Professional Documents
Culture Documents
2 Heartburn PDF
2 Heartburn PDF
2 Heartburn PDF
DOI 10.1007/s10620-011-1708-9
ORIGINAL ARTICLE
George Triadafilopoulos
Received: 1 April 2009 / Accepted: 4 April 2011 / Published online: 22 April 2011
Ó Springer Science+Business Media, LLC 2011
123
2872 Dig Dis Sci (2011) 56:2871–2878
123
Dig Dis Sci (2011) 56:2871–2878 2873
123
2874 Dig Dis Sci (2011) 56:2871–2878
of the pH differential between the distal (intra-gastric) and complicated esophagitis or BE were assigned to the GERD
proximal (intra-esophageal) sensors and previous LES group. Ninety-four of the remaining 118 patients with
identification by esophageal motility. The positioning of normal endoscopy had an abnormality in hiatal hernia,
the Bravo capsule was determined on the basis of the esophageal biopsy, pH study, and/or motility study and
previous LES identification by esophageal motility and the were assigned the NERD group. The remaining 24 patients
location of the esophago–gastric junction by endoscopy. with normal endoscopy had no evidence of hiatal hernia,
Patients then returned home with instructions to keep a negative biopsy, and normal pH and motility studies and
diary for recording symptoms, meal intake times, and body were assigned to the RLD group.
position. They were also instructed to separately record the
time they remained supine at night, irrespective of sleep. Data Collection/Validation
Patients were encouraged to carry out normal daily activ-
ities without dietary restrictions. No antacid or anti-secre- Data were collected in two stages. One-hundred and ten
tory drugs were given or allowed during the study. Data patients comprised the first stage and were defined as the
were analyzed using EsopHogram software (Medtronic). derivation cohort. The second stage consisted of 63
The percentage of time with pH \4.0 in the distal esoph- patients who were defined as the validation cohort. After
agus was analyzed separately for total, upright, and supine data obtained from the validation cohort were compared
periods and the DeMeester score was calculated and used against data collected in the derivation cohort, reproduc-
for scoring [14]. Because the Bravo system monitors pH ibility and validity were assessed.
for 48 h, we only used the data from the worse of the two
24-h periods of pH recording to assign a pH score to Statistical Analysis
patients who underwent pH monitoring with this technique.
The level of significance was set at P \ 0.05. Data are
presented in figures as bar graphs or in tables, as appro-
Scoring
priate. Receiver operating characteristic (ROC) curves that
graphically plot the sensitivity versus (1 - specificity) of
Depending on the findings upon clinical, endoscopic, histo-
the model were also performed in order to confirm the
logic, and functional evaluation, three groups were identified:
value of the proposed model.
1. reflux-like dyspepsia (RLD) group, where a normal
endoscopy was associated with normal esophageal
biopsy, no hiatal hernia and normal pH and motility
Results
studies (score range 2–4);
2. non-erosive reflux disease (NERD), where normal
Over a period of 24 months (January 2005–December
endoscopy was associated with more esophageal
2006), 159 patients (59 males, 100 females) presenting
symptoms, abnormal pH studies, and possibly with
with heartburn and epigastric pain partly refractory to PPI
hiatal hernia, low LESP and inflammation on esoph-
treatment entered the study. Their mean age was 52 (range
ageal biopsy (score range 3–11); and
13–87). Table 2 depicts baseline demographics and clinical
3. GERD, where erosive esophagitis or BE were found
characteristics of our study patients. Upon symptom
together with more esophageal symptoms, hiatal
questioning, all patients reported heartburn and epigastric
hernia, abnormal pH studies and LES hypotension
pain, as this was a prerequisite for entry into the study.
(score range 4–15).
Additionally, 84% reported regurgitation and 39% had
According to this system, a minimum score for patients dysphagia. The mean total symptom scores in the three
included in this study would be 2 (2 points for epigastric study groups were indistinguishable from each other
pain and heartburn, no dysphagia or regurgitation, negative (Table 2).
endoscopy and biopsy, no hiatal hernia, and normal LES Upon endoscopy, 41 patients had evidence of GERD, 30
pressure and pH study) and such patients would be clas- (19%) had esophagitis, ulcers or strictures (classified col-
sified as having RLD. At the other extreme, a patient with lectively as CE), and 11 (7%) had endoscopically dis-
severe, complicated GERD and BE would have a score of cernable BE. The other 118 (74%) patients had normal
15 (4 points for all four symptoms, 3 points for endoscopic esophagus. Thirty-nine patients (24.5%) had a hiatal her-
BE, 2 points for histologic intestinal metaplasia, 2 points nia, 25 (15.7%) small (\2 cm) and 14 (8.8%) large
for hiatal hernia, 1 point for LESP hypotension, and 3 ([2 cm).
points for pathologic pH profile). Upon review of distal esophageal biopsies, 49 (30.8%)
On the basis of these data, patients were assigned to one patients had evidence of inflammation, 11 (6.9%) patients
of three groups: The 41 patients with evidence of had intestinal metaplasia, and 99 (62.3%) patients had a
123
Dig Dis Sci (2011) 56:2871–2878 2875
Table 2 Patients’
RLD NERD GERD TOTAL
characteristics
N (%) 15 59 26 100
Patient mean age (years, range) 50 (23–87) 51 (13–82) 54 (22–78) 52 (21–87)
Males:females 11:13 29:65 19:22 59:100
Symptoms (%)
Epigastric pain 15 59 26 100
Heartburn 15 59 26 100
Acid regurgitation 13 50 21 84
Dysphagia 7 23 9 39
Endoscopy (%)
Normal 15 59 0 174
Esophagitis/ulcer 0 0 18 18
Esophageal stricture 0 0 1 1
Barrett’s esophagus 0 0 7 7
Hiatal hernia (%)
Absent 15.1 44.7 15.7 75.5
\2 cm 0 10.7 5.0 15.7
[2 cm 0 3.8 5.0 8.8
Esophageal biopsy (%)
Negative 15.1 41.5 5.7 62.3
Inflammation 0 17.6 13.2 30.8
Barrett’s esophagus 0 0 7 6.9
LESP (%)
C10 mm Hg 15.1 28.3 8.8 52.2
\10 mm Hg 0 30.8 16.9 47.8
DeMeester score (%)
B15 15.1 12.6 0 27.7
[15–25 0 11.9 3.1 15.0
[25–50 0 21.4 8.2 29.6
C51 0 13.2 14.5 27.7
normal biopsy. At motility testing, 83 (52.2%) patients had Mean total scores for each of the three groups were:
LESP greater than 10 mmHg, and the other 76 (47.8%) had GERD (mean score 9.5), NERD (mean score 5.94), and
a LESP less than or equal to 10 mmHg. On pH testing, 44 RLD (mean score 3.34) (Fig. 2). Given such score distri-
(27.7%) patients had a DeMeester score less than or equal bution, a score higher than 4 excludes RLD; a score higher
to 15 (normal), 24 patients (15%) scored between 16 and than 10 excludes NERD (Fig. 3). In the overall study
25, 47 (29.6%) patients had a score between 26 and 50, and cohort, the prevalence of RLD was 15%, NERD 59%,
44 (27.7%) of patients had a score greater than or equal GERD 26%.
to 51. For our derivation cohort, 110 patients (35 men, 75
Data from each of the three groups were then compared. women) were evaluated. Endoscopy showed erosive or
Not surprisingly, significantly fewer (24%) patients had a complicated GERD in 33 patients (30%) and was normal in
hiatal hernia in the NERD group compared with 41.5% of 77 patients (70%). Of this latter group, 62 (56%) had
patients in the GERD group. Significantly fewer (30%) of abnormal pH and motility studies and were classified as
the NERD group had a positive distal esophageal biopsy patients with NERD. The remaining 15 (14%) had normal
(either inflammation or BE) compared with 78% of the functional studies and were classified as patients with RLD.
GERD group. Similarly, 52% of the NERD group had The validation cohort comprised 63 patients (29 males, 34
abnormal motility studies, compared with 66% in the females). In this group, endoscopy showed erosive or
GERD group. Without exception, RLD patients had no complicated GERD in 22 patients (35%) and was normal in
hiatal hernia, negative esophageal biopsy, normal motility, 41 (65%). Of this latter group, 32 (51%) had abnormal pH
and normal pH scores. and motility studies and were classified as patients with
123
2876 Dig Dis Sci (2011) 56:2871–2878
Fig. 2 Total mean patient scores for each cohort, incorporating all
clinical, endoscopic, histologic, and functional variables used in this Discussion
study (as shown in Table 1). Scores are higher with erosive and
complicated esophagitis, intermediate with non-erosive disease, and
low in reflux-like dyspepsia Our study suggests that, in a community cohort of patients
presenting with heartburn and epigastric pain partly
refractory to empiric PPI therapy, the prevalence of CE is
19%, BE 7%, NERD 59%, and RLD 15%. Further, an
algorithmic approach, coupled with a new, simple, reliable,
and reproducible scoring system, effectively distinguishes
GERD from NERD and RLD and facilitates further man-
agement decisions.
On the basis of the pattern of their symptoms, patients
with dyspepsia are commonly classified into one of three
subgroups: ulcer-like, dysmotility-like, and reflux-like. In a
study of 1,040 adult patients with dyspepsia, analysis based
on the dominant symptom demonstrated that 463 (45%)
patients had ulcer-like, 393 (38%) had reflux-like, and 184
(18%) had dysmotility-like dyspepsia [6]. This classifica-
tion system is based on the assumption that dyspeptic
Fig. 3 Score distribution among the study patients. No patient with
symptom patterns remain stable over time and as such they
RLD had a score higher than 4; no patient with NERD had a score
higher than 10, thus effectively distinguishing among the three would guide management. However, recent studies have
entities demonstrated significant problems in this classification.
In one study, most dyspeptic symptoms changed continu-
NERD. The remaining nine (14%) had normal functional ously over time and without the effect of diagnostic
studies and were classified as patients with RLD. The mean procedures or therapy [15]. In another three-year follow-
symptom and total disease severity scores for each up study, changes from one dyspepsia subtype to
group within each cohort are listed in Table 3; graphic another were common, ulcer-like and reflux-like often
representations of comparative symptom scores and changed into dysmotility-like dyspepsia [16]. Few patients
Table 3 The mean symptom and total disease severity scores for each group within each cohort
Derivation cohort Validation cohort
N (%) Mean symptom Mean total N (%) Mean symptom Mean total
score (range) score (range) score (range) score (range)
RLD 15 (14) 3.27 (2–4) 3.27 (2–4) 9 (14) 3.44 (3–4) 3.44 (3–4)
NERD 62 (56) 3.33 (2–4) 6.23 (3–10) 32 (51) 3.00 (2–4) 5.34 (3–9)
GERD 33 (30) 3.24 (2–4) 8.70 (5–15) 22 (35) 3.06 (2–4) 9.50 (5–15)
Total 110 (100) 3.30 (2–4) 6.49 (2–15) 63 (100) 3.09 (2–4) 6.52 (3–15)
123
Dig Dis Sci (2011) 56:2871–2878 2877
123
2878 Dig Dis Sci (2011) 56:2871–2878
its results are applicable to large Western population 2. Chronic Disease Epidemiology and Control Section, Department
cohorts that are referred to gastroenterology practices from of Health Services, Sacramento, California 94234-7320, USA.
3. Moayyedi P, Duffy J, Delaney B. New approaches to enhance the
primary care. Using such a simple validated system, cli- accuracy of the diagnosis of reflux disease. Gut. 2004;53:iv55–
nicians may easily and objectively establish the underlying iv57.
etiology of the patients’ symptoms, establish prognosis and 4. Management of dyspepsia: Report of a working party. Lancet.
plan therapy. One could argue that the value of our score in 1988;1:576–579.
5. Talley NJ, Stanghellini V, Heading RC, et al. Functional gas-
daily practice is limited, because the score is constructed troduodenal disorders. Gut. 1999;45:II37–II42.
on the basis of an extensive algorithmic approach that 6. Thomson AB, Barkun AN, Armstrong D, et al. The prevalence of
involves, beyond symptoms, the performance of endoscopy clinically significant endoscopic findings in primary care patients
and biopsy, and esophageal motility and pH monitoring with uninvestigated dyspepsia: The Canadian Adult Dyspepsia
Empiric Treatment–Prompt Endoscopy (CADET-PE) study.
tests. However, using such a validated score, clinicians Aliment Pharmacol Ther. 2003;17:1481–1491.
could easily exclude the possibility of RLD if a score 7. Moayyedi P, Talley NJ, Fennerty MB, et al. Can the clinical
exceeded 4, that is, if a patient simply reported all four history distinguish between organic and functional dyspepsia?
symptoms, in addition to exhibiting a hiatal hernia upon an JAMA. 2006;295:1566–1576.
8. Savary M, Miller G. Manuel et Atlas d’ Endoscopie. Solothurn
otherwise normal endoscopy. Such a hypothetical patient (Switzerland): Verlag Gassmann, 1977.
would not require any further testing and would be com- 9. Dent J, Brun J, Fendrick AM, et al. An evidence-based appraisal
fortably characterized and treated as suffering from NERD. of reflux disease management–the Genval Workshop Report. Gut.
Although our numbers are relatively small for the vali- 1999;44:S1–S16.
10. Gerson LB, Boparai V, Ullah N, Triadafilopoulos G. Oesopha-
dation cohort, the idea of an algorithmic approach coupled geal and gastric pH profiles in patients with gastro-oesophageal
with a scoring system to aid in distinguishing patients with reflux disease and Barrett’s oesophagus treated with proton pump
functional dyspepsia from patients with GERD and NERD inhibitors. Aliment Pharmacol Ther. 2004;20:637–643.
is novel and warrants further investigation, given that there 11. Ismail-Beigi F, Horton PF, Pope CE 2nd. Histological conse-
quences of gastroesophageal reflux in man. Gastroenterology.
remains considerable difficulty in distinguishing these 1970;58:163–174.
three entities. In both the derivation and validation cohorts, 12. Bowery DJ, Williams GT, Clark GW. Histological changes in the
one could not differentiate between the three groups on the oesophageal squamous mucosa: Correlation with ambulatory 24
basis of symptoms alone. However, when utilizing the hour pH monitoring. J Clin Pathol. 2003;56:205–208.
13. Triadafilopoulos G, Castillo T. Nonpropulsive esophageal con-
multi-factorial scoring system, one can effectively dis- tractions and gastroesophageal reflux. Am J Gastroenterol.
criminate among the groups. 1991;86:153–159.
In conclusion, in a community cohort of patients pre- 14. Johnson LF, Demeester TR. Twenty-four-hour pH monitoring of
senting with heartburn and epigastric pain partly refractory the distal esophagus. A quantitative measure of gastroesophageal
reflux. Am J Gastroenterol. 1974;62:325–332.
to empiric PPI therapy, the prevalence of CE was 19%, BE 15. Laheij RJ, De Koning RW, Horrevorts AM, et al. Predominant
7%, NERD 59%, and RLD 15%. An algorithmic approach symptom behavior in patients with persistent dyspepsia during
coupled with a novel scoring system effectively distin- treatment. J Clin Gastroenterol. 2004;38:490–495.
guishes GERD from NERD and RLD and facilitates further 16. Meineche-Schmidt V, Jorgensen T. Fluctuation in dyspepsia
subgroups over time. A three-year follow-up of patients con-
management decisions. Furthermore, this novel multi- sulting general practice for dyspepsia. Dig Liver Dis.
factorial scoring system is simple, reliable, and reproduc- 2002;34:332–338.
ible as a diagnostic aid in evaluating patients presenting 17. Heikkinen M, Farkkila M. What is the long-term outcome of the
with both epigastric pain and heartburn. different subgroups of functional dyspepsia? Aliment Pharmacol
Ther. 2003;18:223–229.
18. Meineche-Schmidt V. Classification of dyspepsia and response to
Conflict of interests Dr Triadafilopoulos has received honoraria for treatment with proton-pump inhibitors. Aliment Pharmacol Ther.
lectures from Astra-Zeneca LLP and Takeda. Drs Marcus and Roorda 2004;20:1171–1179.
have no conflicts to declare. This study was not sponsored. 19. Wong WM, Wong BC, Hung WK, et al. Double blind, ran-
domised, placebo controlled study of four weeks of lansoprazole
for the treatment of functional dyspepsia in Chinese patients. Gut.
References 2002;51:502–506.
20. Talley NJ. What the physician needs to know for correct man-
1. Tack J, Talley NJ, Camilleri M, et al. Functional gastroduodenal agement of gastro-oesophageal reflux disease and dyspepsia.
disorders. Gastroenterology. 2006;130:1466–1479. Aliment Pharmacol Ther. 2004;20:23–30.
123