Mean nocturnal baseline impedance: Influencing factors and diagnostic value in gastroesophageal reflux disease

Abstract

BACKGROUND:

At present, there are few studies related to mean nocturnal baseline impedance (MNBI), esophageal dynamic reflux monitoring, high-resolution esophageal manometry (HRM) parameter indexes, and its diagnostic value in gastroesophageal reflux disease (GERD).

OBJECTIVE:

To analyze the factors influencing MNBI and examine the diagnostic value of MNBI in GERD.

METHODS:

A retrospective analysis on 434 patients with typical reflux symptoms who underwent gastroscopy, 24-hour multichannel intraluminal impedance and pH monitoring (MII/pH) and HRM. They were divided into the conclusive evidence group (103 cases), borderline evidence group (229 cases), and exclusion evidence group (102 cases) according to the level of diagnostic evidence of GERD based on the Lyon Consensus. We analyzed the differences in MNBI, esophagitis grade, MII/pH and HRM index among the groups; the correlation between MNBI and the above indexes and its influence on MNBI; and to evaluate the diagnostic value of MNBI in GERD.

RESULTS:

There were significant differences in MNBI, Acid Exposure Time (AET) 4%, DeMeester score, and total reflux episodes among the three groups ( $P<$ 0.001). EGJ contractile integral (EGJ-CI) of the conclusive evidence group and the borderline evidence group was significantly lower than that in the exclusion evidence group ( $P<$ 0.001). MNBI was significantly and negatively correlated with age, BMI, AET 4%, DeMeester score, total reflux episodes, EGJ classification, esophageal motility abnormalities, and esophagitis grade (all $P<$ 0.05), and significantly and positively correlated with EGJ-CI ( $P<$ 0.001). Age, BMI, AET 4%, EGJ classification, EGJ-CI, and esophagitis grade had significant effects on MNBI ( $P<$ 0.05); MNBI was used to diagnose GERD with a diagnostic cutoff of 2061 $\Omega$ , and AUC was 0.792 (sensitivity 74.9%, specificity 67.4%); MNBI was used to diagnose exclusion evidence group with a diagnostic cutoff of 2432 $\Omega$ , AUC was 0.774 (sensitivity 67.6%, specificity 72%).

CONCLUSION:

AET, EGJ-CI, and esophagitis grade are the most important influence factors of MNBI. MNBI has good diagnostic value in identifying conclusive GERD.

Keywords

Diagnosis gastroesophageal reflux disease high resolution manometry of esophagus mean nocturnal baseline impedance 24-hour multichannel intraluminal impedance and pH monitoring

1. Introduction

The incidence of gastroesophageal reflux disease (GERD) is increasing every year [1]. Based on clinical studies pertaining to the diagnosis and treatment of GERD in recent years, gastroenterologists worldwide published the Lyon Consensus on Gastroesophageal Reflux Disease (hereinafter referred to as the “Lyon Consensus”) in Gut magazine in 2018. In the Lyon Consensus, according to the results of gastroscopy, 24-hour pH impedance monitoring, and high-resolution manometry (HRM), the levels of evidence for the diagnosis of GERD were divided into conclusive evidence, borderline evidence, and exclusion evidence. Additionally, new indicators for esophageal impedance-pH monitoring [2, 3], such as the mean nocturnal baseline impedance (MNBI) and post-reflux swallow-induced peristaltic wave (PSPW), were included as the basis for auxiliary judgment.

Of late, several studies have shown that when the integrity of esophageal mucosa is damaged, the tight junction between the esophageal epithelium also gets compromised, and the intercellular space widens, followed by the decline of mucosal baseline impedance. Therefore, it is believed that MNBI can reflect the integrity of esophageal mucosa. The MNBI was found to be successively increased in patients with reflux esophagitis, non-erosive gastroesophageal reflux disease (NERD), and esophageal hypersensitivity [4, 5].

According to the Lyon Consensus, pathological MNBI was defined as less than 2292 $\Omega$ . Frazzoni et al. performed a prospective study with 289 GERD patients and 50 healthy controls in Italy, which showed that 2292 $\Omega$ could be used as the cut-off impedance values to distinguish GERD patients from healthy controls [6]. In addition, a study pointed out that MNBI is $>$ 2291 $\Omega$ in healthy people [7], and this standard is also derived from the Lyon consensus. So it is considered as abnormal if the MNBI value is $<$ 2292 $\Omega$ . However, normative MNBI cut-off values could vary between regions and ethnicities. We also found there were some study involved in MNBI cutoff value in China. A single-center study from China showed that 1764 $\Omega$ could be used as the cut-off impedance values to discriminate patients from healthy controls, which included 92 patients with typical reflux symptoms and 10 healthy controls [8]. Given this, we speculate that abnormal MNBI cut-off values may be lower than 2292 $\Omega$ in Asia, which could explain the high proportion of pathological MNBI ( $<$ 2292 $\Omega$ ) in patients with conclusive evidence of GERD in our study. Studies involving a larger sample size of healthy controls will be needed in Asia.

At present, there are few studies related to MNBI, esophageal dynamic reflux monitoring, HRM parameter indexes, and its diagnostic value in GERD. The purpose of this study is to observe the differences in MNBI among different evidence level groups for the diagnosis of GERD based on the Lyon Consensus, analyze the related factors influencing MNBI, and explore the diagnostic value of MNBI in identifying conclusive GERD.

2. Materials and methods

2.1 Study details and respondents

We conducted a retrospective analysis on the clinical data of 434 adult patients with typical symptoms of gastroesophageal reflux who visited the Department of Gastroenterology, Beijing Tongren Hospital Affiliated to Capital Medical University between August 2015 and May 2021. All patients answered the GerdQ questionnaire and scored $\geqslant$ 8 points, and underwent gastroscopy, 24-hour esophageal pH impedance monitoring, and HRM. Exclusion criteria: (1) History of upper gastrointestinal surgery; (2) Coexisting digestive system diseases such as digestive tract tumors, peptic ulcer, and esophageal and gastric varices; (3) Infective esophagitis and eosinophilic esophagitis; (4) Primary or secondary severe esophageal dysmotility; (5) Pregnant and lactating women; (6) Patients with severe cardiopulmonary diseases and severe coagulation disorders that cannot withstand the examination.

2.2 Methods

2.2.1 Gastroscopy

All patients underwent electronic gastroscopy to determine the severity of reflux esophagitis as per the Los Angeles (LA) classification of GERD [9].

2.2.2 24-hour multichannel intraluminal impedance and pH monitoring (MII/pH)

All patients stopped taking prokinetic drugs, proton pump inhibitors, H2 receptor blockers, and other drugs at least 2 weeks before the examination. The position of the lower esophageal sphincter was determined by HRM. The pH impedance monitoring catheter was inserted and fixed from the nasal cavity to a position 5 cm above the upper edge of the lower esophageal sphincter. The Ohmega impedance-pH monitor (MMS, the Netherlands) was used for examination. The patients were asked to continue all daily activities and maintain a diary. After 24 h, the monitoring catheter was removed, and the recorded data were analyzed. Determination of MNBI: During the night sleeping position of patients, three 10-minute windows (1 a.m., 2 a.m., and 3 a.m.) were selected (Patients were cautioned to avoid swallowing during reflux events), and the baseline impedance value of the most distal impedance channel was measured. The average impedance value in the above three periods was calculated using a software, namely, MNBI [5, 10, 11]. The total reflux episodes, acid exposure time percentage (AET (%)) and DeMeester score were also recorded.

2.2.3 High-resolution manometry of esophagus

Patients stopped using drugs that affect gastrointestinal mobility (such as domperidone and mosapride) 1 week before the manometry examination, and were fasting for $>$ 8 hours before the examination. Solar GI high-resolution pressure measurement system manufactured by Medical Measurement Systems Inc. of the Netherlands was used. A silica gel catheter with a diameter of 3.6 mm pressure channels (No. 22) was inserted into the pressure measuring tube through the nose, and the catheter was adjusted in a suitable position and fixed on the nasal ala. The patients were in a supine position. After the patients adjusted to the intubation, the resting pressure was recorded and the patients were asked to swallow 5 ml of drinking water with an interval of more than 30 s each time. Data from a total of 10 swallows were collected and the catheter measuring pressure was removed at the end of the examination. Data analysis software (MMS, version 9.3) was used for analysis and the pressure measurements were interpreted according to the Chicago Classification of esophageal motility disorders v3.0. The following parameters were recorded using the high-resolution manometry of the esophagus: morphological classification of the esophagogastric junction (EGJ), EGJ contractile integral (EGJ-CI), and esophageal motility abnormality. EGJ was classified into three types according to the relationship between the lower esophageal sphincter (LES) and diaphragm: (1) Type I: LES and diaphragm were completely overlapped, and the spatial pressure diagram showed a single peak during inspiration; (2) Type II: LES was spatially separated from the diaphragm with an interval of $<$ 3 cm. The spatial pressure diagram presented as two peaks during inspiration, but the lowest pressure between the two peaks did not decrease with intragastric pressure; (3) Type III: LES and diaphragmatic were separated spatially with the separation interval $\geqslant$ 3 cm. EGJ-CI, a new index for evaluating the barrier function of EGJ, was set at the top of the gastric pressure area for three consecutive quiet breathing cycles, and calculated using DCI and the formula for calculation [1, 3]. Esophageal motility abnormalities included the following: esophageal aperistalsis – the diagnosis was made on the basis of non-contraction of the esophageal body during 10 swallows; ineffective esophageal motility – the diagnostic criterion was invalid contractions with $\geqslant$ 50% contraction, that is, loss of contraction and weak contraction; and segmental aperistalsis – the diagnostic criterion was that $\geqslant$ 50% of the contraction was segmental, that is, the contraction with a defect of $>$ 5 cm on the 20 mmHg isobar provided the distal contraction score was $>$ 450 mmHg $\cdot$ s $\cdot$ cm [12].

2.2.4 Grouping

According to the level of evidence for the diagnosis of GERD in the Lyon Consensus, the respondents were divided into three groups: (1) Conclusive evidence group: LA-C and D grade erosive esophagitis as observed under gastroscope; or long segment Barrett’s mucosa; or combined with esophageal stenosis; or AET (%) $>$ 6%; (2) Borderline evidence group: LA-A and B grade erosive esophagitis as observed under gastroscope; or AET 4(%) is between 4% and 6%; or reflux episodes of 40–80 times/24 hours; (3) Exclusion evidence group: no erosive esophagitis was observed under the endoscope; AET 4 (%) $<$ 4% and reflux episodes were $<$ 40 times/24 h [2, 3].

2.3 Statistical analysis

We used SPSS version 22.0 for statistical analysis. The classified data are expressed as numbers (percentages), continuous data with normal distribution are expressed as mean with standard deviation, and continuous data with non-normal distribution are expressed as medians (interquartile interval). The comparison of multiple groups of classified data was performed using Chi-square test. The Kruskal Wallis test was used to compare multiple groups of continuous data with non-normal distribution. One-way ANOVA was used to compare the continuous data of multiple normal distributions. The correlation between MNBI and other reflux indicators was analyzed using Spearman correlation analysis. Taking MNBI as the dependent variable, we used multi-factor linear regression analysis to study the influence of other reflux indicators on it. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of MNBI for the definitive evidence group, and Youden’s J statistic was used to calculate the diagnostic threshold. $P<$ 0.05 was used to indicate statistically significant difference.

3. Results

3.1 General data

A total of 434 patients were included in this study, consisting of 277 females (63.8%) and 157 males (36.2%) and median age of 60 (51–66) years old, ranging from 26–86 years old. As per the level of evidence for the diagnosis of GERD in the Lyon Consensus, the patients were divided into the conclusive evidence group, the borderline evidence group and the exclusion evidence group, with 103 cases (23.7%), 229 cases (52.8%), and 102 cases (23.5%), respectively. There was no significant difference in age and BMI among the three groups of patients ( $P>$ 0.05). The proportion of female patients in the conclusive evidence group was higher than that in the exclusion evidence group, and the difference was statistically significant ( $P<$ 0.05) (Table 1).

Table 1
Comparison of general data, MNBI, 24-hour pH impedance monitoring and HRM parameters across the groups ( $n=$ 434)

	Conclusive evidence group ( $n=$ 103)	Borderline evidence group ( $n=$ 229)	Exclusion evidence group ( $n=$ 102)	$F$ ( $\chi^{2}$ ) value	$P$
Age (y)	60.0 $\pm$ 11.8	57.5 $\pm$ 12.8	55.9 $\pm$ 13.0	2.261	0.105
Female cases (%)	76 (73.8%)	146 (63.8%)	55 (53.9%)	8.150	0.017a
BMI (kg/m2)	23.5 $\pm$ 3.7	23.4 $\pm$ 3.7	24.3 $\pm$ 3.2	2.291	0.102
MNBI ( $\Omega$ )	1658.3	2209.7	2721.8	110.5	$<$ 0.001b
	(760.9 $\sim$ 2114.7)	(1760.2 $\sim$ 2585.1)	(2262.8 $\sim$ 3166.5)
Abnormal MNBI cases (%)	85 (82.5%)	124 (54.1%)	28 (27.5%)	62.75	$<$ 0.001b
AET4 (%)	8.3 (6.2 $\sim$ 15.6)	1.3 (0.3 $\sim$ 3.3)	0.6 (0.1 $\sim$ 1.3)	174.4	$<$ 0.001b
DeMeester score	28.4 (19.0 $\sim$ 48.0)	5.0 (1.6 $\sim$ 11.4)	2.2 (0.7 $\sim$ 4.8)	167.1	$<$ 0.001b
Total reflux time	38.0 (19.0 $\sim$ 72.0)	43.0 (23.0 $\sim$ 73.0)	24.5 (17.0 $\sim$ 36.0)	27.9	$<$ 0.001c
EGJ classification				38.79	$<$ 0.001e
Type I, $n$ (%)	14 (13.6%)	49 (21.4%)	42 (41.2%)
Type II, $n$ (%)	62 (60.2%)	159 (69.4%)	48 (47.1%)
Type III, $n$ (%)	27 (26.2%)	21 (9.2%)	12 (11.8%)
EGJ-CI (mm Hg $\cdot$ cm)	15.5 (9.1 $\sim$ 22.6)	16.3 (9.8 $\sim$ 24.0)	23.1 (12.1 $\sim$ 30.3)	13.1	0.001d
Esophageal motility				4.481	0.106
Normal esophageal motility	32 (31.1%)	99 (43.2%)	42 (41.2%)
Abnormal esophageal motility	71 (68.9%)	130 (56.8%)	60 (58.8%)
Segmental esophageal aperistalsis	14 (13.6%)	27 (11.8%)	21 (20.6%)
Ineffective esophageal motility	55 (53.4%)	101 (44.1%)	39 (38.2%)
Esophageal aperistalsis	2 (1.9%)	2 (0.9%)	0 (0%)

a. Comparison between conclusive and exclusion evidence groups shows a significant difference $P=$ 0.006. Bonferroni correction test $P=$ 0.016 was considered as test level. b. There is a significant difference between any two groups ( $P=$ 0.000 after Bonferroni correction test). c. There are significant differences between the conclusive evidence group and the exclusion evidence group, borderline evidence group and exclusion evidence with $P=$ 0.001, $P<$ 0.001 after Bonferroni correction test. d. There are significant differences between the conclusive evidence group and the exclusion evidence group, borderline evidence group and the exclusion evidence group with $P=$ 0.002, $P=$ 0.006 after Bonferroni correction test. e. Type I: Significant differences are found between the conclusive evidence group and the remaining two groups, $P$ value has been adjusted by Bonferroni method. Type II: Comparison between the borderline and exclusion evidence group shows significant difference, $P$ value has been adjusted by Bonferroni method. Type III: There is significant difference between the conclusive evidence group and the other two groups, $P$ value has been adjusted by Bonferroni method.

3.2 Comparison of MNBI, 24h pH impedance, and HRM parameters of patients in each group based on the Lyon Consensus

We found significant differences in MNBI, proportion of abnormal MNBI, AET4 (%), DeMeester score, and total reflux episodes among the three groups ( $P<$ 0.001), as shown in Table 1. The MNBI of the conclusive evidence group was lower than that of the borderline and exclusion evidence group, and the MNBI of the borderline evidence group was lower than that of the exclusion evidence group ( $P<$ 0.001). The proportion of abnormal MNBI in the conclusive evidence group was higher than that in the borderline and exclusion evidence groups, and the proportion of abnormal MNBI in the borderline evidence group was higher than that in the exclusion evidence group ( $P<$ 0.001). The AET4 (%) and DeMeester scores in the conclusive evidence group were higher than those in the borderline and exclusion evidence groups, while those in the borderline evidence group were higher than that in the exclusion evidence group ( $P<$ 0.001). The total number of reflux episodes in the conclusive and borderline evidence groups was significantly higher than that in the exclusion evidence group ( $P<$ 0.001), and the above differences were statistically significant.

The morphological distribution of EGJ showed that the proportions of type II and type III EGJ in the conclusive and borderline evidence groups were higher than that in the exclusion evidence group. The proportion of type II and type III EGJ in the conclusive evidence group was higher than that in the borderline evidence group, and the differences were statistically significant ( $P<$ 0.001). The EGJ-CIs in the conclusive and borderline evidence groups were lower than those in the exclusion evidence group, and the differences were statistically significant ( $P=$ 0.002 and $P=$ 0.006, respectively).

In terms of esophageal motility, there was no significant difference in the proportion of abnormal esophageal motility between the three groups ( $P>$ 0.05) (Table 1).

3.3 Correlation analysis between MNBI and 24h pH impedance, HRM and other parameters, as well as endoscopic esophagitis grading

In Spearman’s correlation analysis, MNBI was significantly and negatively correlated with age, BMI, AET 4%, DeMeester score, total reflux episodes, EGJ classification, esophageal motility abnormality, and endoscopic esophagitis grading ( $r=-$ 0.174, $P<$ 0.001; $r=-$ 0.107, $P=$ 0.002; $r=-$ 0.537, $P<$ 0.001; $r=-$ 0.540, $P<$ 0.001; $r=-$ 0.100, $P=$ 0.003; $r=-$ 0.320, $P<$ 0.001; $r=-$ 0.179, $P<$ 0.001; $r=-$ 0.265, $P<$ 0.001, respectively). There was a significant positive correlation between MNBI and EGJ-CI ( $r=$ 0.192, $P<$ 0.001) (Table 2).

Table 2
Correlation analysis between MNBI and demographic indicators and other reflux monitoring parameters

	$r$	$p$
Age	$-$ 0.174	$<$ 0.001
BMI	$-$ 0.107	0.002
AET4%	$-$ 0.537	$<$ 0.001
DeMeester score	$-$ 0.540	$<$ 0.001
Total reflux time	$-$ 0.100	0.003
EGJ classification	$-$ 0.320	$<$ 0.001
EGJ-CI	0.192	$<$ 0.001
Abnormal esophageal motility	$-$ 0.179	$<$ 0.001
Endoscopic esophagitis grading	$-$ 0.265	$<$ 0.001

3.4 Regression analysis of influencing factors in MNBI

Multivariate linear regression analysis showed that age, BMI, AET 4%, EGJ classification, EGJ-CI, and endoscopic esophagitis grading all had significant effects on MNBI ( $\beta$ was $-$ 0.108, $-$ 0.081, $-$ 0.394, $-$ 0.102, 0.142, $-$ 0.155, respectively; all $P<$ 0.05). The total number of reflux episodes and esophageal motility abnormality had no significant effect on MNBI ( $P>$ 0.05) (Table 3).

Table 3
Multivariate linear regression analysis of MNBI related to reflux

	B OR (95% CI)		$\beta$	$p$
Age	$-$ 7.420	( $-$ 12.852, $-$ 1.987)	$-$ 0.108	0.008
BMI	$-$ 19.458	( $-$ 39.849, $-$ 1.419)	$-$ 0.081	0.044
AET4%	$-$ 34.069	( $-$ 41.160, $-$ 26.978)	$-$ 0.394	0.000
Total reflux time	$-$ 1.312	( $-$ 2.935, 0.311)	$-$ 0.064	0.113
EGJ classification	$-$ 146.098	( $-$ 286.325, $-$ 5.961)	$-$ 0.102	0.041
EGJ-CI	10.353	(3.199, 17.507)	0.142	0.005
Esophageal motility	$-$ 110.574	( $-$ 256.829, 35.68)	$-$ 0.062	0.138
Endoscopic esophagitis grading	$-$ 176.969	( $-$ 268.561, $-$ 85.376)	$-$ 0.155	0.000

Figure 1.

Diagnostic value of MNBI in the conclusive evidence group for GERD.

Figure 2.

Diagnostic value of MNBI in the exclusion evidence group for GERD.

3.5 Diagnostic value of MNBI in the conclusive evidence group and exclusion evidence group

The area under the curve (AUC) was 0.792 (95% CI 0.732–0.832) when the confirmatory evidence group for MNBI diagnosis was analyzed ( $P<$ 0.05). Youden’s J statistic was used to calculate the diagnostic cutoff value for MNBI as 2061 $\Omega$ ; the sensitivity and specificity were 74.9% and 67.4%, respectively (Fig. 1). When MNBI was used to diagnose exclusion evidence group with a diagnostic cutoff of 2432 $\Omega$ , and AUC was 0.774, (95% CI 0.724–0.823) ( $p<$ 0.001), the sensitivity and specificity were 67.6% and 72% (Fig. 2).

4. Discussion

GERD is a common disease of the digestive system, and its prevalence is increasing worldwide. The guidelines for the diagnosis and treatment of GERD are constantly updated [13, 14, 15, 16] to improve the level of diagnosis and treatment of GERD. The Lyon Consensus pointed out that GERD has a complex pathogenesis and diverse clinical manifestations. In order to facilitate individualized diagnosis and treatment, it proposed for the first time to grade the evidence for the diagnosis of GERD based on the results of gastroscopy, dynamic esophageal reflux monitoring, and HRM pressure measurement [2, 3]. The grades for level of evidence are conclusive evidence, borderline evidence, and exclusion evidence. If a patient has only borderline evidence, further supporting evidence is required to confirm or rule out the diagnosis of GERD [2, 3]. At present, there are few studies on GERD in China based on the evidence level proposed in the Lyon Consensus. In this study, we included a total of 434 patients with typical gastroesophageal reflux symptoms, who were divided into three groups according to the above evidence level. The results showed that 23.7% patients were in the conclusive evidence group, 52.8% patients were in the borderline evidence group, and 23.5% the patients were in the exclusion evidence group. The AET 4%, DeMeester score, total reflux episodes, and the proportion of EGJ type III in the conclusive evidence group were significantly higher than those in the borderline and exclusion evidence groups.

In recent years, some studies have focused on the use of MNBI in the diagnosis of GERD, and MNBI is considered as a marker that reflects the integrity of esophageal mucosa. When the integrity of esophageal mucosa is damaged, the tight junction between esophageal epithelium is often destroyed, and the intercellular space is widened, followed by a reduction of the MNBI [16, 17]. Other studies have shown that MNBI rises sequentially in patients with reflux esophagitis, NERD, and esophageal hypersensitivity [4, 5, 10]. Zhong et al. [18] found that the MNBI of the erosive esophagitis group (1752 $\pm$ 1018 $\Omega$ ) was significantly lower than that of the NERD group (2640 $\pm$ 1143 $\Omega$ ) and the normal control group (3360 $\pm$ 1258 $\Omega$ ). At the same time, the MNBI values in LA-C and D-grade erosive esophagitis were significantly lower than those in LA-A and B-grade erosive esophagitis (70 $\pm$ 505 $\Omega$ vs. 1921 $\pm$ 1024 $\Omega$ ). Our study results are consistent with these findings: the esophageal MNBI values in the conclusive evidence group were significantly lower than those in the borderline and exclusion evidence group ( $P<$ 0.001), and the proportion of abnormal MNBI was significantly higher than those in the other two groups ( $P<$ 0.001) (Table 1). Thus, MNBI could be a parameter in differentiating between the various levels of evidence for the Lyon Consensus diagnosis of GERD.

At present, there are few studies on the correlation between MNBI and parameters monitored by esophageal dynamic reflux monitoring and HRM, as well as on its influencing factors. Petal et al. [19] found a negative correlation between MNBI and AET ( $r=-$ 0.5, $P<$ 0.01), and some of the results in this study were consistent with this as we found that apart from the negative correlation between MNBI and AET, it also had a significant negative correlation with age, DeMeester score, EGJ classification, esophageal motility abnormality, and endoscopic esophagitis grading ( $P<$ 0.001), and also had a significant negative correlation with BMI and total reflux episodes ( $P<$ 0.05) (Table 2). Specifically, with the increase in age, BMI, episodes of esophageal acid exposure and reflux, EGJ relaxation, esophageal motility abnormality, prolonged esophageal acid clearance time, and greater severity of esophagitis seen with a gastroscope, the integrity of esophageal mucosa was affected and esophageal mucosal damage worsened [20, 21], and MNBI gradually decreased.

In this study, we also found that the EGJ-CI in the conclusive evidence group was significantly lower than that in the other two groups (Table 1), and there was a significant positive correlation between MNBI and EGJ-CI ( $r=$ 0.192, $P<$ 0.001) (Table 2). EGJ-CI could reflect the anti-reflux barrier function of EGJ. That is, there was a significant impairment of anti-reflux barrier function in the conclusive evidence group. Along with the decrease of EGJ-CI, it indicated that the barrier function of EGJ was damaged, and reflux increased, leading to the increase of the destruction of esophageal mucosal integrity, and thus the decrease of esophageal MNBI.

In this study, we found that many indicators had a significant correlation with MNBI. Along with the mechanism of esophageal mucosal damage in GERD, and considering the possible causal relationship between them, the above indicators were taken as independent variables, and MNBI was taken as a dependent variable for the linear regression analysis. The results showed that age, BMI, AET, EGJ classification, EGJ-CI, and endoscopic esophagitis grade all had significant effects on MNBI ( $P<$ 0.001), among which AET, EGJ-CI, and endoscopic esophagitis grade were the top three factors that most affected MNBI, that is, the increase in acid reflux load and abnormal EGJ barrier function could lead to impaired esophageal mucosal integrity and aggravation of mucosal damage, and decreased MNBI value [20, 21], while MNBI also decreased with the increase in the severity of endoscopic esophagitis. The results of this study also showed that the total number of reflux episodes and esophageal motility abnormality had no significant effect on MNBI (Table 3). This aspect requires further study with a larger sample size.

Several scholars have found that MNBI is significant in distinguishing GERD from NERD, and functional heartburn (FH). Frazzoni et al. [10] compared MNBI in patients with GERD and healthy controls and found that the AUC of MNBI in the diagnosis of GERD was 0.876 with the diagnostic cutoff value of 2292 $\Omega$ . In the study by Sun et al. [4] the AUC for distinguishing GERD from FH by MNBI was found to be 0.721 with the diagnostic cutoff value of 1890.6 $\Omega$ . Studies by Tenca and Yoshimine et al. [22, 23] found the AUC for the identification of NERD and FH by MNBI to be 0.73–0.96, with the diagnostic cutoff value of 2874/2934 $\Omega$ , respectively. Therefore, the Lyon Consensus proposed that MNBI could be used as an auxiliary parameter for the diagnosis of GERD, but the diagnostic borderline values for conclusive evidence and adjunctive evidence have not been clearly proposed. There is not much research on the diagnostic value of MNBI in the classification based on evidence level as per the Lyon Consensus. The results of this study showed that MNBI had good diagnostic value in the conclusive evidence group for the diagnosis of GERD when the diagnostic cutoff value of MNBI was 2061 $\Omega$ , AUC was 0.792, sensitivity was 74.9%, and specificity was 67.4%. Also, when MNBI was used to diagnose exclusion evidence group with a diagnostic cutoff of 2432 $\Omega$ , AUC was 0.774, the sensitivity was 67.6%, and specificity was 72%. That is to say, when MNBI $<$ 2061 $\Omega$ , a conclusive diagnosis of GERD is more likely. While when MNBI $>$ 2432 $\Omega$ , the patient is more considered as the exclusive evidence group, which can assist in ruling out the diagnosis of GERD. In conclusion, MNBI can be better used to confirm or rule out the diagnosis of GERD, and has certain clinical application value.

In the Lyon Consensus, AET and gastroscopic esophagitis grading are two important indicators for grouping the levels of evidence for the diagnosis of GERD. However, AET can only reflect the acid exposure in 24-hour pH impedance monitoring with a certain degree of randomness, while MNBI reflects the integrity of esophageal mucosa [16, 17]. In theory, it indicates the presence of reflux for a period of time followed by the destruction of mucosal integrity, so it may be more objective than AET in reflecting the presence and results of acid reflux. As an indicator of long-term reflux, whether AET plays a similar role as random blood glucose and MNBI plays a similar role as glycated hemoglobin in glycemic monitoring of diabetes, needs further study and verification. In addition, Gastroscope can directly observe erosive esophagitis and its severity, but different endoscopic physicians may have some subjective bias in judging the severity of esophagitis. There may also be missed diagnosis in the judgment of minor esophagitis. For some patients, they may only show “esophagitis under the microscope”, which is difficult to diagnose through ordinary endoscope. We found that MNBI had a negative correlation with the level of esophagitis, which could reflect the level of esophageal mucosal injury – MNBI decreased significantly in the borderline evidence group. Previous studies have also found that MNBI decreased in patients with NERD [4, 24]. Considering that MNBI could identify the damage to mucosal integrity even before the results of gastroscopy, and that the measurement of MNBI was not affected by the patients’ logs, which can be subjectively biased, MNBI may be more objective and more sensitive than AET and gastroscopic esophagitis grading. In addition, there are more and more studies on the aid of AI in diagnosing clinical diseases. If the AI system can be used for the diagnosis of GERD and endoscopic esophagitis grading in the future, the subjective bias of different physicians may be avoided, which is more conducive to the accuracy of clinical studies. It is hoped that more studies on AI endoscopic diagnosis can be carried out in the future.

5. Conclusion

In this study, we found that there were significant differences in MNBI among different groups with varying evidence levels as per the diagnosis of GERD based on the Lyon Consensus. In addition, MNBI was significantly correlated with age, BMI, AET, DeMeester score, total reflux episodes, EGJ classification, EGJ-CI, esophageal motility abnormality, and endoscopic esophagitis grading. Among them, AET, EGJ-CI, and endoscopic esophagitis grading had significant influence on the MNBI value. In addition, MNBI had better diagnostic value in the conclusive evidence group. MNBI can objectively reflect the existence of acid reflux and its results, and it can be obtained easily. In addition, it has been reported in literature that MNBI can also predict the therapeutic effect and prognosis of PPI in patients with GERD [19, 25, 26], and we recommend that MNBI should be routinely measured and reported during 24-h pH impedance monitoring.

This was a single-center study with a limited number of selected cases. In the future, more detailed and larger prospective, multi-center studies need to be designed to further explore the value of MNBI in the diagnosis and prognosis of GERD.

Funding

No external funding was received to conduct this study.

Availability of data and materials

All data generated or analysed during this study is included in this article. Further enquiries can be directed to the corresponding author.

Footnotes

Acknowledgments

The authors would like to acknowledge the hard and dedicated work of all staff that implemented the intervention and evaluation components of the study.

Conflict of interest

The authors declare that they have no competing interests.

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Mean nocturnal baseline impedance: Influencing factors and diagnostic value in gastroesophageal reflux disease

Abstract

BACKGROUND:

OBJECTIVE:

METHODS:

RESULTS:

CONCLUSION:

Keywords

1. Introduction

2. Materials and methods

2.1 Study details and respondents

2.2 Methods

2.2.1 Gastroscopy

2.2.2 24-hour multichannel intraluminal impedance and pH monitoring (MII/pH)

2.2.3 High-resolution manometry of esophagus

2.2.4 Grouping

2.3 Statistical analysis

3. Results

3.1 General data

Table 1 Comparison of general data, MNBI, 24-hour pH impedance monitoring and HRM parameters across the groups ( n = 434)

3.3 Correlation analysis between MNBI and 24h pH impedance, HRM and other parameters, as well as endoscopic esophagitis grading

Table 2 Correlation analysis between MNBI and demographic indicators and other reflux monitoring parameters

Table 3 Multivariate linear regression analysis of MNBI related to reflux

4. Discussion

5. Conclusion

Funding

Availability of data and materials

Footnotes

Acknowledgments

Conflict of interest

References

Table 1
Comparison of general data, MNBI, 24-hour pH impedance monitoring and HRM parameters across the groups ( $n=$ 434)

Table 2
Correlation analysis between MNBI and demographic indicators and other reflux monitoring parameters

Table 3
Multivariate linear regression analysis of MNBI related to reflux