GERD And Risk Factors Of Age And Obesity
Overview
In this study, the researchers sought to investigate the diagnostic value of nocturnal baseline impedance (MNBI) in identifying gastroesophageal reflux disease (GERD) while considering the potential influence of age and body mass index (BMI) on MNBI levels.
The study involved a cohort of 311 patients, comprising both males and females, with a mean age of 47 ± 13 years, who were experiencing typical GERD symptoms. All participants had undergone high-resolution manometry (HRM) and pH impedance studies without the use of proton pump inhibitors (PPI). MNBI measurements were taken at 3, 5, and 17 cm above the lower esophageal sphincter (LES). GERD was diagnosed if acid exposure time (AET) exceeded 6%.
The average BMI of the participants was 26.6 ± 5.9 kg/cm^2, and GERD was confirmed in 39.2% of them, while 13.5% had inconclusive GERD findings. The researchers found that MNBI levels correlated with the patients’ age, BMI, AET, and the length of LES to diaphragmatic crus (LES-CD) separation. At 3 cm above the LES, MNBI was also correlated with the total number of reflux events and LES hypotension. Multivariate analysis revealed that MNBI at 3 cm and 5 cm was independently associated with age, BMI, and AET.
Patients with confirmed GERD exhibited lower MNBI levels at 3 cm compared to those with inconclusive GERD, although both groups showed lower MNBI values compared to those without GERD. MNBI at 3 cm demonstrated good diagnostic capability for GERD (area under the curve: 0.815, p < 0.001, 95% CI: 0.766–0.863) with an optimal cutoff point of 1281 Ohm.
This study underscores the impact of age and BMI on MNBI values in patients undergoing evaluation for GERD. MNBI emerges as a valuable tool for GERD diagnosis, albeit suggesting that lower MNBI thresholds than previously proposed may be more appropriate for real-world clinical settings.
Introduction
Esophageal baseline impedance serves as a valuable indicator of the integrity of the esophageal mucosa. It reflects changes in the structure and function of the mucosal epithelium of the esophagus. Specifically, distal esophageal baseline impedance exhibits an inverse relationship with acid exposure time (AET), emphasizing its relevance in gastroesophageal reflux disease (GERD) assessment.
According to the Lyon consensus, mean nocturnal baseline impedance (MNBI) can provide substantial insights into the diagnosis of GERD. An MNBI value below 2292 Ohm has been established as supportive evidence for GERD diagnosis, as demonstrated in studies conducted by Frazzoni et al.
In their initial study, Frazzoni and colleagues employed the 2292 Ohm cutoff and utilized ROC curve analysis to ascertain MNBI’s ability to distinguish between patients with erosive reflux disease (ERD), including 68 cases, and those with nonerosive reflux disease (NERD) among symptomatic individuals with otherwise normal pH-impedance parameters (considered as controls).
In a recent study by Sifrim et al., baseline impedance was examined in a large cohort of asymptomatic healthy individuals. The findings revealed that MNBI values below 1500 ohms at 3 and 5 cm above the lower esophageal sphincter (LES) were rare in healthy subjects, suggesting potential impairment of esophageal mucosal integrity. Furthermore, regional and measurement system variations in MNBI values were noted, alongside a slight but significant decrease in MNBI among individuals over 40 years of age.
Evidence also suggests that age-related changes affect baseline impedance levels, as observed in studies involving children. Notably, baseline impedance levels were markedly lower in infants compared to children over 1 year old, irrespective of acid or bolus exposure time.
Experimental data have additionally indicated that obesity has an impact on the esophageal mucosa. In obese patients, both with and without GERD, obesity appears to increase the diameter of the intercellular spaces within the squamous epithelium of the esophageal mucosa.
The primary objective of this study was to reevaluate the MNBI cutoff values for diagnosing GERD in individuals presenting with typical and atypical esophageal symptoms. Additionally, the study aimed to investigate the influence of aging and body mass index (BMI) on esophageal baseline impedance.
Methods
Inclusion Criteria:
- Typical GERD Symptoms: Patients referred to the Upper GI Physiology Unit at the Royal London Hospital for evaluation must exhibit typical symptoms of gastroesophageal reflux disease (GERD), including heartburn and regurgitation.
- Main Symptom of GERD: Patients with extra-esophageal symptoms (such as cough, sore throat, or globus) may be included if their primary reason for referral is the presence of typical GERD symptoms.
- HRM and pH-IM Studies Off PPI: Included patients must have undergone both high-resolution manometry (HRM) and pH-impedance (pH-IM) studies without the use of proton pump inhibitors (PPI).
Exclusion Criteria
- Endoscopic GERD Diagnosis: Patients with a confirmed endoscopic GERD diagnosis, characterized by grade C-D Esophagitis according to the LA classification, a diagnosis of Barrett Esophagus, or benign peptic stricture, undergoing preoperative HRM/pH-IM were excluded.
- Previous GERD Diagnosis on PPI: Patients with a prior definitive GERD diagnosis who were studied while taking PPI medications were not included.
- Opioid Use: Patients currently using opioids were excluded from the study.
- History of Esophageal Surgery: Individuals with a history of esophageal surgery were excluded from participation.
- Major Esophageal Motility Disorders: Patients with major esophageal motility disorders (with the exception of absent contractility or ineffective esophageal peristalsis according to the Chicago IV classification) as determined by HRM were not included in the analysis.
Study Design and Diagnosis Criteria
- GERD Diagnosis: Patients with an acid exposure time (AET) exceeding 6% were classified as having GERD.
- Exclusion of GERD: GERD was ruled out if the AET was less than 4%.
- Inconclusive GERD Diagnosis: Patients with an AET between 4% and 6% were considered to have an inconclusive GERD diagnosis.
- Symptom Evaluation: Symptom index (SI) and symptom association probability (SAP) were assessed only if patients reported more than three symptoms.
Study Procedures:
- Medication Withdrawal: Patients were instructed to discontinue proton pump inhibitors (PPIs) and histamine H2 blockers for a minimum of 7 days prior to the study.
- High-Resolution Manometry: Patients underwent high-resolution manometry using a Medtronic system to identify the proximal margin of the lower esophageal sphincter (LES) and measure the length of LES-crural diaphragm (CD) separation. Manometric findings were evaluated according to the Chicago IV classification.
- Reflux Monitoring: Patients were included in the analysis if they underwent reflux monitoring using a multichannel intraluminal impedance-pH monitoring (MII-pH) catheter system between 2019 and 2022. The MII-pH catheter, specifically the OMOM system with impedance pairs at multiple levels and pH sensors, was utilized. MII-pH tracings were analyzed using dedicated software, including automatic analysis of mean nocturnal baseline impedance (MNBI) based on a standardized protocol.
This study aimed to investigate GERD in patients with typical symptoms and consider the impact of age and body mass index (BMI) on esophageal baseline impedance.
Statistical Analysis
Statistical analysis of the data was conducted using SPSS Version 23 (SPSS software; SPSS Inc, Chicago, IL, USA). The data were presented in the form of frequencies, mean values with standard deviation (SD), or as medians with interquartile ranges (IQR), as appropriate. To compare quantitative variables between different groups, the Student’s t-test was employed for normally distributed data, while the Mann-Whitney test was used for non-normally distributed variables. For qualitative variables, comparisons were made using either the chi-squared test or Fisher’s exact test, as deemed suitable.
The relationships between quantitative variables were assessed through the Spearman’s correlation coefficient. To evaluate the predictive capability of mean nocturnal baseline impedance (MNBI), receiver operating characteristic (ROC) curves were generated, and the area under the ROC curve (AUROC) was calculated. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were also determined. Diagnostic accuracy was considered poor if the c-statistic of the AUROC curve was less than 0.65. The optimal cutoff value was chosen from the ROC curves as the point that maximized the sum of sensitivity and specificity.
Multivariate logistic regression analysis models were utilized to identify independent and significant factors associated with the dependent variable. Only parameters demonstrating either significance or a trend towards significance (p < 0.10) in the univariate analysis were included in the multivariate analysis models. All statistical tests were two-sided, and a significance level of p < 0.05 was deemed as statistically significant.
It is important to note that this study involved a post hoc analysis of de-identified data previously collected from esophageal studies, and there was no direct linkage to individual patients. Therefore, formal ethics approval was not considered necessary for this research.
Results
The study included 311 patients presenting with typical symptoms of gastroesophageal reflux disease (GERD), with a majority of them being female (55.3%). Among these patients, 88.1% reported experiencing heartburn, and 54% reported regurgitation. Additionally, 39 patients (comprising cough, sore throat, and globus symptoms) had extra-esophageal symptoms, but their primary reason for referral was typical GERD symptoms. GERD, defined by an acid exposure time (AET) greater than 6%, was diagnosed in 39.2% of the patients. In contrast, among patients with AET less than 4%, 19.7% exhibited both symptom index (SI) and symptom association probability (SAP) positivity, indicating reflux hypersensitivity.
Key Findings
- MNBI and Age/BMI: Mean MNBI values at different channels decreased gradually with increasing age and BMI. Notably, in the distal esophagus (Z5 and Z6), MNBI was inversely correlated with BMI, indicating that higher BMI was associated with lower distal baseline impedance. This correlation remained independent of age and esophageal acid exposure. However, in the proximal esophagus, this correlation with BMI was not observed.
- MNBI and Reflux/Motility Parameters: Multivariate analysis revealed that MNBI correlated independently with esophageal AET but not with the number of reflux events or the presence of reflux symptom association (SI and SAP). Furthermore, MNBI did not independently correlate with lower esophageal sphincter (LES) pressure or the presence of esophageal body hypomotility, as these parameters were mainly associated with increased AET. Notably, MNBI in Z5 and Z6 channels showed a strong correlation in univariate analysis with LES-CD separation (size of hiatal hernia), but this correlation was not observed in the multivariate analysis.
- MNBI in Patients Without GERD: Among patients definitively without GERD (AET < 4), MNBI values were independently inversely correlated with age. Additionally, MNBI at Z6 tended to be correlated with BMI in patients without GERD. MNBI values at Z6 and Z5 were significantly lower in patients with a definite GERD diagnosis compared to those with inconclusive GERD or without GERD. MNBI at Z6 exhibited good diagnostic ability for predicting GERD diagnosis (AET > 6%) with a cutoff point of 1281 Ohm, showing sensitivity of 68.8% and specificity of 81.1%. In contrast, proximal MNBI at Z1 did not demonstrate a good diagnostic ability for GERD.
The study also highlighted that the original proposed cutoff of 2292 Ohm at channel Z6 had excellent sensitivity but poor specificity for diagnosing GERD, as a substantial number of patients with MNBI < 2292 did not have an AET > 6%.
These findings underscore the significance of MNBI in assessing GERD, particularly its correlation with age, BMI, and esophageal acid exposure. MNBI at specific channels, particularly Z6, can serve as a valuable diagnostic tool for GERD, with the potential to refine cutoff values for enhanced diagnostic accuracy.
Conclusion
In our study, we have underscored the substantial significance of mean nocturnal baseline impedance (MNBI) as a valuable tool in the diagnosis of gastroesophageal reflux disease (GERD). Our research has not only established a new MNBI cutoff value for GERD diagnosis but has also demonstrated that MNBI is independently associated with age and body mass index (BMI).
We found that MNBI decreases with age, a correlation previously reported in a study by Sifrim et al. among patients without GERD and in recent research involving GERD patients. This suggests that as individuals age, MNBI tends to decline, potentially due to alterations in the esophageal epithelium, chronic systemic microinflammation, increased permeability, and possible fibrotic changes affecting MNBI.
Furthermore, our study revealed that higher BMI is independently correlated with lower esophageal MNBI. These findings align with previous research indicating that individuals with central obesity, even in the absence of acid and nonacid reflux, experience increased intercellular space diameter in the esophageal squamous epithelium.
Importantly, our study challenges the previously adopted MNBI cutoff value of 2292 Ohm, as our data indicated significantly lower MNBI values, even among patients definitively without GERD (AET <4). This highlights the need for a revised cutoff value. Recent research from China also supports the notion of a lower MNBI cutoff for ruling out GERD (AET <4%).
In our previous study, we proposed a cutoff of 1785 ohms for MNBI, which proved effective in discriminating GERD patients from those with reflux hypersensitivity and functional heartburn. Similar findings were observed in a recent study from China and by Frazzoni et al., suggesting that lower MNBI cutoff values may provide more accurate assessments of GERD.
Moreover, our study found that MNBI measured at 3 cm above the lower esophageal sphincter (LES) was significantly lower in patients with inconclusive GERD diagnoses compared to those without GERD, corroborating findings from a recent Italian study.
It’s worth noting that the differences in cutoff values between our study and previous research may be attributed to the utilization of different MNBI measurement methods. However, we validated our method and found an excellent correlation with values obtained using the previously published standard method.
Study Limitations
Our study has several limitations. It relies on a retrospective analysis of motility and reflux monitoring in GERD symptom patients. We lack data on the relationship between MNBI and erosive reflux disease. Most of the included patients had persistent GERD symptoms and normal endoscopy, and information on PPI response was not available for all subjects.
In conclusion, our study emphasizes the importance of MNBI in GERD diagnosis, establishes a new MNBI cutoff value, and highlights its independent correlations with age and BMI. Further research and validation studies are warranted to refine MNBI’s diagnostic utility in GERD assessment.
Oncology Related Tools
Other
Latest Research
