PRACA ORYGINALNA

ORIGINAL ARTICLE

Prevalence of acidic and non-acidic refluxes in patients with functional dyspepsia and its risk factors investigated by means of multichannel intraluminal pH-monitoring

Sergii Melashchenko, Viacheslav Chernobrovyi, Oleg Ksenchyn

Department of family and internal medicine, Vinnytsya National Pirogov Memorial Medical University, Vinnytsya, Ukraine

ABSTRACT

Introduction: Previous studies performed by conventional pH-monitors showed that a significant proportion of patients with functional dyspepsia have abnormal acidic gastroesophageal reflux. The investigation, using advantages of multichannel intraluminal pH-monitoring, were not conducted.

The aim to reveal the prevalence of all types of refluxes in patients with functional dyspepsia and to estimate risk provoking factors for abnormal reflux.

Methods and materials: Patients were divided into 6 groups. The 1st, 2nd and 3rd groups covered 127 adult patients with epigastric pain syndrome, postprandial distress syndrome and mixed variant respectively. The 4th included 69 NERD patients suffered from frequent (more than one episode per week) heartburn. The 5th group also consisted of 22 NERD patients without heartburn or with rare heartburn-regurgitation. The reference group included 30 subjects without dyspeptic complaint and established diagnoses of gastro-esophageal diseases. For all persons the 200-min MII-pH-monitoring was performed with standardized stimulating breakfast (507kcal, 100 mg caffeine, 300ml) recording basal and postprandial phases.

Results: It was found that the difference in comparison to the reference group in the number of refluxes is determined by the number of acid refluxes and not by weakly-acidic and weakly-alkaline refluxes. Patients with functional dyspepsia from all subgroups had an excessive amount of acidic refluxes in comparison with the reference group – 3.7±0.7, 4.7±0.8 and 2.8±0.7 vs 1.8±0.3 episodes (p<0.05). Using the previously obtained threshold values for abnormal acidic reflux (> 6 episodes per 200 min.) and total refluxes (>17 episodes per 200 min.) it was revealed that 22.8% patients with FD had abnormal GER. In addition, 16.5% had an isolated excess of non-acidic reflux. All three dyspeptic groups didn’t have a significant difference in the distribution of patients among subtypes of abnormal presence or absence of acidic/non-acidic refluxes.

Conclusion: In functional dyspepsia abnormal acidic reflux are common and affect 22.8% of patients. It is independently associated with hiatal hernia (OR=4.17), previously healed a peptic ulcer (OR=3.90), occasional heartburn (OR=1.25), body mass index (OR=1.11), younger age (OR=0.97).

KEY WORDS: functional dyspepsia; GERD; reflux; pH-monitoring; multichannel intraluminal impedance

Wiad Lek 2019, 72, 4, 604-612

Introduction

Functional dyspepsia (FD) is the most common upper gastrointestinal disorder affecting 11-29.2% of the population around the world [1]. So far, our knowledge of pathophysiological abnormalities in FD has been limited to functional changes in the gastrointestinal tract (visceral hypersensitivity, delayed gastric emptying, abnormal accommodation, gastric dysmotility), and only a small number of studies have investigated the co-existing gastroesophageal reflux (GER). Naturally, this disturbance is more relevant to GERD. Overlap of GERD and dyspepsia/FD is clearly a common situation and it is observed in 13-48% of subjects with FD [2]. Excluding these cases, some types of dyspepsia have a GER as the main pathogenetic factor. For example, it is considered that the leading mechanism for the development of dyspepsia in pregnant women is an excessive GER, although this assumption has not been proven by instrumental research [3,4]. The regular workup protocols for uninvestigated dyspepsia don’t generally include pH-monitoring, that’s why it is unclear how many of the dyspeptic patients had pathologic esophageal acid exposures. Previously performed studies in patients with FD show a prevalence of acid reflux 23-31.7% [5,6]. However, researchers used conventional 24-hour pH-monitoring of esophagus. Multichannel intraluminal impedance (MII)-pH-monitoring allows to expand diagnostic possibilities due to the evaluation of non-acid and gas events.

The aim

We aim to reveal the prevalence of acidic and non-acidic refluxes in patients with functional dyspepsia and to estimate risk provoking factors for abnormal reflux including clinical features and demographic data.

Materials and Methods

IMPEDANCE AND pH RECORDING

In our research we used ambulatory system of MII-pH-monitoring АГ-3рН-4R (“Start Ltd.”, Vinnytsia, Ukraine). We used a specialized catheter (lookalike ПЕ-2рН, Company with additional responsibility “Special construction bureau of medical electrical engineering”, KamianetsPodilskyi, Ukraine) with a 1.8-mm diameter consisting of 1 tungsten oxide pH-sensor and 6 electrodes that make up 4 measuring segments of impedance, located at 3, 5, 7 and 12 cm above the lower oesophageal sphincter (LOS) each 2 cm in length. Electrode pairs were connected to a transducer which delivered a measuring current of less than 6 μA at a frequency of 1 kHz. Impedance was recorded continuously, digitized at 50 Hz, and stored in a computer for subsequent analysis.

The probe is inserted through the inferior nasal conchae to the level of the distal esophagus with the pH sensor placed 5 cm above the LOS. Previously a location of the LOS was determined by the following formula:

L=45+((H – 175)/4) (cm),

where L- distance from the patient’s nostril (cm); H – patients height (cm).

After insertion of the probe, position of LOS was further defined by means of distal impedance electrode pair slipping along the esophagogastric junction. Resistance changes were displayed on the monitor of a connected laptop using a specialized program. The “jump“ of impedance from 0.5-0.8 kΩ to 1.2-1.8 kΩ corresponds to the location of LOS [8].

After an overnight fast, each subject attended the motility laboratory between 9:00 and 9:30 AM.

Previously we tested reduced modification of MII-pH-monitoring instead of 24-hour variant and demonstrated its good diagnostic value in cases of non-erosive GERD [7]. Performing ROC-curve analysis we obtained the best cut-off point for acidic reflux >6 events per 200 min. with 80,3% sensitivity and 82,0% specificity. For total number of liquid reflux the threshold value was >17 events per 200 min with same sensitivity (81,8%) but with slightly less specificity (73,0%) [7].

The 200-minute MII-pH-monitoring simulates usual digestive behavior including rest and postprandial phases. A design of recording is depicted on Fig.1. After placement of the probe, subjects remained in a sitting and a supine position alternately for 45 minutes to obtain a baseline recording. Stimulating breakfast was standardized by using McDonald’s menu: a black currant muffin and a small cup of Americano coffee with sugar – 507 kcal, 300 ml volume, carbohydrates 72 g, fats 27 g, protein 6 g, 100 mg caffeine.

All patients were instructed to keep a diary to record exact timing of symptoms such as heartburn, regurgitation and non-cardiac chest pain.

GASTRO-ESOPHAGEAL REFLUX PARAMETERS

The data received by the digitrapper were transferred to a computer where they were recorded and visualized using the graphical interface of the program. All data were analyzed by one physician who was blinded to patient’s clinical information. The operator looked at all recording channels (1 pH and 4 Z) with the subsequent analysis of events recorded on the charts. He identified a total number of reflux episodes separating theirs in terms of composition (liquid, gas, and mixed), and pH (acidic, weakly acidic, and non-acidic), AET (% time with esophageal pH<4), longest GER, symptom association probability (SAP), symptom index (SI). The criteria for these parameters were described previously in publication including Lyon consensus 2017 [9,10].

ASSESSMENT OF COMPLAINTS

In this study, a face-to-face 30-min interview was conducted using a «Rome III Diagnostic Questionnaire» during the health examination visit. This tool was used as main criteria of FD, irritable bowel syndrome (IBS) and other co-existing digestive functional disorders. Another aim of using this questionnaire was to perform a quantitative assessment of complaints. They offered unified 7-point scale to estimate how often the patient suffered from disturbances of the digestive function within the last 3 months. We included in our analysis the answers on questions #8 (Heartburn), #39 (Belching), #66 (Bloating), #17 (Epigastric pain/ burning), #13 (Postprandial fullness), #15 (Early satiety). Last two questions described the intensity of same item – postprandial distress syndrome (PDS). The greater value from the two was used in assessment. Question #8, describing the frequency of heartburn, gave opportunity to use the criteria of GERD according to the Montreal consensus 2006 and Vevey NERD consensus 2009 [11,12 ]. Occurrence of reflux symptoms more than once per week is considered as a threshold to include patients in clinical trials and population-based studies. It corresponds to answers of 5-6 points from question #8 «Rome III Diagnostic Questionnaire».

STUDY DESIGN

The study was carried out in Diagnostic gastroenterological laboratory at Vinnytsia National Medical University within 2011-2016. Outpatients with upper gastrointestinal symptoms were recruited after referring for consultation by general practitioner. Preliminary checkup selected patients with FD and GERD. All patients were previously underwent esophagogastroduodenoscopy, ultrasound examination of the abdominal cavity, routine laboratory tests. The exclusion criteria were: age up to 20 years or above 76 years, pregnancy and lactation, peptic ulcer (active or healed less than 12 months ago), gastric lesions (polyp, cancer), reflux esophagitis, Barrett’s esophagus, esophageal varices, evidence of cancer or mass lesion in the esophagus, resection of the stomach, previous esophageal or gastric surgery, Zollinger-Ellison syndrome, ulcerative colitis, Crohn’s disease, chronic heart failure above IIIrd FC by NYHA, chronic kidney disease with GFR less than 30 mL/min, pulmonary failure above II st., hepatic encephalopathy above 1st degree, portal hypertension II–IV Baveno stages.

All patients were divided into 5 groups: 1) FD-EPS – epigastric pain syndrome; 2) FD-EPS/PDS – co-existing EPS and PDS; 3) FD-PDS – postprandial distress syndrome; 4) NERD heartburn positive (Hb-pos.); 5) NERD heartburn negative (Hb-neg.). In addition, a reference control group was collected from subjects without suspicious complaints or clinical signs of GERD and functional disorders of upper gastrointestinal tract. Detailed information on age and gender is presented in Table I. Diagnosis of GERD and FD were established by the criteria of the Montreal (2006) and Rome-III/IV (2005/2016) consensuses. NERD was diagnosed if there was confirmation either by MII-pH-monitoring including positive symptom association in cases with normal number GER or by subsequent positive PPI-test in mode describing by de Leone [13]. Subjects with esophageal hypersensitivity (positive symptom association with non-acidic reflux) were defined as NERD.

We separated a special subgroup of NERD if typical symptoms (heartburn and regurgitation) occurred less than once per week. In such cases atypical symptoms were frequent and there was a confirmation by MII-pH-monitoring and PPI-test. The necessity of such approach was caused by subsequent analysis of the triggering factors of the abnormal reflux in very close groups of FD. For example dyspepsia is regular and frequent manifestation of GERD. If frequent heartburn is present simultaneously with dyspepsia, gastroenterologists will define this case as GERD. Therefore, if heartburn is either absent or rare, it will be confusing diagnosis. In our “NERD Hb-neg.” subgroup there were 14 persons from 22 suffered from dyspeptic symptoms at least once per week. All of them had other predominate manifestations (chronic cough, chest pain, lump, etc.) that’s why they were diagnosed GERD. On the other hand, patients with severe dyspeptic complaints, with abnormal reflux and absence of heartburn will be very close to NERD, but formally they are diagnosed with FD by Rome III/IV consensuses.

STATISTICAL ANALYSIS

Data are expressed as mean±SEM (standart error of mean) for each of the measured parameters and age, body mass index (BMI). Gender, co-existing IBS, successfully healed HP-positive peptic ulcer in anamnesis and presence of hiatal hernia are expressed as ratio or absolute number. H. pylori infection rates are expressed as percentages of the total patient number. An independent t-test was used to analyze age, body mass index (BMI), number of refluxes, AET and longest reflux. To find out the relationship between data with a normal distribution, we used the Pearson’s parametric correlation coefficient. Spearman’s and Kendall’s rank correlation coefficients were applied in cases with non-normal distribution. φ (phi) Pearson’s correlation coefficient was used for data with dichotomous distributions. A p-value below 0.05 was considered statistically significant (always two-sided).

The association between abnormal GER in groups without heartburn and potential risk factors was measured by odds ratio with 95% confidence intervals (95%CI) as result of regression analysis by using logistic model (enter method). Statistical data processing was carried out using program «MedCalc 11.3.3.0» (MedCalc software bvba, Holland).

RESULTS

A total of 218 consecutive patients and 30 non-dyspeptic subjects were recruited for the study and completed protocol.

If we generally describe the number of weakly-acid and weakly-alkaline reflux in all groups, they will be equal (Table II). The arithmetic mean of the sum was 11-13 events. The difference was due to increasing number of acid refluxes in patients of certain groups. Unsurprisingly it was found that the most pronounced GER were observed in patients with NERD without frequent heartburn and regurgitation (group “NERD Hb-neg.”). This was related to both – acidic and total number of liquid refluxes. The difference with NERD Hb-pos. was not significant. If we look at all MII-pH parameters, we will observe the same tendency of increasing duration of longest reflux and AET. In group “NERD Hb-pos.“ there were more persons with normal acidification of esophagus. Their diagnoses were confirmed either by SAP/SI or by PPI-test.

Patients from all groups of FD didn’t have longer AET than reference “Non-dyspeptic” group. However, number of acidic refluxes and duration of the longest reflux were almost twofold higher3.8±0.5 vs 1.8±0.3 episodes (p<0.002) and 29.4±7.3 vs 57.3±8.8 s (p<0.02) respectively. Therefore, the total amount of liquid GER was significantly higher – 15.7±0.6 versus 12.8±0.7 (p<0.0036).

Also in PDS group compared with the rest FD patients there was a significant time prolongation of longest reflux: 84.5±17.5 sec vs 35.4±9.3 sec in EPS (p<0.017) and vs 41.3±12.6 sec in co-exist EPS/PDS (p<0.05).

As reported in part “Methods”, the threshold values of the abnormal acidic and total refluxes after MII-pH-monitoring were >6 and >17 respectively. Only in the reference group no persons exceeding these threshold values were registered (Fig.2).

Groups with FD had approximately the same number of individuals exceeding the threshold for acid reflux. Such situation was observed almost in a quarter cases – 22.8% (50 from 127). Attention was drawn to the fact that there were differences in the subgroups “EPS”, “PDS” and “co-existing EBS/PDS” from other patients in terms of the distribution of persons with excessive acidic refluxes, total refluxes, and a combination of these two phenomena. Among patients with NERD, persons with pathological acidic reflux simultaneously demonstrated excess gain of total refluxes in the overwhelming majority of cases. In contrast, 16.5% of FD patients (21 from 127) had an isolated excess of total refluxes due to non-acidic events. Thus, there was a situation of an obviously increased number of weakly-acidic and weakly-alkaline refluxes.

The pathological GER is closely associated with typical GERD complaints – heartburn and regurgitation. If we deal with individuals without such complaints but with registered excessive reflux after functional tests, they will form a special phenotype of FD. It is fascinating what types of manifestations arise in such persons, what factors provoke the abnormal GER and how both relate to the problem of “silent GERD”.

To find out the causes of pathological acid reflux, we conducted a correlation analysis of the assumed risk factors with the number of GERs in the groups of FD and NERD without frequent heartburn. For this and subsequent regression analysis we took patients from all groups excluding “NERD – Heartburn positive” and referent “Non-dyspeptic”. In the analysis there were 149 dyspeptic persons.

We didn’t find a significant effect on the frequency of acidic GER concomitant IBS, gender identity, Helicobacter infection, gallstones (Table III). The frequency of bloating, belching, postprandial filling, early satiety, epigastric pain and burning sensation didn’t correlate with the frequency of reflux occurrence. Variables BMI, age, hiatal hernia, healed PU, occasional heartburn were associated with excess acidic GER (P<0.05).

A similar correlation analysis was performed for total refluxes and its results were less sensitive to the identification of provoking factors (Table IV). The relevance of calculating total refluxes for clinical practice remains unexplained. There is no pathogenetic pharmacotherapy of this disorder.

The best presentation of the interrelations between provoking factors is given by logistic regression analysis performed by the “enter” method (Table V). It makes possible to visually assess the degree of influence. Created regression model assumes the creation of an equation for calculating the risk of the occurrence of abnormal acidic reflux in patients with dyspeptic complaints but with rare heartburn. Logistic analysis, performed using selected five variables, demonstrated that all of them were significantly and independently associated with this condition (P<0.05). The area under the ROC curve (AUC) of our model was 0,710 (CI95% 0,630- 0,781) and the percentage of cases correctly classified 74.5%.

Discussion

Comparing the results obtained from patients with FD and from non-dyspeptic subjects, we saw significantly longer refluxes, a greater frequency of acid refluxes and, correspondingly, all liquid events. However, AET in both groups was not significantly different due to the fact that the fraction of time with reflux was relatively short – approximately 2% of the total test.

Thus there are serious abnormalities of esophagogastric motility in FD. Especially they were noticeable in the subgroup of the PDS, where we observed a twofold increase in time of the longest reflux. The following speculation can be made in connection with this issue. In a meta-analysis of Quartero with co-authors, it was proved that 40% of patients with FD had a significant delay of the food lump after ingestion [14]. Most of them had PDS. The delay will also contribute to a longer period during which there is an excessive amount of content in the stomach. Thus, the probability of GER will be increased. Gourcerol using the MII-pH-monitoring noted that the delayed gastric emptying provoked more proximal GERs and significantly retarded the clearance of the esophagus [15].

Refluxes are frequent occurrences in patients with FD but in comparison with patients with GERD, there is often an excess of the threshold values of total events with a normal amount of acidic ones. This discrepancy can be explained by several factors. Firstly, among persons with this disease there is a significant proportion of patients with hypoacidity. Subjects suffering from GERD usually have a normal or elevated level of acidity because this diagnosis is referred to the acid-related disorders. Thus, if a reflux occurs in person with hypoacidity, the content of esophagus will remain alkaline. Secondly, the thickness of acidic layer in “acid pocket” can influence the composition of refluxate. In patients with dyspepsia, the “acid pocket” is thinner, so there is a low likelihood of acidic reflux happening.

The distribution between the types of reflux in the subgroups of FD was the same with a trend toward a higher frequency of reflux in the PDS (N.S.). We didn’t receive confirmation of a greater frequency of reflux in patients with EBS observed during conventional pH monitoring by Tack [5] and Xiao [6].

As mentioned above, FD is very heterogeneous by its pathogenesis. In clinical trials researchers try to identify potential associations between specific pathophysiological abnormalities and representative symptoms of dyspepsia [16]. For example, a delayed gastric emptying causes a feeling of postprandial fullness and nausea. Weakened accommodation is present in 40% of patients and causes early saturation. Hypersensitivity of the stomach occurs in 37% of patients and is linked with postprandial pain, eructation and loss of body weight [16].

Presumably, refluxes will occur in subjects with more prominent disorders of gastric motility, which is more typical of patients with PDS. In contrast to this the major element of the EPS pathogenesis is hypersensitivity. Thus, reflux activity with this subtype will not be pronounced.

In order to find out the factors that contribute to the appearance of excessive reflux, we carried out a correlation and regression analysis which identified the most significant 5 variables: BMI, hiatal hernia, age, healed PU, occasional heartburn. This agrees with the well-known facts that obesity, even without the presence of hernia, contributes to the development of GERD [17].

The damaged function of the LOS, which is a consequence of a sliding hiatal hernia, strongly associates with increasing reflux symptoms [18] and frequent backflow of gastric contents into the esophagus [19]. In the context of the problem being studied, a hernia can often be detected in subjects without clinical manifestations of GERD. Studies from the Western countries showed that 13-59% of adult subjects without GERD had a hernia [20]. We revealed that people with hiatal hernias, but even without typical complaints of GERD, in most cases have pathological reflux. Nevertheless in some pH-metric studies authors observed that the absence of symptoms in hernial patients indicates a lack of abnormal reflux [21].

In our study the age correlated negatively with the risk of appearance of excessive reflux because there is an age-related lowering of gastric acidity [22]. This decrease in acid secretion is now thought to be the result of H. pylori infection and not the result of physiological aging [23]. Thus, a negative correlation could be expected between the presence of HP and abnormal reflux. But we did not find a significant reduction of reflux activity among HP-positive patients. This coincides with the opinion of most gastroenterologists who conducted epidemiological, instrumental studies, including the most precise method of pH-monitoring [24]. Most researchers, who conducted pH monitoring in the same patients before and after HP eradication, did not find an increase in the number of refluxes and AET [25,26]. Although a small study from Hong Kong reported a worsening in the acid exposure among subjects of preceding esophagitis [27]. Two meta-analyses devoted to this issue didn’t show any association between HP-eradication and the development or an aggravation of GERD [28, 29]. However, in cohort studies (not in RCT), there seems to be a twofold higher risk of development of erosive GERD in patients with PUD [29]. In our study it was interesting to reveal that persons who successfully healed a peptic ulcer by eradicating an HP-infection more often had abnormal GERs. It should be noted that we did not include all subjects with cleared HP infection, but only those who continued to suffer from dyspepsia. Former patients with duodenal ulcer are a special category with extremely high intragastric acidity and therefore a high probability of abnormal GERs.

Excessive number of refluxes in patients with FD forms a particular phenotype of the disease, which is very close to GERD but without the usual manifestations. The pathogenesis of «silent (oligosymptomatic) GERD» is an interesting and unexplored problem. Such GERD patients may actually experience some reflux symptoms, but do not complain about them, perhaps because of the lack of understanding that they are symptoms. Or they may have visceral symptoms, which are different from the typical symptoms of reflux, including dyspepsia. Traditional theory explains the burning of penetration of acid into the esophagus mucosa. However, not all facts corroborate this concept.

The new conceptual framework for esophageal perception is based on the involvement of not only peripheral, but also central mechanisms with a significant influence of psychosocial factors [30,31].

A well-known Japanese researcher Miwa proposes that individuals with GERD without heartburn and regurgitation have not only chemical hyposensitivity to acid but also overall. He found that in this cohort of patients, the quality of life suffered considerably less and less there were the atypical symptoms of GERD [32]. There is an assumption that perception depends on expression levels of capsaicin pain receptors, which, when re-exposed, become less sensitive, including to acid [33]. Unfortunately, we did not analyze the nutritional preferences of our patients and this could be a promising direction for further research.

Conclusions

Thus, in FD abnormal acid gastroesophageal refluxes are common and affect 22.8% of patients. In addition, another 16.5% have an isolated excess of non-acidic reflux. The risk factors of abnormal acid reflux are hiatal hernia, overweight, successfully healed HP-positive peptic ulcer in anamnesis. There is an inverse relationship between age and the risk of excess reflux. Occasional heartburn occurring less than once a week may indicates the pathological refluxes. Patients with isolated PDS-subtype of FD, in contrast to the EPS and the mixed variant of dyspepsia, tend to have longer acid refluxes.

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Authors’ contributions:

According to the order of the Authorship.

Conflict of interest:

The Authors declare no conflict of interest.

CORRESPONDING AUTHOR

Sergii Melashchenko

Vinnytsya National Pirogov Memorial Medical University

Pirogova str., buil. 56, 21018 Vinnytsya, Ukraine

tel: +380973912108; +380432690043

e-mail: melashk15@gmail.com

Received: 27.02.2019

Accepted: 29.03.2019

Table I. Demographic Data

N

Gender ratio (M/F)

Mean age, M±m

HP+,%

IBS, n

Healed
PU (HP+), n

Functional dyspepsia (together):

127

39/88

44.8±1.5

36.8

40

8

EPS

34

11/23

40.7±3.1

36.7

9

0

co-existing EPS/PDS

42

10/32

45.5±2.4

33.3

16

2

PDS

51

18/33

46.8±2.4

40.0

15

6

NERD heartburn-positive

69

25/44

46.7±1.9

32.1

18

11

NERD heartburn-negative

22

12/10

45.6±3.4

22.7

7

5

Non-dyspeptic

30

14/16

42.6±3.1

Table II. GERs registered after 200-minute esophageal МІІ-рН-monitoring with provocative breakfast.

Group

Acidic

reflux, (n)

Weakly acidic, (n)

Weakly alkaline, (n)

Total

liquid, (n)

AET,

(%)

Longest

reflux, (sec)

Functional dyspepsia (together):

3.8±0.5*

9.7±0.5

2.2±0.2

15.7±0.6*

2.9±0.2

57.3± 8.8º

EPS

3.7±0.7†

8.7±0.7

2.5±0.4

14.9±1.0

2.7±0.5

35.4±9.3

coex.EPS/PDS

2.8±0.7

10.6±0.9

2.2±0.3

15.6±1.2º

2.9±0.5

41.3±12.6

PDS

4.7±0.8*

9.6±0.7

2.0±0.2

16.3±0.9*

3.2±0.4

84.5±17.5

NERD Hb-pos

11.2±1.28*

10.0±0.7

2.4±0.5

23.6±1.3*

6.3±0.3

205.0±32.9

NERD Hb-neg

13.4±1.8*

10.2±1.2

1.9±0.5

25.5±2.2*

7.0±0.7

248.2±37.0

Non-dyspeptic

1.8±0.3

8.8±0.7

2.2±0.3

12.8±0.7

2.4±0.6

29.4±7.3

Difference is significant vs reference control group (Non-dyspeptic): º – p<0.05; † – p<0.01; *- p<0.001.

Fig.1 Design of 200-minute esophageal МІІ-рН-monitoring with provocative breakfast and sample pH-tracing. Marks «Б» over timeline indicate symptom occurring (heartburn, chest pain, etc.).

Table III. Correlation between number of acidic GER and clinical manifestations, demographic data of patients with Functional dyspepsia (N=127) and Endoscopy-negative GERD without obvious heartburn (i.e. less than 1 time per week) (N=22).

Variables

Number with abnormal

(acidic >6) and normal (<7) GER among patients with positive sign

Correlation coefficients

CI 95%

P

Age (years)

r’ = –0.177

–0.329 to –0.017

0.0306

Gender (male)

15 / 36

φ = –0.030

0.7169

BMI (kg/m^2)

r = 0.172

0.012 to 0.323

0.0357

Healed PU in anamnesis

7 / 6

φ = 0.150

0.0514

НР-positive status

13 /35

φ = –0.116

0.1780

IBS

17 / 30

φ =0.070

0.3897

Hiatal hernia

7 / 5

φ = 0.172

0.0372

Gallstones/ Cholecystectomy

6 / 6

φ = 0.103

0.1480

Heartburn

r = 0.219

0.061 to 0.366

0.0072

Belching

r = –0.051

–0.209 to 0.110

0.5361

Postp. fullness/ early satiety

τ = –0.142

–0.296 to 0.018

0.0821

Epigastric pain /burning

r = –0.129

–0.284 to 0.032

0.1151

Bloating

r = 0.005

–0.284 to 0.032

0.9485

Correlation coefficients: r – Spearman’s rank; τ – (tau) Kendall’s rank; r’ – Pearson’s parametric ; φ – (phi) Pearson’s for dichotomous distributions.

Indicators «Heartburn», «Belching», «Postprandial fullness/ early satiety», «Epigastric pain», «Bloating» were used with value equal to points from answers of «Rome III Diagnostic Questionnaire».