Diagnosis of Gastroesophageal Reflux Disease: a Systematic Review

Yu Kyung Cho; Gwang Ha Kim; Jeong Hwan Kim; Hwoon-Yong Jung; Joon Seong Lee; Nayoung Kim

doi:10.4166/kjg.2010.55.5.279

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Cho, Kim, Kim, Jung, Lee, Kim, and The Korean Society of Neurogastroenterology and Motility: Diagnosis of Gastroesophageal Reflux Disease: a Systematic Review

Review

Korean J Gastroenterol 2010;55(5):279-295.

Published online: 21 February 2010

DOI: https://doi.org/10.4166/kjg.2010.55.5.279

Diagnosis of Gastroesophageal Reflux Disease: a Systematic Review

Yu Kyung Cho, M.D., Gwang Ha Kim, M.D.^∗, Jeong Hwan Kim, M.D.^†, Hwoon-Yong Jung, M.D.^‡, Joon Seong Lee, M.D.^§, Nayoung Kim, M.D.^∥,; The Korean Society of Neurogastroenterology and Motility

Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea

^∗Department of Internal Medicine, Pusan National University School of Medicine, Busan, Korea

^†Department of Internal Medicine, Kunguk University College of Medicine, Seoul, Korea

^‡Department of Internal Medicine, Ulsan University College of Medicine, Seoul, Korea

^§Institute for Digestive Research, Department of Internal Medicine, Soonchunhyang University College of Medicine, Seoul, Korea

^∥Department of Internal Medicine, Seoul Nationsal University College of Medicine, Seoul Nationsal University Bundang Hospital, Seongnam, Korea

Correspondence to: Nayoung Kim, M.D. Department of Internal Medicine, Seoul National University Bundang Hospital, 300, Gumi-dong, Bundang-gu, Sungnam 463-707, Korea Tel: +82-31-787-7008, Fax: +82-31-787-4051 E-mail: nayoungkim49@empas.com

Abstract

The prevalence of gastoesophageal reflux disease (GERD) has been rapidly increased in Korea during last 20 years. However, there has been no systematic review regarding this disease. The aim of this article was to provide a review of available diagnostic modalities for GERD. This review includes proton pump inhibitor (PPI) test, endoscopy, ambulatory pH monitoring, impedance pH monitoring, and esophageal manometry in order to provide a basis for the currently applicable recommendations in the diagnosis of GERD in Korea. With weekly heartburn or acid regurgitation, the prevalence of GERD has been reported as 3.4% to 7.9%, indicating an increase of GERD in Korea. As the prevalence of Barrett's esophagus has been reported to be low, the screening endoscopy for Barrett's esophagus is not recommended. Several recent meta-analyses re-evaluated the value of the PPI test in patients with typical GERD symptoms and non-cardiac chest pain. That is, the PPI test has been proven to be a sensitive tool for diagnosing GERD in patients with non-cardiac chest pain and in some preliminary trials regarding extraesophageal manifestations of GERD. Ambulatory pH monitoring of the esophagus helps to confirm gastroesophageal reflux in patients with persistent symptoms (both typical and atypical) in the absence of esophageal mucosal dam-age, especially when a trial of acid suppression has failed. Impedance pH test is useful in refractory reflux patients with primary complaints of typical GERD symptoms, but this value has not been proved in patients with non-cardiac chest pain or extraesophageal symptoms. This systematic review is targeted to establish the strategy of GERD diagnosis, which is essential for the current clinical practice.

Keywords: Gastoesophageal reflux disease, Diagnosis, Proton pump inhibitor, Ambulatory 24 hr esophageal pH monitoring, Impedance pH test

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Table 1.

Prevalence, Risk Factors, and Clinical Characteristics of GERD in Korea⁴

Study	Subjects	Year	Case ascertainment	Sample size (response rate, %)	Prevalence by symptoms (%)	Prevalence by endoscopy (%)	Risk factors or clinical characteristics	Odd ratio or % of atypical symptoms among GERD
Yi et al.⁵	Health screening	1993	Endoscopy	2,795	27.3	2.4	S-M class, Stage I 95.1% Stage II 4.5%
Lee et al.⁶	Health screening	1996 -1997	Endoscopy	7,015		3.4	LA-A 98.3%, LA-B 1.7% Hiatal hernia, BMI, alcohol, smoking
Jeon et al.⁷	Health screening	1998	Self reported questionnaire	2,243 (79.6)	Weekly, 3.4 Monthly, 6.1		M＜ F	OR, 24 of chest pain, 1.7 dysphagia, 2.0 globus, 3.5 epigastric pain
Cho et al.⁸	Community	2000-2001	Interview	1,417 (78.4)	Weekly, M 3.5, F 3.5 Monthly, M 7.6, F 8.9		M=F	OR, 9.3 of chest pain, 6.4 dysphagia, 3.9 globus, 4.3 hoarseness, 2.6 asthma among subjects with typical GERD symptoms
Yang et al.⁹	Community	2002	Telephone survey	1,044 (29)	Weekly, 7.1 2/week, 3.8
Hwang et al.¹⁰	Secondary & tertiary hospitals	2003		4,275		11.8	Male, age＞65 years females, typical GERD symptoms
Oh et al.¹¹	Health screening ¹	2003 -2005	Self reported questionnaire	14,624	Weekly, 13.2	4.4	LA-A 85%, LA-B 15%; ERD: Smoking [OR (95%CI) 2.8 (1.7-4.4)] BMI [OR(95% CI) 1.2 (1.1-1.3)]	Globus 14%, hoarseness 27.7%, cough 18.76%, dyspepsia 36%
Kim et al.¹²	Health screening	2005	Self reported questionnaire	d 752	29.2	8.6	LA-A 73.8%, LA-B 17%, LA-C 9.2% Relative risk of GERD was low in H. pylori (＋)	45.7% of atypical reflux symptoms in RE
Kang et al.¹³	Health screening	2006	Self reported questionnaire	1,016	15.5	8.2	Not related to BMI
Yoo et al.¹⁴	Health screening	2006	Endoscopy	6,683		8.5
Shim et al.¹⁵	Health screening	2006	Self reported questionnaire	25,536		7.91	LA-A 5.97%, LA-B 1.84%, LA-C 0.18%, LA-D 0.02 M＞ F; heartburn, hoarseness, globus F＞ M; acid regurgitation
Kim et al.¹⁶	Health screening	2006	Self reported questionnaire	25,536	Weekly, 5		M＞ F in ERD	Chest pain (16.5% in RE 33% in NERD, 13.7% in normal); hoarseness (12.2% in RE, 18.3% in NERD, 9.3% in normal); cough (10.9% in RE, 13.1% in NERD, 6.9% in normal)
								M＜ F in NERD
								ERD: male, H. pylori eradication, alcohol, BMI＞ 25, hiatal hernia.
							NERD: female, age ＜40 and ＞60 years, BMI ＜23, monthly income ＜$1000, glucose ＞126 mg/dL, smoking, stooping posture at work, antibiotic usage
Cho et al.¹⁷	Community	2007	Telephone survey	1,009 (20.2)	Weekly, 7.9		Risk factor- No demographic factors

GERD, gastroesophageal reflux disease; ERD, reflux esophagitis; NERD, nonerosive reflux disease; RE, reflux esophagitis; OR, odds ratio; CI, confidence interval; BMI, body mass index; LA, Los Angeles classification; S-M, Savary miller classification.

Table 2.

Prevalence of Barrett's Esophagus in Korea

Study	Year	Study design	n Organ	Case enrolled	ESBE	BE	Prevalence of reflux esophagitis in BE	Risk factors
Kim et al.⁴⁵	1997-2004	Retrospective	e ?	70,103	1%	0.22%		Old age, male sex, smoking, acid regurgitation symptom
								Mean age of 54±11 yrs
Kim et al.⁵³	2005	Prospective	Patients with upper gastrointestinal symptoms	992	10.9% SSBE 0.3% LSBE	3.6% (0.1% LSBE)	25.0% in BE group (8.6% in non-BE group)	Hiatal hernia
Lee et al.⁵⁴	2006	Prospective	Patients with upper gastrointestinal symptoms	2,048	82	1%		Typical reflux symptoms, reflux esophagitis
Park et al.⁵⁵	2006	Prospective	Health screening	25,536	864	0.84%	RE 22.3% Reflux symptoms 60.1%	Male (OR 1.82, 95% CI 1.32-2.50), NSAID (2.02, 1.28-
							Chest pain (OR 1.48,95% CI 1.04-2.11)	3.20), hiatal hernia (5.66, 3.70-8.66)
							Epigastric soreness [1.42(1.05-1.93] (vs. normal subjects)	Age ＞60 yrs

ESBE, endoscopically suspected Barrett's esophagus; BE, Barrett's esophagus; SSBE, short segment Barrett's esophagus; LSBE, long segment Barrett's esophagus; RE, reflux esophagitis; OR, odds ratio; CI, confidence interval.

Table 3.

PPI Test Performance Summaries Performed in Asia and Korea

Study		N	PPI, dose, duration	Study design	Symptoms	Predictors of PPI response	Responder	Diagnostic accuracy	Reference standard (s)
Cho et al.⁵⁹	Korea	73	Lansoprazole 60 mg, 2 wk	Open label	Typical symptoms	Erosive esophagitis, SAP (＋)	＞50%	Sensitivity 77%, Specificity 56%, PPV 92%, NPV 25%	Bravo pH-metry, endoscopy
Jung et al.⁶⁰	t Korea	100	Esomeprazole 40 mg, 1 wk	Open label	Typical symptoms		Reflux symptom score improvement	Sensitivity, 84.3% t	pH-metry or, endoscopy
Kim et al.⁶¹	Korea	42	Rabeprazole 40 mg, 2 wk	Open label	NCCP		＞50%	Sensitivity 81% Specificity 62%	pH-metry, endoscopy
Sinn et al.⁶²	Korea	64	Rabeprazole 40mg, 2 wk	Open label	Globus	None of endoscopic finding, abnormal pH nor baseline GER symptoms	＞50%	Response rate:34% (＞50% resolution)3% (100% resolution)	pH-metry, endoscopy
Xia et al.⁶³	Hong Kong	68	Lansoprazole 30 mg, 4 wk	RCT, parallel group	NCCP		＞50%	Sensitivity 92%, Specificity 67%, PPV 58%, NPV 94%, Accuracy 75%	pH-metry, endoscopy
Ho et al.⁶⁴	Singapore	47	Esomeprazole 40 mg, 2 wk	Open label	Uninvestigated, dominant reflux symptoms		＞50%	Response rate: 82% of those with dominant reflux symptoms	Endoscopy
Mohd et al.₆₅	Malaysia	27	Rabeprazole 40 mg, 2 wk	Open label	NCCP		Chest pain score improvement	Response rate: 83% of GERD (vs. 11% in control) t	Bravo pH-metry, endoscopy

PPI, proton pump inhibitor; NCCP, noncardiac chest pain; SAP, symptom association probability; RCT, randomized controlled trial; PPV, positive predictive value; NPV, negative predictive value; GER, gastroesophageal reflux.

Table 4.

PPI Test Performance Summaries in Non-cardiac Chest Pain⁷⁰

Study	N	PPI, Dose, Duration	Study Design	GERD (%)	Responder	Reference Standard (s)	Sensitivity (%)	Specificity (%)	y PPV (%)	NPV (%)	LR＋	LR−
Fass 1998	39	Omeprazole, 60 mg, 1 wk	RCT, crossover	62	＞50%	pH-metry, endoscopy	78	86	90	71	5.48	0.25
Bautista 2004	40	Lansoprazole 90 mg, 1 wk	RCT, crossover	45	＞50%	pH-metry, endoscopy	78	91	88	83	8.56	0.24
Fass 2002	20	Rabeprazole 40 mg, 1 wk	RCT, crossover	60	＞50%	pH-metry, endoscopy	83	75	83	75	3.33	0.22
Pandak 2002	44	Omeprazole, 80 mg, 2 wk	RCT, crossover	53	＞50%	pH-metry, endoscopy	95	61	73	92	2.44	0.08
Squillace 1993	17	Omeprazole 80 mg, 1 day	RCT, crossover	76	＞50%	pH-metry	69	75	90	43	2.77	0.41
Xia 2003⁶³	36	Lansoprazole 30 mg, 4 wk	RCT, parallel group	33	＞50%	pH-metry	92	67	58	94	2.75	0.13
Chambers 1998	31	Omeprazole 40 mg, 6 wk	Open label	17	No a priori definition	pH-metry	0	68	0	76	0	1.46
Dickman 2005	35	Rabeprazole 40 mg, 1 wk	RCT, crossover	35	＞50%	pH-metry, endoscopy	75	90	83	75

PPI, proton pump inhibitor; RCT, randomized controlled trial; PPV, positive predictive value; NPV, negative predictive value; LR＋, positive likelihood ratio; LR−, negative likelihood ratio.

Table 5.

PPI Test Performance Summaries in Extraesophageal Symptoms⁷⁴

Study	N	PPI, Dose, Duration	Study design	Symptoms	Responder	Reference standard(s)	OR (95% CI)
Eherer 2003	21	Pantoprazole 80 mg, 12 weeks	RCT, crossover	Cough, nocturnal cough, globus, sore throat, hoarseness, dysphonic attacks	Improvement in SQ	24-h pH-metry	1.36 (0.77-2.43)
El-Serag et al 2001⁷⁵	.22	Lansoprazole 60 mg, 12 weeks	RCT, parallel group	Hoarseness, frequent clearing of the throat, dry cough, globus, persistent sore throat	Complete symptomatic response	Upper endoscopy, dual probe ambulatory 24-h esophageal pH-metry, laryngoscopy	5.00 (0.72-33.92)
Ours et al.1999⁷⁶	17	Omeprazole 80 mg, 12 weeks	RCT, parallel group	Cough	A weekly cough, frequency combined with severity score for daytime or nighttime of ≤1 for ≥2 weeks consecutively	24-h pH-metry	3.33 (0.15-71.90)
Steward 2004	42	Rabeprazole 40 mg, 8 weeks	RCT, parallel group	Hoarseness, throat clearing, non-productive cough, globus sensation, sore throa	Proportion of subjects noting significant global improvement -t	Videostrobolaryngosco py, 24-h dual pH probe	0.83 (0.43-1.85)
Vaezi 2006	145	Esomeprazole 80 mg, 16 weeks	RCT, parallel group	Throat clearing, cough, globus, sore throat, hoarseness	Percentage of patients who had resolution of the primary symptom	Laryngoscopy	0.92 (0.41-2.05)
Overall							1.18 (0.81-1.74)

PPI, proton pump inhibitor; SQ, symptom questionnaire; RCT, randomized controlled trial; OR, odds ratio; CI, confidence interval.

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