J Neurogastroenterol Motil 2024; 30(2): 156-165  https://doi.org/10.5056/jnm23017
Esophageal Motility Abnormalities in Lung Transplant Recipients With Esophageal Acid Reflux Are Different From Matched Controls
Mazen Elsheikh,1* Lekan Akanbi,2 Lisbeth Selby,3 and Bahaaeldeen Ismail3
1Department of Internal Medicine, Faculty of Medicine, Ain Shams University, Cairo, Egypt; 2Department of Gastroenterology and Hepatology, University of Missouri Health Care, Columbia, MO, USA; and 3Division of Digestive Diseases and Nutrition, University of Kentucky, Lexington, KY, USA
Correspondence to: *Mazen Elsheikh, MD
Department of Internal Medicine, Faculty of Medicine, Ain Shams University, 38 Abbasia, Cairo 11591, Egypt
Tel: +202-24346344, E-mail: Mazenmoussa@med.asu.edu.eg
Received: February 2, 2023; Revised: May 10, 2023; Accepted: July 7, 2023; Published online: December 8, 2023
© The Korean Society of Neurogastroenterology and Motility. All rights reserved.

cc This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Background/Aims
There is an increased incidence of gastroesophageal reflux disease (GERD) after lung transplantation (LT) that can be associated with graft dysfunction. It is unclear if the underlying esophageal motility changes in GERD are different following LT. This study aimed to use esophageal high-resolution manometry (HRM) to explore GERD mechanisms in LT recipients compared to matched controls.
Methods
This was a retrospective study including patients with pathologic acid reflux who underwent HRM and pH testing at our healthcare facility July 2012 to October 2019. The study included 12 LT recipients and 36 controls. Controls were matched in a 1:3 ratio for age, gender, and acid exposure time (AET).
Results
LT recipients had less hypotensive esophagogastric junction (EGJ) (mean EGJ-contractile integral 89.2 mmHg/cm in LT vs 33.9 mmHg/cm in controls, P < 0.001). AET correlated with distal contractile integral and total EGJ-contractile integral only in LT group (r = –0.79, P = 0.002 and r = –0.57, P = 0.051, respectively).
Conclusions
Following LT, acid reflux is characterized by a less hypotensive EGJ compared to controls with similar AET. The strongest correlation with AET after LT was found to be esophageal peristaltic vigor. These results add to the understanding of reflux after LT and may help tailor an individualized treatment plan.
Keywords: Esophageal motility disorders; Gastroesophageal reflux; Lung diseases; Manometry
Introduction

Prevalence of gastroesophageal reflux disease (GERD) reportedly increased following lung transplantation (LT), with growing evidence of contribution to graft rejection,1 a serious complication seen in up to 50% of patients within 5 years after surgery.2-4 GERD pathophysiology involves a disturbance in the balance between defensive barriers and intrusive pathological mechanisms which act on 2 main mechanisms: lower esophageal sphincter (LES) reflux barrier and esophageal body clearance capacity. While incompetent LES, hiatus hernia, transient lower esophageal sphincter relaxations (TLESRs), and transdiaphragmatic pressure gradient affect LES barrier function, esophageal motility disorders and hypertensive LES affect esophageal bolus clearance function.5,6 It is also known that some patients’ characteristics such as age, weight, and body mass index (BMI) alter esophageal physiology leading to acid reflux.7,8 Advancements in esophageal high-resolution manometry (HRM) metrics have allowed a detailed understanding of the underlying pathophysiologic changes in acid reflux patients.9-11 This allows the treating provider to individualize the treatment plan, particularly in patients who are refractory to first line medical treatments.12-14 A common example is tailoring fundoplication wrap circumference based on esophageal body peristalsis to prevent post operative dysphagia.15 Furthermore, multiple studies described LES barrier function assessment using novel HRM metrics including lower esophageal sphincter pressure integral (LES-PI), esophagogastric junction contractile integral (EGJ-CI), and total (Total EGJ-CI). These studies showed impaired EGJ barrier function in GERD patients compared to controls.16-18

Few studies evaluated HRM changes in LT patients with GERD, suggesting that ineffective esophageal motility and delayed gastric emptying contribute to reflux in LT recipients.19 These changes are hypothesized to occur secondary to vagal nerve manipulation during surgery, but the exact mechanism is not fully understood.19,20 Moreover, it remains unclear if esophageal pathophysiologic changes are different from non-LT recipients with GERD.

This study aims to evaluate the underlying esophageal HRM motility changes in LT recipients with acid reflux including the use of the novel barrier function metrics to outline any significant changes from non-LT recipient controls.

Materials and Methods

Patient Selection

The study was granted approval by the Institutional Review Board with the reference number 50359. Informed consent was waived due to its retrospective nature. All adult patients (≥ 18 years old) who underwent esophageal physiologic testing at our healthcare facility between October 2010 and October 2019 were reviewed. Patients were initially identified by reviewing their manometry reports database then a detailed electronic chart review was performed to confirm fitting inclusion criteria and for data collection.

Eligible patients were those with pathologic acid reflux who had completed workup including esophageal manometry and pH study. We defined pathologic acid exposure according to the Lyon Consensus Modern Diagnosis of GERD criteria21 (acid exposure time [AET] > 6%, or 4-6% with reflux episodes number > 40, or patients with an endoscopic finding of Los Angeles grades C or D esophagitis). Patients who underwent LT before the time of testing were included in the LT group, while the control group represented those without a prior transplant. To avoid duplication, patients with advanced lung disease undergoing testing before transplant were excluded from the controls. Controls were then selected through a 1:3 ratio matching with the LT recipients.

Variables collected included age, gender, race, weight, height, BMI, presenting symptoms, and history of anti-reflux surgery at the time of performing esophageal tests. We documented the history of opioid use given its effect on esophageal motility.22,23 We reviewed available upper endoscopy, barium esophagram, and gastric emptying studies to document the evidence of esophagitis, Barrett’s esophagus, strictures, or delayed gastric emptying.

Measurement Techniques

Esophageal high-resolution manometry

All subjects had HRM after 1 fasting night. The procedure was performed using a single catheter with 360 circumferential sensors 1 cm apart (ManoScan ESO HRM system; Medtronic, Minneapolis, MN, USA). After calibration, the previously described standard protocol with the patient in a supine position was used.24 Analysis of HRM studies was done using ManoView ESO analysis software version 3.3 (Given Imaging, Los Angeles, CA, USA). We used the automated software readings for mean integrated relaxation pressure and distal contractile integral (DCI) values, while we manually calculated the LES barrier function metrics (LES-PI, EGJ-CI, and Total EJG-CI) as described in previous studies.16-18 Thoraco-abdominal pressure gradient (TAPG), intra-thoracic pressure (TP), and intra-abdominal pressure (AP) were manually measured by setting the isobaric contour to atmospheric pressure, TP was measured by detecting pressure at any point between 3-5 cm above the LES upper border at inspiration, while AP was measured 1-2 cm below the diaphragmatic lower crus at inspiration.25 TAPG was then calculated by subtracting TP from AP. EGJ morphology type was noted and when present, hiatal hernia size was measured according to the relationship between LES and crural diaphragm.26

pH monitoring studies

All patients had distal esophageal pH monitoring with either catheter-based or wireless pH systems. Patients stopped proton pump inhibitors one week before the procedure and histamine H2 blockers for 2 days. Ambulatory catheter-based 24-hour esophageal pH monitoring was done using a dual channel catheter (Digitrapper; Medtronic). After calibration, the catheter was inserted intra-nasally to place the distal pH sensor 5 cm above the monometrically measured LES. Catheter-less pH monitoring was done via a calibrated capsule that was endoscopically placed on the esophageal wall 6 cm above the Z line (Bravo; Medtronic). The capsule was connected by radiofrequency telemetry to a small portable external receiver that recorded intraluminal pH values for 48 hours. In both methods, patients were instructed to record esophageal symptoms (heartburn, regurgitation, chest pain, and dysphagia) and to report mealtime via datalogger to be excluded from the study analysis. Data were analyzed with the software program (Reflux Reader version 6.1, Medtronic) which calculated AET as the total time pH is < 4 divided by the time monitored. It also analyzed AET in relation to patient position, measured reflux episodes number, and DeMeester score.

Statistical Methods

Continuous variables were summarized as mean, standard deviation, and range, while categorical variables were presented as numbers and percentages. Continuous variables were compared using Mann–Whitney U test while the categorical ones were compared using chi-square or Fisher exact tests. A P-value < 0.05 was considered statistically significant. To ensure a similar baseline prior to comparing both groups, a nearest neighbor 1:3 matching was performed using propensity scores calculated through a logistic regression model that included: age, gender, and AET. For purpose of matching, an age cutoff of 65 years was selected given the previous data showing decreased distal esophageal motility in those older than 65.27 Correlation between the HRM metrics and AET was evaluated using Pearson correlation for normally distributed variables and Spearman correlation test for non-normally distributed ones. A two tailed P-value of < 0.05 was considered significant. All data were analyzed using the R statistical package (version 3.4.1; R Foundation for Statistical Computing, Vienna, Austria).

Results

During the study period, we identified 119 LT recipients and 471 controls. After the exclusion of subjects not fulfilling Lyon Consensus Modern Diagnosis of GERD criteria, or those with study technical errors or missing HRM study, 12 LT recipients and 104 controls were identified (Fig. 1). At our institution, LT recipients routinely undergo HRM and pH testing within 3-6 months post-transplantation, or earlier if they experience reflux symptoms or declining graft function. Among our LT group, 4 patients underwent testing as part of routine care, 3 patients due to reflux symptoms, and 5 patients due to concerns regarding graft function. Out of the 12 recipients, 5 individuals underwent HRM and pH testing within 3 months after transplantation. Four additional patients underwent testing within the subsequent 4 months, while the remaining 3 patients underwent evaluation more than 6 months following transplantation.

Figure 1. Flow diagram of patients’ selection, grouping, and matching. LT, lung transplant recipients; AET, acid exposure time; HRM, esophageal high-resolution manometry; pH study, esophageal pH monitoring studies.

In this cohort, the LT recipients had a higher percentage of males compared to controls (50.0% vs 26.0%) and there was a tendency toward higher AET in the LT group 14.6 ± 9.4 versus 11.8 ± 6.3. After 1:3 matching for age, gender, and AET, 36 controls were matched with the 12 LT recipients (Table 1). There was no statistically significant difference between both groups regarding race, weight, or BMI. Only 1 subject of the control group had no esophageal symptoms at the time of testing, compared to 5 (41.6%) of the LT group. Dysphagia and heartburn were statistically more common in controls (P = 0.042) and there was a trend towards more patients with regurgitation (P = 0.095), while chest pain complaint was not different between both groups (Table 2). Although erosive esophagitis was present in 40.6% of controls compared to only 20.0% of LT, this difference was not statistically significant (P = 0.449). The 4 patients who underwent a gastric emptying study in the LT group had delayed gastric emptying compared to 8/14 (57.1%) of the controls (P = 0.245). LT groups had a higher percentage of opioid users at the time of testing compared to controls (45.5% versus 21.6%, P = 0.140). No patients in the LT group underwent previous anti-reflux surgeries compared to only 1 patient in the controls. There was no significant difference regarding upright versus supine AET or the number of acid reflux episodes between the 2 groups.

Table 1 . Selected Baseline Characteristics for Lung Transplant Patients and Controls Before and After Matching

VariablesBefore matchingAfter matching
ControlLTP-valueSMDaControlLTP-valueSMDa
n104123612
Age > 65 yr20 (19.2)2 (16.7)> 0.9990.0676 (16.7)2 (16.7)> 0.999< 0.001
Males27 (26.0)6 (50.0)0.1590.51117 (47.2)6 (50.0)> 0.9990.056
Acid exposure time11.83 (6.33)14.65 (9.43)0.1710.35014.08 (7.15)14.65 (9.43)0.8270.068

aAdequate matching was defined as standardized mean difference (SMD) < 0.1.

LT, lung transplant recipients.

Data are presented as n (%) or mean (SD).



Table 2 . Demographics, Clinical, and Endoscopic Characteristics Data for Lung Transplant Group Versus Controls

VariablesLT group (n = 12)Controls (n = 36)P-value
Gender (male)6 (50)17 (47.2)> 0.999
Age (yr)51.25 (16.08), 21-7054.56 (11.04), 24-750.721
Race
White12 (100.0)34 (94.4)> 0.999
African Americans0 (0.0)1 (2.8)
Asian0 (0.0)1 (2.8)
Weight (lb)179.4 (54.65), 102-277.7186.64 (38.49), 119-2830.615
BMI (kg/m2)28.06 (7.16), 18.1-43.129.35 (4.63), 21.1-39.60.398
Symptoms
Dysphagia3 (25.0)23 (63.9)0.042
Heartburn3 (25.0)23 (63.9)0.042
Regurgitation4 (33.3)23 (63.9)0.095
Chest pain1 (8.3)9 (25.0)0.414
Asymptomatic patients5 (41.6)1 (2.7)0.002
Opioid intake5 (45.5)8 (22.2)0.140
Anti-reflux surgeries01
Delayed gastric emptying study4 (100.0)9 (60.0)0.245
Endoscopic and/or esophogram
Hiatal hernia9 (75.0)23 (63.9)0.725
Erosive esophagitis2 (20.0)13 (40.6)0.449
Barrett’s esophagus2 (20.0)2 (6.2)0.236
Stricture/ring2 (20.0)2 (6.5)0.245

LT, lung transplant recipients; BMI, body mass index.

Data are presented as n (%), mean (SD) and range, or n.



The EGJ-CI was significantly lower in the controls (mean 33.9, range 2.5-195.0) compared to LT recipients (mean 89.2, range 31.2-150.0, P-value < 0.001) (Table 3). A similar statistically significant difference was present regarding the 2 other LES barrier function metrics (LES-PI and Total EGJ-CI). LT recipients had a higher average DCI compared to controls (mean 3490.9 [range 170.8-12024] versus 1995.4 [range 141.8-11365], P-value 0.107). Additionally, the percentage of ineffective swallows was lower in LT patients at 24.1% compared to 34.8% in controls. The AP was significantly higher in the LT group (P = 0.031). Although the TAPG was numerically higher in the LT group, the difference was not statistically significant (20.78 ± 7.12 vs 17.91 ± 5.34, P = 0.203).

Table 3 . Comparison Between pH and High-resolution Manometry Metrics of Lung Transplant Group Versus Controls

VariablesLT group (n = 12)Controls (n = 36)P-value
AET14.65 (9.43), 4.3-35.014.08 (7.15), 4.4-33.00.896
Supine AET10.9 (9.27), 0.0-30.312.96 (11.19), 0.0-37.90.807
Upright AET14.9 (13.67), 3.0-46.014.05 (7.4), 3.1-33.40.442
DeMeester score50.14 (28.68), 13.4-107.950.15 (25.85), 12.9-110.70.942
Number of acid refluxes130.36 (62.95), 51.0-260.0154.34 (102.05), 44.0-513.00.699
SAP54.87 (50.49), 0.0-100.084.41 (26.32), 0.0-100.00.125
SI63.10 (45.1), 0.0-100.064.07 (29.07), 0.0-100.00.753
Esophageal body
Average DCI3490.92 (3590.97), 170.8-12024.01995.43 (2628.78), 141.8-11365.00.107
% of ineffective swallows24.17 (37.28), 0.0-100.034.89 (41.4), 0.0-100.00.469
Patients with IEM3 (25.0)12 (33.3)0.728
Lower esophageal sphincter
IRP6.45 (5.76), 0.6-17.76.19 (9.42), –3.5-43.60.475
LES-PI439.56 (174.25), 154.0-737.4224.2 (362.01), 0.0-1457.90.001
EJG-CI89.22 (33.26), 31.2-150.133.92 (46.83), 2.5-195.3< 0.001
Total EJG-CI113.98 (91.14), 37.1-320.139.67 (45.08), 3.0-217.8< 0.001
Pressure gradient
TP–1.34 (4.79), –8.9-9.0–1.49 (3.1), –7.1-6.20.905
AP19.44 (6.82), 3.0-29.316.42 (5.07), 9.7-32.40.031
TAPG20.78 (7.12), 11.9-37.817.91 (5.34), 5.6-28.70.203
Manometric hiatus hernia
EGJ type I4 (33.3)11 (30.6)0.456
EGJ type II8 (66.7)19 (52.8)
EGJ type III0 (0.0)6 (16.7)

LT, lung transplant recipients; AET, acid exposure time; SAP, symptom association probability; SI, symptom index; DCI, distal contractile integral; IEM, ineffective esophageal motility; IRP, integrated relaxation pressure; LES-PI, lower esophageal sphincter pressure integral; EGJ-CI, esophagogastric junction contractile integral; Total EGJ-CI, total esophagogastric junction contractile integral; TP, intra-thoracic pressure; AP, intra-abdominal pressure; TAPG, thoraco-abdominal pressure gradient; EGJ, esophagogastric junction.

Data are presented as mean (SD) and range, or n (%).



In the LT group, the HRM metrics with the highest correlation with AET were the mean DCI followed by the percentage of ineffective swallows (r = –0.79, P = 0.002 and r = 0.59, P = 0.041 respectively) (Table 4). Although there appeared to be a trend towards an inverse relation between Total EGJ-CI and AET in this subgroup, this did not reach statistical significance (r = –0.57, P = 0.051). There was no correlation between AET and LES-PI, EGJ-CI, or TAPG in the LT group. We did not find a significant correlation between AET and any of the studied manometric parameters in the controls (Fig. 2).

Figure 2. Correlation between acid exposure time (AET) and the studied manometric parameters in the lung transplant (LT) group and the control group. DCI, distal contractile integral; LES-PI, lower esophageal sphincter pressure integral; EGJ-CI, esophagogastric junction contractile integral; TAPG, thoraco-abdominal pressure gradient.

Table 4 . Correlation Coefficients of Acid Exposure Time and Selected Manometric Parameters in the Lung Transplant Group and Controls

VariablesAll patientsLT groupControls
Correlation coefficientP-valueCorrelation coefficientP-valueCorrelation coefficientP-value
% of ineffective swallows0.210.1470.590.0410.080.663
Mean DCI–0.260.073–0.790.002–0.070.699
LES-PI0.020.883–0.030.9140.090.606
EGJ-CI0.030.839–0.220.4850.140.407
Total EGJ-CI–0.140.336–0.570.051–0.060.744
TAPG0.120.401–0.020.9460.200.246

DCI, distal contractile integral; LES-PI, lower esophageal sphincter pressure integral; EGJ-CI, esophagogastric junction contractile integral; Total EGJ-CI, total esophagogastric junction contractile integral; TAPG, thoraco-abdominal pressure gradient.


Discussion

Although GERD is commonly encountered after LT, the underlying mechanism remains unknown, and it is unclear if acid reflux pathophysiology is different in LT recipients from other acid reflux patients. In this study, to evaluate the underlying esophageal motility changes in LT recipients with acid reflux, we compared LT recipients with pH study proven pathologic acid reflux to matched controls with a similar degree of AET.

Comparison Regarding Esophagogastric Junction Metrics Competency

Our study revealed significant differences between both groups regarding EGJ competency. EGJ-CI, Total EGJ-CI, and LES-PI were significantly higher in LT patients despite no history of anti-reflux surgeries in this group of patients. Interestingly, the EGJ competency metrics for LT patients in our study were even higher compared to the normal population studied in previous literature. Jasper et al18 measured LES-PI, EGJ-CI, and Total EGJ-CI in 64 healthy controls to determine normal values. The mean values for these healthy controls were lower than our LT patients as follows (LES-PI: 141.70 ± 143.10 vs 439.56 ± 174.25, EGJ-CI: 67.70 ± 26.00 vs 89.22 ± 33.26, Total EGJ-CI: 67.00 ± 21.90 vs 113.98 ± 91.14, respectively). Similarly, the study by Gor et al28 showed that EGJ CI was 46.20 ± 7.60 in healthy controls vs 89.22 ± 33.26 for LT patients in our study. These results also go along with previous studies that supported increased EGJ competency after LT.29,30

These higher EGJ competency metrics in our LT patients can be attributed to the higher AP in this group of patients and its effect on LES pressure. The relation between AP and LES pressure was illustrated by Mittal et al.31 They showed increased LES pressure during provoked increased AP by straight leg raising and abdominal compression in 15 healthy subjects. They explained this finding by using diaphragmatic electromyography that detects tonic contractions of the crural diaphragm, which encircles LES, after increased AP. Another study confirmed these results after measuring LES pressure during leg raising in 58 individuals.32 LT recipients in our study had higher AP compared to controls (19.44 mmHg vs 16.42 mmHg), which can explain higher EGJ metrics in our LT patients. Another potential explanation is the numerically higher percentage of chronic opioid analgesic users in the LT group (45.5%) vs (22.2%) in controls. Opioids are known to increase tonic spasms of smooth muscles by direct activation of opioid receptors or inhibition of nitric oxide release33,34 and were shown in previous studies to increase the resting LES tone.22,35,36

Comparison Regarding Esophageal Peristalsis Vigor

Although not statistically significant, patients who underwent LT exhibited stronger peristalsis vigor and a lower percentage of ineffective swallows compared to control subjects. This finding suggests that this specific population may tolerate a more circumferential wrap during anti-reflux surgeries, with low incidence of post-surgical dysphagia. In fact, 10 of the included LT patients underwent anti-reflux surgeries, with only 1 patient experiencing persistent (> 3 months)37 post-surgical dysphagia that was mild and did not require intervention. Our results align with previous literature, indicating that anti-reflux surgeries can be safely performed in LT recipients with minimal post-surgical dysphagia.38-40 Additionally, future research could explore the possibility of utilizing alternative modalities such as magnetic sphincter augmentation to control acid reflux after LT, potentially resulting in a lower incidence of dysphagia compared to other reflux patients treated with the same modality.41,42

Comparison Regarding Acid Exposure Time Correlation With Esophageal Peristalsis

AET in LT patients had the most significant correlation with peristaltic vigor (mean DCI r = –0.79 with P-value 0.002, percentage of ineffective swallows r = 0.595 with P-value 0.041). On the other hand, no significant correlation between these metrics and AET was found in controls. This significant correlation within LT acid reflux patients suggests that poor acid clearance is the main driving event for reflux pathogenesis in this group. A study by Davis et al19 showed that esophageal peristalsis, bolus clearance, and esophageal transit time were the main factors for the development of GERD after LT, while LES pressure played a limited role in GERD pathogenesis.

This correlation with peristalsis might be related to the degree of vagal nerve manipulation during LT surgery.43-46 As the vagal nerve controls primary and secondary esophageal peristalsis, reduced vagal tone affects esophageal contraction amplitude and prolongs bolus clearance.6,47,48 On the other hand, using a parasympathomimetic agent, bethanechol was shown to empower vagal innervation and improve peristalsis and bolus transit time in patients with severe ineffective esophageal motility.49

Comparison Regarding Acid Exposure Time Correlation With Lower Esophageal Sphincter Competency Metrics

In LT patients, Total EGJ CI showed a higher correlation with AET (cor –0.573, P = 0.051) contrary to the control group where the correlation was less pronounced (cor –0.142, P = 0.336). We noticed that among the 3 EGJ metrics, Total EGJ-CI correlated the best with AET in LT patients likely denoting a better representation of EGJ competency compared to LES-PI and EGJ-CI. This might be since Total EGJ-CI is referenced to the patient’s gastric and not atmospheric pressure as in LES-PI. Moreover, Total EGJ-CI assesses EGJ competency over several minutes rather than a single point in time, which minimizes the impact of fluctuation in EGJ morphology and pressure.18,50,51

Comparison Regarding Acid Exposure Time Correlation With Thoraco-abdominal Pressure Gradient

More negative TP can drive reflux by increasing TAPG that will overcome the LES reflux barrier,52-56 thus TAPG was proposed as a contributing factor to reflux in advanced respiratory patients. One study evaluated TAPG in LT candidates and showed a significantly lower TP (–7.5 mmHg vs –0.7 mmHg) and a significantly higher TAPG (24.4 mmHg vs 15.3 mmHg) in patients with restrictive lung diseases compared to controls.25 In this study, Masuda et al25 suggested the significant role of TAPG in the pathogenesis of GERD before LT. In our study, the post LT group had a trend towards a higher TAGP compared to controls (20.8 mmHg vs 17.9 mmHg), along with a significantly higher AP which are likely contributing to GERD pathogenesis in this setting. This suggests the possible role of diaphragmatic breathing to alleviate post lung transplant acid reflux. Through its role in increasing LES pressure, diaphragmatic breathing can maintain a normal gastroesophageal pressure gradient against high AP.57 However, this will require formal evaluation in future studies.

Comparison Regarding the Prevalence of Gastroesophageal Reflux Disease Symptoms in Both Groups

We observed a lower prevalence of GERD symptoms in the post LT group compared to the matched controls; 41.6% of LT patients were asymptomatic compared to 2.7% of the matched controls. This can be, at least partially, attributed to the routine ordering of HRM in post LT patients as a part of patient evaluation regardless of symptoms in our institution. These findings are in agreement with prior studies as well58-62 and further support routinely screening the LT recipients for GERD regardless of symptoms.

Study Limitations

Our study has some limitations. First, we only included subjects with pH proven GERD and excluded those incomplete studies which ended up with a small sample size. However, we believe that these strict inclusion criteria are necessary to appropriately assess our research question. Second, being a retrospective study, we were restricted to the standard HRM protocol in our institution and we could not assess other metrics such as TLESR which was implemented in the pathophysiology of GERD in patients with lung diseases according to previous studies.63,64 Moreover, our HRM protocol at that time did not include upright swallows or provocative maneuvers, which complement the standard protocol in evaluating peristaltic vigor and lower esophageal relaxation pressure.65 Furthermore, although our results suggest that hypoperistalsis is the main drive for GERD pathophysiology in the LT group, we are unable to ascertain a causative relation between peristaltic vigor and acid exposure due to the retrospective nature, a limitation that is common in studies of similar design.66-68

In conclusion, this is the first study to our knowledge that compares the underlying manometric changes in LT recipients with pH proven acid reflux to matched controls. EGJ barrier function was less impaired with a higher TAPG in LT recipients. Esophageal peristaltic vigor was the highest correlating factor with AET following LT. These findings can have practical implications for treatment approaches; however, prospective trials are needed to determine causation. Future studies on larger cohorts should also include extended postprandial manometry protocols and ambulatory multichannel impedance reflux testing to evaluate the contribution of TLESR and non-acid reflux to GERD pathogenesis in this setting.

Financial support:

None.

Conflicts of interest

None.

Author contributions

Mazen Elsheikh and Lekan Akanbi: study design, data collection, and drafting of the manuscript; Lisbeth Selby: study design and critical review of the manuscript; and Bahaaeldeen Ismail: study design, data collection, statistical analysis, drafting of the manuscript, and critical review.

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