GERD: A fresh look at a common problem in primary care

Associate Clinical Professor, Department of Family Medicine, University of Alberta, Canada

Without consistent terminology or a “gold standard” for diagnosis, primary care physicians face uncertainty when making disease management decisions about patients presenting with symptoms of gastroesophageal reflux disease (GERD). The need for a patient-centered, symptom-driven approach to GERD assessment and diagnosis was addressed in the Montreal definition and classification published in 2006 (FIGURE).¹

Developed by an expert consensus group consisting of 44 primary and secondary care physicians from 18 countries, the Montreal definition is built on evidence-based medicine and systematic literature reviews. It consists of 51 statements that were developed using an iterative consensus-building process of 4 rounds of discussions, group feedback, revisions, and voting. This definition has been endorsed by the World Organization of Gastroenterology as an important development in a critical area of gastroenterology worldwide.¹

The prevalence of GERD is estimated to be 10% to 20% in Europe and North America and at least 5% in Asia.² This article describes the use of the Montreal definition to manage and diagnose GERD in the primary care setting.

  Defining the hallmark symptoms of GERD

The cardinal symptoms of GERD are heartburn and regurgitation. Heartburn is now defined as a burning sensation in the retrosternal area, and regurgitation as the perception of flow of refluxed gastric content into the mouth or hypopharynx. The effortless quality of the return of gastric contents distinguishes regurgitation from the forceful experience of emesis. Although the reflux of acidic gastric content is usually responsible for the symptoms of GERD, non-acid reflux of substances such as bile may also be important in a minority of patients.³

  Symptoms guide diagnosis and treatment

Gastroesophageal reflux manifests as a continuum of symptom frequency and severity in the general population; a large proportion of the population experiences occasional symptoms. The Montreal definition includes a measure of symptom severity by stating that GERD is “a condition which develops when the reflux of stomach contents causes troublesome symptoms and/or complications.” Population-based studies have shown that most people will find symptoms to be troublesome when mild symptoms occur on 2 or more days a week, or more severe symptoms occur at least once a week.^4,5 Daily life becomes more adversely affected as the frequency and severity of GERD symptoms increase.^4,6

In clinical practice, the patient rather than the physician determines if his or her reflux symptoms are troublesome (See “Evaluating GERD: Grades of Evidence”). To aid patient-physician communication, the severity and impact of reflux symptoms can be assessed by patient-completed questionnaires, such as the Reflux Disease Questionnaire (RDQ), the Gastrointestinal Symptom Rating Scale (GSRS), and the Quality of Life in Reflux and Dyspepsia questionnaire (QOLRAD).^7-9

It is appropriate to begin treatment on the basis of troublesome reflux symptoms without additional diagnostic testing, provided there are no alarm features (TABLE 1). Monitoring treatment response is a useful guide to diagnosis and to assessing the success of disease management.¹ When heartburn is alleviated by acid-suppressive therapy, this is a strong indication that acid regurgitation is the cause of the symptoms. The recommended duration of initial treatment is 4 to 8 weeks with proton pump inhibitors (PPIs), after which the effectiveness of therapy should be determined, ideally by using a patient reported outcome measure such as the GERD Impact Scale (GIS) or the Proton Pump Inhibitor Acid Suppression Symptom test (PASS).^10-12

Patients who suffer from GERD symptoms may be concerned about the possibility that more serious problems, such as heart disease or cancer, are the cause of their symptoms.¹³ A careful assessment to determine the correct causes of symptoms and communication with the patient about GERD and its treatment are valuable in reassuring the patient. This article will address the diagnosis and treatment of GERD by posing and answering key clinical questions.

Alarm features prompting further investigation

CLINICAL QUESTION: When is endoscopy indicated for patients with symptoms of GERD?

When large groups of patients are evaluated, a correlation can be seen between the severity of reflux symptoms and the severity of the underlying esophageal damage caused by GERD. Unfortunately, the correlation between symptom severity and endoscopic findings is poor when dealing with an individual patient who has GERD.^1,14 indeed, most patients with troublesome GERD symptoms will have no visible evidence of esophagitis at all on endoscopy. These patients are said to have “non-erosive reflux disease.”

Endoscopic findings are thus of only marginal value in guiding a GERD diagnosis, and negative endoscopic findings in the presence of troublesome heartburn or regurgitation are consistent with a diagnosis of GERD. The diagnosis of GERD can almost always be made on the basis of symptoms alone, so that beginning treatment without an endoscopy and on the basis of troublesome symptoms is appropriate, provided there are no alarm features.

CLINICAL QUESTION: What GI disorders should be suspected of causing noncardiac chest pain?

There was strong support among the Montreal definition consensus group that GERD can cause chest pain that closely mimics ischemic cardiac pain.¹ Although esophageal motor disorders can also cause pain resembling ischemic cardiac pain, chest pain is much more frequently caused by acid reflux than by conditions such as nutcracker esophagus or esophageal spasm.¹⁵

In nearly half of patients with noncardiac chest pain, GERD is estimated to be the cause of the pain. Nevertheless, once cardiac causes have been excluded, patients are often left untreated. Study findings show that these patients carry a burden of increased health care use and functional impairment until they are correctly diagnosed and treated.^16,17

CLINICAL QUESTION: Why is it particularly important to assess the presence of nighttime symptoms?

Sleep disturbance is remarkably prevalent in GERD. in a North American population-based survey, approximately one-quarter of the more than 15,000 respondents reported having heartburn during the sleep period.¹⁸ in surveys conducted in patients with GERD, between one in five and four in five respondents reported having their sleep disrupted by heartburn or regurgitation; similar data have emerged from clinical trials that examine sleep disturbance prior to the start of therapy in reflux disease.^1,19 Sleep problems at night caused by GERD symptoms can lead to daytime tiredness, which disrupts daily functioning and productivity.²⁰

A causal link between GERD and sleep disturbance is supported by therapeutic acid-suppression studies in patients with GERD.²¹ Sleep disturbance, as well as nighttime reflux symptoms, improve substantially with PPI therapy.²¹

CLINICAL QUESTION: When is dysphagia a cause for concern?

Dysphagia is common in GERD. in an analysis of more than 11,000 patients with reflux esophagitis, 37% reported dysphagia when a symptom checklist was used.²² Dysphagia resolved in most patients (83%) after treatment with a PPI.²² Dysphagia that persists after the initial 4 to 8 weeks of treatment or gets progressively worse, especially for solids, is far less common and warrants further investigation to look for esophageal malignancy.²³

  GERD is a spectrum disease

An important concept emerging from the consensus process is that of GERD being a spectrum disease that can run from symptomatic GERD through the potential complications of esophagitis, hemorrhage and stricture formation, to Barrett’s esophagus and esophageal adenocarcinoma (TABLE 2). The concept of GERD as a spectrum disease is supported by the findings of a recent large 2-year study in nearly 4000 patients with GERD under routine clinical care, which showed that progression and regression between grades does occur.²⁴

Esophageal adenocarcinoma is now regarded as a complication of GERD, albeit a rare one.¹ The risk of adenocarcinoma appears to rise with increasing frequency and duration of heartburn.²⁵ There also seems to be a worldwide increase in the incidence of esophageal adenocarcinoma that parallels the higher prevalence of reflux disease.²⁶

The Montreal definition of GERD provides a revised global consensus definition of Barrett’s esophagus. The consensus group agreed that terminology is needed to differentiate between an endoscopic suspicion of Barrett’s esophagus and a histologically confirmed diagnosis of esophageal columnar metaplasia. “Endoscopically suspected esophageal metaplasia (ESEM)” is the new consensus terminology for endoscopic findings consistent with Barrett’s esophagus before histological confirmation is obtained.¹ When a biopsy specimen of ESEM shows columnar epithelium, it should be called Barrett’s esophagus, and the presence or absence of intestinal-type metaplasia should be specified.¹ For the primary care physician, the revised terminology is important in understanding endoscopic diagnosis and the rationale for including some patients in surveillance programmes.

The GERD disease spectrum

CLINICAL QUESTION: When are respiratory problems likely to be reflux-related?

The respiratory syndromes associated with GERD are reflux cough, laryngitis, and asthma. in most cases, GERD is probably an aggravating factor rather than the sole cause of chronic cough, laryngitis, or asthma. Potential mechanisms of reflux cough include aspiration of acid material and indirect, neurally mediated pathways. in the absence of heartburn or regurgitation, unexplained asthma or laryngitis are unlikely to be related to GERD. A careful review of medical and surgical trials aimed at improving putative reflux-related respiratory problems by treating GERD showed uncertain and inconsistent effects.²⁷

Individuals who conclusively have reflux-related cough, laryngitis, or asthma usually have typical GERD symptoms as well. in patients whose respiratory symptoms are poorly controlled for no other apparent reason, it will often be helpful to search for GERD symptoms.

The prevalence of dental erosions is also increased in patients who have GERD. The relationship between GERD and sinusitis, pulmonary fibrosis, pharyngitis, or recurrent otitis media remains uncertain.¹

CLINICAL QUESTION: What is the evidence for nonpharmacologic interventions for GERD?

Effective acid suppression is likely to remain the cornerstone of therapy for GERD. Nevertheless, nonpharmacologic measures should always be considered, especially in patients whose GERD symptoms can be classified as inconvenient rather than troublesome. Stopping smoking, reducing heavy drinking, and addressing obesity also have other self-evident health benefits. The role of postural and dietary interventions has been reviewed recently, and there is little evidence for or against the effect of these nonpharmacologic factors on GERD symptoms.²⁸

  Concluding remarks

GERD has substantial adverse effects on patients’ lives. Because of its high prevalence, it also imposes a significant health burden, making accurate diagnosis and appropriate management of particular importance. GERD is associated with significant morbidity and is a risk factor for increased mortality because of its causal link with adenocarcinoma of the esophagus. The Montreal definition provides a patient-centered and symptom-based approach to assist physicians in the diagnosis and management of GERD. It provides valuable information to improve diagnostic precision and complements existing guidance on best practice.

Disclosures

Dr Flook receives honoraria and research support from and is on the advisory board of AstraZeneca R&D.

· Acknowledgements ·

I thank Dr Harley Liker of David Geffen School of Medicine, University of California, Los Angeles, for valuable comments on the manuscript. I also thank Dr Anja Becher of Oxford PharmaGenesis Ltd, who provided editing assistance funded by AstraZeneca R&D.

References

1. Vakil N, Veldhuyzen van Zanten S, Kahrilas P, et al The Montreal definition and classification of Gastro-esophageal Reflux Disease (GERD)—a global evidence-based consensus. Am J Gastroenterol. 2006;101:1900–1920.
2. Dent J, El-Serag HB, Wallander MA, et al. Epidemiology of Gastro-oesophageal reflux disease: a systematic review. Gut. 2005;54:710–717.
3. Sifrim D, Holloway R, Silny J, et al Acid, nonacid, and gas reflux in patients with gastroesophageal reflux disease during ambulatory 24-hour pH-impedance recordings. Gastroenterology. 2001;120:1588–1598.
4. Wiklund I, Carlsson J, Vakil N. Gastroesophageal reflux symptoms and well-being in a random sample of the general population of a Swedish community. Am J Gastroenterol. 2006;101:18–28.
5. Ronkainen J, Aro P, Storskrubb T, et al Gastrooesophageal reflux symptoms and health-related quality of life in the adult general population—the Kalixanda study. Aliment Pharmacol Ther. 2006;23:1725–1733.
6. Ronkainen J, Aro P, Storskrubb T, et al Impact of gastroesophageal reflux symptoms on health-related quality of life in the adult general population: results from the Kalixanda study. Can J Gastroenterol. 2005;19:R0018.
7. Shaw MJ, Talley NJ, Beebe TJ, et al Initial validation of a diagnostic questionnaire for gastroesophageal reflux disease. Am J Gastroenterol. 2001;96:52–57.
8. Wiklund I, Carlsson J, Vakil N. Impact of gastroesophageal reflux symptoms on well-being in a random sample of the general population of a Swedish community: defining the transition from feeling well to feeling unwell. Can J Gastroenterol. 2005;19:R0017.
9. Wiklund IK, Junghard O, Grace E, et al Quality of life in Reflux and Dyspepsia patients. Psychometric documentation of a new disease-specific questionnaire (QOLRAD). Eur J Surg.1998(suppl);583::41–49.
10. Jones R, Coyne K, Wiklund I. The Gastro-oesophageal reflux Disease Impact Scale: a patient management tool for primary care. Aliment Pharmacol Ther. 2007;25:1451–1459.
11. Armstrong D, Veldhuyzen SJ, Chung SA, et al Validation of a short questionnaire in English and French for use in patients with persistent upper gastrointestinal symptoms despite pump inhibitor therapy: the PASS (Proton pump inhibitor Acid Suppression Symptom) test. Can J Gastroenterol. 2005;19:350–358.
12. Flook NW, Wiklund I. Accounting for the effect of GERD symptoms on patients’ health related quality of life: supporting optimal disease management in primary care. Int J Clin Pract. in press.
13. Lydeard S, Jones R. Factors affecting the decision to consult with dyspepsia: comparison of consulters and non-consulters. J R Coll Gen Pract. 1989;39:495–8.
14. El-Serag HB, Johanson JF. Risk factors for the severity of erosive esophagitis in Helicobacter pylori–negative patients with gastroesophageal reflux disease. Scand J Gastroenterol. 2002;37:899–904.
15. Garcia Rodriguez LA, Wallander MA, Johansson S, et al Natural history of chest pain in GERD. Gut. 2005;54 (suppl VII):A226.
16. Flook N, Unge P, Agreus L, et al Approach to managing undiagnosed chest pain: could gastroesophageal reflux disease be the cause? Can Fam Physician. 2007;53:261–266.
17. Ockene IS, Shay MJ, Alpert JS, et al Unexplained chest pain in patients with normal coronary arteriograms: a follow-up study of functional status. N Engl J Med. 1980;303:1249–1252.
18. Shaker R, Castell DO, Schoenfeld PS, et al Nighttime heartburn is an under-appreciated clinical problem that impacts sleep and daytime function: the results of a Gallup survey conducted on behalf of the American Gastroenterological Association. Am J Gastroenterol. 2003;98:1487–1493.
19. Leodolter A, Kulig M, Nocon M, et al Esome-prazole therapy improves sleep disorders in patients with gastroesophageal reflux disease (GERD): a report from the ProGERD study. Gastroenterology. 2003;124:A226.
20. Wahlqvist P, Reilly M, Barkun AN. Systematic review: the impact of Gastro-oesophageal reflux disease on work productivity. Aliment Pharmacol Ther. 2006;24:259–272.
21. Johnson D, Orr WC, Crawley JA, et al Effect of esomeprazole on nighttime heartburn and sleep quality in patients with GERD: a randomized, placebo-controlled trial. Am J Gastroenterol. 2005;100:1914–1922.
22. Vakil NB, Traxler B, Levine D. Dysphagia in patients with erosive esophagitis: prevalence, severity, and response to proton pump inhibitor treatment. Clin Gastroenterol Hepatol. 2004;2:665–668.
23. Fransen GA, Janssen MJ, Muris JW, et al Meta-analysis: the diagnostic value of alarm symptoms for upper gastrointestinal malignancy. Aliment Pharmacol Ther. 2004;20:1045–1052.
24. Labenz J, Nocon M, Lind T, et al Prospective Follow-Up Data from the ProGERD Study Suggest that GERD Is Not a Categorial Disease. Am J Gastroenterol. 2006;101:2457–2462.
25. Lagergren J, Bergstrom R, Lindgren A, et al Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma. N Engl J Med. 1999;340:825–831.
26. EL-Serag HB, Mason AC, Petersen N, et al Epidemiological differences between adeno-carcinoma of the oesophagus and adenocarcinoma of the gastric cardia in the USA. Gut 2002;50:368–372.
27. Gislason T, Janson C, Vermeire P, et al Respiratory symptoms and nocturnal gastroesophageal reflux: a population-based study of young adults in three european countries. Chest. 2002;121:158–163.
28. Meining A, Classen M. The role of diet and lifestyle measures in the pathogenesis and treatment of gastroesophageal reflux disease. Am J Gastroenterol. 2000;95:2692–2697.