Gastroesophageal Reflux Disease: Definition and Scope of the Problem in the United States of America and Worldwide

Definition

GERD is a condition that is defined as troublesome symptoms or complications that result from the reflux of gastric contents into the esophagus or beyond into the oral cavity or lung. Troublesome is defined by consensus as mild symptoms that occur at least 2 times per week or moderate to severe symptoms at least once per week. The pathogenesis is multifactorial. Overall, GERD is a disorder caused by abnormal function of the lower esophageal sphincter (LES). The most frequent abnormality is an increase in so-called transient lower esophageal sphincter relaxations (TLESR), a normal physiologic occurrence of sphincter opening without an antecedent swallow that results in reflux of gastric contents into the esophagus. Basal LES pressure may be low, and transient increases in intraabdominal pressure and a hiatal hernia contribute to LES dysfunction and reflux. Traditional thinking is that acidic gastric contents cause symptoms and/or injury via direct contact with mucosa resulting in inflammation. The role of bile acids in producing symptoms and reflux injury is controversial. In combination with acid there is likely synergy causing esophagitis. A recent study suggests that reflux injury may be a result of an inflammatory reaction. Reflux is cleared by secondary peristalsis and neutralization by salivary bicarbonate. Failure of either of these clearance mechanisms may contribute to injury. In some cases, gastric emptying delay may contribute to GERD by increasing gastric volume and precipitating TLESRs. Other factors such as central obesity can increase intraabdominal pressure and result in GERD.

Symptoms of GERD can be divided into typical, atypical, and extraesophageal ( Fig. 15.1 ). The most common typical symptoms of GERD are heartburn and regurgitation. Many consider dysphagia and chest pain as typical symptoms as well. Atypical symptoms include dyspepsia, epigastric pain, nausea, bloating, and belching. The most common extraesophageal symptoms include chronic cough, asthma, and throat symptoms including chronic voice disturbance and laryngitis. The latter may be associated with typical symptoms or sometimes may be the presenting symptom of the disease. Direct aspiration of gastric contents are believed to be the most common cause of these extraesophageal symptoms, although rarely they may result from distal esophageal acid exposure alone via a reflex event.

Scope

GERD is a common disease affecting millions of people worldwide. The prevalence is up to 30% in Western countries and 10% in Asia ( Table 15.1 and Fig. 15.2 ). These data are based on a number of epidemiologic studies that have been performed and reviewed in the literature (see Table 15.1 and Fig. 15.2 ).

In the United States, the prevalence ranges from 18.1% to 27.8%. A study published in 2007 explored the prevalence of irritable bowel syndrome (IBS) and GERD. The researchers sent a questionnaire to 4194 people with 2273 returning the questionnaire. The study found the overall prevalence of GERD to be 18.1% in a group representative of the United States Caucasian population. The upper range of GERD prevalence in the United States of 27.8% was established in a cross-sectional survey asking questions pertaining to weekly heartburn or regurgitation symptoms.

Studies have been performed in the United States to evaluate if the prevalence of GERD changes based on race. A 2004 cross-sectional survey studied the prevalence of GERD in African American and Caucasian Veterans Affairs (VA) employees. The study included a survey followed by endoscopy. No statistically significant difference in GERD prevalence was found between the two groups (27% and 23% with heartburn, and 16% and 15% for regurgitation in African Americans and Caucasians, respectively). However, there were higher rates of esophagitis in Caucasians compared with African Americans. The prevalence of GERD in Hispanics in the United States is thought to be similar to non-Hispanic whites. A survey-based study performed in Philadelphia found that Hispanics had higher monthly heartburn than other racial groups with a prevalence of 50%. Asians surveyed in the same study were found to have a 20% prevalence of monthly heartburn.

In South America, the prevalence of weekly symptoms of heartburn or regurgitation was approximately 23% in a study published in 2005. This study highlighted the prevalence of GERD only in an Argentinian population. More recently, a Brazilian study echoed findings similar to the 2004 study. In that study, monthly GERD symptoms were found to be approximately 22.7%.

Based on eight studies in two separate epidemiologic reviews, the prevalence of GERD in Europe ranges from 8.8% to 25.9%. This represents an increased prevalence from the previously presented data of 9.8% to 18%. Two studies were large surveys sent via mail to Swedish populations, which established the increased prevalence.

The prevalence of GERD in East Asian populations has increased from 2.5%–4.8% to 3.5%–7.8%. In the epidemiologic review published in 2005, the prevalence was based on three studies conducted in mainland China and Hong Kong. Two of the studies were telephone surveys completed by 3858 individuals; the third was a survey of 5000 people and was conducted with the assistance of physicians and medical students. More recently, the three studies included in the review by El-Serag were conducted in South Korea and China. Between the three studies, 20,833 people were surveyed leading to the findings of 3.5% to 7.8% prevalence of GERD. An additional review performed in Korea between 2005 and 2010 found that the prevalence in eastern Asia may range from 5.2% to 8.5%.

Middle Eastern populations also have a significant prevalence of GERD ranging from 8.7% to 33.1%. When evaluating the data there was one study in Turkey, one in Israel, and five studies in Iran. The Turkish study evaluated 630 patients and the prevalence of GERD symptoms, heartburn or regurgitation, ranged from 10% to 15.6%. The study performed in Israel evaluated 981 patients and found a prevalence of 9.3%. Finally, the Iranian studies of GERD showed a prevalence of 8.7% to 21.2% with the exception of one study evaluating nomads in Iran. Similar to the Israeli study, this particular study evaluated only a subgroup of the population and may falsely increase the prevalence in the general population. A more recent study suggests that the prevalence of GERD may range from 14% to 34% in Iran. If we include a study published in 2014, which surveyed a Saudi Arabian population, the overall prevalence range in the Middle East ranges from 8.7% to 45.4%.

The current body of data does not show a difference in prevalence of GERD in aging patients. Available data do, however, suggest that esophageal sensitivity to acid decreases with age, thus predisposing those older than 55 to 65 years to an increase in higher grades of esophagitis than younger patients. There does not appear to be a large difference in GERD symptoms between men and women. However, some studies suggest women tend to present with nonerosive disease, whereas men tend to have more esophagitis and Barrett esophagus.

GERD is also prevalent in pregnancy and ranges from 30% to 80% at some point during the course of pregnancy. A 2012 study evaluated prevalence throughout the course of pregnancy and found a prevalence of 26.1%, 36.1%, and 51.2% in trimesters one through three. A separate study found that the incidence of GERD is approximately 25% in each trimester of pregnancy. Little information is available on the end organ effects, if any, of GERD in pregnancy, though clinical experience suggests they are minimal. Although some feel that GERD in pregnancy is a risk for long-term disease, the data supporting this are lacking. GERD symptoms commonly resolve with delivery, but may start again at a later date in some patients.

Two longitudinal studies are worth reviewing in some detail. The first was a representative random sample of the normal population of two communities in northern Sweden. Subjects were surveyed and a large number ( n = 1000) underwent endoscopy. GERD symptoms increased with age, the lowest being the 20- to 34-year-old group and peaking in the 50- to 65-year-old and older groups. One thousand participants underwent esophagogastroduodenoscopy (EGD); the prevalence rates for monthly, weekly, and daily GERD symptoms were 40%, 20%, and 6%, respectively, with no statistical differences between females and males. EGD showed normal endoscopic findings, esophagitis, and hiatal hernia in 77%, 15.5%, and 23.9% of subjects, respectively. Of the group with monthly GERD symptoms, 35%, 63%, and 53% had normal endoscopy, esophagitis, and hiatal hernia, respectively. When compared to females, men had more esophagitis (odds ratio: 2.83), especially in the younger age groups (32%). Compared to asymptomatic individuals, those with GERD symptoms, esophagitis, or both reported an increased prevalence of medical treatment—that is, antacids, proton pump inhibitors (PPIs) or any medication—0% to 3% in normal patients versus 8% to 33% in persons with GERD symptoms.

The ProGERD study assessed symptoms and endoscopic findings in a cohort of GERD patients from Germany, Switzerland, and Austria with the intent to examine the natural history of the disease. A total of 3894 patients with GERD symptoms participated in a longitudinal study undergoing EGD at baseline and at 2-year follow-up. After a baseline EGD, all patients received treatment with esomeprazole. Thereafter, further medical treatment was given at the discretion of the physician. After 2 years, 25% of those with non-erosive reflux disease (NERD) were noted to have grade A or B esophagitis, whereas 6% had grade C or D esophagitis. In patients with baseline grade A and B esophagitis, 1.6% progressed to grade C and D, and 61% with baseline A and B esophagitis regressed to NERD (no esophagitis; normal endoscopy) at 2 years. Among those with grade C and D esophagitis, 42% regressed to A and B esophagitis, and 50% of those with grade C and D regressed to NERD. The study tells us that although the endoscopic findings of GERD are not static, the vast majority of patients with esophagitis heal and those with NERD remain stable. A second study from Germany reproduced the trend of the above ProGERD study in a smaller group of GERD patients. Overall GERD symptom prevalence remains stable over time.

Multiple logistic regression analyses show male gender, increased body mass index, regular alcohol consumption, history of GERD longer than 1 year, and smoking were risks for erosive esophagitis. A positive Helicobacter pylori status was associated with a lower risk.

The ProGERD study also examined the history of GERD medication over a 4-year period. PPIs were used in 79%, 84%, 85%, and 87% of patients after 1, 2, 3, and 4 years, respectively. Continuous PPI administration was needed in 53%, 49%, 56%, and 56% of patients after 1, 2, 3, and 4 years. On-demand PPI therapy was administered in 26%, 35%, 29%, and 29% of patients after 1, 2, 3, and 4 years, respectively. The need for continuous PPI treatment increased with advanced grades of esophagitis. After 1, 2, 3, and 4 years, 61%, 56%, 60%, and 60% of those with severe esophagitis at baseline, respectively, remained on continuous PPI treatment.

The next analysis of the ProGERD study examined the effect of GERD on the quality of life of the patients over a 5-year period. Over the 5-year period, medical treatment improved the categories emotional distress, sleep disturbances, eating problems, and vitality by 60% to 69%. In 54% of patients, physical/social function remained unchanged, whereas it improved in 42%. In all dimensions, clinically relevant worsening was observed in less than 6% of patients. Impairment of the quality of life could largely be attributed to advanced disease with a high symptom load and the perception of nighttime reflux with sleep disturbances. These patients need more than medical treatment and should be offered surgical management of GERD.

In addition to typical symptoms, GERD can impair the quality of life because of the generation of so-called extraesophageal or atypical symptoms (chest pain, cough, laryngeal symptoms, asthma). Jaspersen et al. examined the frequency of extraesophageal GERD symptoms in persons who participated in the ProGERD study (48% NERD, 52% GERD). Extraesophageal symptoms were present in 34.9% and 30.5% of GERD and NERD patients, respectively, and included chest pain (14.5%), cough (13%), laryngeal complaints (10.4%), and asthma (4.8%). Except for asthma, all atypical symptoms were more prevalent in GERD. After 5 years, the prevalence of the symptoms remained unchanged, except for asthma, which increased from 4.5% to 7.8%. The resolution of the extraesophageal symptoms was independent of erosive disease, typical symptoms, disease duration, and PPI medication. Risk factors for the presence and persistence of symptoms included female gender, increased age, more severe esophagitis (types C and D), GERD history longer than 1 year, and smoking. The important epidemiologic data indicate that compared to typical symptoms, extraesophageal GERD symptoms may originate from a different or multifactorial pathogenesis, do not correlate with endoscopic findings, and do not reliably respond to medical treatment.

Complications

Complications associated with GERD include strictures, Barrett esophagus, and adenocarcinoma. In addition, significant decreases in quality of life and economic impact are associated with this disease.