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Keywords:

  • Asia;
  • cisapride;
  • disease management;
  • gastro-oesophageal reflux disease;
  • histamine H2-receptor antagonists ;
  • prokinetic drugs;
  • proton pump inhibitors

Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATHOPHYSIOLOGY
  5. COMPARISONS BETWEEN ASIA AND THE WEST
  6. OESOPHAGEAL FUNCTION TESTING
  7. TREATMENT
  8. PRINCIPLES OF MANAGEMENT
  9. CONCLUSION
  10. REFERENCES

Gastro-oesophageal reflux disease (GORD) occurs more frequently in Europe and North America than in Asia but its prevalence is now increasing in many Asian countries. Many reasons have been given for the lower prevalence of GORD in Asia. Low dietary fat and genetically determined factors, such as body mass index and maximal acid output, may be important. Other dietary factors appear to be less relevant. Increased intake of carbonated drinks or aggravating medicines may influence the increasing rates of GORD in some Asian countries but no strong evidence links other factors, such as the age of the population, smoking or alcohol consumption, to GORD. The management of GORD in Asia is similar to that in Europe and North America but the lower incidence of severe oesophagitis in Asia may alter the approach slightly. Also, because Asians tend to develop stomach cancer at an earlier age, endoscopy is used routinely at an earlier stage of investigation. Gastro-oesophageal reflux disease is essentially a motility disorder, so short-term management of the disease can usually be achieved using prokinetic agents (or histamine (H2)-receptor antagonists). More severe and recurrent GORD may require proton pump inhibitors (PPI) or a combination of prokinetic agents and PPI. The choice of long-term treatment may be influenced by the relative costs of prokinetic agents and PPI.

© 2000 Blackwell Science Asia Pty Ltd


INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATHOPHYSIOLOGY
  5. COMPARISONS BETWEEN ASIA AND THE WEST
  6. OESOPHAGEAL FUNCTION TESTING
  7. TREATMENT
  8. PRINCIPLES OF MANAGEMENT
  9. CONCLUSION
  10. REFERENCES

Gastro-oesophageal reflux disease (GORD) is a major clinical problem in many countries but appears to occur less frequently in the Far East and South East Asia (referred to here as Asia) than in Europe and North America (the West). 1,2 Gastro-oesophageal reflux disease is characterized by reflux of gastric acid across an incompetent gastro-oesophageal junction, leading to injury of the oesophagus and oesophageal inflammation (reflux oesophagitis). Other disorders associated with GORD include Barrett’s oesophagus, benign stricture and hiatal hernia.

Classic symptoms of GORD include heartburn, regurgitation, dysphagia and odynophagia. Gastro-oesophageal reflux disease is also thought to be the most frequent cause of non-cardiac chest pain and may be associated with pulmonary disorders, such as asthma, coughing, wheezing and choking, and oral problems, such as tooth decay and gingivitis.

Information on the prevalence of GORD in Asia is limited and no comparative reviews on this subject have been published. In this paper, the Asian experience of GORD is reviewed and the possible reasons for differences between Asia and the West are discussed. Principles of disease management are also presented.

PATHOPHYSIOLOGY

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATHOPHYSIOLOGY
  5. COMPARISONS BETWEEN ASIA AND THE WEST
  6. OESOPHAGEAL FUNCTION TESTING
  7. TREATMENT
  8. PRINCIPLES OF MANAGEMENT
  9. CONCLUSION
  10. REFERENCES

Several factors, alone or in combination, can lead to the development of GORD ( Fig. 1).

image

Figure 1. Factors in the development of gastro-oesophageal reflux disease.

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Anti-reflux barrier

During swallowing, the upper oesophageal sphincter relaxes to enable food to be propelled rapidly into the oesophagus without entering the respiratory tract. The food is forced by peristalsis down the oesophagus and past the lower oesophageal sphincter, which relaxes to allow the food into the stomach. After passage, the lower oesophageal sphincter contracts to prevent regurgitation of the contents of the stomach into the oesophagus. Oesophageal motility is under central and peripheral control, which must be highly integrated.

Erect posture, mucosal folds at the lower end of the oesophagus, the angle between the lower oesophagus and the upper stomach (the angle of His) and contraction of the crura of the diaphragm all help to prevent reflux of gastric acid into the oesophagus.

Decreases in the basal tone of the lower oesophageal sphincter and transient lower oesophageal sphincter relaxations allow gastro-oesophageal reflux to occur. In particular, decreased basal tone is implicated in nocturnal symptoms, when the patient is supine. 3

Oesophageal clearance

When reflux occurs, the degree of injury to the oesophageal mucosa is determined by the time of exposure to refluxate (dwell-time) and, therefore, by the efficiency of oesophageal clearance. One of the most common complications of GORD is Barrett’s oesophagus, which develops as a direct result of increased dwell-time. 4

Clearance of oesophageal acid involves two stages: volume clearance and chemical clearance. Volume clearance occurs by gravity and oesophageal peristalsis. During swallowing, primary peristalsis travels the full length of the oesophagus and forces food and drink downwards; secondary peristalsis occurs in response to irritation caused by gastric reflux and spreads from the point of irritation to the stomach. Any remaining acid is neutralized by bicarbonate in saliva and oesophageal secretions (chemical clearance).

Oesophageal clearance is impaired in patients with GORD. 5 A higher proportion of non-peristaltic primary oesophageal contractions, a higher threshold for the induction of secondary peristalsis and a decreased amplitude of secondary peristaltic waves appear to be the main causes of poor clearance. Decreased saliva-tion can also lengthen the duration of oesophageal acid exposure.

The extent of oesophageal injury depends on the acidity and peptic activity of the refluxate, although hypersecretion of gastric acid is not a primary cause of GORD.

Delayed gastric emptying

Delayed gastric emptying can also contribute to GORD because, when emptying is delayed, the volume of gastric fluid available for reflux and the time during which the oesophagus is exposed to low pH are increased. Gastric distension, caused by delayed emptying, may also increase the frequency of transient lower oesophageal sphincter relaxations. Up to 50% of patients with GORD also have delayed gastric emptying. 6

Hiatal hernia

Hiatal hernia is defined as a circular protrusion of the gastric mucosa at least 2 cm above the oesophageal hiatus of the diaphragm. A relationship between hiatal hernia and GORD has been established in several studies but is not fully understood. 7–9 During the past 30 years, many theories have been proposed to explain this relationship.

One suggestion is that hiatal hernia is a primary cause of GORD. Raised intra-abdominal pressures due to pregnancy, tumours, obesity or straining may result in the formation of a hiatal hernia, which could then disrupt the normal anti-reflux mechanisms. Atrophy of the muscle in the diaphragmatic sphincter may have a similar effect.

Alternatively, hiatal hernia may be a consequence of GORD. Contraction of the oesophagus, as a result of gastric acid-induced oesophageal erosion, may have the effect of ‘pulling up’ the stomach, causing it to herniate.

In recent years, the idea of a ‘sump’ has attracted considerable interest. According to the sump theory, during acid clearance, a small amount of gastric acid is trapped in the herniated section of the stomach above the diaphragm. The trapped acid refluxes into the oesophagus on relaxation of the lower oesophageal sphincter during subsequent swallows. This theory implies that hiatal hernia indeed plays a role in the development of reflux oesophagitis but whether this is a primary abnormality or secondary to disturbed motility is unknown.

Role of Helicobacter pylori

Eradication of H. pylori from the stomach is widespread practice for the treatment of patients with ulcers. However, increasing evidence indicates that, in some patients, H. pylori may lower the amount of gastric acid, thereby reducing the extent of oesophageal injury. Data from recent studies suggest that patients with duodenal ulcers in whom H. pylori was successfully eradicated were twice as likely to develop GORD as those who remain infected; 10,11 however, other reports contradict this. 12 The possible link between H. pylori eradication and the development of GORD has not been demonstrated in patients without duodenal ulcers. 13 Large-scale studies are needed to resolve this contentious issue.

Other factors

Regurgitation of bile acids may also contribute to GORD and to the degree of injury to the oesophageal mucosa. Evidence suggests that duodenogastro-oesophageal reflux of bile acid causes extensive mucosal damage, possibly through toxic synergism between gastric acid and taurine conjugates in the bile. 14,15 Regurgitation of bile acid is more frequent in patients with Barrett’s oesophagus or oesophagitis.

Even prolonged exposure of the oesophagus to acid does not necessarily lead to oesophageal injury or heartburn, 16 demonstrating the inherent robustness of the healthy oesophagus. The strength of the healthy oesophagus, known as oesophageal mucosal resistance, arises from a combination of factors. Pre-epithelial defences include the mucous layer and surface bicarbonate ion concentration. Epithelial defences include cell membranes and intercellular junctional complexes and functions such as cell replication, buffers and epithelial transport. Post-epithelial defences include blood flow and tissue acid–base status. 17 Ultimately, failure of this oesophageal mucosal resistance (e.g. failure of rates of repair to keep up with injury) is necessary for the development of symptomatic GORD.

COMPARISONS BETWEEN ASIA AND THE WEST

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATHOPHYSIOLOGY
  5. COMPARISONS BETWEEN ASIA AND THE WEST
  6. OESOPHAGEAL FUNCTION TESTING
  7. TREATMENT
  8. PRINCIPLES OF MANAGEMENT
  9. CONCLUSION
  10. REFERENCES

Prevalence of gastro-oesophageal reflux disease

The prevalence of GORD and its complications is thought to be higher in the West ( Table 1) 4,7,8,18–24 than in Asia ( Table 2). 1,2,24–33 In Asia, few studies on the prevalence of GORD and its complications have been made. Few reports were published before the 1980s and those that exist indicate considerably lower levels of GORD than in the West. 1,32 Similarly, a low prevalence of hiatal hernia 25 and of Barrett’s oesophagus 34,35 has been recorded in Asians.

Table 1.  Prevalence of gastro-oesophageal reflux disease (GORD),* its associated complications and its symptoms in North America and Europe
Condition or symptomPrevalence
  1. * Symptomatic GORD, the predominant symptom of

  2. which is heartburn/acid regurgitation (reported by 83%

  3. of patients). 24 The overall prevalence of GORD in the West is therefore approximately 20–40% of the adult population. 4

Heartburn20–40% of adult population; 4
 14% reporting symptoms
  weekly, 7% reporting
  symptoms daily 18
Barrett’s oesophagus10–15% of GORD patients 4
Hiatal hernia50% of GORD patients;
 16–22% of general population 7,8
Non-cardiac chest painUp to 50% of cases attributable
  to GORD 19
Oesophageal stricture1% of GORD patients 20
Delayed gastric emptying20–40% of GORD patients 21,22
Reflux oesophagitis7–23% of GORD patients 23
Table 2.  Prevalence of gastro-oesophageal reflux disease (GORD)* and associated complications in Asian studies
SourceLocationYearMain findings
  1. * Symptomatic GORD, the predominant symptom of which is heartburn/acid regurgitation (reported by 83% of patients). 24 The overall prevalence of GORD in Asia is therefore approximately 5–17% of the adult population. 28,33

Burkitt and James 25Asia1973< 2% frequency of hiatal hernia in radiographic examinations
Ke et al.26China199383% of 52 non-cardiac chest-pain patients diagnosed with GORD
Lau et al.27Hong Kong199629% of 108 non-cardiac chest-pain patients diagnosed with GORD
Hu et al.28Hong Kong19975% of 1558 ethnic Chinese assessed by questionnaire had GORD
Lee et al.29Korea19943% prevalence of oesophagitis
Yeom et al.30Korea19985% of 1010 patients assessed by endoscopy had reflux oesophagitis and 4% had
   hiatal hernia
Kang et al.31Singapore19933% prevalence of endoscopic oesophagitis in > 10 000 patients
Wang et al.32Taiwan19789% of 165 patients assessed by endoscopy had mucosal injury
Chen et al.1Taiwan19792% of 1000 patients assessed by endoscopy had erosive oesophagitis
Chang et al.33Taiwan199717% of 2044 patients recorded one GORD symptom, 5% had reflux oesophagitis,
    2% had hiatal hernia
Yeh et al.2Taiwan199715% of 464 patients assessed by endoscopy had erosive oesophagitis, 2% had
    Barrett’s oesophagus and 7% had hiatal hernia

More recent studies suggest that the prevalence of GORD in Asia is either increasing or being recognized more frequently. In Hong Kong, Lau et al. classified almost 30% of patients with non-cardiac chest pain as having GORD by using 24 h ambulatory pH monitoring to measure abnormal reflux patterns. 27 In the West, the proportion of non-cardiac, chest-pain patients with GORD has been reported at higher levels (as high as 50%) 19 but other Western studies 36 have produced similar results to those of Lau et al. In a study conducted in China in 1993, Ke et al. found a very high prevalence of GORD (83%) in patients with non-cardiac chest pain; 26 those investigators used a combination of oesophageal function tests, which could explain the very high rates of GORD. However, Hu et al. showed that only 5% of a Chinese population had GORD; 28 this rate is considerably lower than equivalent reports from the West. 37

In a 1-year study in Taiwan, patients evaluated for upper gastrointestinal tract symptoms had a prevalence of erosive oesophagitis (15%) similar to that recorded in the West. 2 Barrett’s oesophagus was also found in numbers similar to Western reports (2% of the overall study population and 14% of those with oesophagitis). The prevalence of hiatal hernia (7% overall and 29% in patients with erosive oesophagitis) was lower than in Western studies but the method of detection of hiatal hernia can influence significantly the apparent prevalence (e.g. data from barium swallow methods are lacking in Asia). No conclusions were drawn from that study about the overall prevalence of GORD because endoscopy alone was used, without 24 h oesophageal pH monitoring.

In a large study of Taiwanese patients, 17% had at least one of three reflux symptoms (acid regurgitation, heartburn and belching) almost daily. 33 This prevalence confirmed that symptoms of GORD are common among the Chinese. However, endoscopy showed that reflux oesophagitis, with a prevalence of 5%, was less common than in the West and less than reported by Yeh et al.2 Hiatal hernia rates were low in the whole study group and were observed in only 20% of patients with oesophagitis; this is significantly lower than in the West.

In Korea, reflux oesophagitis was found in 5% of patients referred for upper gastrointestinal endoscopy. 30 Although lower than in Western reports, this is higher than the 3% prevalence among Koreans reported previously. 29 The difference may be because the study involved a tertiary medical centre to which only patients with more severe symptoms were referred. The prevalence of hiatal hernia was also higher than expected (32% of patients with reflux oesophagitis). A low frequency of oesophagitis (3%) was found in patients with upper gastrointestinal complaints in Singapore; this study involved 10 000 patients. 31

Delayed gastric emptying occurs in approximately 20–40% of GORD patients in the West 21,22 but has been recorded in up to 50% of patients. 6 In a small-scale study in China, Hou et al. found delayed gastric emptying in a similar proportion of GORD patients (54%). 38

Factors relating to prevalence of gastro-oesophageal reflux disease in Asia

Several factors that influence the prevalence of GORD have been identified ( Table 3). 33,39–45 Differences in these factors are often used to explain the lower prevalence of GORD in Asia but little supportive evidence exists. The reasons for the recent increase in the prevalence of GORD in Asia are also not clear; this increase may be apparent rather than real. In the West, increased medical attention to GORD, improved diagnosis and technological advances led to more patients being diagnosed with GORD. Thus, in Asia, increased referrals for symptoms of GORD, improved diagnosis and an increase in the use of endoscopy may be contributing to the apparent increase in prevalence.

Table 3.  Possible factors contributing to the lower prevalence of gastro-oesophageal reflux disease in Asia than in the West 33,39–45
Genetic factors
Low maximal acid output/small parietal cell mass
High lower oesophageal sphincter pressure
Lower body mass index and lower obesity
Lower consumption of alcohol, coffee and tea
Smoking
Fewer aggravating medicines used
Dietary factors
Lower dietary fat/chocolate
Lower consumption of carbonated soft drinks
Lower consumption of citrus fruit drinks

In a prospective study of Malaysian patients with dyspepsia attending a primary care clinic, 46 heartburn and acid regurgitation were reported by 58 and 50% of patients, respectively. However, few of these patients reported severe symptoms (4% with heartburn; 2% with regurgitation) and the prevalence of oesophagitis, detected by endoscopy, was low. 47 This suggests that mild (endoscopy-negative) GORD is quite prevalent in the Malaysian population.

Diet may be one of the major reasons for lower rates of GORD in Asia. In general, food and drink can make GORD worse because both fill the stomach, induce transient relaxations of the lower oesophageal sphincter and stimulate gastric acid production. However, specific dietary components are a more likely cause of differences between the West and Asia.

Dietary fat has been shown to increase the frequency of transient lower oesophageal sphincter relaxations, 39,48 possibly via release of cholecystokinin. 49 Therefore, the lower fat content of Asian diets may explain, in part, the lower prevalence of GORD. In addition, the increase in GORD in Asia appears to correlate with an increase in dietary fat. Department of Health data from Taiwan showed that dietary fat in Taiwan increased from 11 g/day per person in 1945 to 81 g/day per person in 1978 and 137 g/day per person in 1991. 2 The fat content of chocolate may explain the reported precipitation of GORD symptoms by chocolate.

Another dietary cause of heartburn is acidic drinks. 40 The prevalence of GORD in Asia may be related to the consumption of citrus fruit drinks or carbonated soft drinks (which have very low pH) but no evidence indicates that Asians drink fewer of these drinks than Westerners or that an increase in consumption has contributed to the increase in GORD in recent years.

Other factors that may contribute to the difference in the prevalence of GORD between Asia and the West include cigarette smoking, alcohol consumption, obesity and body mass index. Smoking can increase the risk of GORD by causing transient reduction in lower oesophageal sphincter pressure, reducing salivary output and increasing acid clearance time. 41 The consumption of alcohol may increase the occurrence of GORD by inducing oesophageal motor dysfunction. 42 However, little evidence indicates that smoking or alcohol intake is lower in Asia than in the West or that they have increased in line with the prevalence of GORD.

Obesity has been reported to be associated with hiatal hernia and oesophagitis; 50 therefore, lower rates of obesity (and smaller body mass index) in Asians may contribute to the lower prevalence of GORD and its complications. For example, Chang et al. reported that body mass index was significantly higher in Chinese patients with oesophagitis than in those without oesophagitis. 33

Genetic differences may also account for the contrast between the West and Asia. Higher parietal cell mass in the stomach (resulting in higher gastric acid secretion) has been observed in people with a higher body mass index (i.e. those in the West). Another often overlooked factor is the difference in the maximal acid output between races. Lower rates of maximal and basal acid output have been reported in Indians and Chinese than in Europeans and Americans. 43,51,52 The investigators took into account the lower body mass index in Asians and still found significant differences in maximal acid output. The reason for these differences is not clear but the lower maximal acid output could explain why fewer Asian than Western patients with GORD experience chest pain. 27 Maximal and basal acid output have increased in Japan in the past 20 years but the causative factor is unknown. 53

Widespread H. pylori eradication may also contribute towards increased gastric acid in some patients. In the West, H. pylori infections are decreasing, with a concomitant decrease in peptic ulcer prevalence and this correlates with an increased prevalence of GORD. 54 In Japan, patients with H. pylori infection tended to have decreased gastric acid secretion, possibly because H. pylori infection may contribute to atrophic gastritis, 53,55,56 but the increases in maximal and basal acid output in these patients in the past 20 years was independent of H. pylori. 53 The link between H. pylori eradication and the development of GORD is still in doubt and, therefore, less extensive use of H. pylori eradication therapy in Asia is unlikely to be responsible for lower rates of GORD.

In a recent Korean study, 57 relatively high lower oesophageal sphincter pressures were found even in patients with reflux oesophagitis. The authors suggested that this could contribute to the lower rates of GORD in Korea.

Certain medicines, such as opioid analgesics, anticholinergic agents and calcium antagonists can aggravate reflux. These medications may previously have been used less frequently in Asia but their use appears to be increasing (no evidence to confirm this has been published). Non-steroidal anti-inflammatory drugs are known to induce gastrointestinal damage, such as peptic ulcers, and recent reports also suggest that these drugs can induce GORD or reflux-like symptoms. 58 The data are sparse but certain medicines may contribute to the observed increase in the prevalence of GORD in the elderly. 2,44 Alternatively, the combined effect of ageing and aggravating medicines may decrease lower oesophageal sphincter pressure or oesophageal acid clearance. 2 Hence, lower rates of GORD in Asia may reflect younger populations and recent increases in GORD may be the result of improved life expectancy. The evidence for this is rather weak and, in recent Asian studies, no link was shown between prevalence of reflux oesophagitis and patient age. 30,33

Drinks such as tea and coffee have been linked to GORD but this is also contentious. Although tea has been shown to increase gastric acid secretion, 45 it does not appear to contribute to GORD. By comparison, coffee apparently increases gastro-oesophageal reflux. 59 The irritant effect of coffee may be caused by its higher caffeine content but this has been disputed. 59 Coffee is relatively unpopular in Asia and this could contribute to the lower prevalence of GORD, although no evidence indicates that coffee consumption is on the increase. Chang et al. found no link between coffee or tea consumption and the incidence of oesophagitis. 33

The mechanisms by which many of the above factors influence the rate of GORD are not known and the reasons for the historically lower prevalence of GORD in Asia and the increase in its prevalence in recent years are not clear. Although some form of westernization is often given as the reason for the increase, insufficient evidence exists to reach a firm conclusion. The increase in the prevalence of GORD in Asia has predictably led to a greater need for accurate diagnosis and rapid treatment of symptoms.

OESOPHAGEAL FUNCTION TESTING

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATHOPHYSIOLOGY
  5. COMPARISONS BETWEEN ASIA AND THE WEST
  6. OESOPHAGEAL FUNCTION TESTING
  7. TREATMENT
  8. PRINCIPLES OF MANAGEMENT
  9. CONCLUSION
  10. REFERENCES

Options for oesophageal function testing include barium swallow, endoscopy, manometry and 24 h pH monitoring. Investigation is needed in only a few cases: when symptoms are atypical; when alarm symptoms are present (dysphagia, vomiting, bleeding, anaemia and weight loss); or when symptoms are unresponsive to initial therapy. The investigation of first choice is endoscopy because it allows direct observation of oesophageal damage and enables detection of Barrett’s oesophagus. However, not all patients with symptoms of GORD show endoscopic abnormalities 20 and endoscopy fails to provide any measure of acid reflux. Symptoms of reflux, such as heartburn, are not good predictors of reflux disease and 24 h pH monitoring is the gold standard for objective detection of acid reflux. A barium radiograph series and manometry can be useful for functional measurements.

Additional information on the pathophysiology of GORD may be obtained by a test of gastric emptying (such as scintigraphy or [13C]-octanoid acid breath test) but these are rarely undertaken and not widely available at present.

TREATMENT

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATHOPHYSIOLOGY
  5. COMPARISONS BETWEEN ASIA AND THE WEST
  6. OESOPHAGEAL FUNCTION TESTING
  7. TREATMENT
  8. PRINCIPLES OF MANAGEMENT
  9. CONCLUSION
  10. REFERENCES

The treatment of GORD depends on the severity of the disease, which means the severity of symptoms in most cases. The treatment of GORD does not appear to differ between the West and Asia but the lower incidence of severe oesophagitis in Asia may result in a slightly different approach. 2,30,33 Several therapeutic options are available for the relief of symptoms of GORD and for healing associated damage ( Table 4). 20,60–62

Table 4.  Treatments for gastro-oesophageal reflux disease and their relative effectiveness 20,60–62
Treatment optionTherapeutic benefit
  1. –, no benefit; +, mild benefit; + +, moderate benefit; + + +, strong benefit. Parentheses indicate doubts about true level of benefit. PPI, proton pump inhibitor; H2, histamine H2.

Lifestyle changes(+)
Antacids/alginates+
Helicobacter pylori eradication
Standard-dose H2-receptor antagonists + +
High-dose H2-receptor antagonists (+ +)
Low-dose PPI+ +
Standard-dose PPI+ + +
High-dose PPI+ + +
Prokinetic agents+ +
Prokinetic agents and PPI+ + +

Mild GORD may be relieved by lifestyle modifications, such as raising the head of the bed and increasing the number of pillows. Over-the-counter antacids or standard-dose histamine (H2)-receptor antagonists provide symptomatic relief in mild GORD. 20 However, standard doses of H2-receptor antagonists heal fewer than 50% of patients with erosive oesophagitis after 6 weeks of treatment. 5 High-dose H2-receptor antagonists can achieve better healing rates, although pharmacological tolerance may develop over a 4-week period. 63

More severe disease must be treated with more powerful drugs. In large prospective trials, only proton pump inhibitors (PPI) produced healing rates of more than 90%. 5 In a meta-analysis of trials comparing PPI and H2-receptor antagonists, faster and more complete healing of oesophagitis and relief of heartburn was found to be achieved with PPI. 61 The PPI are also more cost-effective (despite being more expensive drugs) in patients with oesophagitis because of their fast healing properties and prevention of recurrence. 64,65

Because GORD is essentially a motility disorder (30–50% of patients with heartburn report dysmotility symptoms) 66,67 and is not caused by acid hypersecretion, prokinetic agents such as cisapride have been used to enhance lower oesophageal sphincter tone and gastric emptying. In addition, acid suppression does not improve these dysmotility symptoms in patients with GORD, 5 which may explain why 10–30% of patients do not respond to acid suppression. 68,69 Cisapride is as effective as the H2-receptor antagonists at producing symptom relief in patients with GORD (20–75% of patients) 5 and more effective than H2-receptor antagonists in the long-term maintenance treatment of GORD. 62 The combination of cisapride and PPI has also shown benefit in maintaining remission in patients with GORD. 70 The cost of different treatments varies between countries but prokinetic agents are generally cheaper than PPI. In the West, this price difference is relatively small; for example, in the United States, the cost of cisapride ranges from 50 to 100% of the cost of PPI (depending on the cisapride dose used). However, in Asia, the price for the daily dose of PPI is two to 10-fold the cost of prokinetic agents. No cost–benefit comparisons have been made in these countries.

PRINCIPLES OF MANAGEMENT

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATHOPHYSIOLOGY
  5. COMPARISONS BETWEEN ASIA AND THE WEST
  6. OESOPHAGEAL FUNCTION TESTING
  7. TREATMENT
  8. PRINCIPLES OF MANAGEMENT
  9. CONCLUSION
  10. REFERENCES

A basic outline for the management of GORD in Asia is provided in Fig. 2. One of the major differences between Asia and the West is the age at which endoscopic investigation is used before any treatment is given. In Asia, because of the early onset (and higher prevalence) of stomach cancers, endoscopy should be used and a biopsy taken routinely in patients aged more than 35 years but, in the West, screening is not routine in those aged less than 55 years. 71 The use of pH monitoring would also confirm the presence of acid reflux in the absence of abnormal endoscopy findings.

image

Figure 2. Proposed strategy for the management of gastro-oesophageal reflux disease in Asia. LOS, lower oesophageal sphincter.

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Prompt and effective relief of symptoms is the primary goal of short-term management of GORD when alarm symptoms are absent. In addition to obvious advice on lifestyle modifications, a 4-week course of a prokinetic agent such as cisapride (20– 40 mg/day) or an antisecretory agent such as an H2-receptor antagonist is an effective way of achieving this, particularly when symptoms are mild to moderate. When patients are unresponsive to this treatment, another option is required, such as a PPI. When patients continue to fail or have more severe symptoms, a combination of a PPI and a prokinetic agent is effective.

Often GORD symptoms recur within weeks of stopping or reducing a short course of treatment and the patient may then require long-term management. Patients who fail to respond at any stage of treatment should be investigated with endoscopy or 24 h pH monitoring, or both. Higher doses of PPI with or without a prokinetic agent may be used in patients with unresponsive or rapidly relapsing disease and maintenance doses established on resolution of symptoms.

Anti-reflux surgery should be reserved for those who still relapse or for young, fit patients who are unwilling to take long-term treatment. Patients with significant hiatal hernia may also require surgery. The operations, which should be undertaken only by those regularly involved in oesophageal surgery, are very effective and are indicated in patients with volume reflux, which is frequently associated with the respiratory and oropharyngeal symptoms and complications of GORD. Anti-reflux procedures are contraindicated in patients with oesophageal dysmotility and preoperative assessment by manometry is recommended. Laparoscopic anti-reflux operations are gaining popularity.

CONCLUSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATHOPHYSIOLOGY
  5. COMPARISONS BETWEEN ASIA AND THE WEST
  6. OESOPHAGEAL FUNCTION TESTING
  7. TREATMENT
  8. PRINCIPLES OF MANAGEMENT
  9. CONCLUSION
  10. REFERENCES

The available evidence shows that the prevalence of GORD in Asia has increased in recent years but is still lower than in the West. Many factors may explain the differences between Asia and the West but strong evidence is scarce. Further work is needed to determine the relative importance of these factors because they could influence the approach to management of GORD in Asia. The management of GORD in Asia differs slightly from that in the West because of the lower incidence of severe oesophagitis and the higher prevalence of stomach cancer. This leads to earlier routine use of endoscopy in Asia. Short-term management of GORD can usually be achieved with prokinetic agents or H2-receptor antagonists but severe or recurrent illness may require PPI or combination therapy. The cost-effectiveness of the different treatment options in Asia needs to be assessed.

REFERENCES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATHOPHYSIOLOGY
  5. COMPARISONS BETWEEN ASIA AND THE WEST
  6. OESOPHAGEAL FUNCTION TESTING
  7. TREATMENT
  8. PRINCIPLES OF MANAGEMENT
  9. CONCLUSION
  10. REFERENCES
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    Yeh C, Hsu CT, Ho AS, Sampliner RE, Fass R. Erosive esophagitis and Barrett’s esophagus in Taiwan: A higher frequency than expected. Dig. Dis. Sci. 1997; 42: 702 6.
  • 3
    Dent J, Holloway RH, Toouli J, Dodds WJ. Mechanisms of lower oesophageal sphincter incompetence in patients with symptomatic gastro-oesophageal reflux. Gut 1988; 29: 1020 8.
  • 4
    Spechler SJ. Epidemiology and natural history of gastro-oesophageal reflux disease. Digestion 1992; 51 (Suppl. 1): 24 9.
  • 5
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