Gastroesophageal reflux disease: new concepts in pathophysiology

The explanation as to why gastroesophageal reflux disease develops remains unanswered. We have learned much about the regulation of LES pressure, the single most important factor in the development of reflux disease. Our understanding of factors involved in the clearance of refluxed contents has also increased. The presence of reflux in the postprandial period and with belching suggests that it is serving a physiologic function. This may be a response to increases in gastric volume or pressure accompanying these situations. The question that has not been satisfactorily answered is what factor is responsible for the progression of a physiologic phenomenon to a pathologic condition. The answer to this question lies in the development of more physiologic techniques for monitoring LES pressure changes and a better understanding of the neural and hormonal pathways that regulate lower esophageal sphincter tone.     

Gastroesophageal reflux

Gastroesophageal reflux disease (GERD) is the most common disease of the gastrointestinal system. Heartburn, regurgitation, and dysphagia are the most common symptoms of GERD. However, chest pain, chronic cough, laryngitis, hoarseness, and other otolaryngologic manifestation can be the primary manifestations of the disease. Endoscopy, barium studies, and especially pH monitoring and therapeutic trials may help in establishing the diagnosis of GERD. The introduction of H2 antagonists and especially of proton pump inhibitors (PPI) has brought symptomatic relief in most patients. However, surgical procedures, especially laparoscopic fundoplication, are still required in some patients. Barrett's esophagitis is the most common complication of GERD and is associated with a high prevalence of esophageal adenocarcinoma. Whether or not treatment with either PPIs or H2 antagonists can prevent this complication is still under investigation.     

Gastroesophageal reflux disease in pregnancy.

Heartburn during pregnancy occurs in approximately two thirds of all pregnancies. The origin is multifactorial, but the predominant factor is a decrease in LES pressure resulting from female sex hormones, especially progesterone. Mechanical factors play a small role. Serious reflux complications during pregnancy are rare outside the obstetric setting. Therapy involves lifestyle modifications and nonsystemic medications as the initial choices. H2 blockers are probably safe in severe and refractory cases.     

Gastroesophageal reflux disease

GERD is a common chronic gastrointestinal disorder, and its prevalence in Asia is increasing. Classical symptoms of heartburn and regurgitation are common presentations. There is no standard criterion for the diagnosis of GERD, and 24-h pH monitoring lacks sensitivity in NERD. Furthermore, diagnostic studies for gastroesophageal reflux disease have several limitations. A short course of PPI is often used in clinical practice as a diagnostic test for gastroesophageal reflux disease. Elderly patients with GERD usually present with atypical manifestations, and they tend to develop more severe disease. PPI remains the mainstay of treatment for GERD. In a subset of patients who wish to discontinue maintenance treatment, anti-reflux surgery is a therapeutic option.     

Gastroesophageal reflux disease

Opinion Statement Prior to the advent of proton pump inhibitors, internists recommended antireflux surgery primarily for patients whose gastroesophageal reflux disease (GERD) failed to respond to medical therapy. Although many physicians still cling to the notion that antireflux surgery is a procedure best reserved for “medical failures,” today this position is inappropriate. Modern medical treatments for GERD are extraordinarily effective in healing reflux esophagitis. It is uncommon to encounter patients with heartburn or esophagitis due to GERD who do not respond to aggressive antisecretory therapy. Indeed, the very diagnosis of GERD must be questioned for patients whose esophageal signs and symptoms are unaffected by the administration of proton pump inhibitors in high dosages. In the large majority of these so-called refractory patients, protracted esophageal pH monitoring reveals good control of acid reflux by the proton pump inhibitors. This finding indicates that the persistent symptoms usually are not due to acid reflux, but to other problems such as functional bowel disorders. Medical treatment fails in such patients because the diagnosis is mistaken, not because the drugs fail to control acid reflux. Modern antireflux surgery also is highly effective for controlling acid reflux, but fundoplication will not be effective for relieving symptoms in patients whose symptoms are not reflux-induced. Therefore, many patients deemed failures of modern medical therapy would be surgical failures as well. Antireflux surgery is an excellent treatment option for patients with documented GERD who respond well to medical therapy, but who wish to avoid the expense, inconvenience, and theoretical risks associated with lifelong medical treatment. Ironically, surgical therapy for GERD today is best reserved for patients who are medical successes.     

Gastroesophageal reflux disease

Opinion statement Lifestyle modifications should be discussed with every patient with symptoms of chronic gastroesophageal reflux disease (GERD). Proton pump inhibitors are the most efficacious medical therapy for GERD. H₂ receptor antagonists are likely to be effective in patients with mild to moderate GERD and for occasional symptoms. Promotility drugs have limited efficacy and produce frequent side effects. Surgery is a reasonable option for chronic management. Endoscopic therapy remains experimental until more long-term results are available.     

反流性咽喉炎的研究进展

随着对胃食管反流病认识的深入,其对咽喉部的影响越来越受到临床的关注,研究证明它是导致咽喉部疾病的重要致病因素之一。胃食管反流对消化系统影响的研究很多,但其与咽喉反流性疾病的相关研究甚少,很多基层医生对该病还不甚了解。本文主要对反流性咽喉炎的发病机制、临床表现、诊断方法和治疗作一综述。     

Gastroesophageal reflux and bleeding esophageal varices.

The incidence of gastroesophageal reflux was evaluated with the use of a pH probe in 12 patients with cirrhosis and recent variceal hemorrhage and in 15 healthy control subjects. Short episodes of reflux occurred in 42% of the patients and in 47% of the controls. During an observation period of 1 hr, the cumulative duration of reflux was similar in patients (2.5 +/- 1.3 min) and controls (3.1 +/- 1.4 min). Mean lower esophageal sphincter pressures were normal in both groups but did not show a significant correlation with the duration of reflux. These data support previous observations that gastroesophageal reflux dose not appear to be a contributing factor in the development of variceal hemorrhage.     

Gastroesophageal reflux in infants with wheezing.

The relation between silent gastroesophageal reflux (GER) and respiratory problems such as persistent wheezing in infants is not well-established. Between January 1994 and June 1997, we evaluated the incidence of GER in 84 otherwise healthy infants referred to the Pediatric Pulmonary Medicine Division at Kosair Children's Hospital for evaluation of daily wheezing, and we followed their clinical course for 18 months. All underwent 24-hr esophageal pH studies to evaluate GER. The pH probe study was performed at a mean age of 8.74 +/- 4.6 months. Infants with a positive GER study were treated with an H2 receptor antagonist (H2RA) and a prokinetic agent for a mean of 5.6 +/- 2.4 months. At first follow-up visit 3 weeks after esophageal pH studies infants treated with an H2RA and those who did not have GER but continued with daily wheezing were started on flunisolide nasal solution (0.025%) delivered by nebulizer (125 mcg t.i.d.). Infants in both groups were followed every 1-2 months for a mean of 18 months and if clinically improved, attempts to decrease their daily asthma medications were made. Fifty-four of 84 (64%) had positive esophageal pH studies (GER-positive group), and 24 of them (44%) had no gastrointestinal symptoms suggestive of GER. Thirty patients had normal esophageal pH studies (GER-negative group). Twenty-two of these 30 (73%) infants without GER required nebulized flunisolide, compared to 13 of 54 (24%) infants with GER (P < 0.0005). Thirty-five of 54 (64.8%) infants with GER were able to discontinue all daily asthma medications within 3 months of starting antireflux therapy, while none of the infants without GER were able to discontinue daily asthma medications during the follow-up period (P < 0.0005). We conclude that silent GER is common in infants with daily wheezing, and controlling GER improves morbidity and decreases the need for daily asthma medications.     

Gastroesophageal reflux in runners. Characteristics and treatment

STUDY OBJECTIVE: To test the potential of distance running to induce reflux in healthy subjects and the ability of ranitidine to decrease esophageal acid exposure. DESIGN: A randomized, single-blind, crossover study. Objective assessment of reflux was done using an ambulatory intra-esophageal pH monitor during both a baseline hour and 1 hour of running on 2 days of testing. SUBJECTS: Fourteen normal volunteers (10 men, four women) between 22 and 37 years of age were studied. All volunteers ran regularly, completing an average of 20 miles weekly for at least 6 months. INTERVENTIONS: Ranitidine, 300 mg orally, or an identical placebo was administered after a low-fat breakfast just before the baseline hour of pH recording. SETTING: Esophageal motility and pH probe placement was done in the gastroenterology unit at Bowman Gray Medical Center. Running was done on local jogging trials. MEASUREMENTS AND MAIN RESULTS: There was more gastroesophageal reflux during running than during the baseline hour when reflux was measured at a pH threshold of 3.0, 4.0, or 5.0 (P less than 0.05). Reflux episodes were usually associated with belching. Ranitidine, 300 mg administered orally 1 hour before running, significantly (P less than 0.05) reduced the amount of esophageal acid exposure during running. CONCLUSIONS: Gastroesophageal reflux occurs during running in healthy volunteers. It is usually associated with belching. Acid suppression with ranitidine decreases intraesophageal acid exposure during running (P less than 0.05).     

Gastroesophageal reflux disease--from reflux episodes to mucosal inflammation

Gastroesophageal reflux disease (GERD) affects 20-30% of the population in Western countries, and is one of the most common clinical problems in daily practice. GERD-associated functional and structural abnormalities are caused by recurrent exposure of the esophagus to acidic and nonacidic refluxate of gastric contents (containing duodenal and intestinal proteases as well as acid and gastric pepsin) from the stomach. Major progress has been made in the understanding of the molecular pathogenesis of GERD-associated mucosal inflammation, suggesting a complex and multifactorial pathogenesis and immune-mediated effects. This Review summarizes the complexity of mucosal pathogenesis, including microscopic changes, mucosal inflammation and GERD-specific molecular mediators, in the context of the clinical features and pathophysiological characteristics of GERD. The abnormal exposure of the esophagus to luminal contents leads to chronic mucosal inflammation that is characterized by the release of IL-8 specifically, as well as other proinflammatory mediators, from the esophageal mucosa. Evidence from animal studies indicates a stepwise inflammatory response by the epithelium, which attracts immune effector cells to infiltrate the mucosa. From bench to bedside, these novel molecular findings might provide new treatment options beyond current acid-suppressive therapy and the principle of inhibition of transient lower esophageal sphincter relaxation.     

胃食管反流病与趋化性细胞因子

胃食管反流病(GERD)是一种临床常见病,其病因众多,但迄今为止尚无明确的发病机制.目前,诸多研究表明,趋化性细胞因子在胃食管反流病中有重要作用.此文就促炎症趋化性细胞因子与GERD发病等方面的研究作一综述.     

Gastroesophageal reflux disorders and asthma

Gastroesophageal reflux (GERD) may trigger asthma. Approximately 77% of asthmatic people experience reflux symptoms, although GERD may be clinically silent in some. Esophagitis is found in 43% of asthmatic people, and 82% have abnormal esophageal acid contact times on esophageal pH testing. Clearly, GERD is prevalent in asthmatic people. Pathophysiologic mechanisms of acid-induced bronchoconstriction include a vagally mediated reflex and microaspiration. Whether these airway responses are clinically significant is the subject of some debate. Interestingly, peak expiratory flow rates and specific airway resistance alterations persist despite esophageal acid clearance. Preliminary evidence shows that substance P, an inflammatory mediator that causes airway edema, is released with esophageal acid. Although therapeutic studies are limited by their small population sizes and study design, up to 70% of asthmatic people have asthma improvement with antireflux therapy. Possible predictors of asthma response include patients with symptomatic esophageal regurgitation; abnormal proximal esophageal acid exposure; and, in surgical studies, those with normal esophageal motility and asthma response with medical therapy. Future research will further define the association between asthma and gastroesophageal reflux.