005). patients=" with=" gerd=" had=" three=" distinct=" patterns=" of=" abnormal=" gastroesophageal=" reflux,=" with=" upright=" refluxers=" having=" milder=" disease=" and=" supine=" and=" combined=" refluxers=" having=" more=" severe=" disease.=" this=" may=" reflect=" differences=" in=" underlying=" mechanisms=" of=">     

Advances in diagnostic testing for gastroesophageal reflux disease

Gastroesophageal reflux disease (GERD) contributes substantially to morbidity and to costs in the United States health care system. The burden of this disease has resulted in attempts at improving diagnosis and characterizing patients. Numerous research and technical advances have enhanced our understanding of both the utility and limitations of a variety of diagnostic modalities. The purpose of this review is to highlight recent advances in GERD diagnostic testing and to discuss their implications for use in clinical practice. Topics addressed include esophageal pH monitoring, impedance testing, symptom association analyses, narrow-band imaging, and histopathology.