The patients with GERD symptoms were classified into EE, NERD and FH groups based on the result of upper endoscopy, 24-hour esophageal pH testing or acid perfusion test in the present study. There have been few studies which compared FH with EE and NERD because of the difficulty in differentiation between NERD and FH. In our study, these 3 groups were found to be very different from each other in demographics and clinical characteristics although the presenting GERD symptoms were similar. Western reports showed that male gender, frequent hiatal hernia, and a higher BMI were more common in the EE group than in the NERD group,18
similar to our study. EE patients were reported to be older than NERD19
but our study showed that the age of EE group was similar to that of NERD and FH group, which was also observed in the previous Korean report.20
Female gender was predominant in NERD and FH in the present study, a frequent finding in functional disorders.21-23
Our study also showed that alcohol consumption, smoking history, the presence of hiatal hernia, BMI ≥ 25 kg/m2
and triglyceride levels (≥ 150 mg/dL) were significantly more common in patients with EE than in those with NERD and FH, supporting an association of high BMI24
or obesity with EE.25
In addition, hiatal hernia, a significant risk factor for EE, was found to be significantly associated with an increased BMI.26
On the other hand, anxiety and depression tended to be more prevalent in FH patients than in EE or NERD patients.20
In addition, patients whose heartburn was not correlated well with acid reflux events demonstrated greater anxiety and somatization scores as well as poorer social support than those with acid reflux-related symptoms.27
The history of both psychiatric treatment and psychopharmacotherapy was more frequent in patients with FH than in those with EE or NERD in the present study. This result suggests that psychological co-morbidity can modulate esophageal perception and cause patients to perceive low intensity esophageal stimuli as being painful.28
Otherwise there was no difference with regards to endoscopic atrophic gastritis, hypertension, diabetes mellitus, cholesterol and LDL among the 3 groups in our sample, similar to a number of studies,29-31
showing that these factors are not peculiar to any of our subgroups.
Several questionnaires have been developed for the assessment of GERD symptoms in recent years.11,32,33
However, the impact of symptoms on everyday life was not included in most of the questionnaires. GIS questionnaire has been developed with the main intent as a communication tool between patients and their physicians. It is a simple, one page questionnaire for doctors to check the frequency of reflux symptoms and their effect on QOL in primary care, helping clinicians to ask GERD symptoms quickly and to appropriately treat patients' symptoms.14
To evaluate the clinical efficacy of GIS in the tertiary hospital, GERD symptoms and the impact of symptoms were compared in our 3 groups with GERD symptoms using a GIS questionnaire. About 65% of EE patients had not experienced typical GERD symptoms like heartburn or acid regurgitation.34
The main reason of higher number of patients without typical GERD symptoms in Korea is that many of the EE patients reported were diagnosed incidentally by health examinations. However, we only enrolled the patients that visited the hospital for GERD symptoms. So, all enrolled patients had one or more GERD symptoms. Interestingly, the prevalence of chest pain and eating problems and limitation of productive daily activities were significantly higher in the FH group than the EE and NERD groups. GERD symptoms and effects on daily life in FH patients in our study could be explained by psychological co-morbidity modulating esophageal perception.28
Recent studies performed mainly in Western countries demonstrated a bidirectional relationship between GERD and sleep where night-time reflux leads to sleep deprivation and sleep deprivation per se can exacerbate GERD by enhancing perception of intra-esophageal stimuli.35-37
In addition, medical treatment with PPIs of nighttime GERD improved sleep disturbances.38-41
However, there have been no reports regarding a bidirectional relationship between GERD and sleep in Korea, so far, where the incidence of GERD is not so high in comparison to Western countries. Interestingly, the prevalence of sleep disturbance due to GERD symptoms at least once per week was higher in the NERD (23.5%) and FH (16.7%) than in the EE (12.9%) but without statistical significance in the present study. Since this could be a result of the small sample size, there is a possibility of bidirectional relationship between GERD and sleep in a large population, which could be worth investigating.
Classical GERD symptoms no longer provide a complete description of patient disability related to GERD and FH. The limitations of symptom assessments have been emphasized recently by McColl et al.42
It is clear that a new paradigm for the accurate assessment of the true impact of GERD on an individual patient is needed. Accordingly QOL has become a component of the definition of GERD and is essential to the evaluation of therapeutic interventions. One of the benefits of the GIS questionnaire is that it can monitor the GERD symptoms and QOL at a glance in an easily accessible manner. When the correlation between the GERD symptoms and impact of symptoms was compared in our study, there was a close positive correlation between 2 factors in the EE and FH groups. Contrary to our expectations, however, there was no correlation in the NERD group, which could be clarified in large population based studies. In spite of this, the positive correlation in the EE and FH groups suggests the usefulness of GIS questionnaire.
GIS has not been formally validated as a tool to monitor the response of GERD symptoms and QOL to PPI treatment. Our trial to compare the responsiveness of PPIs in subjects with GERD symptoms using a GIS questionnaire is mainly from the practical viewpoint. That is, the clinicians should assess the patient's short term response to GERD treatment effectively, especially in the clinical situation of South Korea. It is very interesting that the response to PPI was found to be different among three groups. That is, chest pain was more improved in the FH group, but acid regurgitation more improved in the EE and NERD groups. In case of QOL, eating problems and limitation of productive daily activities were more improved in the FH group and in the NERD group, respectively. The reason for this different response might be related to the initial severity of GERD symptoms in 3 groups. That is, in FH the prominent symptom was chest pain and this symptom was clearly improved by PPI. The result that an atypical symptom like a chest pain was more improved in FH after PPI treatment suggests a probable overlap between FH and functional dyspepsia. Chest pain has been reported in patients with functional dyspepsia43
and PPI was also superior in relieving the symptoms of functional dyspepsia.44
Similarly, improvement of QOL like eating problems or limitation of productive daily activities in FH could be explained as above. Taken together these results provide another proof that GIS questionnaire could be a useful communication tool between patients and their physicians. We could not suggest 'cut-off value' for responder or non-responder. However, using each score, doctors can detect uncomfortable symptoms of patients and choose appropriate treatment. Also, by comparing total score, doctors can learn the patient's short-term response to GERD treatment. So far, few studies compared the characteristics of EE, NERD and FH groups,29,45
but there has been no study comparing the characteristics of the 3 groups using GIS questionnaire.
Our study has several limitations. That is, the number of patients was small, especially in the case of NERD and FH. However, the diagnosis of NERD and FH is based on Bernstein test and 24-hour esophageal pH meter. It is very difficult to persuade patients to undertake these 2 studies because GERD symptoms are not so critical and PPI test could be used instead of these two studies. However, these strict diagnostic criteria became useful for the differentiation of EE, NERD and FH. Second, follow-up number after PPI therapy became smaller. As the NERD or FH is not life threatening, there is a possibility of follow-up loss in both of the patients who had GERD symptoms improved or not responded. However, there was different response in these 3 groups after 8 weeks of PPI therapy in the present study.
In conclusion, the GERD and impact of symptom pattern as well as demographic and clinical characteristics were different among EE, NERD and FH. In addition, our study is the first study which suggested the usefulness of GIS questionnaire in the follow-up after PPI therapy among patients with EE, NERD or FH.