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Publication data
Submitted 12 September 2007
First decision 24 September 2007
Resubmitted 8 October 2007
Second decision 16 October 2007
Accepted 23 October 2007
SUMMARY
Background
Prospective nationwide multicentre studies that have evaluated endoscopic findings and reflux symptoms using a well-designed questionnaire are very rare.
Aim
To compare the prevalence rates of and risk factors for erosive oesophagitis and non-erosive reflux disease (NERD) in the Korean population.
Methods
A gastroscopic examination was performed on 25 536 subjects who visited 40 Healthcare Centers for a health check-up. A gastro-oesophageal
reflux questionnaire and multivariate analysis were used to determine
the risk factors for erosive oesophagitis and NERD.
Results
2019 (8%) and 996 subjects (4%) had erosive oesophagitis and non-erosive reflux disease, respectively; only 58% of subjects with erosive
oesophagitis had reflux symptoms. Multivariate analysis showed that the
risk factors for erosive oesophagitis and NERD differed, i.e. those of erosive oesophagitis were male, a Helicobacter pylori eradication history,
alcohol, body mass index 25 and hiatal hernia. In contrast, the risk factors for NERD were female, age <40 and 60 vs. 4059 years, body mass
index <23 and a monthly income <$1000, glucose 126 mg dL, smoking, a stooping posture at work and antibiotic usage.
Conclusions
The prevalence rates of erosive oesophagitis and NERD were 8% and
4%, respectively, in Korean health check-up subjects. The risk factors
for erosive oesophagitis and NERD were found to differ, which indicates
that their underlying pathogeneses are distinct.
Aliment Pharmacol Ther 27, 173185
173
174 N . K I M et al.
INTRODUCTION
Gastro-oesophageal reflux disease (GERD) is caused by
abnormal reflux of gastric contents into the oesophagus and is characterized by specific symptoms such as
heartburn and acid regurgitation.15 However, only
about one-third to one-half of GERD patients have
endoscopically positive findings such as erosions and
ulcers, whereas others with GERD symptoms have no
obvious mucosal breaks during endoscopic examination.613 Thus, oesophagitis is being increasingly
viewed as a complication of GERD.14 The 1999 Genval
workshop report15 redefined GERD as a disorder in
which gastric contents recurrently reflux into the
oesophagus causing heartburn and other symptoms.
However, some patients have complications of gastrooesophageal reflux without the typical symptoms. In
2005, the American College of Gastroenterology published practice guidelines,12 and defined the diagnosis
of GERD as symptoms or mucosal damage produced
by abnormal reflux of gastric contents into the
oesophagus. Recently, the Montreal workshop report16
also defined GERD as a condition that develops when
the reflux of stomach contents causes troublesome
symptoms and or complications such as reflux
oesophagitis, stricture, Barretts oesophagus (BE) or
oesophageal adenocarcinoma, and subclassified the
disease into oesophageal or extraoesophageal syndromes. Therefore, GERD includes erosive oesophagitis
and endoscopy-negative reflux disease, which is also
known as non-erosive reflux disease (NERD). The
pathogeneses of these two categories of GERD are
believed to differ. For example, heartburn in NERD is
associated with a lower response to proton pump
inhibitor (PPI) acid suppression than heartburn in the
case of erosive oesophagitis.17 In addition, it is not
clear why some erosive oesophagitis patients suffer
from symptoms such as, heartburn and regurgitation,
while others with an apparently similar reflux profile
do not.1
Gastro-oesophageal reflux disease is known to be a
major clinical problem in Western countries, i.e. 14
24% of adults experience heartburn and acid regurgitation at least once a week,6, 1822 and recently, the
frequency has increased to approximately one-third
of the adult population.23, 24 In contrast, the prevalence of GERD (based on reflux symptoms) in East
Asia ranges from 3% to 7% for at least weekly
symptoms of heartburn and or acid regurgitation.2532 In addition, case study data have shown
METHODS
Preparation of study
The design of this study was prepared by the Scientific
Committee of the Korean College of Helicobacter and
Upper Gastrointestinal Research. A workshop was held
on 25 June 2005 to approve the study design and to
develop a unified description of endoscopic erosive
oesophagitis and to agree on a gastro-oesophageal
reflux questionnaire. After repeated feedbacks from
experts in this field and after conducting practical
field tests over a period of 3 months to validate the
reflux symptom questionnaires,40 the study was started
at the beginning of January 2006 and continued until
2008 The Authors, Aliment Pharmacol Ther 27, 173185
Journal compilation 2008 Blackwell Publishing Ltd
P R E V A L E N C E O F , A N D R I S K F A C T O R S F O R , G E R D 175
antidepressants, tranquilizers, liver drugs and gastroduodenal drugs), (2) the presence of diseases (again
split into seven categories, diabetes mellitus, liver disease, kidney disease, neuromuscular disease, heart
lung disease, gastroduodenal disease and other chronic
illness), (3) history of Helicobacter pylori eradication, (4)
alcohol consumption, (5) smoking, (6) a stooping
posture at work and (7) income per month. Body mass
indices (BMI) and biochemical test results, which
included glucose, cholesterol, triglyceride, H. pylori
tests (anti-H. pylori IgG, CLOtest or histology) and bone
densitometry findings were entered by assistants.
Oesophagogastric examinations
Questionnaire
An assistant conducted face-to-face interviews using
the gastro-oesophageal reflux questionnaire before
endoscopy at the 40 Healthcare Centers. The questionnaire consisted of 14 items, and included questions on
six reflux symptoms, namely, heartburn, acid regurgitation, chest pain, hoarseness, globus sensation and
coughing. The questions were as follows: 1. Have you
experienced heartburn [(a) soreness in the substernal
area, (b) a burning sensation or discomfort in the
substernal area or (c) a burning sensation induced by
water swallowing] within the past year?; 2. Have you
experienced acid regurgitation [(a) sour water brash in
the mouth or throat, (b) a sense of food regurgitation]
within the past year?; 3. Have you experienced chest
pain within the past year?; 4. Have you experienced
hoarseness within the past year?; 5. Have you experienced a globus sensation in the throat [(a) a foreign
body sensation in the throat, (b) a sticky food sensation in the substernal area] within the past year?; 6.
Have you experienced a frequent cough within the
past year? Subjects who responded positively to any
one of these six symptoms were asked to choose the
most bothersome symptom. In addition, the frequency
[(a) 12 times per year, (b) 12 times per month, (c)
12 times per week, (d) 34 times per week and (e)
daily] and severity [(a) mild, (b) moderate, bothersome
to everyday life and (c) severely disturbing work or
sleeping] of the most bothersome symptom were determined. In addition, the subjects were asked whether
they had taken H2 blocker or PPI to relieve these
symptoms. The next seven questions addressed factors
related to GERD, i.e. (1) a drug history (split into seven
major categories, aspirin or nonsteroidal anti-inflammatory drug (NSAID), antihypertensive, antibiotics,
2008 The Authors, Aliment Pharmacol Ther 27, 173185
Journal compilation 2008 Blackwell Publishing Ltd
176 N . K I M et al.
Statistical analysis
Erosive oesophagitis and NERD were compared for the
different variables mentioned above. The ages were
categorized in deciles. BMI was categorized using 23
and 25 (kg m2) as cut-off points in accord with the
WHO recommendations for Asians. Blood glucose,
cholesterol and triglyceride levels were recorded using
the standard clinical cut-off points (126, 200 and
150 mg dL, respectively). The chi-squared test was
used to assess associations between covariates and
the prevalence of erosive oesophagitis and NERD. The
covariates that showed a significant association by the
chi-squared test were analysed by a multiple logistic
regression analyses. Model fit was assessed using the
Hosmer-Lemeshow goodness-of-fit test. The variables
that were significant according to the models or that
improved the model fit were included in the final
models, which showed appropriate goodness-of-fit
(P > 0.10). All analyses were performed using SAS statistical software. Differences were considered significant when the P-values were <0.05.
RESULTS
Characteristics of the participants
The response rate of the participants to the reflux
symptom questionnaire was 100%, and thus a nonresponse study was not required. Totally, 25 536 subjects (male 15 180, 59%; female 10 356, 41%) were
included in this study, and the mean subject age was
46.7 years. When the study population was compared
with the background population data collected in 2005
(http://www.index.go.kr/gams/default.jsp and http://
www.kosis.kr) in terms of gender, age and geographical area, the proportion of males and representation of
the 4059 age group were higher in the study population compared with the background population (Table 1).
However, the geographical distribution was representative of the Seoul population and the six other provinces. Demographic data regarding the educational
P R E V A L E N C E O F , A N D R I S K F A C T O R S F O R , G E R D 177
Gender
Male:female
1619
2029
3039
4049
5059
6069
70
Seoul
Gyeonggi (Seoul vicinity)
Kangwon
Chungcheong
Kyungsang
Cholla
Jeju
Among 24 966
Among 21 875
Among 21 875
57 (0.2)
1235 (5)
5684 (22)
8885 (35)
6126 (24)
2936 (12)
613 (2)
9625 (37)
3085 (12)
1965 (8)
3094 (12)
3646 (14)
3759 (15)
462 (2)
21 571 (86)
8905 (41)
1815 (8)
6529 (26)
10 470 (41)
2691 (11)
1103 (4)
7737 (31)
1616 (6)
Geographic area
Among 24 966
Background population in
Korea, 2005 (%)*
24 191 000:23 947
000 (50:495)
313 000 (7)
7 606 000 (16)
8 520 500 (18)
8 184 000 (17)
5 151 000 (11)
361 000 (8)
270 000 (6)
10 173 000 (21)
13 042 000 (27)
1 521 000 (3)
4 885 000 (10)
12 668 000 (26)
5 294 000 (11)
555 000 (1)
78%
21%
21%
29%
55%
13%
5%
32%
253 (1)
832 (3)
534 (2)
65 (0.3)
EGC:AGC
47 :18 (3:1)
* Source: http://www.index.go.kr/gams, http://www.kosis.nso.go.kr and The Third National Health and Nutrition Examination
Survey in 2005.41
s.d., Standard deviation; EGC, early gastric cancer; AGC, advanced gastric cancer; NSAID, nonsteroidal anti-inflammatory
drug.
178 N . K I M et al.
Normal
(n = 22 521)
Erosive oesophagitis
(n = 2019)
NERD
(n = 996)
Total
(n = 25 536)
P-value between
EE and NERD
12 965 (85)
9556 (92)
1699 (11)
320 (3)
516 (3)
480 (5)
15 180
10 356
0.0006
53
1091
5003
7840
5442
2574
518
(93.0)
(88.3)
(88.0)
(88.2)
(88.8)
(87.7)
(84.5)
2
74
454
723
479
220
67
(3.5)
(6.0)
(8.0)
(8.1)
(7.8)
(7.5)
(10.9)
2
70
227
322
205
142
28
(3.5)
(5.7)
(4.0)
(3.6)
(3.4)
(4.8)
(4.6)
57
1235
5684
8885
6126
2936
613
0.0002
8350
2707
1723
2793
3209
3351
387
(87.7)
(87.7)
(87.7)
(90.3)
(88.0)
(89.2)
(83.8)
798
258
165
199
294
253
52
(8.4)
(8.4)
(8.4)
(6.4)
(8.1)
(6.7)
(11.2)
377
120
77
101
170
155
23
(4.0)
(3.9)
(3.9)
(3.3)
(4.8)
(4.1)
(5.0)
9525
3085
1965
3093
3646
3759
462
0.4275
(a) 20
(b) 20
Erosive oesophagitis
Erosive oesophagitis
Prevalence (%)
15
P < 0.0001
P = 0.0037 P = 0.0003
11.2%
10
10
P < 0.0001
4.6%
3.4% 3.1%
3.9%
8.0%
7.9%
7.5%
7.9%
4.8%
4.3%
3.5%
0
Male
Female
Total
<40
4059
Age (years)
60
Figure 1. Comparisons of erosive oesophagitis and non-erosive reflux disease with respect
to gender (a) and age (b).
P R E V A L E N C E O F , A N D R I S K F A C T O R S F O R , G E R D 179
Normal
Erosive oesophagitis
(n = 20 154) (n = 1810)
NERD (n = 996)
Variable category
Any one of following six symptoms
Heartburn
Acid regurgitation
Chest pain
Hoarseness
Globus sensation
Cough
The most bothersome symptom
Heartburn
Acid regurgitation
Chest pain
Hoarseness
Globus sensation
Cough
8182
4587
4330
2759
1873
3685
1390
(40.6)
(22.8)
(21.1)
(13.7)
(9.3)
(18.3)
(6.9)
1345
1208
1047
584
1772
564
(6.7)
(6.0)
(5.2)
(2.9)
(8.8)
(2.8)
1055
603
644
299
221
413
197
(58.3)
(33.3)
(35.6)
(16.5)
(12.2)
(22.8)
(10.9)
208 (11.5)
237 (13.1)
85 (4.7)
47 (2.6)
161 (8.9)
74 (4.1)
996
704
712
329
182
344
130
(100)
(70.7)
(71.5)
(33.0)
(18.3)
(34.5)
(13.1)
518 (52.0)
478 (48.0)
0
0
0
0
180 N . K I M et al.
Variable
Male
Alcohol consumption
Body mass index 25
Hiatal hernia 1 cm
Helicobacter pylori
eradication history
H. pylori-positive
Glucose 126 mg dL
Triglyceride 150 mg dL
Smoking
Medication for liver disease
Medication for heart disease
Normal
(n = 20 154)
Erosive oesophagitis
(n = 1810)
Odds
ratio
11 401
7681
6523
383
1572
(56.6)
(38.1)
(29.8)
(1.9)
(7.8)
1633
1050
757
212
223
(84.2)
(58.0)
(41.8)
(11.7)
(12.3)
3.0
1.5
1.3
5.4
2.2
2.263.98
1.211.81
1.051.55
3.737.70
1.602.75
12 173
987
4655
4655
504
2096
(60.4)
(4.9)
(23.1)
(23.1)
(2.5)
(10.4)
832
119
653
795
65
250
(46.0)
(6.6)
(36.1)
(41.0)
(3.6)
(13.8)
0.47
1.1
1.2
1.2
1.1
1.1
0.390.58
0.781.45
0.941.41
0.981.45
0.751.47
0.791.50
95% CI
Variable
Normal
(n = 20 154)
NERD
(n = 996)
Odds
ratio
95% CI
Female
Age below 40 than 4059 years
Age 60 than 4059 years
Body mass index <23
Monthly income <$1000
Glucose 126 mg dL
Antibiotic medication history
Smoking
Stooping posture at work
Helicobacter pylori eradication history
Hiatal hernia 1 cm
Medication of NSAIDs
8753
5502
3003
8384
1632
987
198
4655
3396
1572
383
1380
480
299
170
498
120
82
23
270
230
103
30
86
1.3
1.2
1.3
1.2
1.4
1.3
2.1
1.2
1.2
1.3
1.1
1.3
1.101.50
1.061.45
1.021.54
1.061.41
1.061.69
1.041.73
1.283.34
1.031.43
1.061.69
0.991.57
0.761.70
0.971.62
(43.4)
(27.3)
(13.7)
(41.6)
(8.1)
(4.9)
(1.0)
(23.1)
(16.9)
(7.8)
(1.9)
(6.8)
(48.2)
(30.0)
(17.1)
(50.0)
(12.0)
(8.2)
(2.3)
(27.1)
(23.0)
(10.2)
(3.0)
(8.6)
NERD, non-erosive reflux disease; CI, confidence interval; NSAID, nonsteroidal antiinflammatory drug.
Values given in parentheses are percentages.
DISCUSSION
The disease GERD is associated with life style, diet,
socioeconomic factors and co-morbidity. To determine
whether this study population is representative of the
Korean general population, the demographic data in
the study were compared with those of a national population survey conducted in 2005.41 In terms of age,
geographic distribution, proportion living in a rural or
urban community, education level, smoking, alcohol
and presence of co-morbidity, only slight differences
were observed. Specifically, the proportion of males in
P R E V A L E N C E O F , A N D R I S K F A C T O R S F O R , G E R D 181
182 N . K I M et al.
These results suggest that H. pylori-associated inflammation plays a role in the prevention of the development of erosive oesophagitis, which is consistent with
a previous report.55, 56 In contrast, the risk factors for
NERD were: female, an age below 40 or 60 vs. 40
59, a low BMI <23, a monthly income <$1000, a glucose level of 126 mg dL, an antibiotic medication
history, smoking and a stooping posture at work.
These results suggest that physical factors that affect
lower oesophageal pressure or acid secretion are risk
factors for erosive oesophagitis. In contrast, factors
that are affected by socioeconomic status appear to be
related to heartburn and or acid regurgitation in the
absence of mucosal breaks by endoscopy. Different
risk factors for erosive oesophagitis and NERD have
been reported in Japan,9, 13 which support the likelihood that the pathogenesis differs for these two categories of GERD. However, it has been suggested that
GERD is not a categorical disease because 25% of
patients with NERD at baseline progressed to LA A B
and 1% to LA C D after 2 years in Germany, Austria
and Switzerland.57 Further research is needed to
address this issue.
In addition to the GERD findings, another gastrointestinal disease pattern was found in the 25 536 health
check-up subjects, namely, that the prevalence rates of
the active and healing stages of benign gastric ulcer
and duodenal ulcer were 3% and 2%, respectively,
which is lower than that of erosive oesophagitis (8%).
This pattern of gastrointestinal disease might be
related to a decrease in the prevalence of H. pylori
and an increase in BMI (25, 31% in this study). A
two nation-wide seroprevalence survey performed in
1998 and 2005 among asymptomatic Korean adults
over the age 16 found the H. pylori prevalence of
67%58 and 60%,59 respectively. The prevalence of gastric cancer, which is unacceptably high in Korea, by
the age standardized incidence of gastric cancer during
19902001 in South Korea, as determined by the Cancer Registry at the Korean National Cancer Center in
2002, was 65.6 per 100 000 person-years for men and
25.8 for women. The detection rate of gastric cancer
(in histologically confirmed cases) in this study was
0.3% and the proportion of early gastric cancer (47
subjects) to advanced gastric cancer (18 subjects) was
72%, which demonstrate that the instituted health
check-up programmes have been successful in detecting early gastric cancer.
In conclusion, this nationwide, multicentre, well
designed, prospective study shows that the prevalence
2008 The Authors, Aliment Pharmacol Ther 27, 173185
Journal compilation 2008 Blackwell Publishing Ltd
P R E V A L E N C E O F , A N D R I S K F A C T O R S F O R , G E R D 183
ACKNOWLEDGEMENTS
The authors thank the following participating gastroenterologists for their contribution to this study:
Ki-Nam Shim, Ewha Womans University Hospital;
Jun Haeng Lee, Samsung Medical Center; Jae Woo
Kim, Wonju University; Hyun Jin Kim, Kyungsang
University; Moon Gi Chung, Gachon Medical School,
Seon Mee Park, Chungbuk National University;
Gwang Ho Baik, Hallym University; Byung Kyu Nah,
University of Ulsan; Su Youn Nam, Korean National
Cancer Center; Kang Seok Seo, Kwangju Christian
Hospital; Yun-Ju Jo and Byung Sung Ko, Eulji
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